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Lacoste Jeanson A, Romero Morales M, Flores Luna RI. Assessing musculoskeletal injury risk and skeletal changes from backstrap loom weaving and traditional embroidery in Chiapas, Mexico. PLOS GLOBAL PUBLIC HEALTH 2025; 5:e0004574. [PMID: 40299903 PMCID: PMC12040135 DOI: 10.1371/journal.pgph.0004574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Accepted: 04/03/2025] [Indexed: 05/01/2025]
Abstract
Few medical studies are led in places where social security services are almost inexistent, leaving a gap in knowledge about occupational health risks tied to traditional crafts. This study investigates how traditional textile work-specifically embroidery and backstrap loom weaving work-affects the body in the Highlands of Chiapas, where these crafts represent a substantial part of thousands of women daily activity. Using multi-angle video recordings and interviews with adult women skilled in these crafts, the study evaluates musculoskeletal injury risk through biomechanical analysis. It examines movement types, repetition, involved body parts and muscles, and static postures. Tools such as the Rapid Entire Body Assessment (REBA), Standardized Nordic questionnaires, and evaluation of skeletal changes support this assessment. Findings show frequent, repetitive motions in the upper limbs and fingers, often approaching joint mobility limits (e.g., elbows flexed 60-100°, wrists >15°). These are combined with static, physically demanding postures-spine, neck, and legs are under constant strain due to ground-level sitting positions with the hips flexed at 90°, neck >20°, and knees deeply flexed in some cases (cross-legged or kneeling). Potential musculoskeletal injuries include tendinitis, carpal tunnel syndrome, tenosynovitis, bursitis, spinal disc herniation, and spondylolysis. Skeletal changes would mainly affect the hands, wrists, elbows, and spine, with asymmetry in embroidery and more symmetry in backstrap weaving. These may appear as localized entheseal changes and osteoarthritis. The study demonstrates the need of setting out preventive actions to reduce the injuries risk implied by traditional embroidery and backstrap loom weaving crafts. In order to assess actual musculoskeletal changes linked to those activities, a project is underway to examine bone markers specific to textile craftsmanship in ancient peoples of the same Maya area found buried with textile-making tools.
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Affiliation(s)
- Alizé Lacoste Jeanson
- Instituto de Investigaciones Antropológicas, Universidad Nacional Autónoma de México, Coyoacán, Ciudad de México, México
- UMR 5199 PACEA (De la Préhistoire à l’Actuel: Culture, Environnement et Anthropologie), Université de Bordeaux, Talence, France
| | - Monserrat Romero Morales
- Facultad de Ingeniería, Universidad Nacional Autónoma de México, Coyoacán, Ciudad de México, México
| | - Rosa Itzel Flores Luna
- Facultad de Ingeniería, Universidad Nacional Autónoma de México, Coyoacán, Ciudad de México, México
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Terpstra SES, van de Stadt LA, Reijnierse M, Groenwold RHH, Rosendaal FR, Kloppenburg M. Bone marrow lesions and collateral ligament lesions are associated in interphalangeal joints with osteoarthritis: The Hand OSTeoArthritis in Secondary care cohort. Osteoarthritis Cartilage 2025:S1063-4584(25)00999-9. [PMID: 40287123 DOI: 10.1016/j.joca.2025.04.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 04/03/2025] [Accepted: 04/17/2025] [Indexed: 04/29/2025]
Abstract
OBJECTIVES To investigate whether bone activity adjacent to collateral ligaments is present and results in collateral ligament lesions (CLLs) of the proximal and distal interphalangeal joints in patients with hand osteoarthritis (OA), and vice versa. METHODS We used data measured on baseline, year two and year four from the Hand OSTeoArthritis in Secondary care cohort. MR images of the right hand were scored at the radial and ulnar 1/3rd of each joint ("=joint side") for bone marrow lesions (BMLs) and CLLs (=non-visible or non-continuous ligament). Odds ratios (ORs) with 95% confidence intervals were used to quantify longitudinal associations at the same joint side, adjusted for patient effect. RESULTS In 261 patients (mean age 61 years, 84% women), BMLs were present at baseline in 113/4169 joint sides (3%), and at year four in 89/3356 (3%). Any CLL was present at baseline in 500/4169 joint sides (12%), and at year four in 559/3356 (17%). The presence of BMLs and CLL was cross-sectionally associated. In baseline joint sides without CLLs, BMLs were positively associated with CLL development in the corresponding joint side at year two and four (OR 3.7 (1.5;9.1) and 4.9 (2.3;10.7), respectively), compared with no BMLs. In baseline joint sides without BMLs, CLLs were positively associated with BMLs at the same side at year two and four (9.2 (3.9;22.1) and 11.0 (5.8;20.9) respectively), compared with no CLLs. CONCLUSIONS BMLs are rare yet associated with CLLs that are more common, both cross-sectionally and longitudinally, both adding to the OA process.
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Affiliation(s)
- Sietse E S Terpstra
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
| | - Lotte A van de Stadt
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, The Netherlands.
| | - Monique Reijnierse
- Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
| | - Rolf H H Groenwold
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
| | - Frits R Rosendaal
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
| | - Margreet Kloppenburg
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
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Garros CW, Powers MJ, Dyer AD, Currie PJ. Osteohistological analysis of metatarsals reveals new information on pathology and life history of troodontids from the Campanian Dinosaur Park Formation, Alberta, Canada. J Anat 2025. [PMID: 40252006 DOI: 10.1111/joa.14262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 03/21/2025] [Accepted: 04/06/2025] [Indexed: 04/21/2025] Open
Abstract
Troodontidae is a family of small-bodied theropods known predominantly from Asia but are comparatively scarce in North America. In the Dinosaur Park Formation (DPF) of Alberta, Canada, they are known predominantly from isolated material, precluding taxonomic and ontogenetic precision for this clade. Previously never sampled histologically within the DPF, here we attempt to fill in gaps in our knowledge about the life histories of the clade in this formation by histologically surveying metatarsals, which are among the most abundant and identifiable troodontid elements in the DPF. We sampled 11 metatarsals (three metatarsal IIs, three metatarsal IIIs and five metatarsal IVs) of varying sizes and included three pathological individuals to describe the microanatomy of both healthy and pathological metatarsals, determine the ontogenetic status of each element and graph their pattern of growth. Osteohistology reveals that troodontid metatarsals grew and remodelled asymmetrically within the cortex, ceasing growth and remodelling primarily along articular surfaces and entheses. Pathological individuals ranged from displaying features of response to localised stress (chronic callus formation and avulsion/chip fracture) to extreme modification in response to trauma and inflammation at the distal joint. Only the latter appeared to be related to overall growth, suggesting the condition either developed early and stunted growth or another underlying cause was responsible for both the stunted growth and the resulting pathological features observed. Overall, tracking the growth of the specimens reveals that there are at least two growth trajectories within the DPF differentiated by the timing of major growth spurts and growth plateaus. Whether this represents sexual dimorphism, taxonomic diversity, or another form of variation warrants further investigation.
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Affiliation(s)
- Christiana W Garros
- Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
| | - Mark J Powers
- Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
| | - Aaron D Dyer
- Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, Ontario, Canada
- Department of Natural History, Royal Ontario Museum, Toronto, Ontario, Canada
| | - Philip J Currie
- Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
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Karakostis FA. Introducing "Validated entheses-Based reconstruction of activity 2.0" (VERA 2.0): Semi-automated 3D analysis of bone surface changes. PLoS One 2025; 20:e0321479. [PMID: 40238840 PMCID: PMC12002543 DOI: 10.1371/journal.pone.0321479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Accepted: 03/05/2025] [Indexed: 04/18/2025] Open
Abstract
In archaeological sciences, the macroscopic morphology of distinct dry bone structures, such as tubercles, ridges, epicondyles, and fossae, is routinely used to infer habitual activity patterns in past human populations, extinct hominins, and other animals. This study introduces "Validated Entheses-based Reconstruction of Activity 2.0" (VERA 2.0), a new method for precisely quantifying 3D surface irregularities on enthesis-bearing bone structures. Building on VERA 1.0, first introduced by the same author in 2016 and later named in a 2021 literature review, VERA 2.0 enhances the previous approach by incorporating a semi-automated image segmentation technique that reduces manual input while maintaining accuracy. The method involves selecting a predefined broad bone surface region, after which an algorithm automatically detects subtle surface irregularities (see example video in the step-by-step protocol at dx.doi.org/10.17504/protocols.io.5jyl82z8dl2w/v3). Validation analyses confirm VERA 2.0's precision and reliability for activity reconstruction through intra- and inter-observer repeatability tests, experimental research comparing activity and control laboratory specimens, and analyses of historical human skeletons with extensively detailed long-term occupational data. Moreover, while this anthropological 3D measuring protocol paper cannot and does not aim to analyze the anatomical and histological nature of bone surface irregularities, preliminary anatomical dissection and virtual analysis of a cadaveric thumb enthesis suggest a possible association with attaching muscles and ligaments. Future anatomical and histological research aiming to explore soft-hard tissue interactions could clarify how these identified surface changes exactly relate to the attaching tissues. Overall, VERA 2.0 provides a robust, efficient quantitative tool for inferring activity patterns from skeletal remains, with applications across paleontological, paleoanthropological, and bioarchaeological contexts.
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Affiliation(s)
- Fotios Alexandros Karakostis
- Palaeoanthropology, Department of Geosciences, University of Tübingen, Tübingen, Germany
- Senckenberg Centre for Human Evolution and Palaeoenvironment, Senckenberg Research Institute, Tübingen, Germany
- Integrative Prehistory and Archaeological Science, University of Basel, Basel, Switzerland
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Fujihara K, Yoneda T, Sugidono A, Okada Y, Hiyama S, Kajikawa S, Fukunaga Y, Koch M, Izu Y. Collagen XII deficiency promotes ligament-specific heterotopic ossification via fibrochondrocyte differentiation. Biochem Biophys Res Commun 2025; 757:151621. [PMID: 40088675 DOI: 10.1016/j.bbrc.2025.151621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Revised: 03/05/2025] [Accepted: 03/10/2025] [Indexed: 03/17/2025]
Abstract
Heterotopic ossification of tendons and ligaments causes pain and dysfunction, significantly reducing quality of life. However, its underlying mechanisms remain elusive. In addition to injury, tissue organization and stiffness have been implicated in heterotopic ossification. Collagen XII, a member of the fibril-associated collagens with interrupted triple helices (FACIT) family, plays a crucial role in maintaining the structural integrity and function of tendons and ligaments. Its deficiency alters tissue stiffness and predisposes ligaments to rupture. In this study, we investigated whether collagen XII contributes to the development of heterotopic ossification. Three-dimensional microcomputed tomography (3D-μCT) and X-ray analyses revealed heterotopic bone formation in the knee and ankle ligaments, but not in tendons, of Col12a1-deficient mice, with a 100 % incidence in mice older than 19 weeks. Histological analysis showed the presence of Alcian blue- and Toluidine blue-positive fibrochondrocyte-like cells in Col12a1-deficient ligaments, which were subsequently replaced by bone tissue, as indicated by Alizarin red staining. Real-time qPCR analysis of knee ligaments demonstrated a slight increase in chondrogenic markers and a significant upregulation of osteogenic markers in Col12a1-deficient mice compared with wild-type controls. In vitro chondrogenesis and osteogenesis assays using primary tenocytes from wild-type and Col12a1-deficient mice revealed that collagen XII deficiency enhanced osteogenic potential, whereas chondrogenic potential remained comparable. Our findings indicate that collagen XII deficiency specifically induces heterotopic bone formation in knee and ankle ligaments, occurring via fibrochondrocytes rather than through endochondral or intramembranous ossification.
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Affiliation(s)
- Kei Fujihara
- Graduate School of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyounan, Musashino, Tokyo, 180-8602, Japan; Department of Comparative Cell Biology, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyounan, Musashino, Tokyo, 180-8602, Japan; Department of Laboratory Animal Science, Faculty of Veterinary Medicine, Okayama University of Science, 1-3 Ikoinooka, Imabari, Ehime, 794-8555, Japan
| | - Taiju Yoneda
- Department of Laboratory Animal Science, Faculty of Veterinary Medicine, Okayama University of Science, 1-3 Ikoinooka, Imabari, Ehime, 794-8555, Japan
| | - Akira Sugidono
- Department of Laboratory Animal Science, Faculty of Veterinary Medicine, Okayama University of Science, 1-3 Ikoinooka, Imabari, Ehime, 794-8555, Japan
| | - Yukina Okada
- Department of Animal Risk Management, Faculty of Risk and Crisis Management, Chiba Institute of Science, 15-8 Shiomi, Choshi, Chiba, 288-0025, Japan
| | - Sakura Hiyama
- Department of Animal Risk Management, Faculty of Risk and Crisis Management, Chiba Institute of Science, 15-8 Shiomi, Choshi, Chiba, 288-0025, Japan
| | - Shuhei Kajikawa
- Department of Laboratory Animal Science, Faculty of Veterinary Medicine, Okayama University of Science, 1-3 Ikoinooka, Imabari, Ehime, 794-8555, Japan
| | - Yuko Fukunaga
- Department of Animal Risk Management, Faculty of Risk and Crisis Management, Chiba Institute of Science, 15-8 Shiomi, Choshi, Chiba, 288-0025, Japan
| | - Manuel Koch
- Institute for Dental Research and Oral Musculoskeletal Biology, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50931, Cologne, Germany
| | - Yayoi Izu
- Graduate School of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyounan, Musashino, Tokyo, 180-8602, Japan; Department of Comparative Cell Biology, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyounan, Musashino, Tokyo, 180-8602, Japan; Department of Laboratory Animal Science, Faculty of Veterinary Medicine, Okayama University of Science, 1-3 Ikoinooka, Imabari, Ehime, 794-8555, Japan.
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Xu T, Rao J, Mo Y, Lam ACH, Yang Y, Wong SWF, Wong KH, Zhao X. 3D printing in musculoskeletal interface engineering: Current progress and future directions. Adv Drug Deliv Rev 2025; 219:115552. [PMID: 40032068 DOI: 10.1016/j.addr.2025.115552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 02/17/2025] [Accepted: 02/28/2025] [Indexed: 03/05/2025]
Abstract
The musculoskeletal system relies on critical tissue interfaces for its function; however, these interfaces are often compromised by injuries and diseases. Restoration of these interfaces is complex by nature which renders traditional treatments inadequate. An emerging solution is three-dimensional printing, which allows for precise fabrication of biomimetic scaffolds to enhance tissue regeneration. This review summarizes the use of 3D printing in creating scaffolds for musculoskeletal interfaces, mainly focusing on advanced techniques such as multi-material printing, bioprinting, and 4D printing. We emphasize the significance of mimicking natural tissue gradients and the selection of appropriate biomaterials to ensure scaffold success. The review outlines state-of-the-art 3D printing technologies, varying from extrusion, inkjet and laser-assisted bioprinting, which are crucial for producing scaffolds with tailored mechanical and biological properties. Applications in cartilage-bone, intervertebral disc, tendon/ligament-bone, and muscle-tendon junction engineering are discussed, highlighting the potential for improved integration and functionality. Furthermore, we address challenges in material development, printing resolution, and the in vivo performance of scaffolds, as well as the prospects for clinical translation. The review concludes by underscoring the transformative potential of 3D printing to advance orthopedic medicine, offering a roadmap for future research at the intersection of biomaterials, drug delivery, and tissue engineering.
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Affiliation(s)
- Tianpeng Xu
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region
| | - Jingdong Rao
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region
| | - Yongyi Mo
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region
| | - Avery Chik-Him Lam
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region
| | - Yuhe Yang
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region; The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, China
| | - Sidney Wing-Fai Wong
- Industrial Centre, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region
| | - Ka-Hing Wong
- Research Institute for Future Food, Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region
| | - Xin Zhao
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region; The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, China; Research Institute for Intelligent Wearable Systems, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region.
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7
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Pierantoni M, Sharma K, Kok J, Novak V, Eliasson P, Isaksson H. Quantification of 3D microstructures in Achilles tendons during in situ loading reveals anisotropic fiber response. Acta Biomater 2025; 194:246-257. [PMID: 39800097 DOI: 10.1016/j.actbio.2025.01.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 12/19/2024] [Accepted: 01/09/2025] [Indexed: 01/15/2025]
Abstract
While the number of studies investigating Achilles tendon pathologies has grown exponentially, more research is needed to gain a better understanding of the complex relation between its hierarchical structure, mechanical response, and failure. At the microscale, collagen fibers are, with some degree of dispersion, primarily aligned along the principal loading direction. However, during tension, rearrangements and reorientations of these fibers are believed to occur. As 3D micro-movements are hard to capture, the precise nature of this fiber reorganization remains unknown. This study aimed to visualize and quantify the intricate fiber changes occurring within rat Achilles tendons under tension. Rat tendons were in situ loaded with concurrent synchrotron phase contrast microCT imaging. The results are heterogenous and show that collagen fibers' response to loading is nonuniform and depends on anatomical orientation. Furthermore, damage propagation could be visualized, revealing that in the presence of heterotopic ossification, damage proceeds within the ossified deposits rather than at the interface between hard and soft tissues. Our approach could effectively capture the microstructural changes occurring during loading and shows promise in understanding the relation between microstructure and mechanical response for ex-vivo Achilles tendons and other biological tissues. STATEMENT OF SIGNIFICANCE: Achilles tendons endure high mechanical loads during daily motion and physical activities. Understanding the structural and mechanical responses of Achilles tendons to such loads is vital for elucidating their function in health and pathology. We have combined the use of synchrotron phase contrast microCT with in situ mechanical loading to contribute to a better understanding of the relation between microstructural response and organ scale mechanical properties. The proposed methodology will be valuable for future research into the interplay between structure, mechanics, and pathology of tendons, and for the development of more effective strategies to preserve tendon function and possibly mitigating musculoskeletal disorders.
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Affiliation(s)
- Maria Pierantoni
- Department of Biomedical Engineering, Lund University, Box 118, 221 00 Lund, Sweden.
| | - Kunal Sharma
- Department of Biomedical Engineering, Lund University, Box 118, 221 00 Lund, Sweden
| | - Joeri Kok
- Department of Biomedical Engineering, Lund University, Box 118, 221 00 Lund, Sweden
| | - Vladimir Novak
- Swiss Light Source, Paul Scherrer Institute, Villigen PSI 5232, Switzerland
| | - Pernilla Eliasson
- Department of Biomedical and Clinical Sciences, Linköping University, 581 83 Linköping, Sweden; Department of Orthopaedics, Sahlgrenska University Hospital, Gothenburg 413 45, Sweden
| | - Hanna Isaksson
- Department of Biomedical Engineering, Lund University, Box 118, 221 00 Lund, Sweden
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Cheppalli NS, Metikala S, Purudappa PP, Tranchida G, Washer DC. High-Tensile Strength Suture Materials in Orthopaedics. JBJS Rev 2025; 13:01874474-202503000-00007. [PMID: 40130941 DOI: 10.2106/jbjs.rvw.24.00193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/26/2025]
Abstract
» High-tensile strength suture materials (HTSSMs) have significantly advanced the field of orthopaedic surgery by providing superior strength, enhanced handling characteristics, and improved durability compared with first-generation sutures.» These sutures are critical for ensuring repair integrity during the healing process of tendon-to-bone or tendon-to-tendon constructs.» While second-generation HTSSMs such as FiberWire, Orthocord, and Force Fiber offer higher tensile strength, better knot security, and reduced creep, their mechanical and biological properties vary, making it essential for surgeons to tailor their choice based on the tissue type, surgical technique, and patient-specific factors.» The incorporation of advanced materials such as ultra-high molecular weight polyethylene and innovative designs such as core-plus-braid configurations has further minimized risks of failure from abrasion, knot slippage, or tissue cut through.» Despite these advancements, challenges such as potential tissue irritation, granuloma formation, and suture cutout remain. Selecting the appropriate HTSSM involves balancing mechanical strength with handling properties and biological responses.» Flat sutures distribute load more evenly and are less prone to tissue cutout, making them ideal for delicate tissues, while round sutures offer better abrasion resistance in high-stress repairs.» In addition, understanding key properties such as stiffness, creep, and knot security can help optimize outcomes and minimize complications.» Surgeons should remain vigilant about the trade-offs associated with material coatings and knot volume, as these factors can influence both repair success and postoperative tissue health.
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Affiliation(s)
- Naga Suresh Cheppalli
- Department of Orthopedic and Rehabilitation, University of New Mexico, Albuquerque, New Mexico
| | - Sreenivasulu Metikala
- Department of Orthopaedic Surgery, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | | | - Geneva Tranchida
- Department of Orthopedic and Rehabilitation, University of New Mexico, Albuquerque, New Mexico
| | - Daniel C Washer
- Department of Orthopedic Surgery, University of New Mexico, Albuquerque, New Mexico
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Zhang X, Fu B, Li Y, Deng L, Fu W. Effects of habitual foot strike patterns on patellofemoral joint and Achilles tendon loading in recreational runner. Gait Posture 2025; 117:121-128. [PMID: 39701021 DOI: 10.1016/j.gaitpost.2024.12.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 11/08/2024] [Accepted: 12/12/2024] [Indexed: 12/21/2024]
Abstract
BACKGROUND Most running biomechanics studies have focused on either the patellofemoral joint (PFJ) or Achilles tendon (AT) alone, generating fragmented understanding of how these structures interact as components of an integrated kinetic chain during running. This study was to investigate concurrent biomechanical changes in the PFJ and AT in recreational runners. METHODS The recreational runners who are accustomed to run with rearfoot strike (RFS, n = 15) and forefoot strike (FFS, n = 15) patterns were recruited. They were instructed to run at 10 km/h in cushion shoes with their habitual strike patterns on an instrumented split-belt treadmill. Kinematics of the ankle and knee joints in the sagittal plane and ground reaction forces were recorded simultaneously. The contact force and stress at the PFJ, as well as the force, loading rate, impulse, and stress of the AT, were calculated. RESULTS The habitual RFS runners had significantly higher peak extension moment (p = 0.019, ES = 0.906), peak quadriceps force (p = 0.010, ES = 1.008), PFJ contact force (p = 0.007, ES = 1.056) and stress (p = 0.042, ES = 0.958) than habitual FFS runners. The peak plantar flexion moment (p < 0.001, ES = 2.692), peak AT force (p < 0.001, ES = -1.788), average (p < 0.001, ES = -2.337) and peak AT loading rate (p < 0.001, ES =-1.996), AT impulse (p = 0.002, ES = -1.246) and stress (p = 0.006, ES = -1.082) of the habitual RFS runners were significantly lower than those of the habitual FFS runners. CONCLUSION The FFS pattern could decrease PFJ load but simultaneously increased the mechanical load on the AT. Conversely, the RFS pattern increased PFJ load, but imposed less load on the AT.
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Affiliation(s)
- Xini Zhang
- Faculty of Sports Science, Ningbo University, Ningbo, China; Research Academy of Grand Health, Ningbo University, Ningbo, China; Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, China
| | - Baisheng Fu
- Faculty of Sports Science, Ningbo University, Ningbo, China; Research Academy of Grand Health, Ningbo University, Ningbo, China
| | - Yuxin Li
- Faculty of Sports Science, Ningbo University, Ningbo, China; Research Academy of Grand Health, Ningbo University, Ningbo, China
| | - Liqin Deng
- Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, China
| | - Weijie Fu
- Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, China.
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10
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Ishii D, Sato S, Fujie H. Dynamic Deformation Behavior of the Porcine Anterior Cruciate Ligament Enthesis Under Anterior Tibial Loading. Ann Biomed Eng 2025; 53:588-596. [PMID: 39604621 PMCID: PMC11836234 DOI: 10.1007/s10439-024-03654-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 11/13/2024] [Indexed: 11/29/2024]
Abstract
This study determined the insertion angle at the porcine anterior cruciate ligament (ACL) enthesis under joint loading to provide information on the structure and mechanical function of the enthesis. Ten intact porcine knee joints were harvested, and an anterior tibial load was applied using a robotic testing system. After dissecting a portion of the ACL enthesis along ligament fibers, the remaining enthesis was imaged using a digital microscope while reproducing the three-dimensional intact knee motion. Fiber orientation angles (FOAs) in the enthesis region (0-300 µm from the ligament-bone boundary) and the ligament region (500-2000 µm from the ligament-bone boundary) were analyzed in the femoral and tibial entheses of the anteromedial bundle (AMB) of the ACL under loading. On the femoral side, the FOA in the enthesis region was significantly higher than that in the ligament region by approximately 10 degrees under loading (n = 5, p < 0.05 in paired t-test). In contrast, the FOAs in the enthesis and ligament regions on the tibial side were nearly equal under loading, with no significant difference (n = 5, p > 0.15 in paired t-test). Histological examination indicated that uncalcified fibrocartilage (UF) was abundant in the enthesis region of the AMB femoral enthesis while the UF was not observed in the enthesis region of the AMB tibial enthesis. Thus, the current data suggest that the regional dependence and independence in FOA are caused by the presence or absence of UF and contributes to a moderate and subtle load-transduction in the ACL enthesis.
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Affiliation(s)
- Daichi Ishii
- Department of Mechanical Systems Engineering, Graduate School of Systems Design, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji-shi, Tokyo, 192-0397, Japan.
| | - Shiho Sato
- Department of Mechanical Systems Engineering, Graduate School of Systems Design, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji-shi, Tokyo, 192-0397, Japan
| | - Hiromichi Fujie
- Department of Mechanical Systems Engineering, Graduate School of Systems Design, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji-shi, Tokyo, 192-0397, Japan.
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Jeong HJ, Hoang LAP, Chen N, Zhu E, Wang A, Chen B, Wang EY, Ricupero CL, Lee CH. Engineering soft-hard tissue interfaces in dental and craniofacial system by spatially controlled bioactivities. Bioact Mater 2025; 45:246-256. [PMID: 39659726 PMCID: PMC11629151 DOI: 10.1016/j.bioactmat.2024.11.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Revised: 11/20/2024] [Accepted: 11/22/2024] [Indexed: 12/12/2024] Open
Abstract
The interface between soft and hard tissues is constituted by a gradient change of cell types and matrix compositions that are optimally designed for proper load transmission and injury protection. In the musculoskeletal system, the soft-hard tissue interfaces at tendon-bone, ligament-bone, and meniscus-bone have been extensively researched as regenerative targets. Similarly, extensive research efforts have been made to guide the regeneration of multi-tissue complexes in periodontium. However, the other soft-hard tissue interfaces in the dental and craniofacial system have been somewhat neglected. This review discusses the clinical significance of developing regenerative strategies for soft-hard tissue interfaces in the dental and craniofacial system. It also discusses the research progress in the field focused on bioengineering approaches using 3D scaffolds equipped with spatially controlled bioactivities. The remaining challenges, future perspectives, and considerations for the clinical translation of bioactive scaffolds are also discussed.
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Affiliation(s)
- Hun Jin Jeong
- College of Dental Medicine, Columbia University Irving Medical Center, 630 W. 168 St. – VC12-212, New York, NY, 10032, USA
| | - Lan Anh P. Hoang
- College of Dental Medicine, Columbia University Irving Medical Center, 630 W. 168 St. – VC12-212, New York, NY, 10032, USA
| | - Neeve Chen
- College of Dental Medicine, Columbia University Irving Medical Center, 630 W. 168 St. – VC12-212, New York, NY, 10032, USA
| | - Elen Zhu
- College of Dental Medicine, Columbia University Irving Medical Center, 630 W. 168 St. – VC12-212, New York, NY, 10032, USA
| | - Albert Wang
- College of Dental Medicine, Columbia University Irving Medical Center, 630 W. 168 St. – VC12-212, New York, NY, 10032, USA
| | - Bozhi Chen
- College of Dental Medicine, Columbia University Irving Medical Center, 630 W. 168 St. – VC12-212, New York, NY, 10032, USA
| | - Emma Y. Wang
- College of Dental Medicine, Columbia University Irving Medical Center, 630 W. 168 St. – VC12-212, New York, NY, 10032, USA
| | - Christopher L. Ricupero
- College of Dental Medicine, Columbia University Irving Medical Center, 630 W. 168 St. – VC12-212, New York, NY, 10032, USA
| | - Chang H. Lee
- College of Dental Medicine, Columbia University Irving Medical Center, 630 W. 168 St. – VC12-212, New York, NY, 10032, USA
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12
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de Araújo Pereira A, do Amaral E Castro A, Ahn I, Cecy Kuenzer Goes Esmanhotto P, Yui Aihara A, Irochima Pinheiro F, Sakamoto AP, de Medeiros Pinheiro M, Terreri MT. Axial radiographic structural damage in patients with Enthesitis-Related Arthritis presents a distinct phenotype compared to adults with axial spondyloarthritis: A cross-sectional cohort study. Rheumatol Int 2025; 45:54. [PMID: 39976813 DOI: 10.1007/s00296-025-05799-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 02/01/2025] [Indexed: 03/22/2025]
Abstract
Enthesitis-related arthritis (ERA), a distinct subtype of juvenile idiopathic arthritis (JIA) related to HLA-B27 and peripheral and axial involvement, presents with insidious onset of arthritis and/or enthesitis. However, there is a lack of data concerning axial new bone formation in patients transitioning into adulthood. To evaluate the axial radiographic structural damage (axRxSD), encompassing the sacroiliac joints (SIJ), hips, and spine, in ERA patients across various age groups. A cross-sectional cohort study was conducted with patients aged up to 35 years. Specific tools were used for measuring disease activity (BASDAI, ASDAS), function (BASFI, HAQ-S), mobility (BASMI), clinical enthesitis (MASES), ultrasound evaluation (MASEI), and axRxSD, including mSASSS for spine, Kellgren-Lawrence for hips and modified New York criteria for SIJ. A total of 26 patients were included, of whom 76.9% were males, with a mean age at diagnosis and assessment of 11.9 and 19.7 years, respectively. HLA-B27 positivity was found in 58.3%. Current active arthritis and enthesitis were present in 19.2% and 23%, respectively, with mean MASEI score of 12 (IQR 6-17). Peripheral joint limitation was observed in 50%, despite a BASMI score of 2.2 and 16% occurrence of abnormal FABER test. Most patients were in remission or low disease activity [ASDAS-ESR = 1.2 (0.6-2.3); ASDAS-CRP = 1.55 (0.6-2.4)]. Modified New York criteria were fulfilled by 73.1% of patients and 15.4% had radiographic hip involvement. Spine involvement, measured by mSASSS, was low (IQR 0-4.2), with only two patients exhibiting syndesmophytes. There was no statistical association between any imaging methods and clinical, laboratory, and ultrasound variables, including scores for activity, functionality, and mobility. Significant association was found only between axRxSD and BASMI. Our results showed high frequency of SIJ ankylosis alongside lower radiographic involvement in the spine and hips, suggesting a distinct structural damage phenotype. The early recognition of this outcome and the use of immunobiological therapy may mitigate syndesmophyte occurrence over time.
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Affiliation(s)
- Annelyse de Araújo Pereira
- Paediatric Rheumatology Unit, Paediatrics Department, Federal University of São Paulo, São Paulo, SP, Brazil.
| | - Adham do Amaral E Castro
- Division of Musculoskeletal Radiology, Department of Diagnostic Imaging, Federal University of São Paulo / Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
| | - Isabel Ahn
- Paulista School of Medicine, Federal University of São Paulo, São Paulo, SP, Brazil
| | | | - Andre Yui Aihara
- Dasa, Diagnostic Imaging, São Paulo, SP, Brazil
- Division of Musculoskeletal Radiology, Department of Diagnostic Imaging, Federal University of São Paulo, São Paulo, SP, Brazil
| | - Francisco Irochima Pinheiro
- Biotechnology at Universidade Potiguar and Discipline of Ophtalmology at the Federal University of Rio Grande do Norte (UFRN), Natal, RN, Brazil
| | - Ana Paula Sakamoto
- Paediatric Rheumatology Unit, Paediatrics Department, Federal University of São Paulo, São Paulo, SP, Brazil
| | | | - Maria Teresa Terreri
- Paediatric Rheumatology Unit, Paediatrics Department, Federal University of São Paulo, São Paulo, SP, Brazil
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13
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Li J, Kim C, Alizadeh HV, Garg S, Bruyas A, Zhao P, Passos ISD, Pan CC, Pérez ASF, Skylar-Scott MA, Kim S, Yang YP. Development of a Novel Hybprinter-SAM for Functionally Graded Tissue Engineering Constructs with Patterned and Localized Biochemical Signals. RESEARCH SQUARE 2025:rs.3.rs-5898561. [PMID: 39975888 PMCID: PMC11838729 DOI: 10.21203/rs.3.rs-5898561/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
Engineering native-mimetic tissue constructs is challenging due to their intricate biological and structural gradients. To address this, Hybprinter-SAM was developed by integrating three bioprinting technologies: syringe extrusion (SE), acoustic droplet ejection (ADE) and molten material extrusion (MME). This system not only enables the creation of mechanical gradients by integrating soft and rigid materials spanning 7 order magnitude of stiffness but also facilitates precise patterning and controlled localization of biochemical signals within printed scaffolds. This capability is beneficial in replicating the complexity of native tissues to enhance functionality. Both the printing process and biomaterials were optimized to balance printability, mechanical integrity, and biocompatibility. As a proof of concept, Hybprinter-SAM was used in a bone-tendon regeneration study to engineer a multi-material construct with patterned fibroblast growth factor 2 (FGF-2), resulting in markers indicative of fibrocartilage development. These findings highlight the potential of Hybprinter-SAM as a versatile platform for diverse tissue engineering applications that require complex, functionally graded tissue constructs.
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Affiliation(s)
- Jiannan Li
- Department of Orthopaedic Surgery, School of Medicine, Stanford University, Stanford, CA 94305, USA
| | - Carolyn Kim
- Department of Orthopaedic Surgery, School of Medicine, Stanford University, Stanford, CA 94305, USA
- Department of Mechanical Engineering, School of Engineering, Stanford University, Stanford, CA 94305, USA
| | - Hossein V. Alizadeh
- Department of Orthopaedic Surgery, School of Medicine, Stanford University, Stanford, CA 94305, USA
| | - Shreya Garg
- Department of Orthopaedic Surgery, School of Medicine, Stanford University, Stanford, CA 94305, USA
- Department of Bioengineering, School of Engineering, Stanford University, Stanford, CA 94305, USA
| | - Arnaud Bruyas
- Department of Orthopaedic Surgery, School of Medicine, Stanford University, Stanford, CA 94305, USA
| | - Peng Zhao
- Department of Orthopaedic Surgery, School of Medicine, Stanford University, Stanford, CA 94305, USA
| | - Isadora S. D. Passos
- Department of Orthopaedic Surgery, School of Medicine, Stanford University, Stanford, CA 94305, USA
- Department of Mechanical Engineering, School of Engineering, Stanford University, Stanford, CA 94305, USA
| | - Chi-Chun Pan
- Department of Orthopaedic Surgery, School of Medicine, Stanford University, Stanford, CA 94305, USA
| | - Andrea S. Flores Pérez
- Department of Orthopaedic Surgery, School of Medicine, Stanford University, Stanford, CA 94305, USA
- Department of Bioengineering, School of Engineering, Stanford University, Stanford, CA 94305, USA
| | - Mark A. Skylar-Scott
- Department of Bioengineering, School of Engineering, Stanford University, Stanford, CA 94305, USA
| | - Sungwoo Kim
- Department of Orthopaedic Surgery, School of Medicine, Stanford University, Stanford, CA 94305, USA
| | - Yunzhi P. Yang
- Department of Orthopaedic Surgery, School of Medicine, Stanford University, Stanford, CA 94305, USA
- Department of Bioengineering, School of Engineering, Stanford University, Stanford, CA 94305, USA
- Department of Material Science and Engineering, School of Engineering, Stanford University, Stanford, CA 94305, USA
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14
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Tam KT, Baar K. Using load to improve tendon/ligament tissue engineering and develop novel treatments for tendinopathy. Matrix Biol 2025; 135:39-54. [PMID: 39645093 DOI: 10.1016/j.matbio.2024.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 11/15/2024] [Accepted: 12/01/2024] [Indexed: 12/09/2024]
Abstract
Tendon and ligament injuries are highly prevalent but heal poorly, even with proper care. Restoration of native tissue function is complicated by the fact that these tissues vary anatomically in terms of their mechanical properties, composition, and structure. These differences develop as adaptations to diverse mechanical demands; however, pathology may alter the loads placed on the tissue. Musculoskeletal loads can be generally categorized into tension, compression, and shear. Each of these regulate distinct molecular pathways that are involved in tissue remodeling, including many of the canonical tenogenic genes. In this review, we provide a perspective on the stage-specific regulation of mechanically sensitive pathways during development and maturation of tendon and ligament tissue, including scleraxis, mohawk, and others. Furthermore, we discuss structural features of healing and diseased tendon that may contribute to aberrant loading profiles, and how the associated disturbance in molecular signaling may contribute to incomplete healing or the formation of degenerative phenotypes. The perspectives provided here draw from studies spanning in vitro, animal, and human experiments of healthy and diseased tendon to propose a more targeted approach to advance rehabilitation, orthobiologics, and tissue engineering.
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Affiliation(s)
- Kenneth T Tam
- Biomedical Engineering Graduate Group, University of California Davis, Davis, CA 95616, USA; Department of Neurobiology, Physiology and Behavior, University of California Davis, Davis, CA 95616, USA
| | - Keith Baar
- Biomedical Engineering Graduate Group, University of California Davis, Davis, CA 95616, USA; Department of Neurobiology, Physiology and Behavior, University of California Davis, Davis, CA 95616, USA; Department of Physiology and Membrane Biology, University of California Davis, Davis, CA 95616, USA; VA Northern California Health Care System, Mather, CA 95655, USA.
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15
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Hoegsbjerg C, Møbjerg A, Yeung CYC, Schjerling P, Krogsgaard MR, Koch M, Kjaer M, von Keudell AG, Mackey AL. Fibre type differences in the organisation of mononuclear cells and myonuclei at the tips of human myofibres. J Cell Sci 2025; 138:JCS263660. [PMID: 39704232 DOI: 10.1242/jcs.263660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 12/11/2024] [Indexed: 12/21/2024] Open
Abstract
The myotendinous junction (MTJ) is a weak link in the musculoskeletal system. Here, we isolated the tips of single myofibres from healthy (non-injured) human hamstring muscles for confocal microscopy (n=6) and undertook RNAscope in situ hybridisation (n=6) to gain insight into the profiles of cells and myonuclei in this region, in a fibre type manner. A marked presence of mononuclear cells was observed coating the myofibre tips (confirmed by serial block face scanning electron microscopy and cryosection immunofluorescence), with higher numbers for type I (median 29; range 16-63) than type II (16; 9-23) myofibres (P<0.05). The number of these cells expressing COL22A1 was comparable between fibre types. Myonuclear number and density gradually increased from the myofibre proper towards the tip for both fibre types (P<0.05). COL22A1 was expressed by similar proportions of myonuclei in type I (median 26%; range 13-56) and type II (19%; 3-67) myofibre tips. 70% of the COL22A1-positive nuclei in the MTJ region were myonuclei, and the remaining 30% were MTJ cells. This insight refines our fundamental understanding of the human MTJ at the cell and structural levels.
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Affiliation(s)
- Christian Hoegsbjerg
- Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery, Copenhagen University Hospital - Bispebjerg and Frederiksberg, 2400 Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Ask Møbjerg
- Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery, Copenhagen University Hospital - Bispebjerg and Frederiksberg, 2400 Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Ching-Yan Chloé Yeung
- Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery, Copenhagen University Hospital - Bispebjerg and Frederiksberg, 2400 Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Peter Schjerling
- Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery, Copenhagen University Hospital - Bispebjerg and Frederiksberg, 2400 Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Michael R Krogsgaard
- Section for Sports Traumatology M51, Department of Orthopaedic Surgery, Copenhagen University Hospital - Bispebjerg and Frederiksberg, 2400 Copenhagen, Denmark
| | - Manuel Koch
- Institute for Dental Research and Oral Musculoskeletal Biology, Center for Biochemistry, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany
- Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany
| | - Michael Kjaer
- Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery, Copenhagen University Hospital - Bispebjerg and Frederiksberg, 2400 Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Arvind G von Keudell
- Orthopaedic Trauma Section, Department of Orthopaedic Surgery, Copenhagen University Hospital - Bispebjerg and Frederiksberg, 2400 Copenhagen, Denmark
- Brigham and Women's Hospital, Department of Orthopaedic Surgery, Harvard Medical School, Boston, MA 02115, USA
| | - Abigail L Mackey
- Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery, Copenhagen University Hospital - Bispebjerg and Frederiksberg, 2400 Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
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16
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Chen PJ, Wang K, Lin MH, Sharma R, Kalajzic Z, O'Brien M, Yadav S. Alendronate partially rescues the periodontal defects in OIM mouse model of osteogenesis imperfecta. Sci Rep 2025; 15:88. [PMID: 39747677 PMCID: PMC11695738 DOI: 10.1038/s41598-024-84756-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 12/26/2024] [Indexed: 01/04/2025] Open
Abstract
Osteogenesis imperfecta (OI) is a fairly common generalized connective disorder characterized by low bone mass, bone deformities and impaired bone quality that predisposes affected individuals to musculoskeletal fragility. Periodontal ligament (PDL)-alveolar bone and PDL-cementum entheses' roles under OI conditions during physiological loading and orthodontic forces remain largely unknown. In addition, bisphosphonates (e.g., alendronate) are commonly used therapeutics for the treatment of OI. Our knowledge, in terms of the affects of alendronate treatment on the PDL entheses in OI is also far from complete. In this study, we identified craniofacial skeletal defects in an osteogenesis imperfecta (oim) murine model of OI. Relative to wild-type littermates, oim mice were found to have decreased skull length, cranial height/width/length, nose length, nasal length, and frontal length. Next, we discovered that oim mice exhibited defects in several dental structures, including short roots and decreased volumes of the alveolar bone, dentin, and cellular cementum. Further, we specifically investigated periodontal defects in the oim mice. Alveolar bone loss in oim mice was primarily associated with elevated bone resorption due to an increased osteoclast number, along with reduced bone formation related to increased sclerostin (SOST) expression. PDL fibers in oim mice were disrupted and discontinuous, while Sharpey's fibers at the PDL-bone entheses were reduced. Mechanism-based studies showed that catabolism of the PDL was elevated in oim mice, as revealed by an increase in MMP13 and CTSK expression. Meanwhile, the quality of the collagen fibers were impaired in oim mice due to a large accumulation of uncleaved collagen I fibers. With alendronate treatment, however, we could partially rescue these phenotypes. This study, for the first time, characterized periodontal defects in oim mice, detailed craniofacial defects and demonstrated the effectiveness of alendronate in partially restoring these defects.
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Affiliation(s)
- Po-Jung Chen
- Department of Growth and Development, University of Nebraska Medical Center, 4000 East Campus Loop South, 68583-0740, Lincoln, NE, US.
| | - Ke Wang
- Division of Orthodontics, University of Connecticut Health Center, Farmington, US
| | - Meng-Hsuan Lin
- Department of Adult Restorative Dentistry, University of Nebraska Medical Center, Lincoln, US
| | | | - Zana Kalajzic
- University of Connecticut Health Center, Farmington, US
| | - Mara O'Brien
- University of Connecticut Health Center, Farmington, US
| | - Sumit Yadav
- Department of Growth and Development, University of Nebraska Medical Center, 4000 East Campus Loop South, 68583-0740, Lincoln, NE, US
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17
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Alhaskawi A, Dong Y, Zou X, Zhou W, Ezzi SHA, Goutham Kota V, Hasan Abdulla Hasan Abdulla M, Abdalbary S, Lu H. Advancements in biomaterials and scaffold design for tendon repair and regeneration. J Appl Biomater Funct Mater 2025; 23:22808000241310684. [PMID: 40420476 DOI: 10.1177/22808000241310684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/28/2025] Open
Abstract
Tendon injuries present a significant clinical challenge due to their limited natural healing capacity and the mechanical demands placed on these tissues. This review provides a comprehensive evaluation of the current strategies and advancements in tendon repair and regeneration, focusing on biomaterial innovations and scaffold design. Through a systematic literature search of databases such as PubMed, Scopus, and Web of Science, key studies were analyzed to assess the efficacy of biocompatible materials like hydrogels, synthetic polymers, and fiber-reinforced scaffolds in promoting tendon healing. Emphasis is placed on the role of collagen fiber architecture, including fiber diameter, alignment, and crimping, in restoring the mechanical strength and functional properties of tendons. Additionally, the review highlights emerging techniques such as electrospinning, melt electrowriting, and hybrid textile methods that allow for precise scaffold designs mimicking native tendon structures. Cutting-edge approaches in regenerative medicine, including stem cell therapies, bioelectronic devices, and bioactive molecules, are also explored for their potential to enhance tendon repair. The findings underscore the transformative impact of these technologies on improving tendon biomechanics and functional recovery. Future research directions are outlined, aiming to overcome the current limitations in scaffold mechanical properties and integration at tendon-bone and tendon-muscle junctions. This review contributes to the development of more effective strategies for tendon regeneration, advancing both clinical outcomes and the field of orthopedic tissue engineering.
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Affiliation(s)
- Ahmad Alhaskawi
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang Province, P. R. China
| | - Yanzhao Dong
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang Province, P. R. China
| | - Xiaodi Zou
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang Province, P. R. China
- Department of Orthopedics, Zhejiang Chinese Medical University, The Second Affiliated School of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, P.R. China
| | - Weijie Zhou
- Department of Orthopedics, No. 903 Hospital of PLA Joint Logistic Support Force, Hangzhou, Zhejiang Province, P. R. China
| | - Sohaib Hasan Abdullah Ezzi
- Department of Orthopaedics, Third Xiangya Hospital, Central South University, Changsha, Hunan Province, P. R. China
| | - Vishnu Goutham Kota
- Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, P. R. China
| | | | - Sahar Abdalbary
- Faculty of Physical Therapy, Department of Orthopedic Physical Therapy, Nahda University in Beni Suef, Beni Suef, Egypt
| | - Hui Lu
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang Province, P. R. China
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Patel PR, Tamas IP, Van Der Bas M, Kegg A, Hilliard BA, Lambi AG, Popoff SN, Barbe MF. Repetitive Overuse Injury Causes Entheseal Damage and Palmar Muscle Fibrosis in Older Rats. Int J Mol Sci 2024; 25:13546. [PMID: 39769311 PMCID: PMC11679654 DOI: 10.3390/ijms252413546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 12/12/2024] [Accepted: 12/16/2024] [Indexed: 01/11/2025] Open
Abstract
Overuse injury is a frequent diagnosis in occupational medicine and athletics. Using an established model of upper extremity overuse, we sought to characterize changes occurring in the forepaws and forelimbs of mature female rats (14-18 months of age). Thirty-three rats underwent a 4-week shaping period, before performing a high-repetition low-force (HRLF) task for 12 weeks, with the results being compared to 32 mature controls. HRLF animals showed a reduced grip strength versus controls. ELISAs carried out in the HRLF rats, versus controls, showed elevated levels of IL1-α in tendons, IL1-α and TNF-α in distal bones/entheses, and TNF-α, MIP1-α/CCL3, and CINC-2/CXCL-3 in serum, as well as IL-6 in forelimb muscles and tendons, and IL-10 in serum. HRLF rats had elevated collagen deposition in the forepaw intrinsic muscles (i.e., fibrosis), entheseal microdamage, and articular cartilage degradation versus the control rats. CD68/ED1+ osteoclasts and single-nucleated cells were elevated in distal forelimb metaphyses of the HRLF animals, versus controls. Declines in grip strength correlated with muscle fibrosis, entheseal microdamage, articular cartilage damage, distal bone/enthesis IL1-α, and serum IL-6. These data demonstrate inflammatory and persistent degradative changes in the forearm/forepaw tissues of mature female animals exposed to prolonged repetitive tasks, changes with clinical relevance to work-related overuse injuries in mature human females.
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Affiliation(s)
- Parth R. Patel
- Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; (P.R.P.); (I.P.T.); (M.V.D.B.); (A.K.); (B.A.H.)
| | - Istvan P. Tamas
- Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; (P.R.P.); (I.P.T.); (M.V.D.B.); (A.K.); (B.A.H.)
| | - Megan Van Der Bas
- Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; (P.R.P.); (I.P.T.); (M.V.D.B.); (A.K.); (B.A.H.)
| | - Abby Kegg
- Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; (P.R.P.); (I.P.T.); (M.V.D.B.); (A.K.); (B.A.H.)
| | - Brendan A. Hilliard
- Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; (P.R.P.); (I.P.T.); (M.V.D.B.); (A.K.); (B.A.H.)
| | - Alex G. Lambi
- Plastic Surgery Section, New Mexico Veterans Administration Health Care System, Albuquerque, NM 87108, USA;
- Department of Surgery, The University of New Mexico School of Medicine, Albuquerque, NM 87106, USA
| | - Steven N. Popoff
- Department of Biomedical Education and Data Science, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA;
| | - Mary F. Barbe
- Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; (P.R.P.); (I.P.T.); (M.V.D.B.); (A.K.); (B.A.H.)
- Department of Biomedical Education and Data Science, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA;
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19
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Xu Z, Xu W, Zhang T, Luo L. Mechanisms of tendon-bone interface healing: biomechanics, cell mechanics, and tissue engineering approaches. J Orthop Surg Res 2024; 19:817. [PMID: 39623392 PMCID: PMC11613615 DOI: 10.1186/s13018-024-05304-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 11/21/2024] [Indexed: 12/06/2024] Open
Abstract
The healing of tendon-bone contact surfaces involves complex biomechanical and biochemical interactions, with pivotal implications for sports medicine and rehabilitation. This review explores applications from cellular mechanics to tissue engineering, emphasizing how biomechanics impact tendon-bone healing. Cells regulate behavior, including growth, differentiation, and migration, by sensing mechanical signals and translating them into biochemical responses, which are critical in the healing process. Cellular mechanics modulate intracellular signaling, thereby influencing biological function and healing capacity. Optimizing tendon-bone interface repair involves modulating the extracellular mechanical environment. This includes physical stimulation, such as stretching, pressure, or vibration, to promote cellular alignment and enhance tissue structural integrity. Tissue engineering in tendon-bone healing focuses on designing scaffolds that mimic the biomechanical properties of the natural tendon-bone interface. Synthesizing these studies provides an in-depth understanding and utilization of biomechanical principles, significantly improving tendon-bone healing and offering new directions for clinical treatments to achieve better therapeutic outcomes and rehabilitation for patients with sports injuries.
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Affiliation(s)
- Zhixiong Xu
- The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, China
| | - Wensheng Xu
- The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, China.
| | - Tao Zhang
- Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, China
| | - Long Luo
- The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, China
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Yang Z, Gordon D, Chen Y, Li H, Wu Y, Meng Z. Understanding the effects of mineralization and structure on the mechanical properties of tendon-bone insertion using mesoscale computational modeling. J Mech Behav Biomed Mater 2024; 160:106735. [PMID: 39288664 PMCID: PMC11560707 DOI: 10.1016/j.jmbbm.2024.106735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 08/29/2024] [Accepted: 09/08/2024] [Indexed: 09/19/2024]
Abstract
Tendon-bone fibrocartilaginous insertion, or enthesis, is a specialized interfacial region that connects tendon and bone, effectively transferring forces while minimizing stress concentrations. Previous studies have shown that insertion features gradient mineralization and branching fiber structure, which are believed to play critical roles in its excellent function. However, the specific structure-function relationship, particularly the effects of mineralization and structure at the mesoscale fiber level on the properties and function of insertion, remains poorly understood. In this study, we develop mesoscale computational models of the distinct fiber organization at tendon-bone insertions, capturing the branching network from tendon to interface fibers and the different mineralization scales. We specifically analyze three key descriptors: the mineralization scale of interface fibers, the mean, and relative standard deviation of the local branching angles of interface fibers. Tensile test simulations on insertion models with varying mineralization scales of interface fibers and structures are performed to mimic the primary loading condition applied to the insertion. We measure and analyze five representative mechanical properties: Young's modulus, strength, toughness, resilience, and failure strain. Our results reveal that mechanical properties are significantly influenced by the three key descriptors, with tradeoffs observed between mutually exclusive properties. For instance, strength and resilience plateau beyond a certain mineralization scale, while failure strain and Young's modulus exhibit monotonic decreasing and increasing trends, respectively. Consequently, there exists an optimal mineralization scale for toughness due to these tradeoffs. By analyzing the mesoscale deformation and failure mechanisms from simulation trajectories, we identify three fracture regimes closely related to the trends in mechanical properties, supporting the observed tradeoffs. Additionally, we examine in detail the effects of the mean and relative standard deviation of local branching angles on mechanical properties and deformation mechanisms. Overall, our study enhances the fundamental understanding of the composition-structure-function relationships at the tendon-bone insertion, complementing recent experimental studies. The mechanical insights from our work have the potential to guide the future biomimetic design of fibrillar adhesives and interfaces for joining soft and hard materials.
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Affiliation(s)
- Zhangke Yang
- Department of Mechanical Engineering, Clemson University, Clemson, SC, 29634, USA
| | - Daniel Gordon
- Department of Bioengineering, Clemson University, Clemson, SC, 29634, USA
| | - Yitong Chen
- Department of Mechanical Engineering, Clemson University, Clemson, SC, 29634, USA
| | - Hui Li
- Department of Bioengineering, Clemson University, Clemson, SC, 29634, USA
| | - Yongren Wu
- Department of Bioengineering, Clemson University, Clemson, SC, 29634, USA
| | - Zhaoxu Meng
- Department of Mechanical Engineering, Clemson University, Clemson, SC, 29634, USA.
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Briolay A, Duboeuf F, Delplace S, Brizuela L, Peyruchaud O, Magne D, Bougault C. Voluntary exercise in mice triggers an anti-osteogenic and pro-tenogenic response in the ankle joint without affecting long bones. Bone Rep 2024; 23:101810. [PMID: 39493871 PMCID: PMC11530850 DOI: 10.1016/j.bonr.2024.101810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 10/09/2024] [Indexed: 11/05/2024] Open
Abstract
Biomechanical stimulation is proposed to occupy a central place in joint homeostasis, but the precise contribution of exercise remains elusive. We aimed to characterize in vivo the impact of mechanical stimulation on the cell-controlled regulation of ossification within the ankles of healthy mice undergoing mild physical activity. DBA/1 male mice were subjected to voluntary running exercise for two weeks, and compared to mice housed in standard conditions (n = 20 per group). Free access to activity wheels resulted in a running exercise of 5.5 ± 0.8 km/day at 14.5 ± 0.5 m/min. Serum levels of alkaline phosphatase, IL-6, IL-8/Kc, IL-17a, and TNF-α were measured. No change in systemic inflammation was detected. The bone architecture of the femur and the calcaneus was unchanged, as revealed by μCT and histology of the enthesis of the Achilles tendon. mRNAs were extracted from femurs, tibias, and ankle joints before RT-qPCR analysis. The expression of the mechanosensitive genes Sclerostin (Sost) and Periostin (Postn) was not impacted by the exercise in long bones. Oppositely, Sost and Postn levels were modulated by exercise in joints, and osteogenic markers (Col10a1, Runx2, Osx, and Dmp1) were downregulated in the exercise group. In addition, the tenogenic markers Scx, Mkx, and Tnmd were upregulated by exercise. Thus, voluntary exercise affected the phenotype of joint cells without impacting long bones. As gene expression of Bmp2, Bmp4, and Id1 was also reduced in these cells, an off-regulation of BMP signaling could be partly responsible for their mechanosensitive response. Running exercise seemed to preserve the tendon from its progressive ossification, as seen in numerous enthesopathies. This study paves the way to future experiments for investigating the effects of mechanical stimulation in various mouse models.
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Affiliation(s)
- Anne Briolay
- Universite Claude Bernard Lyon 1, CNRS, UMR 5246, ICBMS, F-69622 Villeurbanne, France
| | - François Duboeuf
- Universite Claude Bernard Lyon 1, INSERM, UMR 1033, LYOS, F-69372 Lyon, France
| | - Séverine Delplace
- Universite Littoral-Côte d'Opale, ULR 4490, MABLab, F-62327 Boulogne/Mer, France
| | - Leyre Brizuela
- Universite Claude Bernard Lyon 1, CNRS, UMR 5246, ICBMS, F-69622 Villeurbanne, France
| | - Olivier Peyruchaud
- Universite Claude Bernard Lyon 1, INSERM, UMR 1033, LYOS, F-69372 Lyon, France
| | - David Magne
- Universite Claude Bernard Lyon 1, CNRS, UMR 5246, ICBMS, F-69622 Villeurbanne, France
| | - Carole Bougault
- Universite Claude Bernard Lyon 1, CNRS, UMR 5246, ICBMS, F-69622 Villeurbanne, France
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Rothschild B. Entheseal surface (Sharpey's fiber insertion) alterations identify past trauma; bone base robusticity, level of routine activity. Anat Rec (Hoboken) 2024; 307:3884-3891. [PMID: 38838074 DOI: 10.1002/ar.25515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 05/19/2024] [Accepted: 05/21/2024] [Indexed: 06/07/2024]
Abstract
Sharpey's fiber alterations, referred to as entheseal reaction or enthesopathy, have long been considered an indicator of daily activities. Such semantic transformation seems to conflate processes which alter the characteristics of tendonous and ligamentous attachments to bone with the rugosity and extent of their base/footprint. Rather than reflecting normal activities, it is suggested that surface reactions are actually the response to the application of sudden or unconditioned repetitive stresses-analogous to stress fractures. Thus, they are distinct from enlargement of the base/footprint, the bone remodeling process responsible for the robusticity of the area to which the enthesis attaches, which is actually a measure of actual muscle activity. Surface reactions in attachment areas represent injury, be it mechanical stress fracture-equivalents or inflammation-derived. Bone base/footprint is the reaction of the enthesis to stresses of routine physical activities. The character of underlying bone supporting Sharpey's fibers may be augmented by applied stress, but there is neither a physiologic mechanism nor is there evidence for significant addition of Sharpey's fibers beyond ontogeny. Behavior is responsible for the physiologic response of robusticity; spiculation, pathology.
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Dyment NA, Kamalitdinov TB, Kuntz AF. The 2024 Kappa Delta Young Investigator Award: Leveraging Insights From Development to Improve Adult Repair: Hedgehog Signaling as a Master Regulator of Enthesis Fibrocartilage Formation. J Am Acad Orthop Surg 2024; 32:1074-1086. [PMID: 39589737 PMCID: PMC11753257 DOI: 10.5435/jaaos-d-24-00996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 08/31/2024] [Indexed: 11/27/2024] Open
Abstract
The work in this article summarizes findings from our group on key biochemical cues that govern the formation and repair of tendons and ligaments. Specifically, we summarize the journey that started with a serendipitous discovery that is now being translated into novel therapies to improve tendon-to-bone repair outcomes. This journey began with the discovery that the Hedgehog (Hh) signaling pathway was expressed within the enthesis during development and that its primary role was to promote fibrocartilage production and maturation. Next, we developed an anterior cruciate ligament reconstruction model in novel transgenic mice that allowed us to discover that the Hh pathway promotes fibrocartilaginous tendon-to-bone attachments during the integration process. In addition, we established that the coordinated stages of zonal tendon-to-bone integration after anterior cruciate ligament reconstruction were comparable with the stages required for enthesis formation during development. Now that we have demonstrated that the Hh pathway is a potent therapeutic target, we are currently advancing these findings to develop drug delivery systems to improve tendon-to-bone repair. Ultimately, our group aims to establish key mechanisms that govern tendon and ligament formation that can be leveraged for novel regenerative therapies to improve clinical care.
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Affiliation(s)
- Nathaniel A Dyment
- From the Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA (Dr. Dyment, Dr. Kamalitdinov, and Dr. Kuntz), and the Department of Bioengineering, University of Pennsylvania, Philadelphia, PA (Dr. Dyment and Dr. Kamalitdinov)
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24
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Hildebrand T, Ma Q, Heyward CA, Haugen HJ, Nogueira LP. Advanced soft tissue visualization in conjunction with bone structures using contrast-enhanced micro-CT. J Med Imaging (Bellingham) 2024; 11:066001. [PMID: 39583006 PMCID: PMC11584031 DOI: 10.1117/1.jmi.11.6.066001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 10/18/2024] [Accepted: 11/06/2024] [Indexed: 11/26/2024] Open
Abstract
Purpose Micro-computed tomography (CT) analysis of soft tissues alongside bone remains challenging due to significant differences in X-ray absorption, preventing spatial inspection of bone remodeling including the cellular intricacies of mineralized tissues in developmental biology and pathology. The goal was to develop a protocol for contrast-enhanced micro-CT imaging that effectively visualizes soft tissues and cells in conjunction with bone while minimizing bone attenuation by decalcification. Approach Murine femur samples were decalcified in ethylenediaminetetraacetic acid and treated with three different contrast agents: (i) iodine in ethanol, (ii) phosphotungstic acid in water, and (iii) Lugol's iodine. Micro-CT scans were performed in the laboratory setup SkyScan 1172 and at the synchrotron radiation for medical physics beamline in synchrotron radiation facility Elettra. Soft and hard tissue contrast-to-noise ratio (CNR) and contrast efficiency after decalcification were measured. Results In laboratory micro-CT, Lugol's iodine demonstrated a threefold higher CNR in the bone marrow, representing the soft tissue portion, compared with the bone. Contrast efficiencies, measured in synchrotron micro-CT, were consistent with these findings. Higher resolutions and the specificity of Lugol's iodine to cellular structures enabled detailed visualization of bone-forming cells in the epiphyseal plate. Conclusions The combination of decalcification and the utilization of the contrast agent Lugol's iodine facilitated an enhanced soft tissue visualization in conjunction with bone.
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Affiliation(s)
- Torben Hildebrand
- University of Oslo, Department of Biomaterials, Institute of Clinical Dentistry, Faculty of Dentistry, Oslo, Norway
| | - Qianli Ma
- University of Oslo, Department of Biomaterials, Institute of Clinical Dentistry, Faculty of Dentistry, Oslo, Norway
| | - Catherine A. Heyward
- University of Oslo, Oral Research Laboratory, Institute of Clinical Dentistry, Faculty of Dentistry, Oslo, Norway
| | - Håvard J. Haugen
- University of Oslo, Department of Biomaterials, Institute of Clinical Dentistry, Faculty of Dentistry, Oslo, Norway
| | - Liebert P. Nogueira
- University of Oslo, Oral Research Laboratory, Institute of Clinical Dentistry, Faculty of Dentistry, Oslo, Norway
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Kakizaki H, Vaidya A, Naito M, Takahashi Y. Thickness of the Orbital Septum in Comparison to Periorbita and Periosteum. Ophthalmic Plast Reconstr Surg 2024; 40:706-708. [PMID: 39378215 DOI: 10.1097/iop.0000000000002795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/10/2024]
Abstract
PURPOSE To examine the thickness of the orbital septum in comparison to that of the periorbita and the periosteum of the frontal bone. METHODS Histological evaluation of 11 tissues around the upper arcus marginalis, including the orbital septum, periorbita, and periosteum of the frontal bone (5 right, 6 left) from 11 Japanese cadavers (age range: 63-91-year-old, average: 77.1, male: 5 cases and female: 6 cases) was performed. The specimens were fixed in 10% formalin and stained with Masson's trichrome. The thickness was measured at the 2 mm points from the center of the merging area of these 3 tissues (arcus marginalis). Statistical analyses in 3 groups were performed first with a one-way ANOVA and then with Tukey's multiple comparison test. Differences in ages or sexes were compared with the Mann-Whitney U test. The significance level was set at 0.05. RESULTS The orbital septum showed similar thickness with the periosteum of the frontal bone ( p = 0.784), but was thicker than the periorbita ( p = 0.021). The periosteum of the frontal bone was found to be thicker than the periorbita ( p = 0.004). Differences between ages ( p = 0.315) or sexes ( p = 0.126) did not show statistical significance. CONCLUSION The thickness of the orbital septum was similar to the periosteum of the frontal bone, but was thicker than the periorbita at the 2 mm points from the center of the arcus marginalis. These showed some variation in each case, though. Ages or sexes did not influence the septum thickness after 60 years of age.
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Affiliation(s)
- Hirohiko Kakizaki
- Department of Oculoplastic, Orbital & Lacrimal Surgery, Aichi Medical University Hospital, Nagakute, Aichi, Japan
| | - Aric Vaidya
- Department of Oculoplastic, Orbital & Lacrimal Surgery, Kirtipur Eye Hospital, Kathmandu, Nepal
| | - Munekazu Naito
- Department of Anatomy, Aichi Medical University, Nagakute, Aichi, Japan
| | - Yasuhiro Takahashi
- Department of Oculoplastic, Orbital & Lacrimal Surgery, Aichi Medical University Hospital, Nagakute, Aichi, Japan
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Doi K, Moazamian D, Namiranian B, Statum S, Afsahi AM, Yamamoto T, Cheng KY, Chung CB, Jerban S. The Correlation between the Elastic Modulus of the Achilles Tendon Enthesis and Bone Microstructure in the Calcaneal Crescent. Tomography 2024; 10:1665-1675. [PMID: 39453039 PMCID: PMC11511113 DOI: 10.3390/tomography10100122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 10/07/2024] [Accepted: 10/08/2024] [Indexed: 10/26/2024] Open
Abstract
BACKGROUND The calcaneal enthesis, an osseous footprint where the Achilles tendon seamlessly integrates with the bone, represents a complex interface crucial for effective force transmission. Bone adapts to mechanical stress and remodels based on the applied internal and external forces. This study explores the relationship between the elasticity of the Achilles tendon enthesis and the bone microstructure in the calcaneal crescent. METHODS In total, 19 calcaneal-enthesis sections, harvested from 10 fresh-frozen human cadaveric foot-ankle specimens (73.8 ± 6.0 years old, seven female), were used in this study. Indentation tests were performed at the enthesis region, and Hayes' elastic modulus was calculated for each specimen. Micro-CT scanning was performed at 50-micron voxel size to assess trabecular bone microstructure within six regions of interest (ROIs) and the cortical bone thickness along the calcaneal crescent. RESULTS Significant Spearman correlations were observed between the enthesis elastic modulus and trabecular bone thickness in the distal entheseal (ROI 3) and proximal plantar (ROI 4) regions (R = 0.786 and 0.518, respectively). CONCLUSION This study highlights the potential impacts of Achilles tendon enthesis on calcaneal bone microstructure, which was pronounced in the distal calcaneal enthesis, suggesting regional differences in load transfer mechanism that require further investigation.
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Affiliation(s)
- Kenichiro Doi
- Department of Radiology, University of California—San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA (K.Y.C.); (C.B.C.)
- Department of Orthopedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka 810-0180, Japan
| | - Dina Moazamian
- Department of Radiology, University of California—San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA (K.Y.C.); (C.B.C.)
| | - Behnam Namiranian
- Department of Radiology, University of California—San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA (K.Y.C.); (C.B.C.)
| | - Sheronda Statum
- Department of Radiology, University of California—San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA (K.Y.C.); (C.B.C.)
- Radiology Service, Veterans Affairs San Diego Healthcare System—San Diego, La Jolla, CA 92161, USA
| | - Amir Masoud Afsahi
- Department of Radiology, University of California—San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA (K.Y.C.); (C.B.C.)
| | - Takuaki Yamamoto
- Department of Orthopedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka 810-0180, Japan
| | - Karen Y. Cheng
- Department of Radiology, University of California—San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA (K.Y.C.); (C.B.C.)
| | - Christine B. Chung
- Department of Radiology, University of California—San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA (K.Y.C.); (C.B.C.)
- Radiology Service, Veterans Affairs San Diego Healthcare System—San Diego, La Jolla, CA 92161, USA
| | - Saeed Jerban
- Department of Radiology, University of California—San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA (K.Y.C.); (C.B.C.)
- Radiology Service, Veterans Affairs San Diego Healthcare System—San Diego, La Jolla, CA 92161, USA
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Naňka O, Sedmera D, Rammelt S, Bartoníček J. Anatomy of the Achilles tendon-A pictorial review. ORTHOPADIE (HEIDELBERG, GERMANY) 2024; 53:721-730. [PMID: 39212710 DOI: 10.1007/s00132-024-04555-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/31/2024] [Indexed: 09/04/2024]
Abstract
The Achilles tendon (AT) is the strongest tendon of the human body. The knowledge of AT anatomy is a basic prerequisite for the successful treatment of acute and chronic lesions. The structure of the AT results from a complicated fusion of three parts: the tendons of the medial and lateral gastrocnemius and the soleus muscles. From proximal to distal, the tendon fibers twist in a long spiral into a roughly 90° internal rotation. The tendon is narrowest approximately 5-7 cm above its calcaneal insertion and from there it expands again. The topography of the footprints of the individual AT components reflects the tendon origins. The anterior (deep) AT fibers insert into the middle third of the posterior aspect of the calcaneal tuberosity, the posterior (superficial) fibers pass over the calcaneal tuberosity and fuse with the plantar aponeurosis. A deep calcaneal bursa is interposed between the calcaneal tuberosity and the AT anterior surface. The AT has no synovial sheath but is covered along its entire length with a sliding connective tissue, the paratenon which is, however, absent on its anterior surface. The AT is supplied by the posterior tibial artery (PTA) and the peroneal artery (PA). Motor innervation of the triceps surae muscle is provided by fibers of the tibial nerve which also gives off sensitive fibers for the AT. Sensitive innervation is also provided via the sural nerve. The sural nerve crosses the AT approximately 11 cm proximal to the calcaneal tuberosity. The forces acting on the AT during exercise may be up to 12 times the body weight. Physiological stretching of AT collagen fibers ranges between 2% and 4% of its length. Stretching of the tendon over 4% results in microscopic failure and stretching beyond 8% in macroscopic failure.
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Affiliation(s)
- Ondřej Naňka
- Institute of Anatomy, First Faculty of Medicine, Charles University, U Nemocnice 3, Prague 2, Prague, Czech Republic.
| | - David Sedmera
- Institute of Anatomy, First Faculty of Medicine, Charles University, U Nemocnice 3, Prague 2, Prague, Czech Republic
| | - Stefan Rammelt
- University Center for Orthopaedics, Trauma and Plastic Surgery, University Hospital Carl Gustav Carus, Dresden, Germany
| | - Jan Bartoníček
- Institute of Anatomy, First Faculty of Medicine, Charles University, U Nemocnice 3, Prague 2, Prague, Czech Republic
- Department of Orthopedics, First Faculty of Medicine, Charles University and the Central Military Hospital, U Vojenské nemocnice 1200, Prague 6, Prague, Czech Republic
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Wu B, Zhang T, Chen H, Shi X, Guan C, Hu J, Lu H. Exosomes derived from bone marrow mesenchymal stem cell preconditioned by low-intensity pulsed ultrasound stimulation promote bone-tendon interface fibrocartilage regeneration and ameliorate rotator cuff fatty infiltration. J Orthop Translat 2024; 48:89-106. [PMID: 39189009 PMCID: PMC11345897 DOI: 10.1016/j.jot.2024.07.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 05/28/2024] [Accepted: 07/18/2024] [Indexed: 08/28/2024] Open
Abstract
Background Fibrovascular scar healing of bone-tendon interface (BTI) instead of functional fibrocartilage regeneration is the main concern associated with unsatisfactory prognosis in rotator cuff repair. Mesenchymal stem cells (MSCs) exosomes have been reported to be a new promising cell-free approach for rotator cuff healing. Whereas, controversies abound in whether exosomes of native MSCs alone can effectively induce chondrogenesis. Purpose To explore the effect of exosomes derived from low-intensity pulsed ultrasound stimulation (LIPUS)-preconditioned bone marrow mesenchymal stem cells (LIPUS-BMSC-Exos) or un-preconditioned BMSCs (BMSC-Exos) on rotator cuff healing and the underlying mechanism. Methods C57BL/6 mice underwent unilateral supraspinatus tendon detachment and repair were randomly assigned to saline, BMSCs-Exos or LIPUS-BMSC-Exos injection therapy. Histological, immunofluorescent and biomechanical tests were detected to investigate the effect of exosomes injection on BTI healing and muscle fatty infiltration of the repaired rotator cuff. In vitro, native BMSCs were incubated with BMSC-Exos or LIPUS-BMSC-Exos and then chondrogenic/adipogenic differentiation were observed. Further, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the chondrogenesis/adipogenesis-related miRNA profiles of LIPUS-BMSC-Exos and BMSC-Exos. The chondrogenic/adipogenic potential of the key miRNA was verified through function recover test with its mimic and inhibitor. Results The results indicated that the biomechanical properties of the supraspinatus tendon-humeral junction were significantly improved in the LIPUS-BMSC-Exos group than that of the BMSCs-Exos group. The LIPUS-BMSC-Exos group also exhibited a higher histological score and more newly regenerated fibrocartilage at the repair site at postoperative 2 and 4 weeks and less fatty infiltration at 4 weeks than the BMSCs-Exos group. In vitro, co-culture of BMSCs with LIPUS-BMSC-Exos could significantly promote BMSCs chondrogenic differentiation and inhibit adipogenic differentiation. Subsequently, qRT-PCR revealed significantly higher enrichment of chondrogenic miRNAs and less enrichment of adipogenic miRNAs in LIPUS-BMSC-Exos compared with BMSC-Exos. Moreover, we demonstrated that this chondrogenesis-inducing potential was primarily attributed to miR-140, one of the most abundant miRNAs in LIPUS-BMSC-Exos. Conclusion LIPUS-preconditioned BMSC-Exos can effectively promote BTI fibrocartilage regeneration and ameliorate supraspinatus fatty infiltration by positive regulation of pro-chondrogenesis and anti-adipogenesis, which was primarily through delivering miR-140. The translational potential of this article These findings propose an innovative "LIPUS combined Exosomes strategy" for rotator cuff healing which combines both physiotherapeutic and biotherapeutic advantages. This strategy possesses a good translational potential as a local injection of LIPUS preconditioned BMSC-derived Exos during operation can be not only efficient for promoting fibrocartilage regeneration and ameliorating rotator cuff fatty infiltration, but also time-saving, simple and convenient for patients.
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Affiliation(s)
- Bing Wu
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
| | - Tao Zhang
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
| | - Huabin Chen
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
| | - Xin Shi
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
| | - Changbiao Guan
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
| | - Jianzhong Hu
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Mobile Health Ministry of Education - China Mobile Joint Laboratory, Changsha, 410008, Hunan Province, China
| | - Hongbin Lu
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
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29
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Pelea MA, Serban O, Badarinza M, Gutiu R, Fodor D. Shear-Wave Elastography of the Achilles tendon: reliability analysis and impact of parameters modulating elasticity values. J Ultrasound 2024; 27:559-566. [PMID: 38613661 PMCID: PMC11333681 DOI: 10.1007/s40477-024-00877-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 01/31/2024] [Indexed: 04/15/2024] Open
Abstract
PURPOSE Shear wave elastography (SWE) has seen many advancements in Achilles tendon evaluation in recent years, yet standardization of this technique is still problematic due to the lack of knowledge regarding the optimal way to perform the examination. The purpose of this study was to evaluate the effects of ankle position, probe frequency and physical effort on the shear modulus of the Achilles tendon, but also to determine the intra and inter-observer reliability of the technique. METHODS 37 healthy volunteers were included; SWE protocol was performed by two examiners. We analyzed the shear modulus of the tendon with the ankle in neutral, maximum dorsiflexion and maximum plantar flexion using two different high frequency probes. Afterwards, the subjects performed a brief physical exercise and SWE measurements were repeated. RESULTS The L18-5 probe showed the highest ICC values (ICC = 0.798, 95% CI 0.660-0.880, p < 0.001) when positioned at 2 cm from the calcaneal insertion with the ankle in a neutral state. Conversely, utilizing the same L18-5 probe at 1 cm from the insertion during maximum plantar flexion of the ankle resulted in the lowest ICC (ICC = 0.422, 95% CI 0.032-0.655, p = 0.019). Significant variations in elasticity values were noted among different ankle positions and probe types, while no significant changes in elasticity were observed post-physical exercise. CONCLUSION Ankle position and probe frequency are factors that influence elasticity values of the Achilles tendon. An ankle position between 10 and 20 degrees of plantar flexion is the most suitable for SWE evaluation. However, more research focusing on Achilles tendon SWE is essential due to the challenges encountered in standardizing this region.
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Affiliation(s)
- Michael-Andrei Pelea
- 2nd Internal Medicine Department, "Iuliu Hatieganu" University of Medicine and Pharmacy, 2-4 Clinicilor Street, 400006, Cluj-Napoca Napoca, Romania
| | - Oana Serban
- 2nd Internal Medicine Department, "Iuliu Hatieganu" University of Medicine and Pharmacy, 2-4 Clinicilor Street, 400006, Cluj-Napoca Napoca, Romania
| | - Maria Badarinza
- 2nd Internal Medicine Department, "Iuliu Hatieganu" University of Medicine and Pharmacy, 2-4 Clinicilor Street, 400006, Cluj-Napoca Napoca, Romania
| | - Roxana Gutiu
- 2nd Internal Medicine Department, "Iuliu Hatieganu" University of Medicine and Pharmacy, 2-4 Clinicilor Street, 400006, Cluj-Napoca Napoca, Romania
| | - Daniela Fodor
- 2nd Internal Medicine Department, "Iuliu Hatieganu" University of Medicine and Pharmacy, 2-4 Clinicilor Street, 400006, Cluj-Napoca Napoca, Romania.
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Liang C, Fan Z, Zhang Z, Wang P, Deng H, Tao J. Electrospinning technology: a promising approach for tendon-bone interface tissue engineering. RSC Adv 2024; 14:26077-26090. [PMID: 39161449 PMCID: PMC11332360 DOI: 10.1039/d4ra04043k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 07/29/2024] [Indexed: 08/21/2024] Open
Abstract
The regeneration of tendon-bone interface tissue has become a topic of great interest in recent years. However, the complex nature of this interface has posed challenges in finding suitable solutions. Tissue engineering, with its potential to improve clinical outcomes and play a crucial role in musculoskeletal function, has been increasingly explored for tendon-bone interface regeneration. This review focuses on the research advancements of electrospinning technology in interface tissue engineering. By utilizing electrospinning, researchers have been able to fabricate scaffolds with tailored properties to promote the regeneration and integration of tendon and bone tissues. The review discusses the unique structure and function of the tendon-bone interface, the mechanisms involved in its healing, and the limitations currently faced in achieving successful regeneration. Additionally, it highlights the potential of electrospinning technology in scaffold fabrication and its role in facilitating the development of functional and integrated tendon-bone interface tissues. Overall, this review provides valuable insights into the application of electrospinning technology for tendon-bone interface tissue engineering, emphasizing its significance in addressing the challenges associated with regeneration in this complex interface.
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Affiliation(s)
- Chengzhi Liang
- Department of Orthopaedics, The Second Affiliated Hospital of Nanchang University Nanchang Jiangxi 330000 China
| | - Zaiwei Fan
- Department of Orthopaedics, The Second Affiliated Hospital of Nanchang University Nanchang Jiangxi 330000 China
| | - Zirui Zhang
- Department of Rehabilitation Medicine, The 960th Hospital of the Chinese People's Liberation Army Jinan 250000 China
| | - Pinkai Wang
- Department of Orthopaedics, The Second Affiliated Hospital of Nanchang University Nanchang Jiangxi 330000 China
| | - Hui Deng
- Department of Orthopaedics, The Second Affiliated Hospital of Nanchang University Nanchang Jiangxi 330000 China
| | - Jun Tao
- Department of Orthopaedics, The Second Affiliated Hospital of Nanchang University Nanchang Jiangxi 330000 China
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Camy C, Maurel-Pantel A, Lallemand M, Fovet T, Brioche T, Genovesio C, Chopard A, Pithioux M, Roffino S. Achilles tendon enthesis behavior under cyclic compressive loading: Consequences of unloading and early remobilization. J Biomech 2024; 173:112231. [PMID: 39053291 DOI: 10.1016/j.jbiomech.2024.112231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 05/24/2024] [Accepted: 07/15/2024] [Indexed: 07/27/2024]
Abstract
The Achilles tendon enthesis (ATE) anchors the Achilles tendon into the calcaneus through fibrocartilaginous tissue. The latter is enriched in type II collagen and proteoglycans (PGs), both of which give the enthesis its capacity to withstand compressive stress. Because unloading and reloading induce remodeling of the ATE fibrocartilage (Camy et al., 2022), chronic changes in the mechanical load could modify the mechanical response under compressive stress. Therefore, we investigated the ATE fatigue behavior in mice, under cyclic compressive loading, after 14 days of hindlimb suspension and 6 days of reloading. In addition, we performed a qualitative histological study of PGs in ATE fibrocartilage. The mechanical behavior of ATE was impaired in unloaded mice. A significant loss of 27 % in Δd (difference between the maximum and minimum displacements) was observed at the end of the test. In addition, the hysteresis area decreased by approximately 27 % and the stiffness increased by over 45 %. The increased stiffness and loss of viscosity were thrice and almost twice those of the control, respectively. In the reloaded entheses, where the loss of Δd was not significant, we found a significant 28 % decrease in the hysteresis area and a 26 % increase in stiffness, both of which were higher regarding the control condition. These load-dependent changes in the mechanical response seem partly related to changes in PGs in the uncalficied part of the ATE. These findings highlight the importance of managing compressive loading on ATE when performing prophylactic and rehabilitation exercises.
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Affiliation(s)
- Claire Camy
- Aix Marseille Univ, CNRS, ISM, 13009 Marseille, France; Aix Marseille Univ, APHM, CNRS, ISM, Mecabio Platform, Department of Orthopaedics and Traumatology, 13009 Marseille, France
| | | | - Marylène Lallemand
- Ecole Centrale Marseille, 13013 Marseille, France; Aix Marseille Univ, APHM, CNRS, ISM, Mecabio Platform, Department of Orthopaedics and Traumatology, 13009 Marseille, France
| | - Théo Fovet
- DMEM, Montpellier University, INRAE, UMR 866, Montpellier, France
| | - Thomas Brioche
- DMEM, Montpellier University, INRAE, UMR 866, Montpellier, France
| | - Cécile Genovesio
- Aix Marseille Univ, Faculté de Pharmacie, 13005 Marseille, France
| | - Angèle Chopard
- DMEM, Montpellier University, INRAE, UMR 866, Montpellier, France
| | - Martine Pithioux
- Aix Marseille Univ, CNRS, ISM, 13009 Marseille, France; Aix Marseille Univ, APHM, CNRS, ISM, Mecabio Platform, Department of Orthopaedics and Traumatology, 13009 Marseille, France; Aix Marseille Univ, APHM, CNRS, ISM, Sainte-Marguerite Hospital, Institute for Locomotion, Department of Orthopaedics and Traumatology, 13009 Marseille, France.
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Mutsuzaki H, Nakajima H. Histological differences in cartilage layer growth at various tendon and ligament insertions in rabbits. J Rural Med 2024; 19:181-185. [PMID: 38975044 PMCID: PMC11222623 DOI: 10.2185/jrm.2024-009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 04/30/2024] [Indexed: 07/09/2024] Open
Abstract
Objectives: Histological differences in cartilage layer growth in Achilles tendon (AT), quadriceps tendon (QT), patellar tendon (PT), and anterior cruciate ligament (ACL) insertion are unclear. Therefore, this study aimed to investigate the differences in cartilage layer growth in AT, QT, PT, and ACL insertions. Materials and Methods: Forty-eight male Japanese white rabbits were used. Six animals were euthanized at different stages (day 1 and 1, 2, 4, 6, 8, 12, and 24 weeks). Safranin O-stained glycosaminoglycan (GAG) production area, chondrocyte count, and insertion width were investigated. Results: A two-way analysis of variance (ANOVA) revealed a significant difference in the main effects of time and insertion for all parameters. In addition, the time × insertion interaction was significant. Multiple comparisons showed a significant difference between the ACL insertion and all other variables; however, the GAG production area was not significantly different for the QT, PT, and AT insertions. AT insertions were significantly different from all other groups; however, the number of chondrocytes and insertion width were not significantly different for ACL, QT, and PT insertions. Conclusion: Cartilage layer growth differed between the AT, QT, PT, and ACL insertions. The differences between the insertions may also be due to the differences in their structures, locations, and mechanical environments.
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Affiliation(s)
- Hirotaka Mutsuzaki
- Center for Medical Science, Ibaraki Prefectural University of Health Sciences, Japan
- Department of Orthopedic Surgery, Ibaraki Prefectural University of Health Sciences Hospital, Japan
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Di Matteo A, Smerilli G, Di Donato S, Liu AR, Becciolini A, Camarda F, Cazenave T, Cipolletta E, Corradini D, de Agustín JJ, Destro Castaniti GM, Di Donato E, Di Geso L, Duran E, Farisogullari B, Fornaro M, Francioso F, Giorgis P, Granel A, Hernández-Díaz C, Horvath R, Hurnakova J, Jesus D, Karadag O, Li L, Marin J, Martire MV, Michelena X, Moscioni E, Muntean L, Piga M, Rosemffet M, Rovisco J, Sahin D, Salaffi F, Saraiva L, Scioscia C, Tamas MM, Tanimura S, Venetsanopoulou A, Ventura-Rios L, Villota O, Villota-Eraso C, Voulgari PV, Vukatana G, Zacariaz Hereter J, Marzo-Ortega H, Grassi W, Filippucci E. Power Doppler signal at the enthesis and bone erosions are the most discriminative OMERACT ultrasound lesions for SpA: results from the DEUS (Defining Enthesitis on Ultrasound in Spondyloarthritis) multicentre study. Ann Rheum Dis 2024; 83:847-857. [PMID: 38443140 DOI: 10.1136/ard-2023-225443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/07/2024]
Abstract
OBJECTIVES To assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population. METHODS In this multicentre study involving 20 rheumatology centres, clinical and ultrasound examinations of the lower limb large entheses were performed in 413 patients with SpA (axial SpA and psoriatic arthritis) and 282 disease controls (osteoarthritis and fibromyalgia). 'Active enthesitis' was defined as (1) power Doppler (PD) at the enthesis grade ≥1 plus entheseal thickening and/or hypoechoic areas, or (2) PD grade >1 (independent of the presence of entheseal thickening and/or hypoechoic areas). RESULTS In the univariate analysis, all OMERACT lesions except enthesophytes/calcifications showed a significant association with SpA. PD (OR=8.77, 95% CI 4.40 to 19.20, p<0.001) and bone erosions (OR=4.75, 95% CI 2.43 to 10.10, p<0.001) retained this association in the multivariate analysis. Among the lower limb entheses, only the Achilles tendon was significantly associated with SpA (OR=1.93, 95% CI 1.30 to 2.88, p<0.001) in the multivariate analyses. Active enthesitis showed a significant association with SpA (OR=9.20, 95% CI 4.21 to 23.20, p<0.001), and unlike the individual OMERACT ultrasound lesions it was consistently associated with most clinical measures of SpA disease activity and severity in the regression analyses. CONCLUSIONS This large multicentre study assessed the value of different ultrasound findings of enthesitis in SpA, identifying the most discriminative ultrasound lesions and entheseal sites for SpA. Ultrasound could differentiate between SpA-related enthesitis and other forms of entheseal pathology (ie, mechanical enthesitis), thus improving the assessment of entheseal involvement in SpA.
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Affiliation(s)
- Andrea Di Matteo
- Rheumatology Unit, Department of Clinical and Molecular Sciences, 'Carlo Urbani' Hospital, Polytechnic University of Marche, Ancona, Italy
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
| | - Gianluca Smerilli
- Rheumatology Unit, Department of Clinical and Molecular Sciences, 'Carlo Urbani' Hospital, Polytechnic University of Marche, Ancona, Italy
| | - Stefano Di Donato
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
| | - An Ran Liu
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
| | - Andrea Becciolini
- Department of Medicine, Internal Medicine and Rheumatology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Federica Camarda
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Rheumatology Section, University of Palermo, Palermo, Italy
| | - Tomas Cazenave
- Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina
| | - Edoardo Cipolletta
- Rheumatology Unit, Department of Clinical and Molecular Sciences, 'Carlo Urbani' Hospital, Polytechnic University of Marche, Ancona, Italy
| | | | | | - Giulia Maria Destro Castaniti
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Rheumatology Section, University of Palermo, Palermo, Italy
| | - Eleonora Di Donato
- Department of Medicine, Internal Medicine and Rheumatology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Luca Di Geso
- Department of Internal Medicine, Provincial Hospital Madonna del Soccorso, San Benedetto del Tronto, Italy
| | - Emine Duran
- Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Bayram Farisogullari
- Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Marco Fornaro
- Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J) Rheumatology Unit, University of Bari, Bari, Italy
| | - Francesca Francioso
- Rheumatology Unit, Department of Clinical and Molecular Sciences, 'Carlo Urbani' Hospital, Polytechnic University of Marche, Ancona, Italy
| | - Pamela Giorgis
- Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina
| | - Amelia Granel
- Rheumatology, Hospital San Roque de Gonnet, La Plata, Buenos Aires, Argentina
| | | | - Rudolf Horvath
- Department of Paediatric and Adult Rheumatology, Motol University Hospital, Praha, Czech Republic
| | - Jana Hurnakova
- Department of Paediatric and Adult Rheumatology, Motol University Hospital, Praha, Czech Republic
| | - Diogo Jesus
- Rheumatology Department, Leiria Hospital Centre, Pousos, Portugal
- Faculty of Health Sciences, University of Beira Interior, Covilha, Portugal
| | - Omer Karadag
- Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Ling Li
- Department of Rheumatology and Immunology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
| | - Josefina Marin
- Rheumatology Unit, Department of Internal Medicine, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | | | - Xabier Michelena
- Rheumatology Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - Erica Moscioni
- Rheumatology Unit, Department of Clinical and Molecular Sciences, 'Carlo Urbani' Hospital, Polytechnic University of Marche, Ancona, Italy
| | - Laura Muntean
- Department of Rheumatology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Matteo Piga
- Rheumatology Unit, University of Cagliari, Cagliari, Italy
| | - Marcos Rosemffet
- Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina
| | - João Rovisco
- Rheumatology Department, Centro Hospitalar e Universitário de Coimbra EPE, Coimbra, Portugal
| | - Didem Sahin
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
| | - Fausto Salaffi
- Rheumatology Unit, Department of Clinical and Molecular Sciences, 'Carlo Urbani' Hospital, Polytechnic University of Marche, Ancona, Italy
| | - Liliana Saraiva
- Rheumatology Department, Centro Hospitalar e Universitário de Coimbra EPE, Coimbra, Portugal
| | - Crescenzio Scioscia
- Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J) Rheumatology Unit, University of Bari, Bari, Italy
| | - Maria-Magdalena Tamas
- Department of Rheumatology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Shun Tanimura
- Department of Rheumatology, The Hokkaido Medical Center, Sapporo, Japan
| | - Aliki Venetsanopoulou
- Department of Rheumatology, School of Health Sciences, University of Ioannina Faculty of Medicine, Ioannina, Greece
| | - Lucio Ventura-Rios
- Division of Rheumatology, National Institute of Rehabilitation Luis Guillermo Ibarra, Ciudad de Mexico, Mexico
| | - Orlando Villota
- Division of Rheumatology, Fundación Hospital San Pedro, San Juan de Pasto, Colombia
- Department of Rheumatology, Servicio Integral de Reumatología e Inmunología Doctor Orlando Villota, Pasto, Colombia
| | - Catalina Villota-Eraso
- Department of Rheumatology, Servicio Integral de Reumatología e Inmunología Doctor Orlando Villota, Pasto, Colombia
| | - Paraskevi V Voulgari
- Department of Rheumatology, School of Health Sciences, University of Ioannina Faculty of Medicine, Ioannina, Greece
| | - Gentiana Vukatana
- Rheumatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico di Sant'Orsola, Bologna, Italy
| | - Johana Zacariaz Hereter
- Rheumatology Unit, Department of Internal Medicine, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Helena Marzo-Ortega
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
| | - Walter Grassi
- Rheumatology Unit, Department of Clinical and Molecular Sciences, 'Carlo Urbani' Hospital, Polytechnic University of Marche, Ancona, Italy
| | - Emilio Filippucci
- Rheumatology Unit, Department of Clinical and Molecular Sciences, 'Carlo Urbani' Hospital, Polytechnic University of Marche, Ancona, Italy
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Yambe S, Yoshimoto Y, Ikeda K, Maki K, Takimoto A, Tokuyama A, Higuchi S, Yu X, Uchibe K, Miura S, Watanabe H, Sakuma T, Yamamoto T, Tanimoto K, Kondoh G, Kasahara M, Mizoguchi T, Docheva D, Adachi T, Shukunami C. Sclerostin modulates mineralization degree and stiffness profile in the fibrocartilaginous enthesis for mechanical tissue integrity. Front Cell Dev Biol 2024; 12:1360041. [PMID: 38895158 PMCID: PMC11183276 DOI: 10.3389/fcell.2024.1360041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 04/19/2024] [Indexed: 06/21/2024] Open
Abstract
Fibrocartilaginous entheses consist of tendons, unmineralized and mineralized fibrocartilage, and subchondral bone, each exhibiting varying stiffness. Here we examined the functional role of sclerostin, expressed in mature mineralized fibrochondrocytes. Following rapid mineralization of unmineralized fibrocartilage and concurrent replacement of epiphyseal hyaline cartilage by bone, unmineralized fibrocartilage reexpanded after a decline in alkaline phosphatase activity at the mineralization front. Sclerostin was co-expressed with osteocalcin at the base of mineralized fibrocartilage adjacent to subchondral bone. In Scx-deficient mice with less mechanical loading due to defects of the Achilles tendon, sclerostin+ fibrochondrocyte count significantly decreased in the defective enthesis where chondrocyte maturation was markedly impaired in both fibrocartilage and hyaline cartilage. Loss of the Sost gene, encoding sclerostin, elevated mineral density in mineralized zones of fibrocartilaginous entheses. Atomic force microscopy analysis revealed increased fibrocartilage stiffness. These lines of evidence suggest that sclerostin in mature mineralized fibrochondrocytes acts as a modulator for mechanical tissue integrity of fibrocartilaginous entheses.
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Affiliation(s)
- Shinsei Yambe
- Department of Molecular Biology and Biochemistry, Division of Dental Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuki Yoshimoto
- Department of Molecular Biology and Biochemistry, Division of Dental Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kazutaka Ikeda
- Department of Molecular Biology and Biochemistry, Division of Dental Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Department of Orthodontics and Craniofacial Developmental Biology, Applied Life Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Koichiro Maki
- Laboratory of Biomechanics, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan
| | - Aki Takimoto
- Department of Molecular Biology and Biochemistry, Division of Dental Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | | | - Shinnosuke Higuchi
- Department of Molecular Biology and Biochemistry, Division of Dental Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Xinyi Yu
- Department of Molecular Biology and Biochemistry, Division of Dental Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kenta Uchibe
- Department of Maxillofacial Anatomy and Neuroscience, Division of Oral Health Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shigenori Miura
- Department of Molecular Biology and Biochemistry, Division of Dental Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hitomi Watanabe
- Laboratory of Integrative Biological Science, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan
| | - Tetsushi Sakuma
- Division of Integrated Sciences for Life, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima, Japan
| | - Takashi Yamamoto
- Division of Integrated Sciences for Life, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima, Japan
| | - Kotaro Tanimoto
- Department of Orthodontics and Craniofacial Developmental Biology, Applied Life Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Gen Kondoh
- Laboratory of Integrative Biological Science, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan
| | | | | | - Denitsa Docheva
- Department of Musculoskeletal Tissue Regeneration, Orthopaedic Hospital König-Ludwig-Haus, Julius-Maximilians-University Würzburg, Würzburg, Germany
| | - Taiji Adachi
- Laboratory of Biomechanics, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan
| | - Chisa Shukunami
- Department of Molecular Biology and Biochemistry, Division of Dental Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Zhang S, Hao W, Chen D, Chen S, Li Z, Zhong F, Wang H, Wang J, Zheng Z, Zhan Z, Dai G, Liu H. Intermittent administration of PTH for the treatment of inflammatory bone loss does not enhance entheseal pathological new bone formation. Biochem Biophys Res Commun 2024; 711:149888. [PMID: 38603833 DOI: 10.1016/j.bbrc.2024.149888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 03/21/2024] [Accepted: 04/03/2024] [Indexed: 04/13/2024]
Abstract
OBJECTIVE To investigate the effect of intermittent parathyroid hormone (iPTH) administration on pathological new bone formation during treatment of ankylosing spondylitis-related osteoporosis. METHODS Animal models with pathological bone formation caused by hypothetical AS pathogenesis received treatment with iPTH. We determined the effects of iPTH on bone loss and the formation of pathological new bone with micro-computed tomography (micro-CT) and histological examination. In addition, the tamoxifen-inducible conditional knockout mice (CAGGCre-ERTM; PTHflox/flox, PTH-/-) was established to delete PTH and investigate the effect of endogenous PTH on pathological new bone formation. RESULTS iPTH treatment significantly improved trabecular bone mass in the modified collagen-induced arthritis (m-CIA) model and unbalanced mechanical loading models. Meanwhile, iPTH treatment did not enhance pathological new bone formation in all types of animal models. Endogenous PTH deficiency had no effects on pathological new bone formation in unbalanced mechanical loading models. CONCLUSION Experimental animal models of AS treated with iPTH show improvement in trabecular bone density, but not entheseal pathological bone formation,indicating it may be a potential treatment for inflammatory bone loss does in AS.
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Affiliation(s)
- Shuai Zhang
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China
| | - Wenjun Hao
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China
| | - Dongying Chen
- Department of Rheumatology and Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China
| | - Siwen Chen
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China
| | - Zihao Li
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China
| | - Fangling Zhong
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China
| | - Haitao Wang
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China
| | - Jianru Wang
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China
| | - Zhaomin Zheng
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China
| | - Zhongping Zhan
- Department of Rheumatology and Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China
| | - Guo Dai
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China.
| | - Hui Liu
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China.
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Chen Y, Li Y, Zhu W, Liu Q. Biomimetic gradient scaffolds for the tissue engineering and regeneration of rotator cuff enthesis. Biofabrication 2024; 16:032005. [PMID: 38697099 DOI: 10.1088/1758-5090/ad467d] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 05/02/2024] [Indexed: 05/04/2024]
Abstract
Rotator cuff tear is one of the most common musculoskeletal disorders, which often results in recurrent shoulder pain and limited movement. Enthesis is a structurally complex and functionally critical interface connecting tendon and bone that plays an essential role in maintaining integrity of the shoulder joint. Despite the availability of advanced surgical procedures for rotator cuff repair, there is a high rate of failure following surgery due to suboptimal enthesis healing and regeneration. Novel strategies based on tissue engineering are gaining popularity in improving tendon-bone interface (TBI) regeneration. Through incorporating physical and biochemical cues into scaffold design which mimics the structure and composition of native enthesis is advantageous to guide specific differentiation of seeding cells and facilitate the formation of functional tissues. In this review, we summarize the current state of research in enthesis tissue engineering highlighting the development and application of biomimetic scaffolds that replicate the gradient TBI. We also discuss the latest techniques for fabricating potential translatable scaffolds such as 3D bioprinting and microfluidic device. While preclinical studies have demonstrated encouraging results of biomimetic gradient scaffolds, the translation of these findings into clinical applications necessitates a comprehensive understanding of their safety and long-term efficacy.
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Affiliation(s)
- Yang Chen
- Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Yexin Li
- Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Weihong Zhu
- Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Qian Liu
- Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China
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Liu N, Jiang J, Liu T, Chen H, Jiang N. Compositional, Structural, and Biomechanical Properties of Three Different Soft Tissue-Hard Tissue Insertions: A Comparative Review. ACS Biomater Sci Eng 2024; 10:2659-2679. [PMID: 38697939 DOI: 10.1021/acsbiomaterials.3c01796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/05/2024]
Abstract
Connective tissue attaches to bone across an insertion with spatial gradients in components, microstructure, and biomechanics. Due to regional stress concentrations between two mechanically dissimilar materials, the insertion is vulnerable to mechanical damage during joint movements and difficult to repair completely, which remains a significant clinical challenge. Despite interface stress concentrations, the native insertion physiologically functions as the effective load-transfer device between soft tissue and bone. This review summarizes tendon, ligament, and meniscus insertions cross-sectionally, which is novel in this field. Herein, the similarities and differences between the three kinds of insertions in terms of components, microstructure, and biomechanics are compared in great detail. This review begins with describing the basic components existing in the four zones (original soft tissue, uncalcified fibrocartilage, calcified fibrocartilage, and bone) of each kind of insertion, respectively. It then discusses the microstructure constructed from collagen, glycosaminoglycans (GAGs), minerals and others, which provides key support for the biomechanical properties and affects its physiological functions. Finally, the review continues by describing variations in mechanical properties at the millimeter, micrometer, and nanometer scale, which minimize stress concentrations and control stretch at the insertion. In summary, investigating the contrasts between the three has enlightening significance for future directions of repair strategies of insertion diseases and for bioinspired approaches to effective soft-hard interfaces and other tough and robust materials in medicine and engineering.
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Affiliation(s)
- Nian Liu
- West China School of Stomatology, Sichuan University, Chengdu, Sichuan 610207, China
| | - Jialing Jiang
- West China School of Stomatology, Sichuan University, Chengdu, Sichuan 610207, China
| | - Tiancheng Liu
- West China Hospital, Sichuan University, Chengdu, Sichuan 610207, China
| | - Haozhe Chen
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
| | - Nan Jiang
- State Key Laboratory of Oral Diseases, & National Clinical Research Center for Oral Disease, & West China Hospital of Stomatology and the Research Center for Nano Biomaterials, Analytical & Testing Center, Sichuan University, Chengdu, Sichuan 610041, China
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Fenech M. Sonographic anatomy and technique to image the plantar digital nerves and aid identification of a Morton's neuroma. ULTRASOUND (LEEDS, ENGLAND) 2024; 32:114-126. [PMID: 38694832 PMCID: PMC11060124 DOI: 10.1177/1742271x231215716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 11/05/2023] [Indexed: 05/04/2024]
Abstract
Introduction The anatomy of the forefoot is complex, and the sonographic assessment to image the plantar digital nerves and exclude, diagnose or discriminate between a Morton's neuroma and intermetatarsal bursitis can be challenging. Topic description and discussion A good appreciation of the sonographic anatomy, technique, normal and abnormal appearances is required to undertake a sonographic assessment of the forefoot and its interspaces, particularly the plantar digital nerves. This is unpacked in this paper with associated pictorial aids. Muscles, tendons, and ligaments of the interspaces and the nearby metatarsophalangeal joints and their associated soft-tissue structures are helpful sonographic landmarks to guide imaging and assessment of the common and proper plantar digital nerves and the intermetatarsal bursa. These need to be appreciated from both dorsal and plantar sonographic approaches, in both short- and long-axis imaging planes. Conclusion Improved understanding of the anatomy and sonographic appearances of the interspace structures can enhance the sonographic assessment of the forefoot and improve diagnosis of a Morton's neuroma and/or intermetatarsal bursitis when present to guide patient management.
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Affiliation(s)
- Michelle Fenech
- College of Clinical Sciences, School of Health, Medical and Applied Sciences, Central Queensland University, Brisbane, QLD, Australia; Department of Medical Imaging, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia
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Khasanah N, Peng CW, Fang JJ, Rahman MN, Sulistiawan D, Chin HY. Pain in the enthesis of levator ani muscle: A novel source of chronic pelvic pain. J Chin Med Assoc 2024; 87:505-510. [PMID: 38551348 DOI: 10.1097/jcma.0000000000001093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/12/2024] Open
Abstract
BACKGROUND Managing chronic pelvic pain (CPP) remains a challenge due to its diverse range of causes. A newly identified anatomical entity known as the enthesis of the levator ani muscle (LAM) and its associated disorders might play a role. This paper describes a novel insight into CPP's origin, aiming to improve accurate diagnosis and treatment. METHODS Data were collected from medical records (paper or electronic) retrospectively. The study included 112 patients meeting the criteria, divided into CPP and non-CPP groups. Clinical symptoms, including location of LAM enthesis, referred pain from pain in LAM enthesis, and related lower urinary tract symptoms (LUTSs) were discussed. To identify differences in symptoms between the groups, a Chi-squared test and descriptive analyses were conducted. RESULTS Bimanual examination revealed tender sites in the attachment of the LAM to the pubic bone. LAM enthesis pain presumably caused referred pain in at least 10 areas, primarily in the lower abdominal quadrate (40.2%-47.3%) followed by the inguinal area (8.9%-15.1%). Multiple LUTSs were observed, including urinary frequency (72.3%), urgency (42.9%), nocturia (53.6%), residual urine sensation (64.3%), urinary incontinence (30.3%), painful bladder (34.8%), and weak urine stream (47.9%). Patients in the CPP groups experienced significant residual urine sensation (53.6%) and bearing-down sensation (42%) compared to the non-CPP group. CONCLUSION Pain in LAM enthesis is a novel cause of pelvic pain and LUTSs that warrants attention for the evaluation and management of CPP.
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Affiliation(s)
- Nurida Khasanah
- Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan, ROC
- Faculty of Medicine Public Health and Nursing, Department of Obstetrics and Gynecology, Universitas Gadjah Mada-Dr Sardjito General Hospital, Yogyakarta, Indonesia
| | - Chih-Wei Peng
- Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan, ROC
- School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan, ROC
- School of Gerontology and Long-Term Care, College of Nursing, Taipei Medical University, Taipei, Taiwan, ROC
- Research Center of Biomedical Device, Taipei Medical University, Taipei, Taiwan, ROC
| | - Jessica Jay Fang
- Department of Obstetrics and Gynecology, Taipei Medical University Hospital and School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
| | - Muhammad Nurhadi Rahman
- Faculty of Medicine Public Health and Nursing, Department of Obstetrics and Gynecology, Universitas Gadjah Mada-Dr Sardjito General Hospital, Yogyakarta, Indonesia
| | - Dedik Sulistiawan
- School of Public Health, Taipei Medical University, Taipei, Taiwan, ROC
- Departement of Public Health, Universitas Ahmad Dahlan, Yogyakarta, Indonesia
| | - Hung-Yen Chin
- Department of Obstetrics and Gynecology, Taipei Medical University Hospital and School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
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Cirimele V, D’Amone G, Stellato L, Ferrini A, Gregori P, Faiella E. Magnetic Resonance Imaging in the Evaluation of Avulsion Injuries of the Pelvis and Hip in Adolescent Professional Footballers: A Case Series. J Orthop Case Rep 2024; 14:147-152. [PMID: 38784877 PMCID: PMC11111240 DOI: 10.13107/jocr.2024.v14.i05.4466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 03/13/2024] [Indexed: 05/25/2024] Open
Abstract
Introduction Pelvic apophyseal avulsion fractures are uncommon injuries that frequently affect adolescents while participating in sports. This occurs because the enthesis cannot withstand the tractional force applied because the apophysis has not yet fully fused. Due to its complex muscular structure, being the origin of several muscles that cross two lower extremity joints, the pelvis has an increased risk for such injuries. The diagnosis of pelvic avulsion injuries depends heavily on imaging. The best way to detect soft-tissue changes, including tendon or muscle strain, bone marrow edema, hematomas, and soft tissue avulsion injuries, is with an magnetic resonance imaging . It is also the best at showing tendon retraction and can help the clinician spot patients who might benefit from surgical treatment. Case Report We report six cases of adolescents professional footballers that suffered avulsion injuries while playing football. The patients had painfully restricted hip range of motion and were unable to bear weight. Some of them on physical examination felt pain at the palpation of the injured area. Magnetic resonance revealed apophysis growth plate avulsion with or without displaced bone fragments that were treated conservatively with an excellent clinical and radiological outcome. Conclusion For an accurate diagnosis of pelvic avulsion injuries and clinical management, it is important that everyone caring for this patient population is aware of the common injury mechanisms, radiographic findings, and available treatments.
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Affiliation(s)
- Vincenzo Cirimele
- Department of Radiology, Fondazione Policlinico Universitario Campus Bio-Medico di Roma, Roma, Italy
| | - Giulia D’Amone
- Department of Radiology, Fondazione Policlinico Universitario Campus Bio-Medico di Roma, Roma, Italy
| | - Luigi Stellato
- Department of Radiology, Fondazione Policlinico Universitario Campus Bio-Medico di Roma, Roma, Italy
| | - Augusto Ferrini
- Department of Orthopaedic and Trauma Surgery Fondazione Policlinico Univeristario Campus Bio-Medico di Roma, Roma, Italy
- Department of Medicine and Surgery, Orthopaedic and Trauma Surgery Unit, Univeristà Campus Bio-Medico di Roma, Roma, Italy
| | - Pietro Gregori
- Department of Orthopaedic and Trauma Surgery Fondazione Policlinico Univeristario Campus Bio-Medico di Roma, Roma, Italy
- Department of Medicine and Surgery, Orthopaedic and Trauma Surgery Unit, Univeristà Campus Bio-Medico di Roma, Roma, Italy
| | - Eliodoro Faiella
- Department of Radiology, Fondazione Policlinico Universitario Campus Bio-Medico di Roma, Roma, Italy
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Ahmed BA, Alotaibi RM, ALJuhani WS. Knotless Anchor with FiberTape® for Fixing Pure Distal Patellar Tendon Rupture. A Case Report. J Orthop Case Rep 2024; 14:130-135. [PMID: 38784873 PMCID: PMC11111231 DOI: 10.13107/jocr.2024.v14.i05.4460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 03/21/2024] [Indexed: 05/25/2024] Open
Abstract
Introduction The extensor mechanism and patellar tendon (PT) are considered essential components. Adult PT avulsion from the tibial tubercle is uncommon, with little information in the literature. Technical challenges arise during injury management. Knotless anchors have several applications in treating tendon injuries, such as the rotator cuff, distal biceps, and quadriceps tendons but were not used to repair distal PT avulsions. Case Report A 50-year-old male patient, an active adult, presented to emergency department with significant right knee pain, giving away and limitation of range of motion (ROM) that had started after he sustained direct trauma with a ground-level fall on his knee that morning. Conclusion In this paper, we report a case and describe a technique to manage a rare presentation of pure distal PT rupture without an avulsion fracture using knotless anchors with FiberTape®, which showed excellent results. To the best of our knowledge, this technique has never been used before in such injury and anatomical location. At 2 years of follow-up, the patient is free of complaints with almost full ROM at the knee and back to his standard daily life activity.
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Affiliation(s)
- Bandar A Ahmed
- Division of Orthopedics, Department of Surgery, King Abdullah Bin Abdulaziz University Hospital, Riyadh, Saudi Arabia
- Department of Orthopedics, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Razan Mohammed Alotaibi
- Division of Orthopedics, Department of Surgery, King Abdullah Bin Abdulaziz University Hospital, Riyadh, Saudi Arabia
| | - Wazzan Saleh ALJuhani
- Department of Surgery, Ministry of the National Guard - Health Affairs, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
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Na Y, Jue H, Xia T, Xue X, Sun L, Chen J, Hua Y. Histologic and biomechanical comparison of fascia lata autograft, acellular dermal xenograft, and synthetic patch for bridging massive rotator cuff tear in a rabbit model. Asia Pac J Sports Med Arthrosc Rehabil Technol 2024; 36:28-39. [PMID: 38584973 PMCID: PMC10998002 DOI: 10.1016/j.asmart.2024.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 01/17/2024] [Indexed: 04/09/2024] Open
Abstract
Background Bridging repair has emerged as a promising and reliable treatment strategy for the massive rotator cuff tears (MRCTs). However, there remains a lack of evidence on which bridging graft provides the better repair results, and a dearth of animal studies comparing bridging repairs with different grafts. The purpose of this study was to evaluate the histological and biomechanical outcomes of commonly used grafts (autologous fascia lata (FL), acellular dermal matrix graft (ADM), and polyethylene terephthalate (PET) patch). Methods A total of 66 male New Zealand White Rabbits were used to mimic a model of unilateral chronic MRCTs. The rabbits were randomly divided into three groups: (1) FL group, which underwent bridging repair with autologous FL; (2) ADM group, which underwent bridging with ADM; and (3) PET group, which underwent bridging with PET patch. Tissue samples were collected and subjected to histological analysis using Hematoxylin and eosin, Picrosirius red, Safranin O/Fast green staining, and Immunostaining. Collagen diameter and fibril density in the regenerated tendon was analyzed with transmission electron microscopy (TEM). Additionally, biomechanical tests were performed at 6 and 12 weeks after repair. Results The regenerated tendon successfully reattached to the footprint in all experimental groups. At 6 weeks after repair, the FL group had a significantly higher Modified Tendon Histological Evaluation (MTHE) score at the regenerated tendon than the PET group (13.2 ± 1.64 vs 9.6 ± 1.95, respectively; P = 0.038). The picrosirius red staining results showed that the FL group had a significantly higher type I collagen content than the ADM and PET groups at 6 weeks, and this difference was sustained with the PET group at 12 weeks (P < 0.05). Immunofluorescence analysis against CD68 indicated that the number of macrophage infiltrates was significantly lower in the FL group than in the ADM and PET groups (P < 0.05). At 12 weeks after repair, the area of Safranin O metachromasia was significant greater in ADM group than that in the PET group (P = 0.01). The FL group showed a significantly larger collagen diameter in the regenerated tendon than the PET group (P < 0.05), as indicated by TEM results. Furthermore, the FL group resulted in a greater failure load (at 6 weeks; 118.40 ± 16.70 N vs 93.75 ± 9.06 N, respectively; P = 0.019) and elastic modulus (at 6 weeks; 12.28 ± 1.94 MPa vs 9.58 ± 0.79 MPa, respectively; P = 0.024; at 12 weeks; 15.02 ± 2.36 MPa vs 11.63 ± 1.20 MPa, respectively; P = 0.032) than the ADM group. Conclusions This study demonstrated that all three grafts could successfully bridging chronic MRCTs in a rabbit model. However, autologous FL promoted tendon regeneration and maturation, and enhanced the tensile properties of the tendon-to-bone complex when compared with ADM and PET grafts.
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Affiliation(s)
| | | | | | - Xiaoao Xue
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Luyi Sun
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Jun Chen
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Yinghui Hua
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
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Tharnmanularp S, Muro S, Nimura A, Ibara T, Akita K. Significant relationship between musculoaponeurotic attachment of the abdominal and thigh adductor muscles to the pubis: implications for the diagnosis of groin pain. Anat Sci Int 2024; 99:190-201. [PMID: 37985575 PMCID: PMC10902015 DOI: 10.1007/s12565-023-00750-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 10/28/2023] [Indexed: 11/22/2023]
Abstract
Groin pain is prevalent in orthopedic and sports medicine, causing reduced mobility and limiting sports activity. To effectively manage groin pain, understanding the detailed anatomy of supporting muscles is crucial. This study aimed to investigate the musculoaponeurotic attachments on the pubis and the relationship among intramuscular aponeuroses of abdominal and thigh adductor musculatures. Macroscopic analyses were performed in 10 pelvic halves. The bone morphology of the pubis was assessed in two pelvic halves using microcomputed tomography. Histological investigations were conducted in two pelvic halves. The external oblique aponeurosis extended to the adductor longus aponeurosis, forming conjoined aponeurosis, which attached to a small impression distal to the pubic crest. The gracilis aponeurosis merges with the adductor brevis aponeurosis and is attached to the proximal part of the inferior pubic ramus. The rectus abdominis and pyramidalis aponeuroses were attached to the pubic crest and intermingled with the gracilis-adductor brevis aponeurosis, forming bilateral conjoined aponeurosis, which attached to a broad area covering the anteroinferior surface of the pubis. Histologically, these two areas of conjoined aponeuroses were attached to the pubis via the fibrocartilage enthesis. Microcomputed tomography revealed two distinctive bone morphologies, a small impression and an elongated osseous prominence on pubis, corresponded to the two areas of conjoined aponeuroses. This study demonstrated close relationships between the aponeurotic attachment of the external oblique and adductor longus, and between the rectus abdominis, pyramidalis, gracilis, and adductor brevis. The findings of aponeurotic complexes would aid in diagnostic and surgical approaches for athletic groin pain.
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Affiliation(s)
- Suthasinee Tharnmanularp
- Department of Clinical Anatomy, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8510, Japan
| | - Satoru Muro
- Department of Clinical Anatomy, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8510, Japan.
| | - Akimoto Nimura
- Department of Functional Joint Anatomy, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Takuya Ibara
- Department of Functional Joint Anatomy, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Keiichi Akita
- Department of Clinical Anatomy, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8510, Japan
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Wang C, Zhang X, Wang DM, Yung PSH, Tuan RS, Ker DFE. Optimized design of an enthesis-mimicking suture anchor-tendon hybrid graft for mechanically robust bone-tendon repair. Acta Biomater 2024; 176:277-292. [PMID: 38244656 DOI: 10.1016/j.actbio.2024.01.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 11/22/2023] [Accepted: 01/09/2024] [Indexed: 01/22/2024]
Abstract
Repair of functionally graded biological interfaces requires joining dissimilar materials such as hard bone to soft tendon/ligament, with re-injuries/re-tears expected to be minimized by incorporating biomimicking, stress-reducing features within grafts. At bone-tendon interfaces (entheses), stress can be reduced via angled insertion, geometric flaring, mechanical gradation, and interdigitation of tissues. Here, we incorporated enthesis attributes into 3D in silico and physical models of a unique suture anchor-tendon hybrid graft (SATHG) and investigated their effects on stress reduction via finite element analyses (FEA) studies. Over 20 different simulations altering SATHG angulation, flaring, mechanical gradation, and interdigitation identified an optimal design, which included 90° angulation, 25° flaring, and a compliant (ascending then descending) mechanical gradient in SATHG's bone-to-tendon-like transitional region. This design reduced peak stress concentration factor (SCF) by 43.6 % relative to an ascending-only mechanical gradient typically used in hard-to-soft tissue engineering. To verify FEA results, SATHG models were fabricated using a photocrosslinkable bone-tendon-like polyurethane (QHM polymer) for ex vivo tensile assessment. Tensile testing showed that ultimate load (132.9 N), displacement-at-failure (1.78 mm), stiffness (135.4 N/mm), and total work-to-failure (422.1 × 10-3 J) were highest in the optimized design. Furthermore, to assess envisioned usage, SATHG pull-out testing and 6-week in vivo implantation into large, 0.5-cm segmental supraspinatus tendon defects was performed. SATHG pull-out testing showed secure bone attachment while histological assessment such as hematoxylin and eosin (H&E) together with Safranin-O staining showed biocompatibility including enthesis regeneration. This work demonstrates that engineering biomaterials with FEA-optimized, enthesis-like attributes shows potential for enhancing hard-to-soft tissue repair. STATEMENT OF SIGNIFICANCE: Successful repair of hard-to-soft tissue injuries is challenging due to high stress concentrations within bone-tendon/ligament grafts that mechanically compromise repair strength. While stress-reducing gradient biomaterials have been reported, little-to-no attention has focused on other bone-tendon/ligament interface (enthesis) features. To this end, a unique bone-tendon graft (SATHG) was developed by combining two common orthopaedic devices along with biomimetic incorporation of four enthesis-like features to reduce stress and encourage widespread clinician adoption. Notably, utilizing designs based on natural stress dissipation principles such as anchor insertion angle, geometric flaring, and mechanical gradation reduced stress by 43.6 % in silico, which was confirmed ex vivo, while in vivo studies showed SATHG's ability to support native enthesis regeneration. Thus, SATHG shows promise for hard-to-soft tissue repairs.
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Affiliation(s)
- Chenyang Wang
- Institute for Tissue Engineering and Regenerative Medicine, Lo Kwee-Seong Biomedical Sciences Building, Area 39, The Chinese University of Hong Kong, Hong Kong SAR; School of Biomedical Sciences, Lo Kwee-Seong Biomedical Sciences Building, Area 39, The Chinese University of Hong Kong, Hong Kong SAR
| | - Xu Zhang
- Institute for Tissue Engineering and Regenerative Medicine, Lo Kwee-Seong Biomedical Sciences Building, Area 39, The Chinese University of Hong Kong, Hong Kong SAR; School of Biomedical Sciences, Lo Kwee-Seong Biomedical Sciences Building, Area 39, The Chinese University of Hong Kong, Hong Kong SAR; Center for Neuromusculoskeletal Restorative Medicine, InnoHK, Hong Kong Science Park, Hong Kong SAR
| | - Dan Michelle Wang
- Institute for Tissue Engineering and Regenerative Medicine, Lo Kwee-Seong Biomedical Sciences Building, Area 39, The Chinese University of Hong Kong, Hong Kong SAR; School of Biomedical Sciences, Lo Kwee-Seong Biomedical Sciences Building, Area 39, The Chinese University of Hong Kong, Hong Kong SAR; Ministry of Education Key Laboratory for Regenerative Medicine, Lo Kwee-Seong Biomedical Sciences Building, Area 39, The Chinese University of Hong Kong, Hong Kong SAR; Center for Neuromusculoskeletal Restorative Medicine, InnoHK, Hong Kong Science Park, Hong Kong SAR; Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Lui Che Woo Clinical Science Building, Prince of Wales Hospital, Hong Kong SAR
| | - Patrick S H Yung
- Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Lui Che Woo Clinical Science Building, Prince of Wales Hospital, Hong Kong SAR; Center for Neuromusculoskeletal Restorative Medicine, InnoHK, Hong Kong Science Park, Hong Kong SAR; Institute for Tissue Engineering and Regenerative Medicine, Lo Kwee-Seong Biomedical Sciences Building, Area 39, The Chinese University of Hong Kong, Hong Kong SAR
| | - Rocky S Tuan
- Institute for Tissue Engineering and Regenerative Medicine, Lo Kwee-Seong Biomedical Sciences Building, Area 39, The Chinese University of Hong Kong, Hong Kong SAR; School of Biomedical Sciences, Lo Kwee-Seong Biomedical Sciences Building, Area 39, The Chinese University of Hong Kong, Hong Kong SAR; Center for Neuromusculoskeletal Restorative Medicine, InnoHK, Hong Kong Science Park, Hong Kong SAR; Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Lui Che Woo Clinical Science Building, Prince of Wales Hospital, Hong Kong SAR
| | - Dai Fei Elmer Ker
- Institute for Tissue Engineering and Regenerative Medicine, Lo Kwee-Seong Biomedical Sciences Building, Area 39, The Chinese University of Hong Kong, Hong Kong SAR; School of Biomedical Sciences, Lo Kwee-Seong Biomedical Sciences Building, Area 39, The Chinese University of Hong Kong, Hong Kong SAR; Ministry of Education Key Laboratory for Regenerative Medicine, Lo Kwee-Seong Biomedical Sciences Building, Area 39, The Chinese University of Hong Kong, Hong Kong SAR; Center for Neuromusculoskeletal Restorative Medicine, InnoHK, Hong Kong Science Park, Hong Kong SAR; Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Lui Che Woo Clinical Science Building, Prince of Wales Hospital, Hong Kong SAR.
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Oda T, Maeyama A, Ishimatsu T, Tachibana K, Yoshimitsu K, Yamamoto T. Soft Tissue Stabilization of the Hinge Position for Lateral Closing-Wedge Distal Femoral Osteotomy: An Anatomic Study. Orthop J Sports Med 2024; 12:23259671241233014. [PMID: 38510318 PMCID: PMC10952986 DOI: 10.1177/23259671241233014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 09/06/2023] [Indexed: 03/22/2024] Open
Abstract
Background Soft tissue plays an important role in stabilizing the hinge point for osteotomy around the knee. However, insufficient data are available on the anatomic features of the soft tissue around the hinge position for lateral closing-wedge distal femoral osteotomy (LCWDFO). Purpose To (1) anatomically analyze the soft tissue around the hinge position for LCWDFO, (2) histologically analyze the soft tissue based on the anatomic analysis results, and (3) radiologically define the appropriate hinge point to prevent unstable hinge fracture based on the results of the anatomic and histological analyses. Study Design Descriptive laboratory study. Methods In 20 cadaveric knees (age, 82.7 ± 7.8 years; range, 60-96 years), the soft tissue of the distal medial side of the femur was anatomically analyzed. The thicknesses of the periosteum and direct insertion of the adductor tendon (AT) were histologically examined and measured using an electron microscope. The thickness of the periosteum was visualized graphically, and the graph of the periosteum and radiograph of the knee were overlaid using image editing software. The appropriate hinge position was determined based on the periosteal thickness and attachment of the AT. Results The mean thickness of the periosteum of the metaphysis was 352.7 ± 58.6 µm (range, 213.6-503.4 µm). The overlaid graph and radiograph revealed that the thickness of the periosteum changed at the part corresponding to the transition between the diaphyseal and metaphyseal ends of the femur. The mean width of the AT attached to the distal medial femur from the adductor tubercle toward the distal direction was 7.9 ± 1.3 mm (range, 6.3-9.7 mm). Conclusion Results indicated that the periosteum and AT support the hinge for LCWDFO within the area surrounded by the apex of the adductor tubercle and the upper border of the posterior part of the lateral femoral condyle. Clinical Relevance When the hinge point is located within the area surrounded by the apex of the adductor tubercle and the upper border of the posterior part of the lateral femoral condyle, these soft tissues work as stabilizers, and there is no risk of cutting into the joint space.
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Affiliation(s)
- Taiga Oda
- Department of Orthopedic Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan
| | - Akira Maeyama
- Department of Orthopedic Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan
| | - Tetsuro Ishimatsu
- Department of Orthopedic Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan
| | - Katsuro Tachibana
- Department of Anatomy, Fukuoka University Faculty of Medicine, Fukuoka, Japan
| | - Kengo Yoshimitsu
- Department of Radiology, Fukuoka University Faculty of Medicine, Fukuoka, Japan
| | - Takuaki Yamamoto
- Department of Orthopedic Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan
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Rotman D, Bokhari N, Wright A, Watts AC. The posterolateral ligament of the elbow: anatomy and clinical relevance. J Shoulder Elbow Surg 2024; 33:573-582. [PMID: 37783309 DOI: 10.1016/j.jse.2023.08.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 08/24/2023] [Accepted: 08/31/2023] [Indexed: 10/04/2023]
Abstract
BACKGROUND The posterolateral capsule was recognized in the past as an important structure for elbow stability but was later disregarded. Two recent biomechanical studies demonstrated its role in preventing posterolateral instability, and thus it should be identified as a distinct ligament: the posterolateral ligament (PLL). This study includes 2 parts: an anatomic study of the PLL's footprint and a collection of 5 cases of pathologic lesions of the PLL. METHODS Six cadaveric upper limbs were assessed. The attachments of the PLL were dissected, the footprints were marked and photographed, and the 2-dimensional area and length were measured. RESULTS The mean proximal attachment dimensions were a length of 13 mm and an area of 101 mm2, and the mean distal attachment dimensions were 19 mm and 111 mm2, respectively. There were 2 cases of posterolateral elbow pain in professional cricket bowlers, diagnosed radiographically as enthesopathy of the PLL's proximal attachment on the posterior capitellum, probably due to repeated forced hyperextension of the elbow. Both patients were treated by débridement of the posterior capitellum and reattachment of the PLL, with complete resolution of symptoms. In addition, there were 3 cases of clinical posterolateral rotatory instability in young patients. Two athletes had an isolated acute tear of the PLL, and on physical examination, both had positive posterior draw test results but negative pivot-shift test results. Both underwent elbow arthroscopy and repair of the PLL with resolution of symptoms. The third patient had long-standing recurrent elbow instability, following a failed lateral ulnar collateral ligament reconstruction, in the presence of an Osborne-Cotterill lesion. He underwent revision lateral ulnar collateral ligament reconstruction, bone grafting of the bony lesion, and reattachment of the PLL, with complete resolution of symptomatic posterolateral rotatory instability. CONCLUSIONS The PLL of the elbow has a significant role in the elbow's posterolateral stability. Its footprints were described, and its clinical significance was demonstrated in cases of elbow instability caused by acute ligament tears and elbow pain due to ligament enthesopathy. Surgeons should be aware of this structure and potential pathology related to its injury.
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Affiliation(s)
- Dani Rotman
- Wrightington Upper Limb Unit, Wrightington Wigan and Leigh NHS Trust, Wigan, UK; Department of Orthopedics, Laniado Hospital, Netanya, Israel
| | - Nawal Bokhari
- Wrightington Upper Limb Unit, Wrightington Wigan and Leigh NHS Trust, Wigan, UK
| | - Andrew Wright
- Wrightington Upper Limb Unit, Wrightington Wigan and Leigh NHS Trust, Wigan, UK
| | - Adam C Watts
- Wrightington Upper Limb Unit, Wrightington Wigan and Leigh NHS Trust, Wigan, UK.
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Shi Q, Chen Y, Xu Y, Chen C, Lu H. Engineering a functional ACL reconstruction graft containing a triphasic enthesis-like structure in bone tunnel for the enhancement of graft-to-bone integration. J Orthop Translat 2024; 45:155-167. [PMID: 38559900 PMCID: PMC10979121 DOI: 10.1016/j.jot.2024.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 12/27/2023] [Accepted: 01/16/2024] [Indexed: 04/04/2024] Open
Abstract
Background Anterior cruciate ligament (ACL) rupture is a common sports injury, which causes knee instability and abnormal joint kinematics. The current ACL graft was single-phasic, and not convenient for the formation of enthesis-like tissue in the bone tunnel, resulting in poor integration of graft-to-bone. Methods A band-shaped acellular tendon (BAT) was prepared as the core component of the ACL reconstruction graft at first, while sleeve-shaped acellular cartilage (SAC) or sleeve-shaped acellular bone (SAB) was fabricated using a vacuum aspiration system (VAS)-based decellularization protocol. The biocompatibility of the three acellular matrixes was evaluated. Furthermore, a collagen-binding peptide (CBP) derived from the A3 domain of von Willebrand factor was respectively fused into the N-terminal of GDF7, TGFβ3, or BMP2 to synthesize three recombinant growth factors capable of binding collagen (named C-GDF7, C-TGFβ3, or C-BMP2), which were respectively tethered to the BAT, SAC or SAB for improving their inducibilities in stem cell differentiation. An in-vitro experiment was performed to evaluate theirs osteogenic, chondrogenic, and tenogenic inducibilities. Then, C-TGFβ3-tethering SAC (C-TGFβ3@SAC) and C-BMP2-tethering SAB (C-BMP2@SAB) were sequentially surrounded at the bone tunnel part of C-GDF7-tethering BAT (C-GDF7@BAT), thus a sleeve-shaped acellular graft with a triphasic enthesis-like structure in bone tunnel part (named tissue-engineered graft, TE graft) was engineered. Lastly, a canine ACL reconstruction model was used to evaluate the in-vivo performance of this TE graft in enhancing graft-to-bone integration. Results The BAT, SAC, and SAB well preserved the structure and components of native tendon, cartilage, and bone, showing good biocompatibility. C-GDF7, C-TGFβ3, or C-BMP2 showed a stronger binding ability to BAT, SAC, and SAB. The C-GDF7@BAT, C-TGFβ3@SAC, or C-BMP2@SAB was a controlled delivery system for the scaffold-specific release of GDF7, TGFβ3, and BMP2, thus showing superior tenogenic, chondrogenic, or osteogenic inducibility, respectively. Using a canine ACL reconstruction model, abundant newly-formed bone and connective collagen fibers could be observed at the integration site between TE graft and bone tunnel at postoperative 16 weeks. Meanwhile, the failure load of the reconstructed ACL by TE graft was significantly higher than that of the autograft. Conclusion The TE graft could be used to reconstruct ruptured ACL and augment graft-to-bone integration, thus demonstrating high potential for clinical translation in ACL reconstruction. Translational potential of this article The findings of the study indicated that the TE graft could be a novel graft for ACL reconstruction with the ability to augment graft-to-bone integration, which may provide a foundation for future clinical application.
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Affiliation(s)
- Qiang Shi
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Yang Chen
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Yan Xu
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Can Chen
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Hongbin Lu
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
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Geng Y, Cui P, Hu M, Zhang B, Dai L, Han F, Patrick YH, Fu SC, Li B, Zhang X. Biomimetic triphasic silk fibroin scaffolds seeded with tendon-derived stem cells for tendon-bone junction regeneration. Biomater Sci 2024; 12:1239-1248. [PMID: 38231128 DOI: 10.1039/d3bm00548h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
The regeneration of tendon and bone junctions (TBJs), a fibrocartilage transition zone between tendons and bones, is a challenge due to the special triphasic structure. In our study, a silk fibroin (SF)-based triphasic scaffold consisting of aligned type I collagen (Col I), transforming growth factor β (TGF-β), and hydroxyapatite (HA) was fabricated to mimic the compositional gradient feature of the native tendon-bone architecture. Rat tendon-derived stem cells (rTDSCs) were loaded on the triphasic SF scaffold, and the high cell viability suggested that the scaffold presents good biocompatibility. Meanwhile, increased expressions of tenogenic-, chondrogenic-, and osteogenic-related genes in the TBJs were observed. The in vivo studies of the rTDSC-seeded scaffold in a rat TBJ rupture model showed tendon tissue regeneration with a clear transition zone within 8 weeks of implantation. These results indicated that the biomimetic triphasic SF scaffolds seeded with rTDSCs have great potential to be applied in TBJ regeneration.
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Affiliation(s)
- Yiyun Geng
- Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
- School of Biotechnology and Food Engineering, Changshu Institute of Technology, Changshu, Jiangsu, China
| | - Penglei Cui
- Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
| | - Muli Hu
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China.
- Orthopaedic Institute, Medical College, Soochow University, Suzhou, Jiangsu, China
| | - Bingjun Zhang
- Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
- National Facility for Translational Medicine, Shanghai, China
| | - Liming Dai
- Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
| | - Fengxuan Han
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China.
- Orthopaedic Institute, Medical College, Soochow University, Suzhou, Jiangsu, China
| | - Yungshu-Hang Patrick
- Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China
| | - Sai-Chuen Fu
- Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China
| | - Bin Li
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China.
- Orthopaedic Institute, Medical College, Soochow University, Suzhou, Jiangsu, China
| | - Xiaoling Zhang
- Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
- National Facility for Translational Medicine, Shanghai, China
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D'Amato G, Tofangchiha M, Sheikhdavoodi N, Mohammadi Z, Ranjbaran M, Jabbarian R, Patini R. Relationship between Skeletal Malocclusion and Radiomorphometric Indices of the Mandible in Long Face Patients. Diagnostics (Basel) 2024; 14:459. [PMID: 38472932 DOI: 10.3390/diagnostics14050459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 01/25/2024] [Accepted: 01/30/2024] [Indexed: 03/14/2024] Open
Abstract
This study aimed to assess the relationship between skeletal malocclusion and radiomorphometric indices of the mandible in long face patients. This cross-sectional study evaluated 174 lateral cephalograms and panoramic radiographs of long face patients between the ages of 17 and 30 presenting at the Orthodontics Department of Qazvin Dental School. The gonial angle, antegonial angle, type of antegonial notch, and depth of antegonial notch were measured bilaterally on panoramic radiographs. The correlation between the radiomorphometric parameters and the type of occlusion was analyzed using one-way ANOVA, independent t-test, Chi-square test, and Fisher's exact test (alpha = 0.05). The mean size of gonial angle was significantly different among the three classes of occlusion (p = 0.046), while the difference was not significant regarding the antegonial angle size and antegonial notch depth (p > 0.05). An independent t-test showed that the mean sizes of gonial angle (p = 0.026) and antegonial angle (p = 0.036), and the antegonial notch depth (p = 0.046) in males, were significantly greater than the values in females. According to the Chi-square and Fisher's exact test, the right antegonial notch type was significantly different among the three classes of malocclusion (p = 0.006), while this difference was not significant in the left side (p = 0.318). The right antegonial notch type II was more common in males, while the right antegonial notch type I was more common in females (p = 0.014). According to the results, the indices of gonial angle and type of antegonial notch can be clinically useful for predicting the growth rate of the mandible and designing the appropriate treatment in long face patients.
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Affiliation(s)
- Giuseppe D'Amato
- Department of Faculty of Medicine and Surgery, Unicamillus International Medical University, 00131 Rome, Italy
| | - Maryam Tofangchiha
- Department of Oral and Maxillofacial Radiology, Dental Caries Prevention Research Center, Qazvin University of Medical Sciences, Qazvin 34197-59811, Iran
| | - Nima Sheikhdavoodi
- Department of Orthodontics, School of Dentistry, Qazvin University of Medical Sciences, Qazvin 34197-59811, Iran
| | - Zahra Mohammadi
- Department of Endodontics, School of Dentistry, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan 81551-39998, Iran
| | - Mehdi Ranjbaran
- Metabolic Diseases Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin 34197-59811, Iran
| | - Razieh Jabbarian
- Dental Caries Prevention Research Center, Qazvin University of Medical Sciences, Qazvin 34197-59811, Iran
- Department of Pediatric Dentistry, Qazvin University of Medical Sciences, Qazvin 34197-59811, Iran
| | - Romeo Patini
- Department of Head, Neck and Sense Organs, School of Dentistry, Catholic University of Sacred Heart, 00135 Rome, Italy
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Zhang J, Cai Z, Feng F, Peng Y, Cui Y, Xu Y. Age-different BMSCs-derived exosomes accelerate tendon-bone interface healing in rotator cuff tears model. Gene 2024; 895:148002. [PMID: 37979948 DOI: 10.1016/j.gene.2023.148002] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 11/07/2023] [Accepted: 11/14/2023] [Indexed: 11/20/2023]
Abstract
BACKGROUND Rotator cuff tears (RCTs) are culprit of shoulder pain and dysfunction. Tendon-bone interface (TBI) mal-healing is an essential contributor to retear after RCTs. Consequently, present project was conducted to investigate the role of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes on TBI healing. METHOD Young BMSCs (Y-BMSCs) and Aged BMSCs (A-BMSCs) were isolated from Young (3-month-old) and old (24-month-old) SD rats, and their-derived exosomes (A-BMSCs-exo and Y-BMSCs-exo) were identified. RCTs model was established, and A-BMSCs-exo and Y-BMSCs-exo were injected at the rotator cuff using hydrogel as a vehicle. Pathological changes of TBI were observed by HE, Sirius Red and Oil Red O staining. Western blotting and RT-qPCR were applied to assess the expression of extracellular matrix (ECM)-, tendon cell (TCs)-, osteogenic-, tendon-derived stem cell (TDSCs)- and angiogenic-associated proteins and mRNAs in TBI. RESULT Y-BMSCs exhibited increased activity, osteogenic and lipogenic abilities than A-BMSCs. After A-BMSCs-exo and Y-BMSCs-exo treatment, TBI displayed massive sharpey's fibers growing along the tendon longitudinally, and a collagen fiber-chondrocyte migration zone forming a typical tendon-noncalcified fibrocartilage-calcified fibrocartilage-bone structure. A-BMSCs-exo and Y-BMSCs-exo significantly upregulated the expression of collagen Col I/II/III, Aggrecan, TNMD, SCX, Runx2, OPN, CD45, Sox2, CD31 and VEGFR2 in TBI. In vitro, A-BMSCs-exo and Y-BMSCs-exo significantly enhanced the activity of TCs and TDSCs, TDSCs stemness, and reduced the osteogenic and lipogenic capacity of TDSCs. The effect of Y-BMSCs-exo was significantly stronger than that of A-BMSCs-exo. CONCLUSION BMSCs-derived exosomes facilitate ECM remodeling, osteogenic differentiation, angiogenesis, and stemness of TDSCs, thereby accelerating TBI healing in RCTs, with better outcomes using young individual-derived BMSCs.
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Affiliation(s)
- Jianping Zhang
- Department of Orthopaedics, 920th Hospital of Joint Logistic Support Force, PLA, No. 212 Daguan Road, Kunming, Yunnan 650032, China.
| | - Zhijun Cai
- Department of Orthopaedics, 920th Hospital of Joint Logistic Support Force, PLA, No. 212 Daguan Road, Kunming, Yunnan 650032, China.
| | - Fanzhe Feng
- Department of Orthopaedics, 920th Hospital of Joint Logistic Support Force, PLA, No. 212 Daguan Road, Kunming, Yunnan 650032, China
| | - Yufeng Peng
- Department of Orthopaedics, 920th Hospital of Joint Logistic Support Force, PLA, No. 212 Daguan Road, Kunming, Yunnan 650032, China
| | - Yi Cui
- Department of Orthopaedics, 920th Hospital of Joint Logistic Support Force, PLA, No. 212 Daguan Road, Kunming, Yunnan 650032, China.
| | - Yongiqing Xu
- Department of Orthopaedics, 920th Hospital of Joint Logistic Support Force, PLA, No. 212 Daguan Road, Kunming, Yunnan 650032, China.
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