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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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Yu X, Hu J, Li Y, Wen Y, Li B. ACL injury management: a comprehensive review of novel biotherapeutics. Front Bioeng Biotechnol 2024; 12:1455225. [PMID: 39650235 PMCID: PMC11620901 DOI: 10.3389/fbioe.2024.1455225] [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: 06/26/2024] [Accepted: 11/12/2024] [Indexed: 12/11/2024] Open
Abstract
The anterior cruciate ligament (ACL) is integral to the stability of the knee joint, serving to limit anterior tibial translation and regulate rotational movements. ACL injuries are among the most common and debilitating forms of knee trauma, often resulting in joint effusion, muscular atrophy, and diminished athletic capabilities. Despite the established efficacy of ACL reconstruction as the standard treatment, it is not uniformly successful. Consequently, there is a growing interest in novel biotherapeutic interventions as potential alternatives. This comprehensive review examines the latest advancements in ACL biotherapy, encompassing the application of hyaluronic acid, self-assembled short peptides, growth factors, stem cell therapy, gene therapy, platelet-rich plasma therapy, bone marrow aspirate concentrate cells, extracorporeal shock wave, electrical stimulation and cross bracing protocol. The collective aim of these innovative treatments is to facilitate the restoration of the ACL's native biological and biomechanical integrity, with the ultimate goal of enhancing clinical outcomes and the functional recovery of affected individuals.
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Affiliation(s)
- Xuezhi Yu
- Department of Joint Surgery and Sports Medicine, Shengjing Hospital, China Medical University, Shenyang, China
| | - Jiahui Hu
- Department of Joint Surgery and Sports Medicine, Shengjing Hospital, China Medical University, Shenyang, China
| | - Yifan Li
- Department of Histology and Embryology, College of Basic Medical Sciences, China Medical University, Shenyang, China
| | - Yu Wen
- Department of Histology and Embryology, College of Basic Medical Sciences, China Medical University, Shenyang, China
| | - Bin Li
- Department of Joint Surgery and Sports Medicine, Shengjing Hospital, China Medical University, Shenyang, China
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Gheisari A, Ristaniemi A, Haghighatnejad M, Mohammadi A, Sawatsky A, Saarakkala S, Herzog W, Korhonen RK, Finnilä MAJ. Alterations in mechanical properties of rabbit collateral ligaments eight weeks after anterior cruciate ligament transection. J Biomech 2024; 176:112350. [PMID: 39378770 DOI: 10.1016/j.jbiomech.2024.112350] [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: 03/18/2024] [Revised: 09/24/2024] [Accepted: 09/24/2024] [Indexed: 10/10/2024]
Abstract
Anterior cruciate ligament (ACL) injury is a common knee ligament injury among young, active adults; however, little is known about its impact on the viscoelastic properties of the knee joint's collateral ligaments. This study aimed to characterize and compare the viscoelastic properties of rabbit collateral ligaments in healthy control knees, injured knees, and knees contralateral to the injured knees. Unilateral anterior cruciate ligament transection was performed on six New Zealand white rabbits to create an ACL injury model. Medial and lateral collateral ligaments (MCL and LCL) were collected from the injured and contralateral knees eight weeks after ACL transection. Ligaments were also harvested from both knees of four unoperated rabbits. The ligaments underwent tensile stress-relaxation testing at strain levels of 2, 4, 6, and 8 %, and a sinusoidal loading test at 8 % strain with 0.5 % strain amplitude using frequencies of 0.01, 0.05, 0.1, 0.5, 1, and 2 Hz. The results showed that collateral ligaments of ACL-transected knees relaxed slower compared to control knees. Sinusoidal testing revealed that contralateral knee LCLs had significantly higher storage and loss modulus across all test frequencies. The results indicate that contralateral knee LCLs become stiffer compared to LCLs from control and ACL-transected knees, while LCLs from ACL-transected knees become less viscous compared to LCLs from control and contralateral knees. This study suggests that knee ligaments undergo adaptations following an ACL injury that may affect the mechanics of the ACL-transected knee, which should be considered in biomechanical and rehabilitation studies of patients with an ACL injury.
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Affiliation(s)
- Anahita Gheisari
- Research Unit of Health Sciences and Technology, University of Oulu, Oulu, Finland.
| | - Aapo Ristaniemi
- Department of Technical Physics, University of Eastern Finland, Kuopio, Finland
| | | | - Ali Mohammadi
- Department of Technical Physics, University of Eastern Finland, Kuopio, Finland
| | - Andrew Sawatsky
- Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada
| | - Simo Saarakkala
- Research Unit of Health Sciences and Technology, University of Oulu, Oulu, Finland
| | - Walter Herzog
- Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada; Mechanical & Manufacturing Engineering, Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada
| | - Rami K Korhonen
- Department of Technical Physics, University of Eastern Finland, Kuopio, Finland
| | - Mikko A J Finnilä
- Research Unit of Health Sciences and Technology, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland
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Iacobescu GL, Iacobescu L, Popa MIG, Covache-Busuioc RA, Corlatescu AD, Cirstoiu C. Genomic Determinants of Knee Joint Biomechanics: An Exploration into the Molecular Basis of Locomotor Function, a Narrative Review. Curr Issues Mol Biol 2024; 46:1237-1258. [PMID: 38392197 PMCID: PMC10888373 DOI: 10.3390/cimb46020079] [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: 12/30/2023] [Revised: 01/20/2024] [Accepted: 01/25/2024] [Indexed: 02/24/2024] Open
Abstract
In recent years, the nexus between genetics and biomechanics has garnered significant attention, elucidating the role of genomic determinants in shaping the biomechanical attributes of human joints, specifically the knee. This review seeks to provide a comprehensive exploration of the molecular basis underlying knee joint locomotor function. Leveraging advancements in genomic sequencing, we identified specific genetic markers and polymorphisms tied to key biomechanical features of the knee, such as ligament elasticity, meniscal resilience, and cartilage health. Particular attention was devoted to collagen genes like COL1A1 and COL5A1 and their influence on ligamentous strength and injury susceptibility. We further investigated the genetic underpinnings of knee osteoarthritis onset and progression, as well as the potential for personalized rehabilitation strategies tailored to an individual's genetic profile. We reviewed the impact of genetic factors on knee biomechanics and highlighted the importance of personalized orthopedic interventions. The results hold significant implications for injury prevention, treatment optimization, and the future of regenerative medicine, targeting not only knee joint health but joint health in general.
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Affiliation(s)
- Georgian-Longin Iacobescu
- Orthopaedics and Traumatology Department, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania
- University Emergency Hospital, 050098 Bucharest, Romania
| | - Loredana Iacobescu
- Orthopaedics and Traumatology Department, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania
- University Emergency Hospital, 050098 Bucharest, Romania
| | - Mihnea Ioan Gabriel Popa
- Orthopaedics and Traumatology Department, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania
- University Emergency Hospital, 050098 Bucharest, Romania
| | - Razvan-Adrian Covache-Busuioc
- Orthopaedics and Traumatology Department, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Antonio-Daniel Corlatescu
- Orthopaedics and Traumatology Department, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Catalin Cirstoiu
- Orthopaedics and Traumatology Department, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania
- University Emergency Hospital, 050098 Bucharest, Romania
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Yaghoobi H, Clarke A, Kerr G, Frampton J, Kreplak L. Multifilament Collagen Fiber Bundles with Tendon-like Structure and Mechanical Performance. Macromol Rapid Commun 2023; 44:e2300204. [PMID: 37291949 DOI: 10.1002/marc.202300204] [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: 05/15/2023] [Revised: 06/07/2023] [Indexed: 06/10/2023]
Abstract
Collagen multifilament bundles comprised of thousands of monofilaments are prepared by multipin contact drawing of an entangled polymer solution consisting of collagen and poly(ethylene oxide) (PEO). The multifilament bundles are hydrated in graded concentrations of PEO and phosphate buffered saline (PBS) to promote assembly of collagen fibrils within each monofilament while preserving the structure of the multifilament bundle. Multiscale structural characterization reveals that the hydrated multifilament bundle contains properly folded collagen molecules packed in collagen fibrils containing microfibrils, staggered by exactly one-sixth of the microfibril D-band spacing to produce a periodicity of 11 nm. Sequence analysis predicts that in this structure, phenylalanine residues are close enough within and between microfibrils to become ultraviolet C (UVC) crosslinked. In agreement with this analysis, the ultimate tensile strength (UTS) and Young's modulus of the hydrated collagen multifilament bundles crosslinked by UVC radiation increase nonlinearly with total UVC energy to reach values in the range of native tendons without damage to the collagen molecules. This fabrication method recapitulates the structure of a tendon across multiple length scales and offers tunability in tensile properties using only collagen molecules and no other chemical additives in addition to PEO, which is almost entirely removed during the hydration process.
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Affiliation(s)
- Hessameddin Yaghoobi
- Department of Physics & Atmospheric Science, Dalhousie University, Halifax, Nova Scotia, B3H 4R2, Canada
- School of Biomedical Engineering, Dalhousie University, Halifax, Nova Scotia, B3H 4R2, Canada
| | - Alison Clarke
- Department of Physics & Atmospheric Science, Dalhousie University, Halifax, Nova Scotia, B3H 4R2, Canada
| | - Gavin Kerr
- Department of Physics & Atmospheric Science, Dalhousie University, Halifax, Nova Scotia, B3H 4R2, Canada
| | - John Frampton
- School of Biomedical Engineering, Dalhousie University, Halifax, Nova Scotia, B3H 4R2, Canada
- Department of Biochemistry & Molecular Biology, Dalhousie University, Halifax, Nova Scotia, B3H 4R2, Canada
| | - Laurent Kreplak
- Department of Physics & Atmospheric Science, Dalhousie University, Halifax, Nova Scotia, B3H 4R2, Canada
- School of Biomedical Engineering, Dalhousie University, Halifax, Nova Scotia, B3H 4R2, Canada
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Govindaraju DT, Chen CH, Shalumon KT, Kao HH, Chen JP. Bioactive Nanostructured Scaffold-Based Approach for Tendon and Ligament Tissue Engineering. NANOMATERIALS (BASEL, SWITZERLAND) 2023; 13:1847. [PMID: 37368277 PMCID: PMC10302175 DOI: 10.3390/nano13121847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 06/05/2023] [Accepted: 06/09/2023] [Indexed: 06/28/2023]
Abstract
An effective therapeutic strategy to treat tendon or ligament injury continues to be a clinical challenge due to the limited natural healing capacity of these tissues. Furthermore, the repaired tendons or ligaments usually possess inferior mechanical properties and impaired functions. Tissue engineering can restore the physiological functions of tissues using biomaterials, cells, and suitable biochemical signals. It has produced encouraging clinical outcomes, forming tendon or ligament-like tissues with similar compositional, structural, and functional attributes to the native tissues. This paper starts by reviewing tendon/ligament structure and healing mechanisms, followed by describing the bioactive nanostructured scaffolds used in tendon and ligament tissue engineering, with emphasis on electrospun fibrous scaffolds. The natural and synthetic polymers for scaffold preparation, as well as the biological and physical cues offered by incorporating growth factors in the scaffolds or by dynamic cyclic stretching of the scaffolds, are also covered. It is expected to present a comprehensive clinical, biological, and biomaterial insight into advanced tissue engineering-based therapeutics for tendon and ligament repair.
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Affiliation(s)
- Darshan Tagadur Govindaraju
- Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan City 33302, Taiwan;
| | - Chih-Hao Chen
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital at Keelung, Chang Gung University College of Medicine, Anle, Keelung 20401, Taiwan;
- Craniofacial Research Center, Chang Gung Memorial Hospital at Linkou, Kwei-San, Taoyuan City 33305, Taiwan
| | - K. T. Shalumon
- Department of Chemistry, Sacred Heart College, Mahatma Gandhi University, Kochi 682013, India;
| | - Hao-Hsi Kao
- Division of Nephrology, Chang Gung Memorial Hospital at Keelung, Chang Gung University College of Medicine, Anle, Keelung 20401, Taiwan;
| | - Jyh-Ping Chen
- Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan City 33302, Taiwan;
- Craniofacial Research Center, Chang Gung Memorial Hospital at Linkou, Kwei-San, Taoyuan City 33305, Taiwan
- Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou, Kwei-San, Taoyuan City 33305, Taiwan
- Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Kwei-San, Taoyuan City 33305, Taiwan
- Department of Materials Engineering, Ming Chi University of Technology, Tai-Shan, New Taipei City 24301, Taiwan
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7
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VEGFA-Enriched Exosomes from Tendon-Derived Stem Cells Facilitate Tenocyte Differentiation, Migration, and Transition to a Fibroblastic Phenotype. BIOMED RESEARCH INTERNATIONAL 2022; 2022:8537959. [PMID: 36119932 PMCID: PMC9481323 DOI: 10.1155/2022/8537959] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 08/15/2022] [Accepted: 08/26/2022] [Indexed: 11/24/2022]
Abstract
Tendon-derived stem cells (TDSCs) play a vital role in repair of rotator cuff tear injuries by secreting paracrine proteins that regulate resident cell functions. Secreted exosomes may play a role in tendon injury repair by mediating intercellular communication; however, the detailed mechanisms by which TDSC-derived exosomes affect tenocyte development remain unknown. Here, we examined the effects of exosomes isolated from conditioned medium of TDSCs on tenocyte differentiation, migration, and transition to a fibroblastic phenotype in vitro. Successful isolation of exosomes from TDSCs was confirmed by high expression levels of CD81, CD63, CD9, and TSG101. Treatment with TDSC-derived exosomes promoted the growth and migration of cultured rat tenocytes, and increased the levels of the fibrosis markers collagen I, collagen III, scleraxis, tenascin C, and α-smooth muscle actin. Furthermore, vascular endothelial growth factor A (VEGFA) expression was higher in TDSC-derived exosomes than in TDSCs, and genetic knockdown of VEGFA suppressed the stimulatory effect of TDSC-derived exosomes on tenocyte development. Overall, these results demonstrate that VEGFA-enriched exosomes isolated from TDSCs promote differentiation and migration of cultured tenocytes and their transition to a fibroblastic phenotype. These data provide a new potential clinical treatment strategy for tendon injury.
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8
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Xue Y, Kim HJ, Lee J, Liu Y, Hoffman T, Chen Y, Zhou X, Sun W, Zhang S, Cho HJ, Lee J, Kang H, WonHyoung R, Chang-Moon L, Ahadian S, Dokmeci MR, Lei B, Lee K, Khademhosseini A. Co-Electrospun Silk Fibroin and Gelatin Methacryloyl Sheet Seeded with Mesenchymal Stem Cells for Tendon Regeneration. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2022; 18:e2107714. [PMID: 35487761 PMCID: PMC9714686 DOI: 10.1002/smll.202107714] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 03/07/2022] [Indexed: 05/03/2023]
Abstract
Silk fibroin (SF) is a promising biomaterial for tendon repair, but its relatively rigid mechanical properties and low cell affinity have limited its application in regenerative medicine. Meanwhile, gelatin-based polymers have advantages in cell attachment and tissue remodeling but have insufficient mechanical strength to regenerate tough tissue such as tendons. Taking these aspects into account, in this study, gelatin methacryloyl (GelMA) is combined with SF to create a mechanically strong and bioactive nanofibrous scaffold (SG). The mechanical properties of SG nanofibers can be flexibly modulated by varying the ratio of SF and GelMA. Compared to SF nanofibers, mesenchymal stem cells (MSCs) seeded on SG fibers with optimal composition (SG7) exhibit enhanced growth, proliferation, vascular endothelial growth factor production, and tenogenic gene expression behavior. Conditioned media from MSCs cultured on SG7 scaffolds can greatly promote the migration and proliferation of tenocytes. Histological analysis and tenogenesis-related immunofluorescence staining indicate SG7 scaffolds demonstrate enhanced in vivo tendon tissue regeneration compared to other groups. Therefore, rational combinations of SF and GelMA hybrid nanofibers may help to improve therapeutic outcomes and address the challenges of tissue-engineered scaffolds for tendon regeneration.
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Affiliation(s)
- Yumeng Xue
- State Key Laboratory of Solidification Processing, Center for Nano Energy Materials, School of Materials Science and Engineering, Northwestern Polytechnical University, Xi’an, 710072, China
- Department of Bioengineering and Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA 90095, USA
- Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an, 710000, China
| | - Han-Jun Kim
- Department of Bioengineering and Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA 90095, USA
- Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA
| | - Junmin Lee
- Department of Bioengineering and Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA 90095, USA
- Department of Mechanical Engineering, YONSEI University, Seoul, 03722, South Korea
- Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA
| | - Yaowen Liu
- Department of Bioengineering and Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA 90095, USA
- College of Food Science, Sichuan Agricultural University, Yaan, 625014, China
| | - Tyler Hoffman
- Department of Bioengineering and Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA 90095, USA
| | - Yi Chen
- Department of Bioengineering and Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA 90095, USA
| | - Xingwu Zhou
- Department of Bioengineering and Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA 90095, USA
| | - Wujin Sun
- Department of Bioengineering and Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA 90095, USA
- Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA
| | - Shiming Zhang
- Department of Bioengineering and Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA 90095, USA
- Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA
| | - Hyun-Jong Cho
- College of Pharmacy, Kangwon National University, Chuncheon, 23431, South Korea
| | - JiYong Lee
- Department of Bioengineering and Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA 90095, USA
- Department of Mechanical Engineering, YONSEI University, Seoul, 03722, South Korea
- Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA
| | - Heemin Kang
- Department of Materials Science and Engineering, Korea University, Seoul, 02841, South Korea
| | - Ryu WonHyoung
- Department of Mechanical Engineering, YONSEI University, Seoul, 03722, South Korea
| | - Lee Chang-Moon
- Department of Healthcare and Biomedical Engineering, Chonnam National University, Yeosu, 59626, South Korea
| | - Samad Ahadian
- Department of Bioengineering and Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA 90095, USA
- Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA
| | - Mehmet R. Dokmeci
- Department of Bioengineering and Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA 90095, USA
- Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA
| | - Bo Lei
- Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an, 710000, China
| | - KangJu Lee
- Department of Bioengineering and Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA 90095, USA
- Department of Healthcare and Biomedical Engineering, Chonnam National University, Yeosu, 59626, South Korea
- Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA
| | - Ali Khademhosseini
- Department of Bioengineering and Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA 90095, USA
- Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA
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UYAR İ, ALTUNTAŞ Z, FINDIK S, YILDIRIM MEC, YARAR S, AKTAN M, AVCI A. The effects of a combination treatment with mesenchymal stem cell and platelet-rich plasma on tendon healing: an experimental study. Turk J Med Sci 2022; 52:237-247. [PMID: 36161600 PMCID: PMC10734839 DOI: 10.3906/sag-2105-145] [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: 05/13/2021] [Revised: 02/22/2022] [Accepted: 10/17/2021] [Indexed: 11/03/2022] Open
Abstract
BACKGROUND The objective of this study was to investigate the effects that the application of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) following tendon repair have on the strength and healing of the tendon and also to examine the possible mechanisms of action that take place. METHODS The Achilles tendons of 80 rats were repaired and divided into eight groups. Following the repairs, MSCs obtained from humans were injected into the rat tendons in groups 1 and 2, a combination of MSCs from humans and PRP from rats was injected into the tendons in groups 3 and 4, and PRP from rats was injected into the tendons in groups 5 and 6. These procedures all took place simultaneously. Groups 7 and 8 did not receive any injections following the repairs. The rats were sacrificed at the end of the first and second months following the procedures, and biomechanical and histopathological analyses were performed. RESULTS Inflammatory cell density increased most significantly in the combined group when compared to the first and second months. T he fibroblast density on the tendon repair region was significantly lower in the second-months groups of each intervention compared to their first-month groups (p = 0.001). For the analysis of the maximum tensile breaking force, the behaviors of the groups over time were significant when compared to the control groups (p = 0.0015). Also, the mean maximum breaking force in the combined group was statistically significantly higher at the end of the second month than at the end of the first month (p = 0.0008).
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Affiliation(s)
- İlker UYAR
- Department of Plastic, Reconstructive and Aesthetic Surgery, Faculty of Medicine, İzmir Katip Çelebi University, İzmir,
Turkey
- Department of Plastic, Reconstructive and Aesthetic Surgery, Faculty of Medicine, Necmettin Erbakan University, Konya,
Turkey
| | - Zeynep ALTUNTAŞ
- Department of Plastic, Reconstructive and Aesthetic Surgery, Faculty of Medicine, Necmettin Erbakan University, Konya,
Turkey
| | - Sıddıka FINDIK
- Department of Pathology, Faculty of Medicine, Necmettin Erbakan University, Konya,
Turkey
| | - Mehmet Emin Cem YILDIRIM
- Department of Plastic, Reconstructive and Aesthetic Surgery, Faculty of Medicine, Necmettin Erbakan University, Konya,
Turkey
- Department of Plastic, Reconstructive and Aesthetic Surgery, Faculty of Medicine, İstinye University, İstanbul,
Turkey
| | - Serhat YARAR
- Department of Plastic, Reconstructive and Aesthetic Surgery, Faculty of Medicine, Necmettin Erbakan University, Konya,
Turkey
- Plastic, Reconstructive and Aesthetic Surgery Clinic, Konya City Hospital, Konya,
Turkey
| | - Murat AKTAN
- Department of Histology and Embryology, Faculty of Medicine, Necmettin Erbakan University, Konya,
Turkey
| | - Ahmet AVCI
- Department of Biomedical Engineering, Faculty of Medicine, Necmettin Erbakan University, Konya,
Turkey
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10
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Hanhan S, Goren K, Rivkin A, Saba F, Nevo H, Dar N, Shilo D, Liebergall M, Shoseyov O, Deutsch D, Blumenfeld A, Haze A. Regeneration of grade 3 ankle sprain, using the recombinant human amelogenin protein (rHAM + ) in a rat model. J Orthop Res 2021; 39:1540-1547. [PMID: 32410235 DOI: 10.1002/jor.24718] [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: 12/24/2019] [Revised: 04/03/2020] [Accepted: 05/08/2020] [Indexed: 02/04/2023]
Abstract
Lateral ligament tears, also known as high-grade ankle sprains, are common, debilitating, and usually heal slowly. Ten to thirty percent of patients continue to suffer from chronic pain and ankle instability even after 3 to 9 months. Previously, we showed that the recombinant human amelogenin (rHAM+ ) induced regeneration of fully transected rat medial collateral ligament, a common proof-of-concept model. Our aim was to evaluate whether rHAM+ can regenerate torn ankle calcaneofibular ligament (CFL), an important component of the lateral ankle stabilizers. Right CFLs of Sabra rats were transected and treated with 0, 0.5, or 1 µg/µL rHAM+ dissolved in propylene glycol alginate (PGA). Results were compared with the normal group, without surgery. Healing was evaluated 12 weeks after treatment by mechanical testing (ratio between the right and left, untransected ligaments of the same rat), and histology including immunohistochemical staining of collagen I and S100. The mechanical properties, structure, and composition of transected ligaments treated with 0.5 μg/μL rHAM+ (experimental) were similar to untransected ligaments. PGA (control) treated ligaments were much weaker, lax, and unorganized compared with untransected ligaments. Treatment with 1 μg/μL rHAM+ was not as efficient as 0.5 μg/μL rHAM+ . Normal arrangement of collagen I fibers and of proprioceptive nerve endings, parallel to the direction of the force, was detected in ligaments treated with 0.5 μg/μL rHAM+ , and scattered arrangement, resembling scar tissue, in control ligaments. In conclusion, we showed that rHAM+ induced significant mechanical and structural regeneration of torn rat CFLs, which might be translated into treatment for grades 2 and 3 ankle sprain injuries.
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Affiliation(s)
- Salem Hanhan
- Faculty of Dental Medicine, Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
| | - Koby Goren
- Faculty of Dental Medicine, Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
| | - Amit Rivkin
- Faculty of Agriculture, Food and Environment, Institute of Plant Sciences and Genetics in Agriculture, Hebrew University, Rehovot, Israel
| | - Faris Saba
- Faculty of Dental Medicine, Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
| | - Hani Nevo
- Department of Orthopedics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Naama Dar
- Faculty of Dental Medicine, Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
| | - Dekel Shilo
- Faculty of Dental Medicine, Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
| | - Meir Liebergall
- Department of Orthopedics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Oded Shoseyov
- Faculty of Agriculture, Food and Environment, Institute of Plant Sciences and Genetics in Agriculture, Hebrew University, Rehovot, Israel
| | - Dan Deutsch
- Faculty of Dental Medicine, Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
| | - Anat Blumenfeld
- Faculty of Dental Medicine, Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
| | - Amir Haze
- Department of Orthopedics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
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11
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Gögele C, Hoffmann C, Konrad J, Merkel R, Schwarz S, Tohidnezhad M, Hoffmann B, Schulze-Tanzil GG. Cyclically stretched ACL fibroblasts emigrating from spheroids adapt their cytoskeleton and ligament-related expression profile. Cell Tissue Res 2021; 384:675-690. [PMID: 33835257 PMCID: PMC8211585 DOI: 10.1007/s00441-021-03416-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 01/13/2021] [Indexed: 01/09/2023]
Abstract
Mechanical stress of ligaments varies; hence, ligament fibroblasts must adapt their expression profile to novel mechanomilieus to ensure tissue resilience. Activation of the mechanoreceptors leads to a specific signal transduction, the so-called mechanotransduction. However, with regard to their natural three-dimensional (3D) microenvironment cell reaction to mechanical stimuli during emigrating from a 3D spheroid culture is still unclear. This study aims to provide a deeper understanding of the reaction profile of anterior cruciate ligament (ACL)-derived fibroblasts exposed to cyclic uniaxial strain in two-dimensional (2D) monolayer culture and during emigration from 3D spheroids with respect to cell survival, cell and cytoskeletal orientation, distribution, and expression profile. Monolayers and spheroids were cultured in crosslinked polydimethyl siloxane (PDMS) elastomeric chambers and uniaxially stretched (14% at 0.3 Hz) for 48 h. Cell vitality, their distribution, nuclear shape, stress fiber orientation, focal adhesions, proliferation, expression of ECM components such as sulfated glycosaminoglycans, collagen type I, decorin, tenascin C and cell-cell communication-related gap junctional connexin (CXN) 43, tendon-related markers Mohawk and tenomodulin (myodulin) were analyzed. In contrast to unstretched cells, stretched fibroblasts showed elongation of stress fibers, cell and cytoskeletal alignment perpendicular to strain direction, less rounded cell nuclei, increased numbers of focal adhesions, proliferation, amplified CXN43, and main ECM component expression in both cultures. The applied cyclic stretch protocol evoked an anabolic response and enhanced tendon-related marker expression in ACL-derived fibroblasts emigrating from 3D spheroids and seems also promising to support in future tissue formation in ACL scaffolds seeded in vitro with spheroids.
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Affiliation(s)
- Clemens Gögele
- Institute of Anatomy and Cell Biology, Paracelsus Medical University, Prof.-Ernst-Nathan Str. 1, 90419 Nuremberg and Salzburg, Nuremberg, Germany
- Department of Biosciences, Paris Lodron University Salzburg, Hellbrunnerstr. 34, 5020 Salzburg, Austria
| | - Christina Hoffmann
- Institute of Biological Information Processing: IBI-2, Forschungszentrum Jülich, 52425 Jülich, Germany
| | - Jens Konrad
- Institute of Biological Information Processing: IBI-2, Forschungszentrum Jülich, 52425 Jülich, Germany
| | - Rudolf Merkel
- Institute of Biological Information Processing: IBI-2, Forschungszentrum Jülich, 52425 Jülich, Germany
| | - Silke Schwarz
- Institute of Anatomy and Cell Biology, Paracelsus Medical University, Prof.-Ernst-Nathan Str. 1, 90419 Nuremberg and Salzburg, Nuremberg, Germany
| | - Mersedeh Tohidnezhad
- Department of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany
| | - Bernd Hoffmann
- Institute of Biological Information Processing: IBI-2, Forschungszentrum Jülich, 52425 Jülich, Germany
| | - Gundula Gesine Schulze-Tanzil
- Institute of Anatomy and Cell Biology, Paracelsus Medical University, Prof.-Ernst-Nathan Str. 1, 90419 Nuremberg and Salzburg, Nuremberg, Germany
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12
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Sánchez M, Beitia M, Pompei O, Jorquera C, Sánchez P, Knörr J, Soldado F, López L, Oraa J, Miren Bilbao A, Fiz N, Guadilla J, Aizpurua B, Azofra J, Delgado D. Isolation, Activation, and Mechanism of Action of Platelet-Rich Plasma and Its Applications for Joint Repair. Regen Med 2020. [DOI: 10.5772/intechopen.90543] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
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13
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Laguette MJN, Barrow K, Firfirey F, Dlamini S, Saunders CJ, Dandara C, Gamieldien J, Collins M, September AV. Exploring new genetic variants within COL5A1 intron 4-exon 5 region and TGF-β family with risk of anterior cruciate ligament ruptures. J Orthop Res 2020; 38:1856-1865. [PMID: 31922278 DOI: 10.1002/jor.24585] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 01/03/2020] [Indexed: 02/04/2023]
Abstract
Variants within genes encoding structural and regulatory elements of ligaments have been associated with musculoskeletal soft tissue injury risk. The role of intron 4-exon 5 variants within the α1 chain of type V collagen (COL5A1) gene and genes of the transforming growth factor-β (TGF-β) family, TGFBR3 and TGFBI, was investigated on the risk of anterior cruciate ligament (ACL) ruptures. A case-control genetic association study was performed on 210 control (CON) and 249 participants with surgically diagnosed ruptures (ACL), of which 147 reported a noncontact mechanism of injury (NON). Whole-exome sequencing data were used to prioritize variants of potential functional relevance. Genotyping for COL5A1 (rs3922912 G>A, rs4841926 C>T, and rs3124299 C>T), TGFBR3 (rs1805113 G>A and rs1805117 T>C), and TGFBI (rs1442 G>C) was performed using Taqman SNP genotyping assays. Significant overrepresentation of the G allele of TGFBR3 rs1805113 was observed in CON vs ACL (P = .014) and NON groups (P = .021). Similar results were obtained in a female with the G allele (CON vs ACL: P = .029; CON vs NON: P = .016). The TGFBI rs1442 CC genotype was overrepresented in the female ACL vs CON (P = .013). Associations of inferred allele combinations were observed in line with the above results. COL5A1 intron 4-exon 5 genomic interval was not associated with the risk of ACL ruptures. Instead, this novel study is the first to use this approach to identify variants within the TGF-β signaling pathway to be implicated in the risk of ACL ruptures. A genetic susceptibility interval was identified to be explored in the context of extracellular matrix remodeling.
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Affiliation(s)
- Mary-Jessica N Laguette
- Division of Exercise Science and Sports Medicine (ESSM), University of Cape Town, Cape Town, South Africa.,International Federation of Sports Medicine (FIMS) Collaborative Centre of Sports Medicine, ESSM, University of Cape Town, Cape Town, South Africa.,Research Centre for Health Through Physical Activity and Sport, University of Cape Town, Cape Town, South Africa
| | - Kelly Barrow
- Department of Human Genetics, University of Cape Town, Cape Town, South Africa
| | - Firzana Firfirey
- Division of Exercise Science and Sports Medicine (ESSM), University of Cape Town, Cape Town, South Africa.,International Federation of Sports Medicine (FIMS) Collaborative Centre of Sports Medicine, ESSM, University of Cape Town, Cape Town, South Africa.,Research Centre for Health Through Physical Activity and Sport, University of Cape Town, Cape Town, South Africa
| | - Senanile Dlamini
- Division of Exercise Science and Sports Medicine (ESSM), University of Cape Town, Cape Town, South Africa.,International Federation of Sports Medicine (FIMS) Collaborative Centre of Sports Medicine, ESSM, University of Cape Town, Cape Town, South Africa.,Research Centre for Health Through Physical Activity and Sport, University of Cape Town, Cape Town, South Africa
| | - Colleen J Saunders
- South African National Bioinformatics Institute/MRC Unit for Bioinformatics Capacity, University of the Western Cape, Cape Town, Bellville, South Africa.,Division of Emergency Medicine, Department of Surgery, University of Cape Town, Cape Town, South Africa
| | - Collet Dandara
- Department of Human Genetics, University of Cape Town, Cape Town, South Africa
| | - Junaid Gamieldien
- South African National Bioinformatics Institute/MRC Unit for Bioinformatics Capacity, University of the Western Cape, Cape Town, Bellville, South Africa
| | - Malcolm Collins
- Division of Exercise Science and Sports Medicine (ESSM), University of Cape Town, Cape Town, South Africa.,International Federation of Sports Medicine (FIMS) Collaborative Centre of Sports Medicine, ESSM, University of Cape Town, Cape Town, South Africa.,Research Centre for Health Through Physical Activity and Sport, University of Cape Town, Cape Town, South Africa
| | - Alison V September
- Division of Exercise Science and Sports Medicine (ESSM), University of Cape Town, Cape Town, South Africa.,International Federation of Sports Medicine (FIMS) Collaborative Centre of Sports Medicine, ESSM, University of Cape Town, Cape Town, South Africa.,Research Centre for Health Through Physical Activity and Sport, University of Cape Town, Cape Town, South Africa
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14
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Ryan CNM, Zeugolis DI. Engineering the Tenogenic Niche In Vitro with Microenvironmental Tools. ADVANCED THERAPEUTICS 2019. [DOI: 10.1002/adtp.201900072] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Christina N. M. Ryan
- Regenerative, Modular and Developmental Engineering LaboratoryBiomedical Sciences BuildingNational University of Ireland Galway Galway H91 W2TY Ireland
- Science Foundation Ireland, Centre for Research in Medical DevicesBiomedical Sciences BuildingNational University of Ireland Galway Galway H91 W2TY Ireland
| | - Dimitrios I. Zeugolis
- Regenerative, Modular and Developmental Engineering LaboratoryBiomedical Sciences BuildingNational University of Ireland Galway Galway H91 W2TY Ireland
- Science Foundation Ireland, Centre for Research in Medical DevicesBiomedical Sciences BuildingNational University of Ireland Galway Galway H91 W2TY Ireland
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15
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Stuckensen K, Lamo-Espinosa JM, Muiños-López E, Ripalda-Cemboráin P, López-Martínez T, Iglesias E, Abizanda G, Andreu I, Flandes-Iparraguirre M, Pons-Villanueva J, Elizalde R, Nickel J, Ewald A, Gbureck U, Prósper F, Groll J, Granero-Moltó F. Anisotropic Cryostructured Collagen Scaffolds for Efficient Delivery of RhBMP-2 and Enhanced Bone Regeneration. MATERIALS 2019; 12:ma12193105. [PMID: 31554158 PMCID: PMC6804013 DOI: 10.3390/ma12193105] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 09/18/2019] [Accepted: 09/19/2019] [Indexed: 01/22/2023]
Abstract
In the treatment of bone non-unions, an alternative to bone autografts is the use of bone morphogenetic proteins (BMPs), e.g., BMP–2, BMP–7, with powerful osteoinductive and osteogenic properties. In clinical settings, these osteogenic factors are applied using absorbable collagen sponges for local controlled delivery. Major side effects of this strategy are derived from the supraphysiological doses of BMPs needed, which may induce ectopic bone formation, chronic inflammation, and excessive bone resorption. In order to increase the efficiency of the delivered BMPs, we designed cryostructured collagen scaffolds functionalized with hydroxyapatite, mimicking the structure of cortical bone (aligned porosity, anisotropic) or trabecular bone (random distributed porosity, isotropic). We hypothesize that an anisotropic structure would enhance the osteoconductive properties of the scaffolds by increasing the regenerative performance of the provided rhBMP–2. In vitro, both scaffolds presented similar mechanical properties, rhBMP–2 retention and delivery capacity, as well as scaffold degradation time. In vivo, anisotropic scaffolds demonstrated better bone regeneration capabilities in a rat femoral critical-size defect model by increasing the defect bridging. In conclusion, anisotropic cryostructured collagen scaffolds improve bone regeneration by increasing the efficiency of rhBMP–2 mediated bone healing.
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Affiliation(s)
- Kai Stuckensen
- Department for Functional Materials in Medicine and Dentistry and Bavarian Polymer Institute, University of Würzburg, D-97070 Würzburg, Germany
| | - José M Lamo-Espinosa
- Department of Orthopaedic Surgery and Traumatology, Clínica Universidad de Navarra, 31008 Pamplona, Spain
| | - Emma Muiños-López
- Cell Therapy Area. Clínica Universidad de Navarra, 31008 Pamplona, Spain
| | - Purificación Ripalda-Cemboráin
- Department of Orthopaedic Surgery and Traumatology, Clínica Universidad de Navarra, 31008 Pamplona, Spain
- Cell Therapy Area. Clínica Universidad de Navarra, 31008 Pamplona, Spain
| | | | - Elena Iglesias
- Cell Therapy Area. Clínica Universidad de Navarra, 31008 Pamplona, Spain
| | - Gloria Abizanda
- Cell Therapy Area. Clínica Universidad de Navarra, 31008 Pamplona, Spain
| | - Ion Andreu
- Department of Materials CEIT-TECNUN, Universidad de Navarra, 20018 San Sebastian, Spain
| | | | - Juan Pons-Villanueva
- Department of Orthopaedic Surgery and Traumatology, Clínica Universidad de Navarra, 31008 Pamplona, Spain
| | - Reyes Elizalde
- Department of Materials CEIT-TECNUN, Universidad de Navarra, 20018 San Sebastian, Spain
| | - Joachim Nickel
- Department Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, D-97070 Würzburg, Germany
| | - Andrea Ewald
- Department for Functional Materials in Medicine and Dentistry and Bavarian Polymer Institute, University of Würzburg, D-97070 Würzburg, Germany
| | - Uwe Gbureck
- Department for Functional Materials in Medicine and Dentistry and Bavarian Polymer Institute, University of Würzburg, D-97070 Würzburg, Germany
| | - Felipe Prósper
- Cell Therapy Area. Clínica Universidad de Navarra, 31008 Pamplona, Spain
- Department of Haematology, Clínica Universidad de Navarra, 31008 Pamplona, Spain
| | - Jürgen Groll
- Department for Functional Materials in Medicine and Dentistry and Bavarian Polymer Institute, University of Würzburg, D-97070 Würzburg, Germany.
| | - Froilán Granero-Moltó
- Department of Orthopaedic Surgery and Traumatology, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
- Cell Therapy Area. Clínica Universidad de Navarra, 31008 Pamplona, Spain.
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16
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Sivertsen EA, Haug KBF, Kristianslund EK, Trøseid AMS, Parkkari J, Lehtimäki T, Mononen N, Pasanen K, Bahr R. No Association Between Risk of Anterior Cruciate Ligament Rupture and Selected Candidate Collagen Gene Variants in Female Elite Athletes From High-Risk Team Sports. Am J Sports Med 2019; 47:52-58. [PMID: 30485117 DOI: 10.1177/0363546518808467] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Several single-nucleotide variants (SNVs) in collagen genes have been reported as predisposing factors for anterior cruciate ligament (ACL) tears. However, the evidence is conflicting and does not support a clear association between genetic variants and risk of ACL ruptures. PURPOSE To assess the association of previously identified candidate SNVs in genes encoding for collagen and the risk of ACL injury in a population of elite female athletes from high-risk team sports. STUDY DESIGN Cohort study; Level of evidence, 2. METHODS A total of 851 female Norwegian and Finnish elite athletes from team sports were included from 2007 to 2011. ACL injuries acquired before inclusion in the cohort were registered by interview. The participants were followed prospectively through 2015 to record new complete ACL injuries. Six selected SNVs were genotyped ( COL1A1: rs1800012, rs1107946; COL3A1: rs1800255; COL5A1: rs12722, rs13946; COL12A1: rs970547). RESULTS No associations were found between ACL rupture and the SNVs tested. CONCLUSION The study does not support a role of the 6 selected SNVs in genes encoding for collagen proteins as risk factors for ACL injury. CLINICAL RELEVANCE Genetic profiling to identify athletes at high risk for ACL rupture is not yet feasible.
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Affiliation(s)
- Einar Andreas Sivertsen
- Department of Surgery, Diakonhjemmet Hospital, Oslo, Norway.,Oslo Sports Trauma Research Center, Department of Sports Medicine, Norwegian School of Sport Sciences, Oslo, Norway
| | - Kari Bente Foss Haug
- Department of Medical Biochemistry, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Eirik Klami Kristianslund
- Oslo Sports Trauma Research Center, Department of Sports Medicine, Norwegian School of Sport Sciences, Oslo, Norway.,Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
| | - Anne-Marie Siebke Trøseid
- Department of Medical Biochemistry, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Jari Parkkari
- Tampere Research Center of Sports Medicine, UKK Institute, Tampere, Finland
| | - Terho Lehtimäki
- Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center-Tampere; Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Nina Mononen
- Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center-Tampere; Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Kati Pasanen
- Tampere Research Center of Sports Medicine, UKK Institute, Tampere, Finland.,Sport Injury Prevention Research Centre, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada
| | - Roald Bahr
- Oslo Sports Trauma Research Center, Department of Sports Medicine, Norwegian School of Sport Sciences, Oslo, Norway
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17
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Jones IA, Togashi R, Hatch GFR, Weber AE, Vangsness CT. Anabolic steroids and tendons: A review of their mechanical, structural, and biologic effects. J Orthop Res 2018; 36:2830-2841. [PMID: 30047601 DOI: 10.1002/jor.24116] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Accepted: 07/13/2018] [Indexed: 02/04/2023]
Abstract
One of the suspected deleterious effects of androgenic-anabolic steroids (AAS) is the increased risk for tendon rupture. However, investigations to date have produced inconsistent results and it is still unclear how AAS influence tendons. A systematic review of the literature was conducted to identify studies that have investigated the mechanical, structural, or biologic effects that AAS have on tendons. In total, 18 highly heterogeneous studies were identified. Small animal studies made up the vast majority of published research, and contradictory results were reported frequently. All of the included studies focused on the potential deleterious effects that AAS have on tendon, which is striking given the recent use of AAS in patients following tendon injury. Rather than providing strong evidence for or against the use of AAS, this review highlights the need for additional research. Future studies investigating the use of AAS as a possible treatment for tendon injury/pathology are supported by reports suggesting that AAS may counteract the irreparable structural/functional changes that occur in the musculotendinous unit following rotator cuff tears, as well as studies suggesting that the purported deleterious effects on tendon may be transient. Other possible areas for future research are discussed in the context of key findings that may have implications for the therapeutic application of AAS. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2830-2841, 2018.
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Affiliation(s)
- Ian A Jones
- Department of Orthopaedic Surgery, Keck School of Medicine of USC, HCT 1520 San Pablo Street, Suite 2000, Los Angeles 90033, California
| | - Ryan Togashi
- Department of Orthopaedic Surgery, Keck School of Medicine of USC, HCT 1520 San Pablo Street, Suite 2000, Los Angeles 90033, California
| | - George F Rick Hatch
- Department of Orthopaedic Surgery, Keck School of Medicine of USC, HCT 1520 San Pablo Street, Suite 2000, Los Angeles 90033, California
| | - Alexander E Weber
- Department of Orthopaedic Surgery, Keck School of Medicine of USC, HCT 1520 San Pablo Street, Suite 2000, Los Angeles 90033, California
| | - C Thomas Vangsness
- Department of Orthopaedic Surgery, Keck School of Medicine of USC, HCT 1520 San Pablo Street, Suite 2000, Los Angeles 90033, California
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18
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Hochleitner G, Chen F, Blum C, Dalton PD, Amsden B, Groll J. Melt electrowriting below the critical translation speed to fabricate crimped elastomer scaffolds with non-linear extension behaviour mimicking that of ligaments and tendons. Acta Biomater 2018; 72:110-120. [PMID: 29555458 DOI: 10.1016/j.actbio.2018.03.023] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 03/04/2018] [Accepted: 03/09/2018] [Indexed: 11/20/2022]
Abstract
Ligaments and tendons are comprised of aligned, crimped collagen fibrils that provide tissue-specific mechanical properties with non-linear extension behaviour, exhibiting low stress at initial strain (toe region behaviour). To approximate this behaviour, we report fibrous scaffolds with sinusoidal patterns by melt electrowriting (MEW) below the critical translation speed (CTS) by exploitation of the natural flow behaviour of the polymer melt. More specifically, we synthesised photopolymerizable poly(L-lactide-co-ε-caprolactone-co-acryloyl carbonate) (p(LLA-co-ε-CL-co-AC)) and poly(ε-caprolactone-co-acryloyl carbonate) (p(ε-CL-co-AC)) by ring-opening polymerization (ROP). Single fibre (fØ = 26.8 ± 1.9 µm) tensile testing revealed a customisable toe region with Young's Moduli ranging from E = 29 ± 17 MPa for the most crimped structures to E = 314 ± 157 MPa for straight fibres. This toe region extended to scaffolds containing multiple fibres, while the sinusoidal pattern could be influenced by printing speed. The synthesized polymers were cytocompatible and exhibited a tensile strength of σ = 26 ± 7 MPa after 104 cycles of preloading at 10% strain while retaining the distinct toe region commonly observed in native ligaments and tendon tissue. STATEMENT OF SIGNIFICANCE Damaged tendons and ligaments are serious and frequently occurring injuries worldwide. Recent therapies, including autologous grafts, still have severe disadvantages leading to a demand for synthetic alternatives. Materials envisioned to induce tendon and ligament regeneration should be degradable, cytocompatible and mimic the ultrastructural and mechanical properties of the native tissue. Specifically, we utilised photo-cross-linkable polymers for additive manufacturing (AM) with MEW. In this way, we were able to direct-write cytocompatible fibres of a few micrometres thickness into crimp-structured elastomer scaffolds that mimic the non-linear biomechanical behaviour of tendon and ligament tissue.
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Affiliation(s)
- Gernot Hochleitner
- Department of Functional Materials in Medicine and Dentistry and Bavarian Polymer Institute (BPI), University Hospital of Würzburg, Pleicherwall 2, 97070 Würzburg, Germany.
| | - Fei Chen
- Department of Chemical Engineering and Human Mobility Research Centre, Queen's University, Kingston, Ontario K7L 3N6, Canada.
| | - Carina Blum
- Department of Functional Materials in Medicine and Dentistry and Bavarian Polymer Institute (BPI), University Hospital of Würzburg, Pleicherwall 2, 97070 Würzburg, Germany.
| | - Paul D Dalton
- Department of Functional Materials in Medicine and Dentistry and Bavarian Polymer Institute (BPI), University Hospital of Würzburg, Pleicherwall 2, 97070 Würzburg, Germany.
| | - Brian Amsden
- Department of Chemical Engineering and Human Mobility Research Centre, Queen's University, Kingston, Ontario K7L 3N6, Canada.
| | - Jürgen Groll
- Department of Functional Materials in Medicine and Dentistry and Bavarian Polymer Institute (BPI), University Hospital of Würzburg, Pleicherwall 2, 97070 Würzburg, Germany.
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19
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Association of polymorphisms rs1800012 in COL1A1 with sports-related tendon and ligament injuries: a meta-analysis. Oncotarget 2018; 8:27627-27634. [PMID: 28206959 PMCID: PMC5432363 DOI: 10.18632/oncotarget.15271] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Accepted: 01/26/2017] [Indexed: 12/01/2022] Open
Abstract
It has been reported that the single nucleotide polymorphism (SNP) rs1800012 in COL1A1 might be associated with the susceptibility to sports-related tendon and ligament injuries such as ACL injuries, Achilles tendon injuries, shoulder dislocations and tennis elbow. But the data from different studies have been conflicting. Here we attempted to systematically summarize and clarify the association between the SNP and sports-related tendon and ligament injuries risk. Six eligible studies including 933 cases and 1,381 controls were acquired from PubMed, Web Of Science and Cochrane library databases. Significant association was identified in homozygote model (TT versus GG: OR=0.17, 95%CI 0.08-0.35, PH=0.00) and recessive model (TT versus GT/GG: OR=0.21, 95%CI 0.10-0.44, PH=0.00). Our results indicated that COL1A1 rs1800012 polymorphism may be associated with the reduced risk of sports-related tendon or ligament injuries, especially in ACL injuries, and that rare TT may played as a protective role.
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Zhang R, Han D, Luo G, Ling L, Li G, Ji Q, Li J. Macroscopic and microscopic analyses in flexor tendons of the tarsometatarso-phalangeal joint of ostrich (Struthio camelus) foot with energy storage and shock absorption. J Morphol 2017; 279:302-311. [PMID: 29148083 DOI: 10.1002/jmor.20772] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Revised: 10/23/2017] [Accepted: 10/27/2017] [Indexed: 12/31/2022]
Abstract
Flexor tendons function as energy storage and shock absorption structures in the tarsometatarso-phalangeal joint (TMTPJ) of ostrich feet during high-speed and heavy-load locomotion. In this study, mechanisms underlying the energy storage and shock absorption of three flexor tendons of the third toe were studied using histology and scanning electron microscopy (SEM). Macroscopic and microscopic structures of the flexor tendons in different positions of TMTPJ were analyzed. Histological slices showed collagen fiber bundles of all flexor tendons in the middle TMTPJ were arranged in a linear-type, but in the proximal and distal TMTPJ, a wavy-type arrangement was found in the tendon of the M. flexor digitorum longus and tendon of the M. flexor perforans et perforatus digiti III, while no regular-type was found in the tendon of the M. flexor perforatus digiti III. SEM showed that the collagen fiber bundles of flexor tendons were arranged in a hierarchically staggered way (horizontally linear-type and vertically linear-type). Linear-type and wavy-type both existed in the proximal TMTPJ for the collagen fiber bundles of the tendon of the M. flexor perforatus digiti III, but only the linear-type was found in the distal TMTPJ. A number of fibrils were distributed among the collagen fiber bundles, which were likely effective in connection, force transmission and other functions. The morphology and arrangement of collagen fiber bundles were closely related to the tendon functions. We present interpretations of the biological functions in different positions and types of the tendons in the TMTPJ of the ostrich feet.
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Affiliation(s)
- Rui Zhang
- Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun, People's Republic of China
| | - Dianlei Han
- Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun, People's Republic of China
| | - Gang Luo
- Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun, People's Republic of China
| | - Lei Ling
- Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun, People's Republic of China
| | - Guoyu Li
- Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun, People's Republic of China
| | - Qiaoli Ji
- Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun, People's Republic of China
| | - Jianqiao Li
- Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun, People's Republic of China
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Development of Multilayered Chlorogenate-Peptide Based Biocomposite Scaffolds for Potential Applications in Ligament Tissue Engineering - An <i>In Vitro</i> Study. JOURNAL OF BIOMIMETICS BIOMATERIALS AND BIOMEDICAL ENGINEERING 2017. [DOI: 10.4028/www.scientific.net/jbbbe.34.37] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
In this work, for the first time, chlorogenic acid, a natural phytochemical, was conjugated to a lactoferrin derived antimicrobial peptide sequence RRWQWRMKKLG to develop a self-assembled template. To mimic the components of extracellular matrix, we then incorporated Type I Collagen, followed by a sequence of aggrecan peptide (ATEGQVRVNSIYQDKVSL) onto the self-assembled templates for potential applications in ligament tissue regeneration. Mechanical properties and surface roughness were studied and the scaffolds displayed a Young’s Modulus of 169 MP and an average roughness of 72 nm respectively. Thermal phase changes were studied by DSC analysis. Results showed short endothermic peaks due to water loss and an exothermic peak due to crystallization of the scaffold caused by rearrangement of the components. Biodegradability studies indicated a percent weight loss of 27.5 % over a period of 37 days. Furthermore, the scaffolds were found to adhere to fibroblasts, the main cellular component of ligament tissue. The scaffolds promoted cell proliferation and displayed actin stress fibers indicative of cell motility and attachment. Collagen and proteoglycan synthesis were also promoted, demonstrating increased expression and deposition of collagen and proteoglycans. Additionally, the scaffolds exhibited antimicrobial activity against Staphylococcus epidermis bacteria, which is beneficial for minimizing biofilm formation if potentially used as implants. Thus, we have developed a novel biocomposite that may open new avenues to enhance ligament tissue regeneration.
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Prządka P, Kiełbowicz Z, Osiński B, Dzimira S, Madej JA, Nowacki W, Kubiak K, Reichert P, Cegielski M. Reconstruction of cranial cruciate ligament in rabbits using polyester implants saturated with PRP, antlerogenic stem cells MIC-1 and their homogenate. Connect Tissue Res 2017; 58:464-478. [PMID: 27791406 DOI: 10.1080/03008207.2016.1251911] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
AIM OF THE STUDY The attempt to limit the negative effects of polyester implants on the articular cavity by using preparations containing growth factors. MATERIALS AND METHODS Polyester implants used for the reconstruction of a rabbit's cranial cruciate ligament (CCL) were saturated with autogenic platelet-rich plasma (PRP), antlerogenic stem cells MIC-1 and their homogenate prior to the surgery. Six months after CCL reconstruction, morphological, and biochemical blood tests were carried out, including proteinogram and acute phase proteins. The knee joints were also examined macro- and microscopically. RESULTS The results, compared to the control group, showed a favorable effect of the PRP and homogenate of antlerogenic cells on limiting the inflammation caused by the presence of polyester implant in the knee joint. The addition of growth factors caused covering the implant faster with the recipient's connective tissue, thus contributing to reducing the inflammatory reaction of the articular capsule to the presence of polyester. At the same time, no enhanced local or general reaction of the rabbit organism was observed to the presence of xenogenic antlerogenic stem cells MIC-1 homogenate which, like the PRP, may provide an easily available source of growth factors, increasingly often used in regenerative medicine. CONCLUSIONS Applying antlerogenic stem cells, their homogenate or PRP increases the volume of connective tissue that surrounds and intertwines polyester CCL implant, separating it from synovial cavity environment.
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Affiliation(s)
- Przemysław Prządka
- a Department of Surgery, Faculty of Veterinary Medicine , Wroclaw University of Environmental and Life Sciences , Wroclaw , Poland
| | - Zdzisław Kiełbowicz
- a Department of Surgery, Faculty of Veterinary Medicine , Wroclaw University of Environmental and Life Sciences , Wroclaw , Poland
| | - Bogdan Osiński
- a Department of Surgery, Faculty of Veterinary Medicine , Wroclaw University of Environmental and Life Sciences , Wroclaw , Poland
| | - Stanisław Dzimira
- b Department of Pathology , Wroclaw University of Environmental and Life Sciences , Wroclaw , Poland
| | - Janusz A Madej
- b Department of Pathology , Wroclaw University of Environmental and Life Sciences , Wroclaw , Poland
| | - Wojciech Nowacki
- c Department of Immunology, Pathophysiology and Preventive Medicine , Wroclaw University of Environmental and Life Sciences , Wroclaw , Poland
| | - Krzysztof Kubiak
- d Department of Internal Medicine and Clinic of Disease of Horses, Dogs and Cats , Wroclaw University of Environmental and Life Sciences , Wroclaw , Poland
| | - Paweł Reichert
- e Department and Clinic of Traumatology and Hand Surgery , Medical University of Wroclaw , Wroclaw , Poland
| | - Marek Cegielski
- f Department of Histology and Embryology , Medical University of Wroclaw , Wroclaw , Poland.,g Stem Cells Spin , Wroclaw , Poland
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23
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Chailakhyan RK, Shekhter AB, Ivannikov SV, Tel'pukhov VI, Suslin DS, Gerasimov YV, Tonenkov AM, Grosheva AG, Panyushkin PV, Moskvina IL, Vorob'eva NN, Bagratashvili VN. Reconstruction of Ligament and Tendon Defects Using Cell Technologies. Bull Exp Biol Med 2017; 162:563-568. [PMID: 28243921 DOI: 10.1007/s10517-017-3660-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Indexed: 12/14/2022]
Abstract
We studied the possibility of restoring the integrity of the Achilles tendon in rabbits using autologous multipotent stromal cells. Collagen or gelatin sponges populated with cells were placed in a resorbable Vicryl mesh tube and this tissue-engineered construct was introduced into a defect of the middle part of the Achilles tendon. In 4 months, histological analysis showed complete regeneration of the tendon with the formation of parallel collagen fibers, spindle-shaped tenocytes, and newly formed vessels.
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Affiliation(s)
- R K Chailakhyan
- N. F. Gamaleya Research Centre of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
| | - A B Shekhter
- I. M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, Russia
| | - S V Ivannikov
- I. M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, Russia
| | - V I Tel'pukhov
- I. M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, Russia
| | - D S Suslin
- I. M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, Russia
| | - Yu V Gerasimov
- N. F. Gamaleya Research Centre of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia
| | - A M Tonenkov
- I. M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, Russia
| | - A G Grosheva
- N. F. Gamaleya Research Centre of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia
| | - P V Panyushkin
- I. M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, Russia
| | - I L Moskvina
- N. F. Gamaleya Research Centre of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia
| | - N N Vorob'eva
- Institute of Photonics Technologies, Russian Academy of Sciences, Federal Research Center "Crystallography and Photonics", Russian Academy of Sciences, Moscow, Russia
| | - V N Bagratashvili
- Institute of Photonics Technologies, Russian Academy of Sciences, Federal Research Center "Crystallography and Photonics", Russian Academy of Sciences, Moscow, Russia
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24
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Best one hundred papers of International Orthopaedics: a bibliometric analysis. INTERNATIONAL ORTHOPAEDICS 2017; 41:689-697. [DOI: 10.1007/s00264-016-3376-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Accepted: 12/11/2016] [Indexed: 01/05/2023]
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25
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Elnikety S, Pendegrass CJ, de Godoy RF, Holden C, Blunn GW. Augmentation and repair of tendons using demineralised cortical bone. BMC Musculoskelet Disord 2016; 17:483. [PMID: 27855678 PMCID: PMC5114756 DOI: 10.1186/s12891-016-1323-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Accepted: 11/01/2016] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND In severe injuries with loss of tendon substance a tendon graft or a synthetic substitute is usually used to restore functional length. This is usually associated with donor site morbidity, host tissue reactions and lack of remodelling of the synthetic substitutes, which may result in suboptimal outcome. A biocompatible graft with mechanical and structural properties that replicate those of normal tendon and ligament has so far not been identified. The use of demineralised bone for tendon reattachment onto bone has been shown to be effective in promoting the regeneration of a normal enthesis. Because of its properties, we proposed that Demineralised Cortical Bone (DCB) could be used in repair of a large tendon defect. METHODS Allogenic DCB grafts in strip form were prepared from sheep cortical bone by acid decalcification and used to replace the enthesis and distal 1 cm of the ovine patellar tendon adjacent to the tibial tuberosity. In 6 animals the DCB strip was used to bridge the gap between the resected end of the tendon and was attached with bone anchors. Force plate analysis was done for each animal preoperatively and at weeks 3, 9, and 12 post operatively. At week 12, after euthanasia x-rays were taken and range of movements were recorded for hind limbs of each animal. Patella, patellar tendon - DCB and proximal tibia were harvested as a block and pQCT scan was done prior to histological analysis. RESULTS Over time functional weight bearing significantly increased from 44% at 3 weeks post surgery to 79% at week 12. On retrieval none of the specimens showed any evidence of ossification of the DCB. Histological analysis proved formation of neo-enthesis with presence of fibrocartilage and mineralised fibrocartilage in all the specimens. DCB grafts contained host cells and showed evidence of vascularisation. Remodelling of the collagen leading to ligamentisation of the DCB was proved by the presence of crimp in the DCB graft on polarized microscopy. CONCLUSION Combined with the appropriate surgical techniques, DCB can be used to achieve early mobilization and regeneration of a tendon defect which may be applicable to the repair of chronic rotator cuff injury in humans.
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Affiliation(s)
- Sherif Elnikety
- John Scales Centre for Biomedical Engineering, Institute of Orthopaedics and Musculo-Skeletal Science, University College London, Brockley Hill, Stanmore, Middlesex, HA7 4LP, United Kingdom
| | - Catherine J Pendegrass
- John Scales Centre for Biomedical Engineering, Institute of Orthopaedics and Musculo-Skeletal Science, University College London, Brockley Hill, Stanmore, Middlesex, HA7 4LP, United Kingdom
| | - Roberta Ferro de Godoy
- John Scales Centre for Biomedical Engineering, Institute of Orthopaedics and Musculo-Skeletal Science, University College London, Brockley Hill, Stanmore, Middlesex, HA7 4LP, United Kingdom
| | - Charles Holden
- John Scales Centre for Biomedical Engineering, Institute of Orthopaedics and Musculo-Skeletal Science, University College London, Brockley Hill, Stanmore, Middlesex, HA7 4LP, United Kingdom
| | - Gordon W Blunn
- John Scales Centre for Biomedical Engineering, Institute of Orthopaedics and Musculo-Skeletal Science, University College London, Brockley Hill, Stanmore, Middlesex, HA7 4LP, United Kingdom.
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26
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Walden G, Liao X, Donell S, Raxworthy MJ, Riley GP, Saeed A. A Clinical, Biological, and Biomaterials Perspective into Tendon Injuries and Regeneration. TISSUE ENGINEERING PART B-REVIEWS 2016; 23:44-58. [PMID: 27596929 PMCID: PMC5312458 DOI: 10.1089/ten.teb.2016.0181] [Citation(s) in RCA: 107] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Tendon injury is common and debilitating, and it is associated with long-term pain and ineffective healing. It is estimated to afflict 25% of the adult population and is often a career-ending disease in athletes and racehorses. Tendon injury is associated with high morbidity, pain, and long-term suffering for the patient. Due to the low cellularity and vascularity of tendon tissue, once damage has occurred, the repair process is slow and inefficient, resulting in mechanically, structurally, and functionally inferior tissue. Current treatment options focus on pain management, often being palliative and temporary and ending in reduced function. Most treatments available do not address the underlying cause of the disease and, as such, are often ineffective with variable results. The need for an advanced therapeutic that addresses the underlying pathology is evident. Tissue engineering and regenerative medicine is an emerging field that is aimed at stimulating the body's own repair system to produce de novo tissue through the use of factors such as cells, proteins, and genes that are delivered by a biomaterial scaffold. Successful tissue engineering strategies for tendon regeneration should be built on a foundation of understanding of the molecular and cellular composition of healthy compared with damaged tendon, and the inherent differences seen in the tissue after disease. This article presents a comprehensive clinical, biological, and biomaterials insight into tendon tissue engineering and regeneration toward more advanced therapeutics.
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Affiliation(s)
- Grace Walden
- 1 School of Pharmacy, University of East Anglia, Norwich, United Kingdom
| | - Xin Liao
- 1 School of Pharmacy, University of East Anglia, Norwich, United Kingdom
| | - Simon Donell
- 2 Norfolk and Norwich University Hospital, Norwich, United Kingdom .,3 Norwich Medical School, University of East Anglia, Norwich, United Kingdom
| | - Mike J Raxworthy
- 4 Neotherix Limited, York, United Kingdom .,5 University of Leeds, Leeds, United Kingdom
| | - Graham P Riley
- 6 School of Biological Sciences, University of East Anglia, Norwich, United Kingdom
| | - Aram Saeed
- 1 School of Pharmacy, University of East Anglia, Norwich, United Kingdom
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27
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Wagner ER, Bravo D, Dadsetan M, Riester SM, Chase S, Westendorf JJ, Dietz AB, van Wijnen AJ, Yaszemski MJ, Kakar S. Ligament Tissue Engineering Using a Novel Porous Polycaprolactone Fumarate Scaffold and Adipose Tissue-Derived Mesenchymal Stem Cells Grown in Platelet Lysate. Tissue Eng Part A 2016; 21:2703-13. [PMID: 26413793 DOI: 10.1089/ten.tea.2015.0183] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
PURPOSE Surgical reconstruction of intra-articular ligament injuries is hampered by the poor regenerative potential of the tissue. We hypothesized that a novel composite polymer "neoligament" seeded with progenitor cells and growth factors would be effective in regenerating native ligamentous tissue. METHODS We synthesized a fumarate-derivative of polycaprolactone fumarate (PCLF) to create macro-porous scaffolds to allow cell-cell communication and nutrient flow. Clinical grade human adipose tissue-derived human mesenchymal stem cells (AMSCs) were cultured in 5% human platelet lysate (PL) and seeded on scaffolds using a dynamic bioreactor. Cell growth, viability, and differentiation were examined using metabolic assays and immunostaining for ligament-related markers (e.g., glycosaminoglycans [GAGs], alkaline phosphatase [ALP], collagens, and tenascin-C). RESULTS AMSCs seeded on three-dimensional (3D) PCLF scaffolds remain viable for at least 2 weeks with proliferating cells filling the pores. AMSC proliferation rates increased in PL compared to fetal bovine serum (FBS) (p < 0.05). Cells had a low baseline expression of ALP and GAG, but increased expression of total collagen when induced by the ligament and tenogenic growth factor fibroblast growth factor 2 (FGF-2), especially when cultured in the presence of PL (p < 0.01) instead of FBS (p < 0.05). FGF-2 and PL also significantly increased immunostaining of tenascin-C and collagen at 2 and 4 weeks compared with human fibroblasts. SUMMARY Our results demonstrate that AMSCs proliferate and eventually produce a collagen-rich extracellular matrix on porous PCLF scaffolds. This novel scaffold has potential in stem cell engineering and ligament regeneration.
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Affiliation(s)
- Eric R Wagner
- 1 Department of Orthopedic Surgery, Mayo Clinic , Rochester, Minnesota
| | - Dalibel Bravo
- 1 Department of Orthopedic Surgery, Mayo Clinic , Rochester, Minnesota
| | - Mahrokh Dadsetan
- 2 Department of Orthopedic Surgery and Biomedical Engineering, Mayo Clinic College of Medicine , Rochester, Minnesota
| | - Scott M Riester
- 2 Department of Orthopedic Surgery and Biomedical Engineering, Mayo Clinic College of Medicine , Rochester, Minnesota
| | - Steven Chase
- 2 Department of Orthopedic Surgery and Biomedical Engineering, Mayo Clinic College of Medicine , Rochester, Minnesota
| | | | - Allan B Dietz
- 2 Department of Orthopedic Surgery and Biomedical Engineering, Mayo Clinic College of Medicine , Rochester, Minnesota
| | - Andre J van Wijnen
- 2 Department of Orthopedic Surgery and Biomedical Engineering, Mayo Clinic College of Medicine , Rochester, Minnesota
| | - Michael J Yaszemski
- 2 Department of Orthopedic Surgery and Biomedical Engineering, Mayo Clinic College of Medicine , Rochester, Minnesota
| | - Sanjeev Kakar
- 1 Department of Orthopedic Surgery, Mayo Clinic , Rochester, Minnesota
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Artells R, Pruna R, Dellal A, Maffulli N. Elastin: a possible genetic biomarker for more severe ligament injuries in elite soccer. A pilot study. Muscles Ligaments Tendons J 2016; 6:188-192. [PMID: 27900291 PMCID: PMC5115249 DOI: 10.11138/mltj/2016.6.2.188] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND The study of new genetic biomarkers in genes related to connective tissue repair and regeneration may help to identify individuals with greater predisposition to injury, who may benefit from targeted preventive measures, and those who require longer recovery time following a muscle, ligament or tendon injury. The present study investigated whether single nucleotide polymorphisms of the Elastin gene could be related to MCL injury. METHODS 60 top class football players were studied to identify single nucleotide polymorphisms for the Elastin (ELN) gene using Allelic Discrimination analysis. Each player was followed for 7 seasons, and each MCL injury was noted. RESULTS Ligament injury rate, severity and recovery time are related to specific genotypes observed in the elastin gene, especially the ELN-AA (16 MCL) and the ELN-AG (3 MCL). Players with the ELN-GG genotype sustained no MCL injury during the 7 seasons of the study. CONCLUSIONS The identification of polymorphisms in the ELN gene may be used as a novel tool to better define an athlete's genotype, and help to plan training and rehabilitation programmes to prevent or minimize MCL ligament injuries, and optimize the therapeutic and rehabilitation process after soft tissue injuries, and manage the workloads during trainings and matches.
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Affiliation(s)
- Rosa Artells
- SM Genomics, Barcelona Science Park, Barcelona, Spain
| | - Ricard Pruna
- FC Barcelona Medical Services, FIFA Medical Center of Excellence, Barcelona, Spain
| | - Alexandre Dellal
- FIFA Medical Center of Excellence, Centre Orhopedique Santy, Lyon, France
| | - Nicola Maffulli
- Department of Musculoskeletal Disorders Faculty of Medicine, Surgery and Dentistry, University of Salerno, Salerno, Italy; Centre for Sports and Exercise Medicine Barts and London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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Hanhan S, Ejzenberg A, Goren K, Saba F, Suki Y, Sharon S, Shilo D, Waxman J, Spitzer E, Shahar R, Atkins A, Liebergall M, Blumenfeld A, Deutsch D, Haze A. Skeletal ligament healing using the recombinant human amelogenin protein. J Cell Mol Med 2016; 20:815-24. [PMID: 26917487 PMCID: PMC4831364 DOI: 10.1111/jcmm.12762] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Accepted: 11/22/2015] [Indexed: 12/27/2022] Open
Abstract
Injuries to ligaments are common, painful and debilitating, causing joint instability and impaired protective proprioception sensation around the joint. Healing of torn ligaments usually fails to take place, and surgical replacement or reconstruction is required. Previously, we showed that in vivo application of the recombinant human amelogenin protein (rHAM+) resulted in enhanced healing of the tooth‐supporting tissues. The aim of this study was to evaluate whether amelogenin might also enhance repair of skeletal ligaments. The rat knee medial collateral ligament (MCL) was chosen to prove the concept. Full thickness tear was created and various concentrations of rHAM+, dissolved in propylene glycol alginate (PGA) carrier, were applied to the transected MCL. 12 weeks after transection, the mechanical properties, structure and composition of transected ligaments treated with 0.5 μg/μl rHAM+ were similar to the normal un‐transected ligaments, and were much stronger, stiffer and organized than control ligaments, treated with PGA only. Furthermore, the proprioceptive free nerve endings, in the 0.5 μg/μl rHAM+ treated group, were parallel to the collagen fibres similar to their arrangement in normal ligament, while in the control ligaments the free nerve endings were entrapped in the scar tissue at different directions, not parallel to the axis of the force. Four days after transection, treatment with 0.5 μg/μl rHAM+ increased the amount of cells expressing mesenchymal stem cell markers at the injured site. In conclusion application of rHAM+ dose dependently induced mechanical, structural and sensory healing of torn skeletal ligament. Initially the process involved recruitment and proliferation of cells expressing mesenchymal stem cell markers.
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Affiliation(s)
- Salem Hanhan
- Faculty of Dental Medicine, Institute of Dental Sciences, Hebrew University, Jerusalem, Israel
| | - Ayala Ejzenberg
- Faculty of Dental Medicine, Institute of Dental Sciences, Hebrew University, Jerusalem, Israel
| | - Koby Goren
- Faculty of Dental Medicine, Institute of Dental Sciences, Hebrew University, Jerusalem, Israel
| | - Faris Saba
- Faculty of Dental Medicine, Institute of Dental Sciences, Hebrew University, Jerusalem, Israel
| | - Yarden Suki
- Faculty of Dental Medicine, Institute of Dental Sciences, Hebrew University, Jerusalem, Israel
| | - Shay Sharon
- Faculty of Dental Medicine, Institute of Dental Sciences, Hebrew University, Jerusalem, Israel
| | - Dekel Shilo
- Faculty of Dental Medicine, Institute of Dental Sciences, Hebrew University, Jerusalem, Israel
| | - Jacob Waxman
- Faculty of Dental Medicine, Institute of Dental Sciences, Hebrew University, Jerusalem, Israel
| | - Elad Spitzer
- Orthopaedic Department, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
| | - Ron Shahar
- Faculty of Agriculture, Kort School of Veterinary Medicine, Hebrew University, Rehovot, Israel
| | - Ayelet Atkins
- Faculty of Agriculture, Kort School of Veterinary Medicine, Hebrew University, Rehovot, Israel
| | - Meir Liebergall
- Orthopaedic Department, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
| | - Anat Blumenfeld
- Faculty of Dental Medicine, Institute of Dental Sciences, Hebrew University, Jerusalem, Israel
| | - Dan Deutsch
- Faculty of Dental Medicine, Institute of Dental Sciences, Hebrew University, Jerusalem, Israel
| | - Amir Haze
- Orthopaedic Department, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
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Tenogenic induction of equine mesenchymal stem cells by means of growth factors and low-level laser technology. Vet Res Commun 2016; 40:39-48. [PMID: 26757735 DOI: 10.1007/s11259-016-9652-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Accepted: 01/05/2016] [Indexed: 12/20/2022]
Abstract
Tendons regenerate poorly due to a dense extracellular matrix and low cellularity. Cellular therapies aim to improve tendon repair using mesenchymal stem cells and tenocytes; however, a current limitation is the low proliferative potential of tenocytes in cases of severe trauma. The purpose of this study was to develop a method useful in veterinary medicine to improve the differentiation of Peripheral Blood equine mesenchymal stem cells (PB-MSCs) into tenocytes. PB-MSCs were used to study the effects of the addition of some growth factors (GFs) as TGFβ3 (transforming growth factor), EGF2 (Epidermal growth factor), bFGF2 (Fibroblast growth factor) and IGF-1 (insulin-like growth factor) in presence or without Low Level Laser Technology (LLLT) on the mRNA expression levels of genes important in the tenogenic induction as Early Growth Response Protein-1 (EGR1), Tenascin (TNC) and Decorin (DCN). The singular addition of GFs did not show any influence on the mRNA expression of tenogenic genes whereas the specific combinations that arrested cell proliferation in favour of differentiation were the following: bFGF2 + TGFβ3 and bFGF2 + TGFβ3 + LLLT. Indeed, the supplement of bFGF2 and TGFβ3 significantly upregulated the expression of Early Growth Response Protein-1 and Decorin, while the use of LLLT induced a significant increase of Tenascin C levels. In conclusion, the present study might furnish significant suggestions for developing an efficient approach for tenocyte induction since the external administration of bFGF2 and TGFβ3, along with LLLT, influences the differentiation of PB-MSCs towards the tenogenic fate.
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Lombana KG, Goodrich LR, Phillips JN, Kisiday JD, Ruple-Czerniak A, McIlwraith CW. An Investigation of Equine Mesenchymal Stem Cell Characteristics from Different Harvest Sites: More Similar Than Not. Front Vet Sci 2015; 2:67. [PMID: 26664993 PMCID: PMC4672231 DOI: 10.3389/fvets.2015.00067] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2015] [Accepted: 11/16/2015] [Indexed: 01/04/2023] Open
Abstract
Diseases of the musculoskeletal system are a major cause of loss of use and retirement in sport horses. The use of bone marrow-derived mesenchymal stem cells (BMDMSCs) for healing of traumatized tissue has gained substantial favor in clinical settings and can assist healing and tissue regeneration in orthopedic injuries. There are two common sites of harvest of BMDMSCs, the sternum and the ilium. Our objective was to determine if any differences exist in BMDMSCs acquired from the sternum and the ilium. We compared the two harvest sites in their propensity to undergo multilineage differentiation, differences in cell surface markers, or gene transduction efficiencies. BMDMSCs were isolated and culture-expanded from 5 ml aspirates of bone marrow from sternum and ilium. The cells were then plated and cultured with appropriate differentiation medium to result in multi-lineage differentiation and cell characteristics were compared between sternal and ilial samples. Cell surface antibody expression of CD11a/18, CD34, CD44, and CD90 were evaluated using flow cytometry, and gene transduction efficiencies were evaluated using GFP scAAV. There were no statistically significant differences in cell characteristics between MSCs cultured from the sternum and the ilium under any circumstances.
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Affiliation(s)
- Karla G Lombana
- Gail Holmes Equine Orthopaedic Research Center, College of Veterinary Medicine and Biomedical Science, Colorado State University , Fort Collins, CO , USA
| | - Laurie R Goodrich
- Gail Holmes Equine Orthopaedic Research Center, College of Veterinary Medicine and Biomedical Science, Colorado State University , Fort Collins, CO , USA
| | - Jennifer Nikki Phillips
- Gail Holmes Equine Orthopaedic Research Center, College of Veterinary Medicine and Biomedical Science, Colorado State University , Fort Collins, CO , USA
| | - John David Kisiday
- Gail Holmes Equine Orthopaedic Research Center, College of Veterinary Medicine and Biomedical Science, Colorado State University , Fort Collins, CO , USA
| | - Audrey Ruple-Czerniak
- Department of Comparative Pathobiology, Purdue University , West Lafayette, IN , USA
| | - C Wayne McIlwraith
- Gail Holmes Equine Orthopaedic Research Center, College of Veterinary Medicine and Biomedical Science, Colorado State University , Fort Collins, CO , USA
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Zaffagnini S, Marcheggiani Muccioli GM, Franchi M, Bacchelli B, Grassi A, Agati P, Quaranta M, Marcacci M, De Pasquale V. Collagen fibre and fibril ultrastructural arrangement of the superficial medial collateral ligament in the human knee. Knee Surg Sports Traumatol Arthrosc 2015; 23:3674-82. [PMID: 25261220 DOI: 10.1007/s00167-014-3276-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2014] [Accepted: 08/26/2014] [Indexed: 11/26/2022]
Abstract
PURPOSE The aim of the study was to investigate the collagen fibre ultrastructural arrangement and collagen fibril diameters in the superficial medial collateral ligament (sMCL) in the human knee. Considering sMCL's distinctive functions at different angles of knee flexion, it was hypothesized a significant difference between the collagen fibril diameters of each portion of the sMCL. METHODS Fourteen sMCL from seven fresh males (by chance because of the availability) cadavers (median age 40 years, range 34-59 years) were harvested within 12 h of death. sMCLs were separated into two orders of regions for analysis. The first order (divisions) was anterior, central and posterior. Thereafter, each division was split into three regions (femoral, intermediate and tibial), generating nine portions. One sMCL from each cadaver was used for transmission electron microscopy (TEM) and morphometric analyses, whereas the contralateral sMCL was processed for light microscopy (LM) or scanning electron microscopy (SEM). RESULTS LM and SEM analyses showed a complex tridimensional architecture, with the presence of wavy collagen fibres or crimps. TEM analysis showed significant differences in median collagen fibril diameter among portions inside the anterior, central and posterior division of the sMCL (p < 0.0001 within each division). Significant differences were also present among the median [interquartile range] collagen fibril diameters of anterior (39.4 [47.8-32.9]), central (38.5 [44.4-34.0]) and posterior (41.7 [52.2-35.4]) division (p = 0.0001); femoral (38.2 [45.0-32.7]), intermediate (40.3 [47.3-36.1]) and tibial (40.7 [55.0-32.2]) region (p = 0.0001). CONCLUSIONS Human sMCL showed a complex architecture that allows restraining different knee motions at different angles of knee flexion. The posterior division of sMCL accounted for the largest median collagen fibril diameter. The femoral region of sMCL accounted for the smallest median collagen fibril diameter. The presence of crimps in the medial collateral ligament, previously identified in the rat, was confirmed in humans (taking into consideration differences between these two species).
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Affiliation(s)
| | | | - Marco Franchi
- Faculty of Sport Sciences, University of Bologna, Bologna, Italy.
| | | | | | - Patrizia Agati
- Statistical Science Department, University of Bologna, Bologna, Italy.
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Noh MJ, Lee KH. Orthopedic cellular therapy: An overview with focus on clinical trials. World J Orthop 2015; 6:754-61. [PMID: 26601056 PMCID: PMC4644862 DOI: 10.5312/wjo.v6.i10.754] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2015] [Revised: 08/22/2015] [Accepted: 09/25/2015] [Indexed: 02/06/2023] Open
Abstract
In this editorial, the authors tried to evaluate the present state of cellular therapy in orthopedic field. The topics the authors try to cover include not only the clinical trials but the various research areas as well. Both the target diseases for cellular therapy and the target cells were reviewed. New methods to activate the cells were interesting to review. Most advanced clinical trials were also included because several of them have advanced to phase III clinical trials. In the orthopedic field, there are many diseases with a definite treatment gap at this time. Because cellular therapies can regenerate damaged tissues, there is a possibility for cellular therapies to become disease modifying drugs. It is not clear whether cellular therapies will become the standard of care in any of the orthopedic disorders, however the amount of research being performed and the number of clinical trials that are on-going make the authors believe that cellular therapies will become important treatment modalities within several years.
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Wan C, Hao Z, Tong L, Lin J, Li Z, Wen S. An update on the constitutive relation of ligament tissues with the effects of collagen types. J Mech Behav Biomed Mater 2015; 50:255-67. [DOI: 10.1016/j.jmbbm.2015.06.018] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Revised: 06/01/2015] [Accepted: 06/15/2015] [Indexed: 12/26/2022]
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Zhang B, Luo Q, Sun J, Xu B, Ju Y, Yang L, Song G. MGF enhances tenocyte invasion through MMP-2 activity via the FAK-ERK1/2 pathway. Wound Repair Regen 2015; 23:394-402. [PMID: 25847391 DOI: 10.1111/wrr.12293] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2014] [Accepted: 03/16/2015] [Indexed: 11/30/2022]
Abstract
Tendon regeneration and healing requires tenocytes to move to the repair site followed by proliferation and synthesis of the extracellular matrix. A novel synthetic growth factor, mechano-growth factor (MGF), has been discovered to have positive roles in tissue repair through the improvement of cell proliferation and migration and the protection of cells against injury-induced apoptosis. However, it remains unclear whether MGF has the potential to accelerate tendon repair. In this study, using a transwell system, we found that MGF-C25E (a synthetic mechano-growth factor E peptide) significantly promotes tenocyte invasion, which was accompanied by the increased phosphorylation of focal adhesion kinase (FAK) and extracellular signal regulated kinase1/2 (ERK1/2) as well as the increased activity of matrix metalloproteinases-2 (MMP-2). The MMP-2 inhibitor OA-Hy blocked MGF-C25E-promoted tenocyte invasion. Inhibitors of FAK or ERK1/2 blocked MGF-C25E-promoted tenocyte invasion and MMP-2 activity as well. These results indicate that MGF-C25E promotes tenocyte invasion by increasing MMP-2 activity via the FAK-ERK1/2 signaling pathway. Taken together, our findings provide the first evidence that MGF-C25E enhances tenocyte invasion and indicate that it may serve as a potential repair material for promoting the healing and regeneration of injured tendons.
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Affiliation(s)
- Bingyu Zhang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, People's Republic of China
| | - Qing Luo
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, People's Republic of China
| | - Jinghui Sun
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, People's Republic of China
| | - Baiyao Xu
- Department of Mechanical Science and Engineering, Nagoya University, Nagoya, Japan
| | - Yang Ju
- Department of Mechanical Science and Engineering, Nagoya University, Nagoya, Japan
| | - Li Yang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, People's Republic of China
| | - Guanbin Song
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, People's Republic of China
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Gaspar D, Spanoudes K, Holladay C, Pandit A, Zeugolis D. Progress in cell-based therapies for tendon repair. Adv Drug Deliv Rev 2015; 84:240-56. [PMID: 25543005 DOI: 10.1016/j.addr.2014.11.023] [Citation(s) in RCA: 134] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2014] [Revised: 11/08/2014] [Accepted: 11/12/2014] [Indexed: 02/07/2023]
Abstract
The last decade has seen significant developments in cell therapies, based on permanently differentiated, reprogrammed or engineered stem cells, for tendon injuries and degenerative conditions. In vitro studies assess the influence of biophysical, biochemical and biological signals on tenogenic phenotype maintenance and/or differentiation towards tenogenic lineage. However, the ideal culture environment has yet to be identified due to the lack of standardised experimental setup and readout system. Bone marrow mesenchymal stem cells and tenocytes/dermal fibroblasts appear to be the cell populations of choice for clinical translation in equine and human patients respectively based on circumstantial, rather than on hard evidence. Collaborative, inter- and multi-disciplinary efforts are expected to provide clinically relevant and commercially viable cell-based therapies for tendon repair and regeneration in the years to come.
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Affiliation(s)
- Diana Gaspar
- Network of Excellence for Functional Biomaterials (NFB), National University of Ireland, Galway (NUI Galway), Galway, Ireland
| | - Kyriakos Spanoudes
- Network of Excellence for Functional Biomaterials (NFB), National University of Ireland, Galway (NUI Galway), Galway, Ireland
| | - Carolyn Holladay
- Network of Excellence for Functional Biomaterials (NFB), National University of Ireland, Galway (NUI Galway), Galway, Ireland
| | - Abhay Pandit
- Network of Excellence for Functional Biomaterials (NFB), National University of Ireland, Galway (NUI Galway), Galway, Ireland
| | - Dimitrios Zeugolis
- Network of Excellence for Functional Biomaterials (NFB), National University of Ireland, Galway (NUI Galway), Galway, Ireland.
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Ghebes CA, Kelder C, Schot T, Renard AJ, Pakvis DFM, Fernandes H, Saris DB. Anterior cruciate ligament- and hamstring tendon-derived cells: in vitro differential properties of cells involved in ACL reconstruction. J Tissue Eng Regen Med 2015; 11:1077-1088. [PMID: 25758215 DOI: 10.1002/term.2009] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2014] [Revised: 12/08/2014] [Accepted: 01/12/2015] [Indexed: 01/13/2023]
Abstract
Anterior cruciate ligament (ACL) reconstruction involves the replacement of the torn ligament with a new graft, often a hamstring tendon (HT). Described as similar, the ACL and HT have intrinsic differences related to their distinct anatomical locations. From a cellular perspective, identifying these differences represents a step forward in the search for new cues that enhance recovery after the reconstruction. The purpose of this study was to characterize the phenotype and multilineage potential of ACL- and HT-derived cells. ACL- and HT-derived cells were isolated from tissue harvest from patients undergoing total knee arthroplasty (TKA) or ACL reconstruction. In total, three ACL and three HT donors were investigated. Cell morphology, self-renewal potential (CFU-F), surface marker profiling, expression of tendon/ligament-related markers (PCR) and multilineage potential were analysed for both cell types; both had fibroblast-like morphology and low self-renewal potential. No differences in the expression of tendon/ligament-related genes or a selected set of surface markers were observed between the two cell types. However, differences in their multilineage potential were observed: while ACL-derived cells showed a high potential to differentiate into chondrocytes and adipocytes, but not osteoblasts, HT-derived cells showed poor potential to form adipocytes, chondrocytes and osteoblasts. Our results demonstrated that HT-derived cells have low multilineage potential compared to ACL-derived cells, further highlighting the need for extrinsic signals to fully restore the function of the ACL upon reconstruction. Copyright © 2015 John Wiley & Sons, Ltd.
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Affiliation(s)
- Corina Adriana Ghebes
- MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands
| | - Cindy Kelder
- MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands
| | - Thomas Schot
- MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands
| | - Auke J Renard
- Department of Orthopaedic Surgery, Medisch Spectrum Twente Hospital, Enschede, The Netherland
| | - Dean F M Pakvis
- Department of Orthopaedics and Traumatology, Orthopaedic Centre OCON, Hengelo, The Netherlands
| | - Hugo Fernandes
- MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.,Center for Neuroscience and Cell Biology (CNC), Stem Cells and Drug Screening group, University of Coimbra, Coimbra, Portugal
| | - Daniel B Saris
- MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.,Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands
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Steplewski A, Fertala J, Beredjiklian P, Wang ML, Fertala A. Matrix-specific anchors: a new concept for targeted delivery and retention of therapeutic cells. Tissue Eng Part A 2015; 21:1207-16. [PMID: 25435302 DOI: 10.1089/ten.tea.2014.0401] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Biomedical strategies for tissue engineering and repair utilize specific cells, scaffolds, and growth factors to reconstruct elements of damaged tissue. The cellular element of these strategies is limited, however, by poor efficiency of delivery and retention of therapeutic cells in target sites. We propose that the presence of a cellular anchor that is able to specifically bind a defined element of target tissue will facilitate efficient binding and retention of therapeutic cells, thereby promoting repair of the target site. To do so, we engineered an artificial collagen-specific anchor (ACSA) that is able to specifically bind collagen I. The ACSA was engineered by creating a construct comprising rationally designed consecutive domains. The binding specificity of the ACSA was achieved by employing variable regions of a monoclonal antibody that recognizes a unique epitope present in human collagen I. Meanwhile, cell membrane localization of the ACSA was provided by the presence of a transmembrane domain. We determined that the ACSA was localized within cell membranes and interacted with its intended target, that is, collagen I. We have demonstrated that, in comparison to the control, the cells expressing the ACSA attached better to collagen I and exhibited improved retention in sites of seeding. We have also demonstrated that the presence of the ACSA did not interfere with cell proliferation, the biosynthesis of endogenous collagen I, or the biological functions of native collagen receptors. Since the presented cell delivery system utilizes a common characteristic of major connective tissues, namely the presence of collagen I, the findings described here could have a broad positive impact for improving the repair processes of tendon, ligament, bone, intervertebral disc, skin, and other collagen I-rich connective tissues. If successful, the ACSA approach to deliver cells will serve as an outline for developing cell delivery methods that target other elements of extracellular matrices, including other collagen types, laminins, and fibronectins.
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Affiliation(s)
- Andrzej Steplewski
- 1 Division of Orthopaedic Research, Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, Pennsylvania
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Does the A9285G Polymorphism in Collagen Type XII α1 Gene Associate with the Risk of Anterior Cruciate Ligament Ruptures? Balkan J Med Genet 2014; 17:41-6. [PMID: 25741214 PMCID: PMC4347476 DOI: 10.2478/bjmg-2014-0022] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
One of the most severe injuries sustained by athletes is rupture of the anterior cruciate ligament (ACL). Recent investigations suggest that a predisposition for ACL rupture may be the result of specific genetic sequence variants. In light of this, we decided to investigate whether the COL12A1 A9285G polymorphism was associated with ACL ruptures in Polish football players. We compared genotypic and allelic frequencies of the COL12A1 A9285G polymorphism in two groups of athletes: 91 male football players (23 ± 3 years) with surgically diagnosed primary ACL ruptures who qualified for ligament reconstruction (cases) and 143 apparently healthy, male football players of the same ethnicity, a similar age category, and a comparable level of exposure to ACL injury, who were without any self-reported history of ligament or tendon injury (controls). DNA samples extracted from the oral epithelial cells were genotyped by using a real-time polymerase chain reaction (Ri-Ti-PCR) method. The genotype distribution in the cases were not different from those in controls (p = 0.70). The frequency of the G allele was lower in the cases (18.1%) but not statistically significant (p = 0.40) when compared with controls (21.3%). Our results are in contradiction to the hypothesis that the COL12A1 A9285G polymorphism is associated with a predisposition for ACL injury. However, these conclusions should be supported with more experimental studies on COL12A1 polymorphisms.
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Cardwell RD, Dahlgren LA, Goldstein AS. Electrospun fibre diameter, not alignment, affects mesenchymal stem cell differentiation into the tendon/ligament lineage. J Tissue Eng Regen Med 2014; 8:937-45. [PMID: 23038413 DOI: 10.1002/term.1589] [Citation(s) in RCA: 89] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2011] [Revised: 02/13/2012] [Accepted: 07/05/2012] [Indexed: 12/30/2022]
Abstract
Efforts to develop engineered tendons and ligaments have focused on the use of a biomaterial scaffold and a stem cell source. However, the ideal scaffold microenvironment to promote stem cell differentiation and development of organized extracellular matrix is unknown. Through electrospinning, fibre scaffolds can be designed with tailorable architectures to mimic the intended tissue. In this study, the effects of fibre diameter and orientation were examined by electrospinning thin mats, consisting of small (< 1 µm), medium (1-2 µm) or large (> 2 µm) diameter fibres with either random or aligned fibre orientation. C3H10T1/2 model stem cells were cultured on the six different electrospun mats, as well as smooth spin-coated films, and the morphology, growth and expression of tendon/ligament genes were evaluated. The results demonstrated that fibre diameter affects cellular behaviour more significantly than fibre alignment. Initially, cell density was greater on the small fibre diameter mats, but similar cell densities were found on all mats after an additional week in culture. After 2 weeks, gene expression of collagen 1α1 and decorin was increased on all mats compared to films. Expression of the tendon/ligament transcription factor scleraxis was suppressed on all electrospun mats relative to spin-coated films, but expression on the large-diameter fibre mats was consistently greater than on the medium-diameter fibre mats. These results suggest that larger-diameter fibres (e.g. > 2 µm) may be more suitable for in vitro development of a tendon/ligament tissue.
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Affiliation(s)
- Robyn D Cardwell
- School of Biomedical Engineering and Sciences and Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
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Platelet rich plasma and knee surgery. BIOMED RESEARCH INTERNATIONAL 2014; 2014:890630. [PMID: 25302310 PMCID: PMC4167644 DOI: 10.1155/2014/890630] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Accepted: 07/30/2014] [Indexed: 12/24/2022]
Abstract
In orthopaedic surgery and sports medicine, the knee joint has traditionally been considered the workhorse. The reconstruction of every damaged element in this joint is crucial in achieving the surgeon's goal to restore the knee function and prevent degeneration towards osteoarthritis. In the last fifteen years, the field of regenerative medicine is witnessing a boost of autologous blood-derived platelet rich plasma products (PRPs) application to effectively mimic and accelerate the tissue healing process. The scientific rationale behind PRPs is the delivery of growth factors, cytokines, and adhesive proteins present in platelets and plasma, as well as other biologically active proteins conveyed by the plasma such as fibrinogen, prothrombin, and fibronectin; with this biological engineering approach, new perspectives in knee surgery were opened. This work describes the use of PRP to construct and repair every single anatomical structure involved in knee surgery, detailing the process conducted in ligament, meniscal, and chondral surgery.
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Abstract
OBJECTIVE The objective of this prospective study was assessment of efficacy of bone marrow aspirate (BMA) (containing plasma rich in growth factors and mesenchymal stem cells) injection in treatment of tennis elbow. MATERIALS AND METHODS A total of 30 adult patients of previously untreated tennis elbow were administered single injection of BMA. This concentrate was made by centrifugation of iliac BMA at 2000 rpm for 20-30 min and only upper layer containing platelet rich plasma and mononuclear cells was injected. Assessment was performed at baseline, 2 weeks, 6 weeks and 12 weeks using Patient-rated Tennis Elbow Evaluation (PRTEE) score. RESULTS Baseline pre-injection mean PRTEE score was 72.8 ± 6.97 which decreased to a mean PRTEE score of 40.93 ± 5.94 after 2 weeks of injection which was highly significant (P < 0.0001). The mean PRTEE score at 6 week and 12 week follow-up was 24.46 ± 4.58 and 14.86 ± 3.48 respectively showing a highly significant decrease from baseline scores (P < 0.0001). CONCLUSION Treatment of tennis elbow patients with single injection of BMA showed a significant improvement in short to medium term follow-up. In future, such growth factors and/or stem cells based injection therapy can be developed as an alternative conservative treatment for patients of tennis elbow, especially who have failed non-operative treatment before surgical intervention is taken.
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Affiliation(s)
- Ajit Singh
- Department of Orthopaedics, Rohilkhand Medical College, Bareilly, Uttar Pradesh, India
| | | | - Shekhar Singh
- Department of Physiotherapy, Jaipur College of Physiotherapy, Jaipur, Rajasthan, India
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Bone marrow derived stem cells in joint and bone diseases: a concise review. INTERNATIONAL ORTHOPAEDICS 2014; 38:1787-801. [PMID: 25005462 DOI: 10.1007/s00264-014-2445-4] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/10/2014] [Accepted: 06/21/2014] [Indexed: 12/11/2022]
Abstract
Stem cells have huge applications in the field of tissue engineering and regenerative medicine. Their use is currently not restricted to the life-threatening diseases but also extended to disorders involving the structural tissues, which may not jeopardize the patients' life, but certainly influence their quality of life. In fact, a particularly popular line of research is represented by the regeneration of bone and cartilage tissues to treat various orthopaedic disorders. Most of these pioneering research lines that aim to create new treatments for diseases that currently have limited therapies are still in the bench of the researchers. However, in recent years, several clinical trials have been started with satisfactory and encouraging results. This article aims to review the concept of stem cells and their characterization in terms of site of residence, differentiation potential and therapeutic prospective. In fact, while only the bone marrow was initially considered as a "reservoir" of this cell population, later, adipose tissue and muscle tissue have provided a considerable amount of cells available for multiple differentiation. In reality, recently, the so-called "stem cell niche" was identified as the perivascular space, recognizing these cells as almost ubiquitous. In the field of bone and joint diseases, their potential to differentiate into multiple cell lines makes their application ideally immediate through three main modalities: (1) cells selected by withdrawal from bone marrow, subsequent culture in the laboratory, and ultimately transplant at the site of injury; (2) bone marrow aspirate, concentrated and directly implanted into the injury site; (3) systemic mobilization of stem cells and other bone marrow precursors by the use of growth factors. The use of this cell population in joint and bone disease will be addressed and discussed, analysing both the clinical outcomes but also the basic research background, which has justified their use for the treatment of bone, cartilage and meniscus tissues.
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Abstract
CONTEXT Aging changes the biology, healing capacity, and biomechanical function of tendons and ligaments and results in common clinical pathologies that present to orthopedic surgeons, primary care physicians, physical therapists, and athletic trainers. A better understanding of the age-related changes in these connective tissues will allow better patient care. EVIDENCE ACQUISITION The PubMed database was searched in December 2012 for English-language articles pertaining to age-related changes in tendons and ligaments. LEVEL OF EVIDENCE Level 5. RESULTS The mature athlete faces challenges associated with age-dependent changes in the rotator cuff, Achilles tendon, lateral humeral epicondylar tendons, quadriceps tendon, and patellar tendon. The anterior cruciate ligament and the medial collateral ligament are the most studied intra-articular and extra-articular ligaments, and both are associated with age-dependent changes. CONCLUSION Tendons and ligaments are highly arranged connective tissue structures that maintain joint motion and joint stability. These structures are subject to vascular and compositional changes with increasing age that alter their mechanotransduction, biology, healing capacity, and biomechanical function. Emerging research into the etiology of age-dependent changes will provide further information to help combat the age-related clinical complications associated with the injuries that occur to tendons and ligaments.
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Wang X, Wang Y, Gou W, Lu Q, Peng J, Lu S. Role of mesenchymal stem cells in bone regeneration and fracture repair: a review. INTERNATIONAL ORTHOPAEDICS 2013; 37:2491-8. [PMID: 23948983 DOI: 10.1007/s00264-013-2059-2] [Citation(s) in RCA: 231] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Accepted: 07/26/2013] [Indexed: 12/15/2022]
Abstract
Mesenchymal stem cells (MSCs) are non-haematopoietic stromal stem cells that have many sources, such as bone marrow, periosteum, vessel walls, adipose, muscle, tendon, peripheral circulation, umbilical cord blood, skin and dental tissues. They are capable of self-replication and of differentiating into, and contributing to the regeneration of, mesenchymal tissues, such as bone, cartilage, ligament, tendon, muscle and adipose tissue. The homing of MSCs may play an important role in the repair of bone fractures. As a composite material, the formation and growth of bone tissue is a complex process, including molecular, cell and biochemical metabolic changes. The recruitment of factors with an adequate number of MSCs and the micro-environment around the fracture are effective for fracture repair. Several studies have investigated the functional expression of various chemokine receptors, trophic factors and adhesion molecules in human MSCs. Many external factors affect MSC homing. MSCs have been used as seed cells in building tissue-engineered bone grafts. Scaffolds seeded with MSCs are most often used in tissue engineering and include biotic and abiotic materials. This knowledge provides a platform for the development of novel therapies for bone regeneration with endogenous MSCs.
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Affiliation(s)
- Xin Wang
- Key Laboratory of Peoples Liberation Army, Institute of Orthopedics, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China
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Maffulli N, Margiotti K, Longo UG, Loppini M, Fazio VM, Denaro V. The genetics of sports injuries and athletic performance. Muscles Ligaments Tendons J 2013; 3:173-189. [PMID: 24367777 PMCID: PMC3838326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
PURPOSE in the last two decades, several evidences have been provided to support the relationship between single nucleotide polymorphisms and the susceptibility to develop injuries participating in sport and performance related to sports activity. We report up-to-date review of the genetics factors involved in tendon injuries and athletic performance. METHODS we searched PubMed using the terms "sports injuries", "athletic performance" and "genetics" over the period 1990 to the present day. We also included non-English journals. RESULTS most of the currently established or putative tendinopathy susceptibility loci have been analyzed by candidate gene studies. The genes currently associated with tendon injuries include gene encoding for collagen, matrix metallopeptidase, tenascin and growth factors. Several genes have been related to the physical performance phenotypes affecting endurance capacity and muscle performance. The most studied include ACE and ACTN3 genes. CONCLUSIONS genetics determines the response of an individual to the surrounding environment. Recently, some of the individual genetic variations contributing to the athletic performance and the onset of musculoskeletal injuries, particularly in tendon and ligament tissues, have been identified. However, the identification of the genetic background related to susceptibility to injuries and physical performance of the athletes is challenging yet and further studies must be performed to establish the specific role of each gene and the potential effect of the interaction of these.
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Affiliation(s)
- Nicola Maffulli
- Centre for Sports and Exercise Medicine, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, Mile End Hospital, London, UKDepartment of Physical and Rehabilitation Medicine, University of Salerno, Italy
| | - Katia Margiotti
- Department of Surgical Pathology, Campus Bio-Medico University, Trigoria, Rome, Italy
| | - Umile Giuseppe Longo
- Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Trigoria, Rome, Italy
| | - Mattia Loppini
- Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Trigoria, Rome, Italy
| | - Vito Michele Fazio
- Department of Surgical Pathology, Campus Bio-Medico University, Trigoria, Rome, Italy
| | - Vincenzo Denaro
- Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Trigoria, Rome, Italy
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Karaoz E, Okcu A, Ünal ZS, Subasi C, Saglam O, Duruksu G. Adipose tissue-derived mesenchymal stromal cells efficiently differentiate into insulin-producing cells in pancreatic islet microenvironment both in vitro and in vivo. Cytotherapy 2013; 15:557-70. [DOI: 10.1016/j.jcyt.2013.01.005] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2012] [Revised: 11/07/2012] [Accepted: 01/07/2013] [Indexed: 12/16/2022]
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Higuchi A, Ling QD, Chang Y, Hsu ST, Umezawa A. Physical Cues of Biomaterials Guide Stem Cell Differentiation Fate. Chem Rev 2013; 113:3297-328. [DOI: 10.1021/cr300426x] [Citation(s) in RCA: 335] [Impact Index Per Article: 27.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Akon Higuchi
- Department of Chemical and Materials
Engineering, National Central University, Jhongli, Taoyuan 32001, Taiwan
- Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Okura,
Setagaya-ku, Tokyo 157-8535, Japan
- Cathay Medical Research Institute, Cathay General Hospital, No. 32, Ln 160, Jian-Cheng Road, Hsi-Chi City, Taipei 221, Taiwan
| | - Qing-Dong Ling
- Cathay Medical Research Institute, Cathay General Hospital, No. 32, Ln 160, Jian-Cheng Road, Hsi-Chi City, Taipei 221, Taiwan
- Institute of Systems Biology
and Bioinformatics, National Central University, No. 300 Jhongda Rd., Jhongli, Taoyuan 32001, Taiwan
| | - Yung Chang
- Department of Chemical Engineering, R&D Center for Membrane Technology, Chung Yuan Christian University, 200 Chung-Bei Rd., Jhongli, Taoyuan 320, Taiwan
| | - Shih-Tien Hsu
- Taiwan Landseed Hospital, 77 Kuangtai Road, Pingjen City, Tao-Yuan
County 32405, Taiwan
| | - Akihiro Umezawa
- Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Okura,
Setagaya-ku, Tokyo 157-8535, Japan
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Martinello T, Bronzini I, Perazzi A, Testoni S, De Benedictis GM, Negro A, Caporale G, Mascarello F, Iacopetti I, Patruno M. Effects of in vivo applications of peripheral blood-derived mesenchymal stromal cells (PB-MSCs) and platlet-rich plasma (PRP) on experimentally injured deep digital flexor tendons of sheep. J Orthop Res 2013; 31:306-14. [PMID: 22893604 DOI: 10.1002/jor.22205] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2012] [Accepted: 07/10/2012] [Indexed: 02/04/2023]
Abstract
Tendon injuries, degenerative tendinopathies, and overuse tendinitis are common in races horses. Novel therapies aim to restore tendon functionality by means of cell-based therapy, growth factor delivery, and tissue engineering approaches. This study examined the use of autologous mesenchymal stromal cells derived from peripheral blood (PB-MSCs), platelet-rich plasma (PRP) and a combination of both for ameliorating experimental lesions on deep digital flexor tendons (DDFT) of Bergamasca sheep. In particular, testing the combination of blood-derived MSCs and PRP in an experimental animal model represents one of the few studies exploring a putative synergistic action of these treatments. Effectiveness of treatments was evaluated at 30 and 120 days comparing clinical, ultrasonographic, and histological features together with immunohistochemical expression of collagen types 1 and 3, and cartilage oligomeric matrix protein (COMP). Significant differences were found between treated groups and their corresponding controls (placebo) regarding tendon morphology and extracellular matrix (ECM) composition. However, our results indicate that the combined use of PRP and MSCs did not produce an additive or synergistic regenerative response and highlighted the predominant effect of MSCs on tendon healing, enhanced tissue remodeling and improved structural organization.
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Affiliation(s)
- Tiziana Martinello
- Department of Comparative Biomedicine and Food Science, University of Padova, Padova, Italy
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Rizzello G, Longo UG, Petrillo S, Lamberti A, Khan WS, Maffulli N, Denaro V. Growth factors and stem cells for the management of anterior cruciate ligament tears. Open Orthop J 2012; 6:525-30. [PMID: 23248722 PMCID: PMC3522096 DOI: 10.2174/1874325001206010525] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2012] [Revised: 09/14/2012] [Accepted: 09/22/2012] [Indexed: 12/27/2022] Open
Abstract
The anterior cruciate ligament (ACL) is fundamental for the knee joint stability. ACL tears are frequent, especially during sport activities, occurring mainly in young and active patients. Nowadays, the gold standard for the management of ACL tears remains the surgical reconstruction with autografts or allografts. New strategies are being developed to resolve the problems of ligament grafting and promote a physiological healing process of ligamentous tissue without requiring surgical reconstruction. Moreover, these strategies can be applicable in association surgical reconstruction and may be useful to promote and accelerate the healing process. The use of growth factors and stem cells seems to offer a new and fascinating solution for the management of ACL tears. The injection of stem cell and/or growth factors in the site of ligamentous injury can potentially enhance the repair process of the physiological tissue. These procedures are still at their infancy, and more in vivo and in vitro studies are required to clarify the molecular pathways and effectiveness of growth factors and stem cells therapy for the management of ACL tears. This review aims to summarize the current knowledge in the field of growth factors and stem cells for the management of ACL tears.
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Affiliation(s)
- Giacomo Rizzello
- Department of Orthopaedic and Trauma Surgery. Campus Bio-Medico University, Via Alvaro del Portillo, 200, 00128 Trigoria, Rome, Italy ; Centro Integrato di Ricerca (CIR) Campus Bio-Medico University, Via Alvaro del Portillo, 21, 00128, Rome, Italy
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