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Lavender CD, Schaver AL, Taylor S, Peluso R, Berdis G, Singh V, Cipriani K, Lycans D, Jasko J, Hewett TE. Anterior Cruciate Ligament Reconstruction Augmentation With Bone Marrow Aspirate Concentrate, Demineralized Bone Matrix, and Suture Tape Shows No Difference in Outcomes-But Faster Functional Recovery-Versus Non-augmented Anterior Cruciate Ligament Reconstruction. Arthroscopy 2025; 41:1496-1508. [PMID: 39047990 DOI: 10.1016/j.arthro.2024.06.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Revised: 06/14/2024] [Accepted: 06/27/2024] [Indexed: 07/27/2024]
Abstract
PURPOSE To compare outcomes after anterior cruciate ligament reconstruction (ACLR) with bone marrow aspirate concentrate (BMAC), demineralized bone matrix (DBM), and suture tape augmentation (STA) versus ACLR without biological augmentation or STA. METHODS We performed a prospective randomized controlled trial at a single institution to compare ACLR with BMAC, DBM, and STA (group A) versus ACLR without biological augmentation or STA (group NA). The study sought to include 100 patients. Skeletally mature patients younger than 25 years received quadriceps tendon autograft, whereas patients aged 25 years or older underwent allograft ACLR with an all-inside technique. Patients with concomitant meniscal pathologies were included. The primary outcomes compared were range of motion (ROM), limb symmetry, and patient-reported outcomes. Secondary outcomes included radiographic outcomes and surgical complications. Univariate and mixed-model regression analyses were used to compare outcomes. RESULTS Fifty-nine patients were included (29 patients in group A [11 female patients, 38%] and 30 patients in group NA [15 female patients, 50%]). Early ROM at 6 weeks (125° of flexion vs 109° of flexion, P < .0001) and limb symmetry at 12 weeks (80.6% vs 36.7% [delta, 43.9%], P < .001) were significantly improved in group A. At 2 years, International Knee Documentation Committee scores were similar (91.1 ± 12.7 vs 85.3 ± 10.8, P = .109). Quality-of-life subscores of the Knee Injury and Osteoarthritis Outcome Score were significantly enhanced in group A (85.2 ± 20.9 vs 72.1 ± 20.4, P = .042). In 22 patients (12 in group A and 10 in group NA), computed tomography scans were obtained at 6 months to compare bone tunnel healing. Overall, the mean increase in bone tunnel diameter was significantly smaller in group A than in group NA. No difference in graft rerupture or reoperation rate was observed. Reoperations were performed for stiffness in 7 of 59 patients (11.9%) (3 [10%] in group A vs 4 [13%] in group NA; P > .999). CONCLUSIONS There were no differences in International Knee Documentation Committee scores between groups at 2-year follow-up. Functional outcomes including early ROM and limb symmetry were significantly improved in patients who received ACLR with BMAC, DBM, and STA. LEVEL OF EVIDENCE Level II, randomized controlled trial.
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Affiliation(s)
- Chad D Lavender
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A..
| | - Andrew L Schaver
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A
| | - Shane Taylor
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A
| | - Richard Peluso
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A
| | - Galen Berdis
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A
| | - Vishapreet Singh
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A
| | - Kara Cipriani
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A
| | - Dana Lycans
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A
| | - John Jasko
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A
| | - Timothy E Hewett
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A
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Yu J, Mi J, Huang K, Qi R. Knotted single lasso loop has a lower stiffness and comparable ultimate failure strength compared with knotless whipstitch fixation in onlay tenodesis. J Orthop Surg Res 2025; 20:348. [PMID: 40189558 PMCID: PMC11974151 DOI: 10.1186/s13018-025-05757-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2025] [Accepted: 03/25/2025] [Indexed: 04/09/2025] Open
Abstract
BACKGROUND Suture and knotless anchor onlay tenodesis are two common treatments for biceps lesions; however, there is a paucity of biomechanical studies evaluating the efficacy and structural integrity of these techniques. METHODS Tendons were harvested from four lower extremity fresh cadaver specimens, including the extensor digitorum longus, peroneus longus, peroneus brevis, and anterior tibialis tendons. Each tendon diameter was recorded using a digital Vernier caliper. Sixteen 3D printed proximal humeri models were allocated to either the single lasso loop with suture anchor (SLL) group or the whipstitch with knotless suture anchor (WSA) group. Each tenodesis model was initially tested on an electrodynamic material testing instrument under a cyclic load ranging from 5 to 70 N at a speed of 1.25 mm/s. The force on the tendon was then returned to 5 N, which was pulled until the ultimate failure of the construct. Displacement during cyclic loading, ultimate failure load, stiffness, and failure modes were assessed. RESULTS Fourteen tenodesis models were validated, and two models were discarded due to technical errors. No significant differences between the two groups were observed regarding tendon diameter, ultimate failure load, and displacement at ultimate failure load. However, the construct stiffness for the SLL group was lower than that of the WSA group (58.02 ± 5.62 N/mm vs. 72.24 ± 15.63 N/mm, P = 0.043). CONCLUSION The SLL group had a lower construct stiffness than the WSA group, whereas construct displacement and ultimate failure load were similar in both groups. Therefore, SLL biceps tenodesis may offer a convenient alternative, with lower tendon migration fixation, while performing an arthroscopic biceps tenodesis. LEVEL OF EVIDENCE Basic Science Study.
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Affiliation(s)
- Jiong Yu
- Department of Sports Medicine, Wuxi Ninth People's Hospital Affiliated to Soochow University, Liangxi Road, No 999, Binhu District, Wuxi, Jiangsu, China.
| | - Jingyi Mi
- Department of Sports Medicine, Wuxi Ninth People's Hospital Affiliated to Soochow University, Liangxi Road, No 999, Binhu District, Wuxi, Jiangsu, China
| | - Kai Huang
- Orthopaedic Institute, Wuxi Ninth People's Hospital Affiliated to Soochow University, Wuxi, Jiangsu, China
| | - Renfei Qi
- Orthopaedic Institute, Wuxi Ninth People's Hospital Affiliated to Soochow University, Wuxi, Jiangsu, China
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Kuan FC, Hsu KL, Lin FH, Hong CK, Chen Y, Shih CA, Su WR. Biomechanical comparisons of all--suture suspensory button vs. interference screw for inlay subpectoral bicep tenodesis. J Shoulder Elbow Surg 2025; 34:163-171. [PMID: 38762151 DOI: 10.1016/j.jse.2024.03.061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 03/21/2024] [Accepted: 03/29/2024] [Indexed: 05/20/2024]
Abstract
BACKGROUND All-suture buttons (ASBs) and interference screw (IS) are commonly utilized in the inlay subpectoral biceps tendon tenodesis. However, the biomechanical characteristics of these two methods have not been compared directly. The aim of present study was to compare the biomechanical properties of ASB vs. IS for inlay subpectoral biceps tendon tenodesis in a human cadaveric model. METHODS Sixteen fresh-frozen human cadaveric shoulders were randomly divided into two experimental inlay biceps tenodesis groups: ASB or IS. After tenodesis, every specimen was preloaded at 5 N for 2 minutes, followed with a cyclic loading test from 5 to 70 N for 500 load cycles. Then the load-to-failure test was performed. Afterward, the humerus was placed in a cylinder tube and secured with anchoring cement. Lastly, a two-point bending test was performed to determine the strength of the humerus. Destructive axial force was applied, and the failure strength and displacement were recorded. RESULTS No difference in stiffness was observed between the two groups (ASB = 27.4 ± 3.5 N/mm vs. IS = 29.7 ± 3.0 N/mm; P = .270). Cyclic displacement was significantly greater in the ASB group (6.8 ± 2.6 mm) than the IS group (3.8 ± 1.1 mm; P = .021). In terms of failure load, there were no statistical differences among the two groups (P = .234). The ASB group was able to withstand significantly greater displacement (11.9 ± 1.6 mm) before failure than the IS group (7.8 ± 1.5 mm; P = .001). During the humeral bending test, the ASB group exhibited significantly greater maximal load (2354.8 ± 285.1 N vs. 2086.4 ± 296.1 N; P = .046) and larger displacement (17.8 ± 2.8 mm vs. 14.1 ± 2.8 mm; P = .027) before fracture. CONCLUSIONS In inlay subpectoral bicep tenodesis, ASB fixation appears to offer comparable stiffness and failure load to that of IS fixation. Additionally, the ASB group exhibited greater resistance to load and displacement before humeral fracture. However, the ASB group did demonstrate increased cyclic displacement compared to IS group.
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Affiliation(s)
- Fa-Chuan Kuan
- Department of Orthopaedic Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Skeleton Materials and Bio-compatibility Core Lab, Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan
| | - Kai-Lan Hsu
- Department of Orthopaedic Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Skeleton Materials and Bio-compatibility Core Lab, Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan
| | - Fang-Hsien Lin
- Department of Physical Medicine and Rehabilitation, Tainan Municipal An-Nan Hospital, Tainan, Taiwan
| | - Chih-Kai Hong
- Department of Orthopaedic Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Skeleton Materials and Bio-compatibility Core Lab, Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan
| | - Yueh Chen
- Department of Orthopaedic Surgery, Kaohsiung Veterans General Hospital Tainan Branch, Tainan, Taiwan
| | - Chien-An Shih
- Department of Orthopaedic Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Skeleton Materials and Bio-compatibility Core Lab, Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan
| | - Wei-Ren Su
- Department of Orthopaedic Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Skeleton Materials and Bio-compatibility Core Lab, Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan.
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Liu YC, Chen SH, Kuan CH, Chen SH, Huang WY, Chen HX, Wang TW. Assembly of Interfacial Polyelectrolyte Complexation Fibers with Mineralization Gradient for Physiologically-Inspired Ligament Regeneration. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2314294. [PMID: 38572797 DOI: 10.1002/adma.202314294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 03/29/2024] [Indexed: 04/05/2024]
Abstract
Current synthetic grafts for ligament rupture repair often fail to integrate well with the surrounding biological tissue, leading to complications such as graft wear, fatigue, and subsequent re-rupture. To address this medical challenge, this study aims at advancing the development of a biological ligament through the integration of physiologically-inspired principles and tissue engineering strategies. In this study, interfacial polyelectrolyte complexation (IPC) spinning technique, along with a custom-designed collection system, to fabricate a hierarchical scaffold mimicking native ligament structure, is utilized. To emulate the bone-ligament interface and alleviate stress concentration, a hydroxyapatite (HAp) mineral gradient is strategically introduced near both ends of the scaffold to enhance interface integration and diminish the risk of avulsion rupture. Biomimetic viscoelasticity is successfully displayed to provide similar mechanical support to native ligamentous tissue under physiological conditions. By introducing the connective tissue growth factor (CTGF) and conducting mesenchymal stem cells transplantation, the regenerative potential of the synthetic ligament is significantly amplified. This pioneering study offers a multifaceted solution combining biomimetic materials, regenerative therapies, and advanced techniques to potentially transform ligament rupture treatment.
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Affiliation(s)
- Yu-Chung Liu
- Department of Materials Science and Engineering, National Tsing Hua University, Hsinchu, 30044, Taiwan
| | - Shih-Heng Chen
- Division of Trauma Plastic Surgery, Department of Plastic & Reconstructive Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan City, 33305, Taiwan
| | - Chen-Hsiang Kuan
- Division of Plastic Surgery, Department of Surgery, National Taiwan University Hospital, Taipei, 100229, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, 100233, Taiwan
- Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, 106, Taiwan
| | - Shih-Hsien Chen
- Division of Trauma Plastic Surgery, Department of Plastic & Reconstructive Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan City, 33305, Taiwan
| | - Wei-Yuan Huang
- Department of Materials Science and Engineering, National Tsing Hua University, Hsinchu, 30044, Taiwan
| | - Hao-Xuan Chen
- Department of Materials Science and Engineering, National Tsing Hua University, Hsinchu, 30044, Taiwan
| | - Tzu-Wei Wang
- Department of Materials Science and Engineering, National Tsing Hua University, Hsinchu, 30044, Taiwan
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Pugliese E, Rossoni A, Zeugolis DI. Enthesis repair - State of play. BIOMATERIALS ADVANCES 2024; 157:213740. [PMID: 38183690 DOI: 10.1016/j.bioadv.2023.213740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 12/17/2023] [Accepted: 12/19/2023] [Indexed: 01/08/2024]
Abstract
The fibrocartilaginous enthesis is a highly specialised tissue interface that ensures a smooth mechanical transfer between tendon or ligament and bone through a fibrocartilage area. This tissue is prone to injury and often does not heal, even after surgical intervention. Enthesis augmentation approaches are challenging due to the complexity of the tissue that is characterised by the coexistence of a range of cellular and extracellular components, architectural features and mechanical properties within only hundreds of micrometres. Herein, we discuss enthesis repair and regeneration strategies, with particular focus on elegant interfacial and functionalised scaffold-based designs.
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Affiliation(s)
- Eugenia Pugliese
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), University of Galway, Galway, Ireland
| | - Andrea Rossoni
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Charles Institute of Dermatology, Conway Institute of Biomolecular & Biomedical Research and School of Mechanical & Materials Engineering, University College Dublin (UCD), Dublin, Ireland
| | - Dimitrios I Zeugolis
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), University of Galway, Galway, Ireland; Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Charles Institute of Dermatology, Conway Institute of Biomolecular & Biomedical Research and School of Mechanical & Materials Engineering, University College Dublin (UCD), Dublin, Ireland.
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Noh S, Lee SJ, Yoo JJ, Jin YJ, Yun HW, Min BH, Park JY, Park DY. Synovium-Derived Mesenchymal Stem Cell-Based Scaffold-Free Fibrocartilage Engineering for Bone-Tendon Interface Healing in an Anterior Cruciate Ligament Reconstruction Model. Tissue Eng Regen Med 2024; 21:341-351. [PMID: 37856071 PMCID: PMC10825091 DOI: 10.1007/s13770-023-00593-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 08/21/2023] [Accepted: 08/27/2023] [Indexed: 10/20/2023] Open
Abstract
BACKGROUND Current tendon and ligament reconstruction surgeries rely on scar tissue healing which differs from native bone-to-tendon interface (BTI) tissue. We aimed to engineer Synovium-derived mesenchymal stem cells (Sy-MSCs) based scaffold-free fibrocartilage constructs and investigate in vivo bone-tendon interface (BTI) healing efficacy in a rat anterior cruciate ligament (ACL) reconstruction model. METHODS Sy-MSCs were isolated from knee joint of rats. Scaffold-free sy-MSC constructs were fabricated and cultured in differentiation media including TGF-β-only, CTGF-only, and TGF-β + CTGF. Collagenase treatment on tendon grafts was optimized to improve cell-to-graft integration. The effects of fibrocartilage differentiation and collagenase treatment on BTI integration was assessed by conducting histological staining, cell adhesion assay, and tensile testing. Finally, histological and biomechanical analyses were used to evaluate in vivo efficacy of fibrocartilage construct in a rat ACL reconstruction model. RESULTS Fibrocartilage-like features were observed with in the scaffold-free sy-MSC constructs when applying TGF-β and CTGF concurrently. Fifteen minutes collagenase treatment increased cellular attachment 1.9-fold compared to the Control group without affecting tensile strength. The failure stress was highest in the Col + D + group (22.494 ± 13.74 Kpa) compared to other groups at integration analysis in vitro. The ACL Recon + FC group exhibited a significant 88% increase in estimated stiffness (p = 0.0102) compared to the ACL Recon group at the 4-week postoperative period. CONCLUSION Scaffold-free, fibrocartilage engineering together with tendon collagenase treatment enhanced fibrocartilaginous BTI healing in ACL reconstruction.
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Affiliation(s)
- Sujin Noh
- Department of Biomedical Sciences, Graduate School of Ajou University, 206 World Cup-Ro, Yeongtong-Gu, Suwon, Republic of Korea
| | - Sang Jin Lee
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA
| | - James J Yoo
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA
| | - Yong Jun Jin
- Department of Orthopedic Surgery, School of Medicine, Ajou University, Suwon, Republic of Korea
| | - Hee-Woong Yun
- Cell Therapy Center, Ajou Medical Center, Suwon, Republic of Korea
| | - Byoung-Hyun Min
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA
| | - Jae-Young Park
- Department of Orthopedics Surgery, CHA University Bundang Medical Center, Bundang-Gu, Seongnam-Si, Gyeonggi-Do, Republic of Korea
| | - Do Young Park
- Department of Biomedical Sciences, Graduate School of Ajou University, 206 World Cup-Ro, Yeongtong-Gu, Suwon, Republic of Korea.
- Department of Orthopedic Surgery, School of Medicine, Ajou University, Suwon, Republic of Korea.
- Cell Therapy Center, Ajou Medical Center, Suwon, Republic of Korea.
- Leading Convergence of Healthcare and Medicine, Institute of Science & Technology (ALCHeMIST), Ajou University, Suwon, Republic of Korea.
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Takashima Y, Matsumoto T, Nakano N, Kamenaga T, Kuroda Y, Hayashi S, Matsushita T, Niikura T, Kuroda R. The influence of ruptured scar pattern of human anterior cruciate ligament remnant tissue on tendon-bone healing in vivo. J Orthop Res 2023; 41:500-510. [PMID: 35634871 DOI: 10.1002/jor.25387] [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: 01/19/2022] [Revised: 04/12/2022] [Accepted: 05/26/2022] [Indexed: 02/04/2023]
Abstract
The purpose of this study was to determine whether the transplantation of human cells from a non-reattached injured anterior cruciate ligament (ACL) remnant could enhance tendon-bone healing. Human ACL remnant tissue was classified into two groups based on the morphologic pattern as per Crain's classification: (1) non-reattachment group (Crain Ⅳ) and (2) reattachment group (Crain Ⅰ-Ⅲ). Seventy-five 10-week-old immunodeficient rats underwent ACL reconstruction followed by intracapsular administration of one of the following: (1) ACL-derived cells from the non-reattached remnant (non-reattachment group) (n = 5), (2) ACL-derived cells from the reattached tissue (reattachment group) (n = 5), or (3) phosphate-buffered saline (PBS) only (PBS group) (n = 5). Histological (Weeks 2, 4, and 8), immunohistochemical (Week 2), radiographic (Weeks 0, 2, 4, and 8), and biomechanical (Week 8) assessments were performed. Histological evaluation showed high and early healing, induction of endochondral ossification-like integration, and mature bone ingrowth at Week 4 in the non-reattachment group. Microcomputed tomography at Week 4 showed that the tibial bone tunnels in the non-reattachment group were significantly reduced compared to those in the reattachment and PBS groups. Moreover, biomechanical testing showed that ultimate load-to-failure in the non-reattachment group tended to be larger than that in the reattachment group, though not statistically significant. The enhanced healing potential in the non-reattachment group was explained by the increase in intrinsic angiogenesis/osteogenesis. In the subacute phase, the ACL-derived cells with the non-reattached morphologic pattern showed greater and earlier tendon bone healing compared with the cells obtained from the reattached morphologic pattern.
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Affiliation(s)
- Yoshinori Takashima
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoyuki Matsumoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Naoki Nakano
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoyuki Kamenaga
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yuichi Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shinya Hayashi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takehiko Matsushita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takahiro Niikura
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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Sinkler MA, Furdock RJ, McMellen CJ, Calcei JG, Voos JE. Biologics, Stem Cells, Growth Factors, Platelet-Rich Plasma, Hemarthrosis, and Scaffolds May Enhance Anterior Cruciate Ligament Surgical Treatment. Arthroscopy 2023; 39:166-175. [PMID: 36370920 DOI: 10.1016/j.arthro.2022.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 11/03/2022] [Indexed: 11/11/2022]
Abstract
Biologics including mesenchymal stem cells (MSCs), growth factors, and platelet-rich plasma may enhance anterior cruciate ligament (ACL) reconstruction and even ACL primary repair. In addition, hemarthrosis after acute ACL injury represents a source of biologic factors. MSCs can differentiate into both fibroblasts and osteoblasts, potentially providing a transition between the ligament or graft and bone. MSCs also produce cytokines and growth factors necessary for cartilage, bone, ligament, and tendon regeneration. MSC sources including bone marrow, synovium, adipose tissue, ACL-remnant, patellar tendon, and umbilical cord. Also, scaffolds may represent a tool for ACL tissue engineering. A scaffold should be porous, which allows cell growth and flow of nutrients and waste, should be biocompatible, and might have mechanical properties that match the native ACL. Scaffolds have the potential to deliver bioactive molecules or stem cells. Synthetic and biologically derived scaffolds are widely available. ACL reconstruction with improved outcome, ACL repair, and ACL tissue engineering are promising goals. LEVEL OF EVIDENCE: Level V, expert opinion.
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Affiliation(s)
- Margaret A Sinkler
- Department of Orthopaedic Surgery, University Hospitals Cleveland Medical Center, Cleveland Ohio, U.S.A..
| | - Ryan J Furdock
- Department of Orthopaedic Surgery, University Hospitals Cleveland Medical Center, Cleveland Ohio, U.S.A
| | - Christopher J McMellen
- Department of Orthopaedic Surgery, University Hospitals Cleveland Medical Center, Cleveland Ohio, U.S.A
| | - Jacob G Calcei
- Department of Orthopaedic Surgery, University Hospitals Cleveland Medical Center, Cleveland Ohio, U.S.A
| | - James E Voos
- Department of Orthopaedic Surgery, University Hospitals Cleveland Medical Center, Cleveland Ohio, U.S.A
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Gao S, Hu C, Wang Y, Zhang J, Tang K. Comparison of cortical versus cancellous bone fixation in tendon-to-bone healing with a rat trans-calcaneal suture model for Achilles tendon sleeve avulsion. J Orthop Surg Res 2023; 18:15. [PMID: 36604674 PMCID: PMC9817399 DOI: 10.1186/s13018-022-03469-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 12/22/2022] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Trans-calcaneal suture technique is an economical and effective method for repairing Achilles tendon sleeve avulsion. Whether cancellous bone fixation upon this technique could accelerate tendon-to-bone healing is unknown. The purpose of this study is to compare the effect of cortical versus cancellous bone fixation on tendon-bone healing with a novel rat trans-calcaneal suture model. METHODS Trans-calcaneal suture treatment was carried out on the right hindlimb in male Sprague-Dawley rats (N = 80). They were randomly divided into the cortical group (Achilles fixed to the calcaneal cortical bone, n = 40) and the cancellous group (Achilles fixed to the calcaneal cancellous bone, n = 40). Gait analysis and immunohistochemistry were performed 1, 4, 7, and 14 days after the operation. Gross observation, biomechanical analysis, micro-CT, and histological analysis were performed 4 and 8 weeks after surgery. Independent-samples t tests were used for comparison between groups. RESULTS At 1, 4, and 7 days, the swing time of the affected limb in the cancellous group decreased, while the duty cycle, the maximum contact area, the print area, and the mean intensity increased significantly. The cross-sectional area of the tendon-bone junction in the cancellous group was smaller, and the failure load and stiffness were higher 4 weeks after the operation. The cancellous group showed more proportion of new bone and a relatively well-organized and dense connective tissue interface with better fibrocartilage-like tissue at 4 weeks after the operation. The ratio of ED2 + macrophages in the cancellous group was significantly higher than in the cortical group on 1, 4, 7, and 14 days. There were no significant differences in gait at 2 weeks, in appearance, biomechanics, new bone formation, and histology at 8 weeks after surgery between the two groups. CONCLUSION In the new rat trans-calcaneal suture model, cancellous fixation can accelerate tendon-to-bone healing in the early stage, which perhaps is related to the abundant bone marrow tissue in the cancellous bone that modulates the inflammatory processes.
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Affiliation(s)
- Shang Gao
- Department of Orthopaedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Gaotanyan Street. 30, Shapingba District, Chongqing, 400038 China
| | - Chao Hu
- Department of Orthopaedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Gaotanyan Street. 30, Shapingba District, Chongqing, 400038 China
| | - Yunjiao Wang
- Department of Orthopaedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Gaotanyan Street. 30, Shapingba District, Chongqing, 400038 China
| | - Jiqiang Zhang
- Department of Neurology, Third Military Medical University, Chongqing, China
| | - Kanglai Tang
- Department of Orthopaedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Gaotanyan Street. 30, Shapingba District, Chongqing, 400038 China
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Forsythe B, Chahla J, Korrapati A, Lavoie-Gagne O, Forlenza E, Diaz CC, Chung CB, Bae WC, Bach BR, Cole B, Yanke AB, Verma NN. Bone Marrow Aspirate Concentrate Augmentation May Accelerate Allograft Ligamentization in Anterior Cruciate Ligament Reconstruction: A Double-Blinded Randomized Controlled Trial. Arthroscopy 2022; 38:2255-2264. [PMID: 35042007 DOI: 10.1016/j.arthro.2022.01.010] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 01/03/2022] [Accepted: 01/06/2022] [Indexed: 02/02/2023]
Abstract
PURPOSE To assess the effect of bone marrow aspiration concentrate (BMAC) augmentation on clinical outcomes and magnetic resonance imaging (MRI) findings in anterior cruciate ligament (ACL) reconstruction (ACLR) with bone-patellar tendon-bone (BTB) allografts. METHODS A double-blinded, randomized controlled trial was conducted on 80 patients undergoing ACL reconstruction using BTB allografts. Patients were randomized to 2 groups: (1) bone marrow aspirate was collected from the iliac crest, concentrated, and approximately 2.5 mL was injected into the BTB allograft, or (2) a small sham incision was made at the iliac crest (control). MRI was performed at 3 months and 9 months postoperatively to determine the signal intensity ratio of the ACL graft. RESULTS Seventy-three patients were available for follow-up at 1-year postoperatively (36 BMAC, 37 control). International Knee Documentation Committee (IKDC) scores were significantly greater in the BMAC group versus the control at the 9-month postoperative period (81.6 ± 10.5 vs 74.6 ± 14.2, P = .048). There was no significant difference in the proportion of patients who met the minimal clinically important difference for IKDC between the BMAC and control groups at 9 months (89% vs 85%; P = .7). Three months postoperatively, signal intensity ratio of the inferior third of the ACL graft was significantly greater in the BMAC group versus the control group (3.2 ± 2.2 vs 2.1 ± 1.5; P = .02). CONCLUSIONS Patients who received BMAC augmentation of the BTB allograft during ACL reconstruction demonstrated greater signal intensity scores on MRI at 3 months, suggesting increased metabolic activity and remodeling, and potentially accelerated ligamentization. Additionally, patients in the BMAC group had greater patient-reported outcomes (IKDC) at 9 months postoperatively when compared with those who underwent a standard surgical procedure. There was no significant difference in the proportion of patients who met the minimal clinically important difference for IKDC between the BMAC and control groups at 9 months, suggesting limited clinical significance at this time point. LEVEL OF EVIDENCE I, randomized control trial.
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Affiliation(s)
- Brian Forsythe
- Department of Sports Medicine, Midwest Orthopaedics at Rush, Chicago, Illinois, U.S.A..
| | - Jorge Chahla
- Department of Sports Medicine, Midwest Orthopaedics at Rush, Chicago, Illinois, U.S.A
| | - Avinaash Korrapati
- Department of Sports Medicine, Midwest Orthopaedics at Rush, Chicago, Illinois, U.S.A
| | - Ophelie Lavoie-Gagne
- Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, Massachusetts, U.S.A
| | - Enrico Forlenza
- Department of Sports Medicine, Midwest Orthopaedics at Rush, Chicago, Illinois, U.S.A
| | - Connor C Diaz
- Department of Sports Medicine, Midwest Orthopaedics at Rush, Chicago, Illinois, U.S.A
| | - Christine B Chung
- Department of Radiology, University of California, San Diego, California, U.S.A
| | - Won C Bae
- Department of Radiology, University of California, San Diego, California, U.S.A
| | - Bernard R Bach
- Department of Sports Medicine, Midwest Orthopaedics at Rush, Chicago, Illinois, U.S.A
| | - Brian Cole
- Department of Sports Medicine, Midwest Orthopaedics at Rush, Chicago, Illinois, U.S.A
| | - Adam B Yanke
- Department of Sports Medicine, Midwest Orthopaedics at Rush, Chicago, Illinois, U.S.A
| | - Nikhil N Verma
- Department of Sports Medicine, Midwest Orthopaedics at Rush, Chicago, Illinois, U.S.A
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11
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Tie K, Cai J, Shi H, Li X, Shangguan Y, Chen L. Autologous Dedifferentiated Osteogenic Bone Marrow Mesenchymal Stem Cells Promote Bone Formation in a Rabbit Model of Anterior Cruciate Ligament Reconstruction versus Bone Marrow Mesenchymal Stem Cells. Arthroscopy 2022; 38:2246-2254.e1. [PMID: 35093495 DOI: 10.1016/j.arthro.2022.01.021] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Revised: 01/14/2022] [Accepted: 01/16/2022] [Indexed: 02/02/2023]
Abstract
PURPOSE This study aimed to verify whether transplantation of dedifferentiated osteogenic bone marrow mesenchymal stem cells (De-BMSCs) at the tendon-bone interface could result in more bone formation than BMSC transplantation in anterior cruciate ligament (ACL) reconstruction. METHODS BMSCs from femur and tibia of New Zealand White rabbit were subjected to osteogenic induction and then cultured in osteogenic factor-free medium; the obtained cell population was termed De-BMSCs. Bilateral ACL reconstruction was performed in 48 adult rabbits. Three groups were established: control group with alginate gel injection, BMSCs group with the BMSCs injection, and De-BMSCs group with the De-BMSCs injection. At week 4 and 12 postoperatively, tendon-bone healing by histologic staining, micro-computed tomography examination, and biomechanical test were evaluated. RESULTS The expression of α1 chain of type I collagen, osteocalcin, and osteopontin at the tendon-bone interface in the De-BMSCs group was greater than in the control or BMSCs group. The bone volume/total volume by micro-computed tomography scan was significantly greater in the De-BMSCs group than that in the control group (P = .013) or BMSCs group (P = .045) at 4 weeks, and greater than that in the control group (P = .014) or BMSCs group (P = .017) at 12 weeks. The tunnel area was significantly smaller in the De-BMSCs group than in the control group (P = .013) or BMSCs group (P = .044) at 12 weeks. The failure load and stiffness in De-BMSCs group were both significantly enhanced at 4 and 12 weeks than control group or De-BMSCs group. CONCLUSIONS De-BMSCs transplantation can promote bone formation at the tendon-bone interface better than BMSCs transplantation in ACL reconstruction and increase the early biomechanical strength of the reconstructed ACL CLINICAL RELEVANCE: De-BMSCs transplantation is a potential choice for enhancing early bone formation in the tunnel in ACL reconstruction.
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Affiliation(s)
- Kai Tie
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jinghang Cai
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Huasong Shi
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Xufeng Li
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Yangfan Shangguan
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Liaobin Chen
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
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12
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Baird JPE, Anz A, Andrews J, Plummer HA, McGowan B, Gonzalez M, Jordan S. Cellular Augmentation of Anterior Cruciate Ligament Surgery Is Not Currently Evidence Based: A Systematic Review of Clinical Studies. Arthroscopy 2022; 38:2047-2061. [PMID: 34921956 DOI: 10.1016/j.arthro.2021.11.056] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 11/15/2021] [Accepted: 11/30/2021] [Indexed: 02/02/2023]
Abstract
PURPOSE To perform a systematic review of clinical outcome studies exploring cellular augmentation of anterior cruciate ligament (ACL) surgery, including stem cell techniques. METHODS A systematic search was performed according to the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines using the Cochrane, PubMed, MEDLINE, SPORTDiscus, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases from 2000 to 2019. The inclusion criteria were clinical studies that reported on ACL surgery augmented with stem cells or cellular therapy and patient-reported outcome measures or graft healing. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomized clinical trials, and nonrandomized trials were assessed using the Methodological Items for Non-randomized Studies (MINORS) tool. Methodologic assessment was performed according to the Modified Coleman Methodology Score. RESULTS Four studies were found: 2 randomized clinical trials, 1 cohort study with a matched historical control group, and 1 case series. The mean Modified Coleman Methodology Score in these studies was 59, and there was a low risk of bias in 1 study. One study reported outcomes of augmented ACL repair, and 3 studies reported the results of augmented ACL reconstruction. Cellular therapies varied and included concentrated bone marrow aspirate, collagenase/centrifuge processed adipose, and marrow stimulation combined with platelet-rich plasma, as well as cells cultured from allograft bone marrow aspirate. The concentrated bone marrow aspirate and adipose tissue study results did not support their use. The marrow stimulation technique combined with repair led to promising clinical results. The use of allograft cultured cells improved patient-reported outcomes and postoperative radiographic findings. CONCLUSIONS Augmentation of ACL surgery with cellular therapy is not supported by clinical evidence at this time. LEVEL OF EVIDENCE Level IV.
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Affiliation(s)
- Joanne P E Baird
- Bayside Orthopaedics Sports Medicine & Rehab, Fairhope, Alabama, U.S.A
| | - Adam Anz
- Andrews Research & Education Foundation, Gulf Breeze, Florida, U.S.A..
| | - James Andrews
- Andrews Research & Education Foundation, Gulf Breeze, Florida, U.S.A
| | - Hillary A Plummer
- Andrews Research & Education Foundation, Gulf Breeze, Florida, U.S.A
| | - Britt McGowan
- John C. Pace Library, University of West Florida, Pensacola, Florida, U.S.A
| | - Melissa Gonzalez
- John C. Pace Library, University of West Florida, Pensacola, Florida, U.S.A
| | - Steve Jordan
- Andrews Research & Education Foundation, Gulf Breeze, Florida, U.S.A
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Lalehzarian SP, Agarwalla A, Liu JN. Management of proximal biceps tendon pathology. World J Orthop 2022; 13:36-57. [PMID: 35096535 PMCID: PMC8771414 DOI: 10.5312/wjo.v13.i1.36] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 08/10/2021] [Accepted: 12/25/2021] [Indexed: 02/06/2023] Open
Abstract
The long head of the biceps tendon is widely recognized as an important pain generator, especially in anterior shoulder pain and dysfunction with athletes and working individuals. The purpose of this review is to provide a current understanding of the long head of the biceps tendon anatomy and its surrounding structures, function, and relevant clinical information such as evaluation, treatment options, and complications in hopes of helping orthopaedic surgeons counsel their patients. An understanding of the long head of the biceps tendon anatomy and its surrounding structures is helpful to determine normal function as well as pathologic injuries that stem proximally. The biceps-labral complex has been identified and broken down into different regions that can further enhance a physician's knowledge of common anterior shoulder pain etiologies. Although various physical examination maneuvers exist meant to localize the anterior shoulder pain, the lack of specificity requires orthopaedic surgeons to rely on patient history, advanced imaging, and diagnostic injections in order to determine the patient's next steps. Nonsurgical treatment options such as anti-inflammatory medications, physical therapy, and ultrasound-guided corticosteroid injections should be utilized before entertaining surgical treatment options. If surgery is needed, the three options include biceps tenotomy, biceps tenodesis, or superior labrum anterior to posterior repair. Specifically for biceps tenodesis, recent studies have analyzed open vs arthroscopic techniques, the ideal location of tenodesis with intra-articular, suprapectoral, subpectoral, extra-articular top of groove, and extra-articular bottom of groove approaches, and the best method of fixation using interference screws, suture anchors, or cortical buttons. Orthopaedic surgeons should be aware of the complications of each procedure and respond accordingly for each patient. Once treated, patients often have good to excellent clinical outcomes and low rates of complications.
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Affiliation(s)
- Simon P Lalehzarian
- The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, United States
| | - Avinesh Agarwalla
- Department of Orthopedic Surgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Joseph N Liu
- USC Epstein Family Center for Sports Medicine, Keck Medicine of USC, Los Angeles, CA 90033, United States
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14
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Tie K, Cai J, Qin J, Xiao H, Shangguan Y, Wang H, Chen L. Nanog/NFATc1/Osterix signaling pathway-mediated promotion of bone formation at the tendon-bone interface after ACL reconstruction with De-BMSCs transplantation. Stem Cell Res Ther 2021; 12:576. [PMID: 34775995 PMCID: PMC8591902 DOI: 10.1186/s13287-021-02643-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 10/25/2021] [Indexed: 11/10/2022] Open
Abstract
Background Bone formation plays an important role in early tendon–bone healing after anterior cruciate ligament reconstruction (ACLR). Dedifferentiated osteogenic bone marrow mesenchymal stem cells (De-BMSCs) have enhanced osteogenic potential. This study aimed to investigate the effect of De-BMSCs transplantation on the promotion of bone formation at the tendon–bone interface after ACLR and to further explore the molecular mechanism of the enhanced osteogenic potential of De-BMSCs. Methods BMSCs from the femurs and tibias of New Zealand white rabbits were subjected to osteogenic induction and then cultured in medium without osteogenic factors; the obtained cell population was termed De-BMSCs. De-BMSCs were induced to undergo osteo-, chondro- and adipo-differentiation in vitro to examine the characteristics of primitive stem cells. An ACLR model with a semitendinosus tendon was established in rabbits, and the animals were divided into a control group, BMSCs group, and De-BMSCs group. At 12 weeks after surgery, the rabbits in each group were sacrificed to evaluate tendon–bone healing by histologic staining, micro-computed tomography (micro-CT) examination, and biomechanical testing. During osteogenic differentiation of De-BMSCs, an siRNA targeting nuclear factor of activated T-cells 1 (NFATc1) was used to verify the molecular mechanism of the enhanced osteogenic potential of De-BMSCs. Results De-BMSCs exhibited some properties similar to BMSCs, including multiple differentiation potential and cell surface markers. Bone formation at the tendon–bone interface in the De-BMSCs group was significantly increased, and biomechanical strength was significantly improved. During the osteogenic differentiation of De-BMSCs, the expression of Nanog and NFATc1 was synergistically increased, which promoted the interaction of NFATc1 and Osterix, resulting in increased expression of osteoblast marker genes such as COL1A, OCN, and OPN. Conclusions De-BMSCs transplantation could promote bone formation at the tendon–bone interface after ACLR and improve the biomechanical strength of the reconstruction. The Nanog/NFATc1/Osterix signaling pathway mediated the enhanced osteogenic differentiation efficiency of De-BMSCs. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-021-02643-9.
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Affiliation(s)
- Kai Tie
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Jinghang Cai
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Jun Qin
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Hao Xiao
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Yangfan Shangguan
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Hui Wang
- Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 430071, China.
| | - Liaobin Chen
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
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15
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Matsumoto T, Sato Y, Kobayashi T, Suzuki K, Kimura A, Soma T, Ito E, Kikuchi T, Kobayashi S, Harato K, Niki Y, Matsumoto M, Nakamura M, Miyamoto T. Adipose-Derived Stem Cell Sheets Improve Early Biomechanical Graft Strength in Rabbits After Anterior Cruciate Ligament Reconstruction. Am J Sports Med 2021; 49:3508-3518. [PMID: 34643475 DOI: 10.1177/03635465211041582] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Although various reconstruction techniques are available for anterior cruciate ligament (ACL) injuries, a long recovery time is required before patients return to sports activities, as the reconstructed ACL requires time to regain strength. To date, several studies have reported use of mesenchymal stem cells in orthopaedic surgery; however, no studies have used adipose-derived stem cell (ADSC) sheets in ACL reconstruction (ACLR). HYPOTHESIS ADSC sheet transplantation can improve biomechanical strength of the autograft used in ACLR. STUDY DESIGN Controlled laboratory study. METHODS A total of 68 healthy Japanese white rabbits underwent unilateral ACLR with a semitendinosus tendon autograft after random enrollment into a control group (no sheet; n = 34) and a sheet group (ADSC sheet; n = 34). At 2, 4, 8, 16, and 24 weeks after surgery, rabbits in each group were sacrificed to evaluate tendon-bone healing using histological staining, micro-computed tomography, and biomechanical testing. At 24 weeks, scanning transmission electron microscopy of the graft midsubstance was performed. RESULTS The ultimate failure load for the control and sheet groups, respectively, was as follows: 17.2 ± 5.5 versus 37.3 ± 10.3 (P = .01) at 2 weeks, 28.6 ± 1.9 versus 47.4 ± 10.4 (P = .003) at 4 weeks, 53.0 ± 14.3 versus 48.1 ± 9.3 (P = .59) at 8 weeks, 66.2 ± 9.3 versus 95.2 ± 43.1 (P = .24) at 16 weeks, and 66.7 ± 27.3 versus 85.3 ± 29.5 (P = .39) at 24 weeks. The histological score was also significantly higher in the sheet group compared with the control group at early stages up to 8 weeks. On micro-computed tomography, relative to the control group, the bone tunnel area was significantly narrower in the sheet group at 4 weeks, and the bone volume/tissue volume of the tendon-bone interface was significantly greater at 24 weeks. Scanning transmission electron microscopy at 24 weeks indicated that the mean collagen fiber diameter in the midsubstance was significantly greater, as was the occupation ratio of collagen fibers per field of view, in the sheet group. CONCLUSION ADSC sheets improved biomechanical strength, prevented bone tunnel enlargement, and promoted tendon-bone interface healing and graft midsubstance healing in an in vivo rabbit model. CLINICAL RELEVANCE ADSC sheets may be useful for early tendon-bone healing and graft maturation in ACLR.
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Affiliation(s)
- Tatsuaki Matsumoto
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Yuiko Sato
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan; Department of Advanced Therapy for Musculoskeletal Disorders II, School of Medicine, Keio University, Tokyo, Japan; Department of Musculoskeletal Reconstruction and Regeneration Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Tami Kobayashi
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan; Department of Advanced Therapy for Musculoskeletal Disorders II, School of Medicine, Keio University, Tokyo, Japan; Department of Musculoskeletal Reconstruction and Regeneration Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Kunika Suzuki
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan; Regenerative Medicine iPS Gateway Center, Tokyo, Japan
| | - Atsushi Kimura
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Tomoya Soma
- Division of Oral and Maxillofacial Surgery, Department of Dentistry and Oral Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Eri Ito
- Institute for Integrated Sports Medicine, School of Medicine, Keio University, Tokyo, Japan
| | - Toshiyuki Kikuchi
- Department of Clinical Research, National Hospital Organization Murayama Medical Center, Tokyo, Japan
| | - Shu Kobayashi
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Kengo Harato
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Yasuo Niki
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Morio Matsumoto
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Masaya Nakamura
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Takeshi Miyamoto
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan; Department of Advanced Therapy for Musculoskeletal Disorders II, School of Medicine, Keio University, Tokyo, Japan; Department of Musculoskeletal Reconstruction and Regeneration Surgery, School of Medicine, Keio University, Tokyo, Japan; Department of Orthopedic Surgery, Kumamoto University, Kumamoto, Japan
- Investigation performed at Keio University, Tokyo, Japan
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16
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Stodolak-Zych E, Ficek K, Wieczorek J, Kajor M, Gryń K, Rapacz-Kmita A, Rajca J, Kosenyuk Y, Stolarz M, Błażewicz S. Assessment of sheep knee joint after ACL replacement with Achilles tendon autograft and PLA-based implant. J Mech Behav Biomed Mater 2021; 125:104923. [PMID: 34753103 DOI: 10.1016/j.jmbbm.2021.104923] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 09/24/2021] [Accepted: 10/24/2021] [Indexed: 11/28/2022]
Abstract
In this study, we propose a new approach in the anterior cruciate ligament (ACL) replacement to provide stability and integration with bone tunnel. A polylactide (PLA)-based tubular implant was used to support the graft stabilization in femoral and tibial bones and to stimulate the healing process after (ACL) replacement on a sheep model. The ACL was replaced with an autologous Achilles tendon split graft. The tendon-to-bone healing in the model was analyzed after 6 and 12 weeks. Two groups of animals were compared, i.e. the group with the PLA-based implant used in the ACL replacement and the control group without the implant. The knee joints were mechanically and clinically evaluated, including the histopathology tests, to determine their stability and integrity. The results indicated that the bioresorbable PLA-based tubular implant may facilitate integration of the tendon graft with bone. Remodeling the allograft inside the implant improves the joint mobility from the first week of healing: no pathological changes were observed at the surgery site and in the animals' mobility. After 6 and 12 weeks of healing no significant changes in the mechanical parameters of the knee joint were observed, regarding the joint failure force, knee displacement, angular mobility range and joint stiffness. Relatively small values of the non-destructive tests in the knee displacement, already 6 weeks after surgery, indicated the early stabilization of the knee joint. The studies showed that the failure forces of knee joints after the ACL replacement with the PLA-based implant are lower than those of an intact joint, although their biomechanical features, including strain-at- failure, are similar. The biomechanical parameters of the knee joint were significantly improved due to the selected method of attaching the autograft ends to the femoral and tibial bone surfaces. After 12 weeks the intra-tunnel tendon-bone site with the PLA implant revealed the better tibia-femur joint mechanical stability, linear force-strain function and the decreasing strain-to-failure value, as compared to the control group.
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Affiliation(s)
- Ewa Stodolak-Zych
- Faculty of Materials Science and Ceramics, University of Science and Technology, 30-059, Krakow, Poland.
| | - Krzysztof Ficek
- The Jerzy Kukuczka Academy of Physical Education, 40-065, Katowice, Poland; Galen - Orthopaedics, 43-150, Bierun, Poland
| | | | - Maciej Kajor
- Medical University of Silesia, Ul. Medyków 18, 40-752, Katowice, Poland
| | - Karol Gryń
- Faculty of Materials Science and Ceramics, University of Science and Technology, 30-059, Krakow, Poland
| | - Alicja Rapacz-Kmita
- Faculty of Materials Science and Ceramics, University of Science and Technology, 30-059, Krakow, Poland
| | | | - Yuriy Kosenyuk
- National Research Institute of Animal Production, 32-083, Balice, Poland
| | | | - Stanisław Błażewicz
- Faculty of Materials Science and Ceramics, University of Science and Technology, 30-059, Krakow, Poland
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17
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Yao SY, Cao MD, He X, Fu BSC, Yung PSH. Biological modulations to facilitate graft healing in anterior cruciate ligament reconstruction (ACLR), when and where to apply? A systematic review. J Orthop Translat 2021; 30:51-60. [PMID: 34611514 PMCID: PMC8458724 DOI: 10.1016/j.jot.2021.07.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 07/21/2021] [Accepted: 07/27/2021] [Indexed: 12/16/2022] Open
Abstract
Background When and where to apply the biological modulations is effective to promote healing in the anterior cruciate ligament (ACL) reconstruction remains unclear. Purpose To perform a systematic review of preclinical animal studies on biological modulation in anterior cruciate ligament reconstruction (ACLR) concerning the time and site of delivery. Study design Systematic review of controlled laboratory studies. Methods PubMed, Ovid, and Scopus were searched until December 2020 using a combination of keywords and their synonym to retrieve all animal studies about biological modulation in ACLR. Studies that assessed mechanical strength after ACLR and compared with negative control were included. The methodological quality of animal studies was evaluated. Results 33 studies were included in this review and the majority reported mechanical strength improvement. 79 % of studies applied the biological modulations intra-operatively with different delivery systems used. For 21 % of post-operative delivery studies, intermittent delivery was tried. 21 of the included studies directly applied the biological modulations in the bone tunnels, 5 studies applied intra-articularly while 7 studies applied both in the bone tunnels and intra-articular part. Biological modulations applied intra-operatively and those applied in both parts showed better mechanical strength increase. A shift of the failure mode of pull-out from the bone tunnel in the early healing phase, to mid-substance rupture in the later phase was observed in most studies. Conclusion The improvement of the mechanical strength depends on how the biological modulations (delivery phase, delivery site, delivery form) are applied. The intra-operative delivery showed an overall higher mechanical strength increase and bone tunnel only delivery or intra-articular and bone tunnel both delivery are preferred than intra-articular only delivery. In addition, intra-articular and bone tunnel both delivery can have better mechanical strength increase for a long follow-up time. Thus, intra-operative application with a carrier to control release rate in both parts should be recommended. Further studies are needed to achieve a better healing outcome and more attention should be given to the intra-articular remodeling of the graft along with the tendon bone healing to increase the final mechanical strength. The Translational potential of this article Here, a systematic review of preclinical evidence of the time, site and the method the biological modulations being applied for ACLR to improve the graft healing would be performed. After reviewing the available studies, a choice of when and where to apply the biological modulations can achieve better mechanical strength after ACLR can be obtained. It provides evidence for both researchers and clinicians to decide when and where to apply the biological modulations can achieve their best effectiveness for ACLR before implementing. Promoting graft healing with targeted time and targeted site may reduce the risk of graft failure, safeguard return to sport.
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Affiliation(s)
- S Y Yao
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - M D Cao
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - X He
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Bruma S C Fu
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Patrick S H Yung
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
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18
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Moon SW, Park S, Oh M, Wang JH. Outcomes of human umbilical cord blood-derived mesenchymal stem cells in enhancing tendon-graft healing in anterior cruciate ligament reconstruction: an exploratory study. Knee Surg Relat Res 2021; 33:32. [PMID: 34530924 PMCID: PMC8447562 DOI: 10.1186/s43019-021-00104-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 05/03/2021] [Indexed: 11/30/2022] Open
Abstract
Background The study investigated whether allogeneic human umbilical cord blood-derived MSCs (hUCB-MSCs) could be safely used without treatment-related adverse events, reducing tunnel enlargement, and improve clinical results in human anterior cruciate ligament (ACL) reconstruction. Methods Thirty patients were enrolled consecutively. They were divided into three groups by randomization. In the negative control group, ACL reconstruction surgery without additional treatment was performed. In the experimental group, a hUCB-MSC and hyaluronic acid mixture was applied to the tendon-bone interface of the femoral tunnels during ACL reconstruction surgery. In the positive control group, only hyaluronic acid was applied. Finally, 27 patients were analyzed after the exclusion of three patients. The incidence of treatment-related adverse events, clinical outcomes, including second-look arthroscopic findings, and the amount of tunnel enlargement, were evaluated. Results There were no treatment-related adverse events in the treatment groups. Tunnel enlargement in the experimental group (579.74 ± 389.85 mm3) was not significantly different from those in the negative (641.97 ± 455.84 mm3) and positive control (421.96 ± 274.83 mm3) groups (p = 0.6468). There were no significant differences between the groups in clinical outcomes such as KT-2000 measurement (p = 0.793), pivot shift test (p = 0.9245), International Knee Documentation Committee subjective score (p = 0.9195), Tegner activity level (p = 0.9927), and second-look arthroscopic findings (synovial coverage of the graft, p = 0.7984; condition of the graft, p = 0.8402). Conclusions Allogeneic hUCB-MSCs were used safely for ACL reconstruction without treatment-related adverse event in a 2-year follow-up. However, our study did not suggest any evidence to show clinical advantage such as the prevention of tunnel enlargement postoperatively and a decrease in knee laxity or improvement of clinical outcomes. Trial registration CRIS, Registration Number: KCT0000917. Registered on 12 November 2013; https://cris.nih.go.kr/cris/index.jsp
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Affiliation(s)
- Sang Won Moon
- Department of Orthopaedic Surgery, Inje University Haeundae Paik Hospital, Busan, Korea
| | - Sinhyung Park
- Department of Orthopaedic Surgery, Soonchunhyang University Hospital Bucheon, Gyeonggi-do, Korea
| | - Minkyung Oh
- Clinical Trial Center, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Joon Ho Wang
- Department of Orthopaedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea. .,Department of Health Sciences and Technology and Department of Medical Device Management and Research, SAIHST, Sungkyunkwan University, Seoul, 06351, Korea.
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19
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Xu Y, Zhang WX, Wang LN, Ming YQ, Li YL, Ni GX. Stem cell therapies in tendon-bone healing. World J Stem Cells 2021; 13:753-775. [PMID: 34367476 PMCID: PMC8316867 DOI: 10.4252/wjsc.v13.i7.753] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 05/08/2021] [Accepted: 06/23/2021] [Indexed: 02/06/2023] Open
Abstract
Tendon-bone insertion injuries such as rotator cuff and anterior cruciate ligament injuries are currently highly common and severe. The key method of treating this kind of injury is the reconstruction operation. The success of this reconstructive process depends on the ability of the graft to incorporate into the bone. Recently, there has been substantial discussion about how to enhance the integration of tendon and bone through biological methods. Stem cells like bone marrow mesenchymal stem cells (MSCs), tendon stem/progenitor cells, synovium-derived MSCs, adipose-derived stem cells, or periosteum-derived periosteal stem cells can self-regenerate and potentially differentiate into different cell types, which have been widely used in tissue repair and regeneration. Thus, we concentrate in this review on the current circumstances of tendon-bone healing using stem cell therapy.
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Affiliation(s)
- Yue Xu
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Wan-Xia Zhang
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Li-Na Wang
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Yue-Qing Ming
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Yu-Lin Li
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Guo-Xin Ni
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China.
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20
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Bone Mesenchymal Stem Cells Contribute to Ligament Regeneration and Graft-Bone Healing after Anterior Cruciate Ligament Reconstruction with Silk-Collagen Scaffold. Stem Cells Int 2021; 2021:6697969. [PMID: 33981343 PMCID: PMC8088362 DOI: 10.1155/2021/6697969] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 01/25/2021] [Accepted: 04/15/2021] [Indexed: 11/29/2022] Open
Abstract
Anterior cruciate ligament (ACL) reconstruction was realized using a combination of bone mesenchymal stem cells (BMSCs) and silk–collagen scaffold, and an in vivo evaluation of this combination was performed. By combining type I collagen and degummed silk fibroin mesh, silk–collagen scaffolds were prepared to simulate ligament components. BMSCs isolated from bone marrow of rabbits were cultured for a homogenous population and seeded on the silk–collagen scaffold. In the scaffold and BMSC (S/C) group, scaffolds were seeded with BMSCs for 72 h and then rolled and used to replace the ACL in 20 rabbits. In the scaffold (S) group, scaffolds immersed only in culture medium for 72 h were used for ACL reconstruction. Specimens were collected at 4 and 16 weeks postoperatively to assess ligament regeneration and bone integration. HE and immunohistochemical staining (IHC) were performed to assess ligament regeneration in the knee cavity. To assess bone integration at the graft–bone interface, HE, Russell–Movat staining, micro-CT, and biomechanical tests were performed. After 4 weeks, vigorous cell proliferation was observed in the core part of the scaffold in the S/C group, and a quantity of fibroblast-like cells and extracellular matrix (ECM) was observed in the center part of the graft at 16 weeks after surgery. At 4 and 16 weeks postoperatively, the tenascin-C expression in the S/C group was considerably higher than that in the S group (4 w, p < 0.01; 16 w, p < 0.01). Furthermore, bone integration was better in the S/C group than in the S group, with histological observation of trabecular bone growth into the graft and more mineralized tissue formation detected by micro-CT (4 w, bone volume fraction (BV/TV), p = 0.0169, bone mineral density (BMD), p = 0.0001; 16 w, BV/TV, p = 0.1233, BMD, p = 0.0494). These results indicate that BMSCs promote ligament regeneration in the knee cavity and bone integration at the graft–bone interface. Silk–collagen scaffolds and BMSCs will likely be combined for clinical practice in the future.
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21
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Lu CC, Ho CJ, Huang HT, Lin SY, Chou SH, Chou PH, Ho ML, Tien YC. Effect of Freshly Isolated Bone Marrow Mononuclear Cells and Cultured Bone Marrow Stromal Cells in Graft Cell Repopulation and Tendon-Bone Healing after Allograft Anterior Cruciate Ligament Reconstruction. Int J Mol Sci 2021; 22:ijms22062791. [PMID: 33801860 PMCID: PMC7998102 DOI: 10.3390/ijms22062791] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 03/07/2021] [Accepted: 03/07/2021] [Indexed: 01/07/2023] Open
Abstract
Graft cell repopulation and tendon-bone tunnel healing are important after allograft anterior cruciate ligament reconstruction (ACLR). Freshly isolated bone marrow mononuclear cells (BMMNCs) have the advantage of short isolation time during surgery and may enhance tissue regeneration. Thus, we hypothesized that the effect of intra-articular BMMNCs in post-allograft ACLR treatment is comparable to that of cultured bone marrow stromal cells (BMSCs). A rabbit model of hamstring allograft ACLR was used in this study. Animals were randomly assigned to the BMMNC, BMSC, and control groups. Fresh BMMNCs isolated from the iliac crest during surgery and cultured BMSCs at passage four were used in this study. A total of 1 × 107 BMMNCs or BMSCs in 100 µL phosphate-buffered saline were injected into the knee joint immediately after ACLR. The control group was not injected with cells. At two and six weeks post operation, we assessed graft cell repopulation with histological and cell tracking staining (PKH26), and tendon-bone healing with histological micro-computed tomography and immunohistochemical analyses for collagen I and monocyte chemoattractant protein-1 (MCP1). At two weeks post operation, there was no significant difference in the total cell population within the allograft among the three groups. However, the control group showed significantly higher cell population within the allograft than that of BM cell groups at six weeks. Histological examination of proximal tibia revealed that the intra-articular delivered cells infiltrated into the tendon-bone interface. Compared to the control group, the BM cell groups showed broader gaps with interfacial fibrocartilage healing, similar collagen I level, and higher MCP1 expression in the early stage. Micro-CT did not reveal any significant difference among the three groups. BMMNCs and BMSCs had comparable effects on cell repopulation and interfacial allograft-bone healing. Intra-articular BM cells delivery had limited benefits on graft cell repopulation and caused higher inflammation than that in the control group in the early stage, with fibrocartilage formation in the tendon-bone interface after allograft ACLR.
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Affiliation(s)
- Cheng-Chang Lu
- Department of Orthopedics, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung 812, Taiwan;
- Department of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (H.-T.H.); (S.-Y.L.); (P.-H.C.)
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan;
| | - Cheng-Jung Ho
- Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-J.H.); (S.-H.C.)
| | - Hsuan-Ti Huang
- Department of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (H.-T.H.); (S.-Y.L.); (P.-H.C.)
- Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Sung-Yen Lin
- Department of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (H.-T.H.); (S.-Y.L.); (P.-H.C.)
- Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-J.H.); (S.-H.C.)
| | - Shih-Hsiang Chou
- Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-J.H.); (S.-H.C.)
| | - Pei-Hsi Chou
- Department of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (H.-T.H.); (S.-Y.L.); (P.-H.C.)
- Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-J.H.); (S.-H.C.)
| | - Mei-Ling Ho
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan;
- Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Yin-Chun Tien
- Department of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (H.-T.H.); (S.-Y.L.); (P.-H.C.)
- Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-J.H.); (S.-H.C.)
- Correspondence: ; Tel.: +886-7-3121101-5751
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22
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Hexter AT, Sanghani-Kerai A, Heidari N, Kalaskar DM, Boyd A, Pendegrass C, Rodeo SA, Haddad FS, Blunn GW. Mesenchymal stromal cells and platelet-rich plasma promote tendon allograft healing in ovine anterior cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthrosc 2021; 29:3678-3688. [PMID: 33331973 PMCID: PMC8514355 DOI: 10.1007/s00167-020-06392-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 11/24/2020] [Indexed: 11/30/2022]
Abstract
PURPOSE The effect of bone marrow mesenchymal stromal cells (BMSCs) and platelet-rich plasma (PRP) on tendon allograft maturation in a large animal anterior cruciate ligament (ACL) reconstruction model was reported for the first time. It was hypothesised that compared with non-augmented ACL reconstruction, BMSCs and PRP would enhance graft maturation after 12 weeks and this would be detected using magnetic resonance imaging (MRI). METHODS Fifteen sheep underwent unilateral tendon allograft ACL reconstruction using aperture fixation and were randomised into three groups (n = 5). Group 1 received 10 million allogeneic BMSCs in 2 ml fibrin sealant; Group 2 received 12 ml PRP in a plasma clot injected into the graft and bone tunnels; and Group 3 (control) received no adjunctive treatment. At autopsy at 12 weeks, a graft maturation score was determined by the sum for graft integrity, synovial coverage and vascularisation, graft thickness and apparent tension, and synovial sealing at tunnel apertures. MRI analysis (n = 2 animals per group) of the signal-noise quotient (SNQ) and fibrous interzone (FIZ) was used to evaluate intra-articular graft maturation and tendon-bone healing, respectively. Spearman's rank correlation coefficient (r) of SNQ, autopsy graft maturation score and bone tunnel diameter were analysed. RESULTS The BMSC group (p = 0.01) and PRP group (p = 0.03) had a significantly higher graft maturation score compared with the control group. The BMSC group scored significantly higher for synovial sealing at tunnel apertures (p = 0.03) compared with the control group. The graft maturation score at autopsy significantly correlated with the SNQ (r = - 0.83, p < 0.01). The tunnel diameter of the femoral tunnel at the aperture (r = 0.883, p = 0.03) and mid-portion (r = 0.941, p = 0.02) positively correlated with the SNQ. CONCLUSIONS BMSCs and PRP significantly enhanced graft maturation, which indicates that orthobiologics can accelerate the biologic events in tendon allograft incorporation. Femoral tunnel expansion significantly correlated with inferior maturation of the intra-articular graft. The clinical relevance of this study is that BMSCs and PRP enhance allograft healing in a translational model, and biological modulation of graft healing can be evaluated non-invasively using MRI.
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Affiliation(s)
- Adam T Hexter
- Division of Surgery and Interventional Science, University College London (UCL), London, UK.
- Institute of Orthopaedics and Musculoskeletal Sciences, Division of Surgery and Interventional Science, Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, London, HA7 4LP, UK.
| | - Anita Sanghani-Kerai
- Division of Surgery and Interventional Science, University College London (UCL), London, UK
| | - Nima Heidari
- Royal London Hospital and Orthopaedic Specialists (OS), London, UK
| | - Deepak M Kalaskar
- Division of Surgery and Interventional Science, University College London (UCL), London, UK
| | - Ashleigh Boyd
- Division of Surgery and Interventional Science, University College London (UCL), London, UK
| | - Catherine Pendegrass
- Division of Surgery and Interventional Science, University College London (UCL), London, UK
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23
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Mengsteab PY, Otsuka T, McClinton A, Shemshaki NS, Shah S, Kan HM, Obopilwe E, Vella AT, Nair LS, Laurencin CT. Mechanically superior matrices promote osteointegration and regeneration of anterior cruciate ligament tissue in rabbits. Proc Natl Acad Sci U S A 2020; 117:28655-28666. [PMID: 33144508 PMCID: PMC7682397 DOI: 10.1073/pnas.2012347117] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The gold standard treatment for anterior cruciate ligament (ACL) reconstruction is the use of tendon autografts and allografts. Limiting factors for this treatment include donor site morbidity, potential disease transmission, and variable graft quality. To address these limitations, we previously developed an off-the-shelf alternative, a poly(l-lactic) acid (PLLA) bioengineered ACL matrix, and demonstrated its feasibility to regenerate ACL tissue. This study aims to 1) accelerate the rate of regeneration using the bioengineered ACL matrix by supplementation with bone marrow aspirate concentrate (BMAC) and growth factors (BMP-2, FGF-2, and FGF-8) and 2) increase matrix strength retention. Histological evaluation showed robust tissue regeneration in all groups. The presence of cuboidal cells reminiscent of ACL fibroblasts and chondrocytes surrounded by an extracellular matrix rich in anionic macromolecules was up-regulated in the BMAC group. This was not observed in previous studies and is indicative of enhanced regeneration. Additionally, intraarticular treatment with FGF-2 and FGF-8 was found to suppress joint inflammation. To increase matrix strength retention, we incorporated nondegradable fibers, polyethylene terephthalate (PET), into the PLLA bioengineered ACL matrix to fabricate a "tiger graft." The tiger graft demonstrated the greatest peak loads among the experimental groups and the highest to date in a rabbit model. Moreover, the tiger graft showed superior osteointegration, making it an ideal bioengineered ACL matrix. The results of this study illustrate the beneficial effect bioactive factors and PET incorporation have on ACL regeneration and signal a promising step toward the clinical translation of a functional bioengineered ACL matrix.
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Affiliation(s)
- Paulos Y Mengsteab
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT 06030
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269
| | - Takayoshi Otsuka
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT 06030
| | - Aneesah McClinton
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT 06030
- Department of Surgery, University of Connecticut School of Medicine, Farmington, CT, 06030
| | - Nikoo Saveh Shemshaki
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT 06030
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269
| | - Shiv Shah
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT 06030
- Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269
| | - Ho-Man Kan
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT 06030
| | - Elifho Obopilwe
- Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT 06030
| | - Anthony T Vella
- Department of Immunology, University of Connecticut School of Medicine, Farmington, CT 06030
| | - Lakshmi S Nair
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT 06030
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269
- Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT 06030
- Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269
| | - Cato T Laurencin
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030;
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT 06030
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269
- Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269
- Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT 06030
- Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269
- Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT 06030
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24
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Morton-Gonzaba N, Carlisle D, Emukah C, Chorath K, Moreira A. Mesenchymal stem cells and their application to rotator cuff pathology: A meta-analysis of pre-clinical studies. OSTEOARTHRITIS AND CARTILAGE OPEN 2020; 2:100047. [PMID: 36474592 PMCID: PMC9718136 DOI: 10.1016/j.ocarto.2020.100047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 02/14/2020] [Indexed: 12/18/2022] Open
Abstract
Background Rotator cuff injury (RCI) is a leading cause of morbidity in orthopaedics. Advances in regenerative medicine have led to the novel pleiotropic effects of mesenchymal stromal cells (MSCs) as therapeutic agents for RCI. Objective Conduct a systematic evaluation of available preclinical studies to quantify the effects of MSCs on RCI. Methods A literature search was performed in PubMed, Scopus, Cochrane, CINAHL, and Google Scholar. At least two independent investigators screened animal studies assessing the therapeutic effects of MSCs on: (i) biomechanical testing, imaging, and/or range-of-motion (primary outcome), and (ii) histologic analyses of wound healing, gene/protein expression of regenerative factors, and safety/long-term outcomes (secondary outcome). Meta-analysis data is reported as standardized mean difference (SMD) with 95% confidence interval (CI). Results A total of 858 titles and abstracts were screened; 18 studies (n=576) met inclusion criteria. MSC therapy improved ultimate load failure [SMD -0.43 (95% CI -0.65, -0.22), p<0.0001; 15 studies, 28 comparisons], site stiffness [SMD -0.29 (95% CI -0.55, -0.04), p<0.05; 9 studies, 17 comparisons], bone mineral density [SMD -0.77 (95% CI -1.16, -0.38), p<0.0001; 2 studies, 6 comparisons], and stimulated fibrocartilage formation [SMD of -1.37 (95% CI -1.99, -0.74), p<0.0001; 4 studies, 7 comparisons]. Heterogeneity between studies was high and risk of bias was unclear. Conclusion Administration of MSCs in preclinical models recapitulating RCI improved aspects of shoulder biomechanics, imaging, and collagen formation. Although these findings are promising, future studies should attempt to limit the risk of bias and focus on optimizing MSCs by standardizing methodologies.
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Affiliation(s)
- Nicolas Morton-Gonzaba
- Department of Pediatrics, Division of Neonatology, University of Texas Health-San Antonio, San Antonio, TX, USA
| | - Daniel Carlisle
- Department of Pediatrics, Division of Neonatology, University of Texas Health-San Antonio, San Antonio, TX, USA
| | - Chimobi Emukah
- Department of Pediatrics, Division of Neonatology, University of Texas Health-San Antonio, San Antonio, TX, USA
| | - Kevin Chorath
- Department of Pediatrics, Division of Neonatology, University of Texas Health-San Antonio, San Antonio, TX, USA
| | - Alvaro Moreira
- Department of Pediatrics, Division of Neonatology, University of Texas Health-San Antonio, San Antonio, TX, USA
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25
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Tei MM, Placella G, Sbaraglia M, Tiribuzi R, Georgoulis A, Cerulli G. Does Manual Drilling Improve the Healing of Bone-Hamstring Tendon Grafts in Anterior Cruciate Ligament Reconstruction? A Histological and Biomechanical Study in a Rabbit Model. Orthop J Sports Med 2020; 8:2325967120911600. [PMID: 32284946 PMCID: PMC7139185 DOI: 10.1177/2325967120911600] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 11/08/2019] [Indexed: 11/16/2022] Open
Abstract
Background: Heat necrosis due to motorized drilling during anterior cruciate ligament
(ACL) reconstruction could be a factor in delayed healing at the bone–tendon
graft interface. Hypothesis: The process of osteointegration could be enhanced using manual drilling. It
reduces the invasiveness of mechanical-thermal stress normally caused by the
traditional motorized drill bit. Study Design: Controlled laboratory study. Methods: ACL reconstruction using semitendinosus tendon autografts was performed in 28
skeletally mature female New Zealand white rabbits, which were randomly
divided into 3 groups. In group A (n = 12), the tunnels were drilled using a
motorized device; in group B (n = 12), the tunnels were drilled using a
manual drill bit; and group C (n = 4) served as a control with sham surgical
procedures. The healing process in the tunnels was assessed histologically
at 2, 4, 8, and 12 weeks and graded according to the Tendon–Bone Tunnel
Healing (TBTH) scoring system. In addition, another 25 rabbits were used for
biomechanical testing. The structural properties of the femur–ACL
graft–tibia complex, from animals sacrificed at 8 weeks postoperatively,
were determined using uniaxial tests. Stiffness (N/mm) and ultimate load to
failure (N) were determined from the resulting load-elongation curves. Results: The time course investigation showed that manual drilling (group B) had a
higher TBTH score and improved mechanical behavior, reflecting better
organized collagen fiber continuity at the bone–fibrous tissue interface,
better integration between the graft and bone, and early mineralized
chondrocyte-like tissue formation at all the time points analyzed with a
maximum difference at 4 weeks (TBTH score: 5.4 [group A] vs 12.3 [group B];
P < .001). Stiffness (23.1 ± 8.2 vs 17.8 ± 6.3 N/mm,
respectively) and ultimate load to failure (91.8 ± 60.4 vs 55.0 ± 18.0 N,
respectively) were significantly enhanced in the specimens treated with
manual drilling compared with motorized drilling (P <
.05 for both). Conclusion: The use of manual drilling during ACL reconstruction resulted in better
tendon-to-bone healing during the crucial early weeks. Manual drilling was
able to improve the biological and mechanical properties of bone–hamstring
tendon graft healing and was able to restore postoperative graft function
more quickly. Tunnel drilling results in bone loss and deficient tendon-bone
healing, and heat necrosis after tunnel enlargement may cause mechanical
stress, contributing to a delay in healing. Manual drilling preserved the
bone stock inside the tunnel, reduced heat necrosis, and offered a better
microenvironment for faster healing at the interface. Clinical Relevance: Based on study results, manual drilling could be used successfully in human
ACL reconstruction, but further clinical studies are needed. A clinical
alternative, called the original “all-inside” technique, has been developed
for ACL reconstruction. In this technique, the femoral and tibial tunnels
are manually drilled only halfway through the bone for graft fixation,
reducing bone loss. Data from this study suggest that hamstring
tendon–to–bone healing can be improved using a manual drilling technique to
form femoral and tibial tunnels.
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Affiliation(s)
- Matteo Maria Tei
- Istituto di Ricerca Traslazionale per l'Apparato Locomotore Nicola Cerulli, Arezzo, Italy
| | - Giacomo Placella
- Istituto di Ricerca Traslazionale per l'Apparato Locomotore Nicola Cerulli, Arezzo, Italy.,Department of Orthopaedic Surgery, Ospedale San Raffaele, Milan, Italy
| | - Marta Sbaraglia
- Istituto di Ricerca Traslazionale per l'Apparato Locomotore Nicola Cerulli, Arezzo, Italy.,Department of Pathology, Azienda Ospedaliera di Padova, Padua, Italy
| | - Roberto Tiribuzi
- Istituto di Ricerca Traslazionale per l'Apparato Locomotore Nicola Cerulli, Arezzo, Italy
| | - Anastasios Georgoulis
- Istituto di Ricerca Traslazionale per l'Apparato Locomotore Nicola Cerulli, Arezzo, Italy.,Department of Orthopaedic Surgery, Ospedale San Raffaele, Milan, Italy.,Department of Pathology, Azienda Ospedaliera di Padova, Padua, Italy.,Orthopaedic Sports Medicine Center, University of Ioannina, Ioannina, Greece
| | - Giuliano Cerulli
- Istituto di Ricerca Traslazionale per l'Apparato Locomotore Nicola Cerulli, Arezzo, Italy
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26
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Zhou Y, Xie S, Tang Y, Li X, Cao Y, Hu J, Lu H. Effect of book-shaped acellular tendon scaffold with bone marrow mesenchymal stem cells sheets on bone-tendon interface healing. J Orthop Translat 2020; 26:162-170. [PMID: 33437635 PMCID: PMC7773951 DOI: 10.1016/j.jot.2020.02.013] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 02/27/2020] [Accepted: 02/28/2020] [Indexed: 12/12/2022] Open
Abstract
Background Tissue engineering has exhibited great effect on treatment for bone-tendon interface (BTI) injury. The aim of this study was to evaluate the effect of a book-shaped acellular tendon scaffold (ATS) with bone marrow mesenchymal stem cells sheets (MSCS) for BTI injury repair. Methods ATS was designed based on the shape of "book", decellularization effect was evaluated by Hematoxylin and eosin (H&E), 4', 6-diamidino-2-phenylindole (DAPI) and scanning electron microscopy (SEM), then bone marrow mesenchymal stem cells (MSCs) were cultured on ATS to assess the differentiation inductivity of ATS. A rabbit right partial patellotomy model was established, and MSCS seeded on ATS were implanted into the lesion site. The patella-patellar tendon (PPT) at 2, 4, 8 or 16 weeks post-operation were obtained for histological, biomechanical and immunofluorescence analysis. Results H&E, DAPI and SEM results confirmed the efficiency of decellularization of ATS, and their in vitro tenogenic and chondrogenic ability were successfully identified. In vivo results showed increased macrophage polarization toward the M2 phenotype, IL-10 expression, regenerated bone and fibrocartilage at the patella-patellar tendon interface of animals received MSCS modified ATS implantation. In addition, the level of tensile strength was also the highest in MSCS modified ATS implantation group. Conclusion This study suggests that ATS combined with MSCS performed therapeutic effects on promoting the regeneration of cartilage layer and enhancing the healing quality of patella-patellar tendon interface. The translational potential of this article This study showed the good biocompatibility of the ATS, as well as the great efficacy of ATS with MSCS on tendon to bone healing. The results meant that the novel book-shaped ATS with MSCS may have a great potential for clinical application.
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Affiliation(s)
- Yongchun Zhou
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.,Department of Orthopedic, Shaanxi Provincial People's Hospital, Xi'an, 710000, People's Republic of China.,Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, People's Republic of China.,Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, People's Republic of China
| | - Shanshan Xie
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.,Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, People's Republic of China.,Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, People's Republic of China
| | - Yifu Tang
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.,Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, People's Republic of China.,Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, People's Republic of China
| | - Xiaoning Li
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.,Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, People's Republic of China.,Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, People's Republic of China
| | - Yong Cao
- Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.,Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, People's Republic of China.,Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, People's Republic of China
| | - Jianzhong Hu
- Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.,Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, People's Republic of China.,Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, People's Republic of China
| | - Hongbin Lu
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.,Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, People's Republic of China.,Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, People's Republic of China
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27
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Al-Fotawi R, Muthurangan M, Siyal A, Premnath S, Al-Fayez M, Ahmad El-Ghannam, Mahmood A. The use of muscle extracellular matrix (MEM) and SCPC bioceramic for bone augmentation. ACTA ACUST UNITED AC 2020; 15:025005. [PMID: 31846944 DOI: 10.1088/1748-605x/ab6300] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Bone augmentation is a challenging problem in the field of maxillofacial surgery. OBJECTIVE In this study, we prepared and evaluated muscle extracellular matrix (MEM) after adding silica calcium phosphate composite (SCPC) seeded with human bone marrow mesenchymal cells (hBMSCs). We then investigated bone augmentation in vivo using the prepared MEM-SCPC. MATERIALS AND METHODS hBMSCs were seeded on MEM-SCPC, and MEM was characterized. Calvarial bone grafts were prepared using nude mice (n = 12) and grafted separately in two experimental groups: grafts with MEM (control, n = 4) and grafts with MEM-SCPC-hBMSCs (experimental group, n = 8) for 8 weeks. Micro-computed tomography (micro-CT) and histological analysis were then performed. RESULTS Micro-CT analysis demonstrated a thinner trabeculae in grafted defects than normal native bone, with a high degree of anisotropy. Quantitative histomorphometric assessment showed a higher median bone percentage surface area of 80.2% ± 6.0% in the experimental group. CONCLUSION The enhanced bone formation and maturation of bone grafted with MEM-SCPC-hBMSCs suggested the potential use of this material for bone augmentation.
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Affiliation(s)
- Randa Al-Fotawi
- Department of Oral and Maxillofacial Surgery, Dental Faculty, King Saud University, Riyadh, Saudi Arabia
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28
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Mengsteab PY, Conroy P, Badon M, Otsuka T, Kan HM, Vella AT, Nair LS, Laurencin CT. Evaluation of a bioengineered ACL matrix's osteointegration with BMP-2 supplementation. PLoS One 2020; 15:e0227181. [PMID: 31910231 PMCID: PMC6946545 DOI: 10.1371/journal.pone.0227181] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 12/13/2019] [Indexed: 01/05/2023] Open
Abstract
A poly (l-lactic) acid bioengineered anterior cruciate ligament (ACL) matrix has previously demonstrated the ability to support tissue regeneration in a rabbit ACL reconstruction model. The matrix was designed for optimal bone and ligament regeneration by developing a matrix with differential pore sizes in its bone and ligament compartments. Building upon past success, we designed a new bioengineered ACL matrix that is easier to install and can be used with endobutton fixation during ACL reconstruction. To achieve this, a new braiding procedure was developed to allow the matrix to be folded in half, making two-limbs, while maintaining its bone and ligament compartments. The osteointegration of the matrix with and without bone morphogenetic protein 2 (BMP-2) supplementation was evaluated in a rabbit ACL reconstruction model. Two doses of BMP-2 were evaluated, 1 and 10 μg, and delivered by saline injection into the bone tunnel at the end of surgery. A fibrous matrix-to-bone interface with occasional Sharpey’s fibers was the primary mode of osteointegration observed. The matrix was also found to support a fibrocartilage matrix-to-bone interface. In some cases, the presence of chondrocyte-like cells was observed at the aperture of the bone tunnel and the center of the matrix within the bone tunnel. Treatment with BMP-2 was associated with a trend towards smaller bone tunnel cross-sectional areas, and 1 μg of BMP-2 was found to significantly enhance osteoid seam width in comparison with no BMP-2 or 10 μg of BMP-2 treatment. Regenerated tissue was well organized within the bioengineered ACL matrix and aligned with the poly (l-lactic) acid fibers. Disorganized tissue was found between the two-limbs of the bioengineered ACL matrix and hypothesized to be due to a lack of structural scaffolding. This study suggests that the bioengineered ACL matrix can undergo similar modes of osteointegration as current autografts and allografts, and that BMP-2 treatment may enhance osteoblastic activity within the bone tunnels.
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Affiliation(s)
- Paulos Y. Mengsteab
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT, United States of America
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT, United States of America
- Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT, United States of America
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT, United States of America
| | - Patrick Conroy
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT, United States of America
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT, United States of America
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT, United States of America
| | - Mary Badon
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT, United States of America
| | - Takayoshi Otsuka
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT, United States of America
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT, United States of America
- Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT, United States of America
| | - Ho-Man Kan
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT, United States of America
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT, United States of America
| | - Anthony T. Vella
- Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, United States of America
| | - Lakshmi S. Nair
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT, United States of America
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT, United States of America
- Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT, United States of America
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT, United States of America
- Department of Materials Science and Engineering, University of Connecticut, Storrs, CT, United States of America
| | - Cato T. Laurencin
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT, United States of America
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT, United States of America
- Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT, United States of America
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT, United States of America
- Department of Materials Science and Engineering, University of Connecticut, Storrs, CT, United States of America
- Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT, United States of America
- Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT, United States of America
- * E-mail:
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Ficek K, Rajca J, Stolarz M, Stodolak-Zych E, Wieczorek J, Muzalewska M, Wyleżoł M, Wróbel Z, Binkowski M, Błażewicz S. Bioresorbable Stent in Anterior Cruciate Ligament Reconstruction. Polymers (Basel) 2019; 11:polym11121961. [PMID: 31795412 PMCID: PMC6960761 DOI: 10.3390/polym11121961] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Revised: 11/19/2019] [Accepted: 11/25/2019] [Indexed: 11/16/2022] Open
Abstract
The exact causes of failure of anterior cruciate ligament (ACL) reconstruction are still unknown. A key to successful ACL reconstruction is the prevention of bone tunnel enlargement (BTE). In this study, a new strategy to improve the outcome of ACL reconstruction was analyzed using a bioresorbable polylactide (PLA) stent as a catalyst for the healing process. The study included 24 sheep with 12 months of age. The animals were randomized to the PLA group (n = 16) and control group (n = 8), subjected to the ACL reconstruction with and without the implantation of the PLA tube, respectively. The sheep were sacrificed 6 or 12 weeks post-procedure, and their knee joints were evaluated by X-ray microcomputed tomography with a 50 μm resolution. While the analysis of tibial and femoral tunnel diameters and volumes demonstrated the presence of BTE in both groups, the enlargement was less evident in the PLA group. Also, the microstructural parameters of the bone adjacent to the tunnels tended to be better in the PLA group. This suggested that the implantation of a bioresorbable PLA tube might facilitate osteointegration of the tendon graft after the ACL reconstruction. The beneficial effects of the stent were likely associated with osteogenic and osteoconductive properties of polylactide.
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Affiliation(s)
- Krzysztof Ficek
- Department of Science, Innovation and Development, Galen-Orthopaedics, 43-150 Bierun, Poland; (K.F.); (M.S.)
- Department of Physiotherapy, Academy of Physical Education, 40-065 Katowice, Poland
| | - Jolanta Rajca
- Department of Science, Innovation and Development, Galen-Orthopaedics, 43-150 Bierun, Poland; (K.F.); (M.S.)
- Correspondence:
| | - Mateusz Stolarz
- Department of Science, Innovation and Development, Galen-Orthopaedics, 43-150 Bierun, Poland; (K.F.); (M.S.)
- Department of Orthopedics and Traumatology, City Hospital in Zabrze, 41-803 Zabrze, Poland
| | - Ewa Stodolak-Zych
- Department of Biomaterials and Composites, Faculty of Materials Science and Ceramics, AGH University of Science and Technology, 30-059 Krakow, Poland; (E.S.-Z.); (S.B.)
| | - Jarosław Wieczorek
- University Center of Veterinary Medicine UJ-UR, University of Agriculture in Krakow, 30-059 Krakow, Poland;
| | - Małgorzata Muzalewska
- Institute of Fundamentals of Machinery Design, Faculty of Mechanical Engineering, Silesian University of Technology, 44-100 Gliwice, Poland; (M.M.); (M.W.)
| | - Marek Wyleżoł
- Institute of Fundamentals of Machinery Design, Faculty of Mechanical Engineering, Silesian University of Technology, 44-100 Gliwice, Poland; (M.M.); (M.W.)
| | - Zygmunt Wróbel
- Institute of Biomedical Engineering, Faculty of Science and Technology, University of Silesia, 41-205 Sosnowiec, Poland;
| | - Marcin Binkowski
- X-ray Microtomography Lab, Department of Computer Biomedical Systems, Institute of Computer Science, Faculty of Computer and Materials Science, University of Silesia, 41-200 Sosnowiec, Poland;
| | - Stanisław Błażewicz
- Department of Biomaterials and Composites, Faculty of Materials Science and Ceramics, AGH University of Science and Technology, 30-059 Krakow, Poland; (E.S.-Z.); (S.B.)
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30
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Kim JS, Kim TH, Kang DL, Baek SY, Lee Y, Koh YG, Kim YI. Chondrogenic differentiation of human ASCs by stiffness control in 3D fibrin hydrogel. Biochem Biophys Res Commun 2019; 522:213-219. [PMID: 31759627 DOI: 10.1016/j.bbrc.2019.11.049] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Accepted: 11/06/2019] [Indexed: 10/25/2022]
Abstract
In cell-based tissue engineering, fibrin hydrogel can be utilized to produce scaffolds to treat cartilage. However, the optimal fibrin formulation for cartilage regeneration has not yet been studied. This study aimed to find the optimal fibrin formulation and determine whether fibrin optimized with human adipose-derived stem cells (hASCs) increased the in-vivo chondrogenic potential. To find the optimal formulation, fibrin constructs were divided into twelve groups with different ratios of fibrinogen (10, 20, 30, and 50 mg/mL) to thrombin (10, 50, and 100 IU/mL), following which the physical and biological properties of cell-free and cell-embedded fibrin were investigated. The results from cell-free hydrogels showed that increases in the concentrations of fibrinogen and thrombin corresponded to increases in stiffness and initial weight. Moreover, hydrogel degradation was inhibited in high-concentration formulations. In cell-embedded fibrin constructs, the variation of gel formulation did not affect cell viability. However, cell behavior depended on the gel formulation. hASCs within high-concentration fibrinogen formulation maintained a round morphology similar to natural chondrocytes. Variations in thrombin concentration had a lesser effect on cell morphology. In terms of in-vivo cartilage formation, the formulation with 30 mg/mL fibrinogen and 100 IU/mL thrombin showed the highest cartilage formation, as evidenced through collagen type II alpha 1 chain (COL2) and safranin-O, 4 weeks after implantation. The results may lead to optimally designed 3D bio-scaffolds in which we can control both cell survival and chondrogenic potential for cartilage tissue engineering. Scaffolds made with the optimal fibrin formulation can be applied to develop cell therapies with mesenchymal stem cells to treat osteoarthritis.
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Affiliation(s)
- Jin-Su Kim
- Department of Stem Cell Research, TJC Life Research and Development Center, TJC Life, Seoul, Republic of Korea
| | - Tae Hyung Kim
- Department of Health Management, Public Health Center, Chuncheon, Republic of Korea
| | - Dong Lim Kang
- Department of Stem Cell Research, TJC Life Research and Development Center, TJC Life, Seoul, Republic of Korea
| | - Song Yeon Baek
- Department of Stem Cell Research, TJC Life Research and Development Center, TJC Life, Seoul, Republic of Korea
| | - Yura Lee
- Department of Stem Cell Research, TJC Life Research and Development Center, TJC Life, Seoul, Republic of Korea
| | - Yong-Gon Koh
- Center for Stem Cell & Arthritis Research, Department of Orthopaedic Surgery, Yonsei Sarang Hospital, Seoul, Republic of Korea.
| | - Yong Il Kim
- Department of Stem Cell Research, TJC Life Research and Development Center, TJC Life, Seoul, Republic of Korea.
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31
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Ruan D, Zhu T, Huang J, Le H, Hu Y, Zheng Z, Tang C, Chen Y, Ran J, Chen X, Yin Z, Qian S, Pioletti D, Heng BC, Chen W, Shen W, Ouyang HW. Knitted Silk-Collagen Scaffold Incorporated with Ligament Stem/Progenitor Cells Sheet for Anterior Cruciate Ligament Reconstruction and Osteoarthritis Prevention. ACS Biomater Sci Eng 2019; 5:5412-5421. [PMID: 33464061 DOI: 10.1021/acsbiomaterials.9b01041] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Current surgical management of anterior cruciate ligament (ACL) rupture still remains an intractable challenge in ACL regeneration due to the weak self-healing capability of ACL. Inadequate cell numbers and vascularization within the articular cavity contribute mainly to the poor prognosis. This time, we fabricated a new tissue engineering scaffold by adding ligament stem/progenitor cell (LSPC) sheets to our previous knitted silk-collagen sponge scaffold, which overcame these limitations by providing sufficient numbers of seed cells and a natural extracellular matrix to facilitate regeneration. LSPCs display excellent proliferation and multilineage differentiation capacity. Upon ectopic implantation, the knitted silk-collagen sponge scaffold incorporated with an LSPC sheet exhibited less immune cells but more fibroblast-like cells, deposited ECM and neovascularization, and better tissue ingrowth. In a rabbit model, we excised the ACL and performed a reconstructive surgery with our scaffold. Increased expression of ligament-specific genes and better collagen fibril formation could be observed after orthotopic transplantation. After 6 months, the LSPC sheet group showed better results on ligament regeneration and ligament-bone healing. Furthermore, no obvious cartilage and meniscus degeneration were observed at 6 months postoperation. In conclusion, these results indicated that the new tissue engineering scaffold can promote ACL regeneration and slow down the progression of osteoarthritis, thus suggesting its high clinical potential as an ideal graft in ACL reconstruction.
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Affiliation(s)
- Dengfeng Ruan
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, 310009, China.,Department of Orthopedics, Research Institute of Zhejiang University, Zhejiang, 310027, China
| | - Ting Zhu
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, 310009, China.,Department of Orthopedics, Research Institute of Zhejiang University, Zhejiang, 310027, China.,Department of Cardiothoracic Surgery, Shaoxing People's Hospital, Shaoxin Hospital, Zhejiang University School of Medicine, Shaoxing, Zhejiang 312000, People's Republic of China
| | - Jiayun Huang
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, 310009, China.,Department of Orthopedics, Research Institute of Zhejiang University, Zhejiang, 310027, China.,Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Zhejiang, 310009, China
| | - Huihui Le
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, 310009, China.,Department of Orthopedics, Research Institute of Zhejiang University, Zhejiang, 310027, China
| | - Yejun Hu
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, 310009, China.,Department of Orthopedics, Research Institute of Zhejiang University, Zhejiang, 310027, China.,Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Zhejiang, 310009, China
| | - Zefeng Zheng
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, 310009, China.,Department of Orthopedics, Research Institute of Zhejiang University, Zhejiang, 310027, China.,Department of Orthopedic Surgery, Children's Hospital, Zhejiang University School of Medicine, Zhejiang, 310052, China
| | - Chenqi Tang
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, 310009, China.,Department of Orthopedics, Research Institute of Zhejiang University, Zhejiang, 310027, China.,Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Zhejiang, 310009, China
| | - Yangwu Chen
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, 310009, China.,Department of Orthopedics, Research Institute of Zhejiang University, Zhejiang, 310027, China.,Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Zhejiang, 310009, China
| | - Jisheng Ran
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, 310009, China.,Department of Orthopedics, Research Institute of Zhejiang University, Zhejiang, 310027, China
| | - Xiao Chen
- Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Zhejiang, 310009, China.,China Orthopaedic Regenerative Medicine (CORMed), Hangzhou, China
| | - Zi Yin
- Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Zhejiang, 310009, China
| | - Shengjun Qian
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, 310009, China.,Department of Orthopedics, Research Institute of Zhejiang University, Zhejiang, 310027, China
| | | | | | - Weishan Chen
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, 310009, China.,Department of Orthopedics, Research Institute of Zhejiang University, Zhejiang, 310027, China
| | - Weiliang Shen
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, 310009, China.,Department of Orthopedics, Research Institute of Zhejiang University, Zhejiang, 310027, China.,Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Zhejiang, 310009, China.,Laboratory of Biomechanical Orthopedics, EPFL, Lausanne, Switzerland.,China Orthopaedic Regenerative Medicine (CORMed), Hangzhou, China
| | - Hong-Wei Ouyang
- Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Zhejiang, 310009, China.,China Orthopaedic Regenerative Medicine (CORMed), Hangzhou, China
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32
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Lu W, Xu J, Dong S, Xie G, Yang S, Huangfu X, Li X, Zhang Y, Shen P, Yan Z, Liu H, Deng Z, Zhao J. Anterior Cruciate Ligament Reconstruction in a Rabbit Model Using a Decellularized Allogenic Semitendinous Tendon Combined with Autologous Bone Marrow-Derived Mesenchymal Stem Cells. Stem Cells Transl Med 2019; 8:971-982. [PMID: 31077578 PMCID: PMC6708071 DOI: 10.1002/sctm.18-0132] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Accepted: 04/08/2019] [Indexed: 12/21/2022] Open
Abstract
As a regular adoptable material for anterior cruciate ligament (ACL) reconstruction, free tendon allograft exhibits unsatisfactory outcomes, such as retarded ligamentization and tendon–bone integration. The application of bone marrow‐derived mesenchymal stem cells (BMSCs), as well as a decellularized free tendon allograft developed by our group, was proven to be effective in improving ACL reconstruction results. This study aimed to investigate the efficacy and feasibility of decellularized allogenic semitendinous tendon (ST) combined with autologous BMSCs used as a substitute to free tendon allograft in a rabbit model. This study finally shows that the decellularized allogenic ST combined with autologous BMSCs could significantly improve ACL reconstruction results compared with allograft. stem cells translational medicine2019;8:971&982
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Affiliation(s)
- Wei Lu
- Department of Sports Medicine, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China
| | - Jian Xu
- Department of Sports Medicine, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China
| | - Shikui Dong
- Department of Arthroscopic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Guoming Xie
- Department of Arthroscopic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Shuanghui Yang
- Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
| | - Xiaoqiao Huangfu
- Department of Arthroscopic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Xiaoxi Li
- Department of Arthroscopic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Yang Zhang
- Department of Arthroscopic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Peng Shen
- Department of Arthroscopic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Zhaowen Yan
- Department of Pathology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Haifeng Liu
- Department of Sports Medicine, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China
| | - Zhenhan Deng
- Department of Sports Medicine, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China
| | - Jinzhong Zhao
- Department of Arthroscopic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
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33
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Hur CI, Ahn HW, Seon JK, Song EK, Kim GE. Mesenchymal Stem Cells Decrease Tunnel Widening of Anterior Cruciate Ligament Reconstruction in Rabbit Model. Int J Stem Cells 2019; 12:162-169. [PMID: 30595005 PMCID: PMC6457700 DOI: 10.15283/ijsc18022] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Revised: 03/23/2018] [Accepted: 11/08/2018] [Indexed: 01/04/2023] Open
Abstract
Background and Objectives The study investigated the effect of mesenchymal stem cells (MSCs) or fibrin glue on tunnel widening after anterior cruciate ligament (ACL) reconstruction compared with biologic free control without any biologic agents in the rabbit model. Methods and Results ACL reconstructions were performed in 18 New Zealand white rabbits. All animals were divided into 3 groups according to the following reconstruction conditions and euthanized 12 weeks postoperatively for radiologic and histologic analyses. Thirty-two knees (control group=10; fibrin group=11; MSCs group=11) were finally evaluated. On micro-CT scan, mean femoral tunnel widening on oblique-sagittal image was 0.7±0.4 mm in the control group, 0.22±0.1 mm in the fibrin group and 0.25±0.1 mm in the MSCs group (p=0.001). Fibrin group and MSCs group showed significant differences compared with control group (p=0.002, 0.002). Mean tibial tunnel widening on oblique-sagittal image was 0.76±0.5 mm, 0.27±0.1 mm and 0.29±0.2 mm in the control, fibrin and MSCs group. Fibrin and MSCs group showed significant differences compared with control group (p=0.017, 0.014). Hounsfield Units (HU) were not significantly different between 3 groups (p>0.05). Histological analysis revealed that the architecture of graft in the MSCs group featured hypercellularity and compact collagen deposit. Conclusion ACL reconstruction using MSCs seemed decrease tunnel widening in rabbit model. Further study with large animals is required to confirm efficacy on decreasing tunnel widening.
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Affiliation(s)
- Chang-Ich Hur
- Center for Joint Disease, Chonnam National University Hwasun Hospital, Hwasun, Korea
| | - Hyeon-Wook Ahn
- Center for Joint Disease, Chonnam National University Hwasun Hospital, Hwasun, Korea
| | - Jong-Keun Seon
- Center for Joint Disease, Chonnam National University Hwasun Hospital, Hwasun, Korea
| | - Eun-Kyoo Song
- Center for Joint Disease, Chonnam National University Hwasun Hospital, Hwasun, Korea
| | - Ga-Eon Kim
- Department of Pathology, Chonnam National University Medical School, Gwangju, Korea
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Affiliation(s)
- Ameer Elbuluk
- Department of Orthopaedic Surgery, NYU Langone Medical Center, Hospital for Joint Diseases, New York, NY
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Abstract
In the last few decades, several techniques have been used to optimize tendon, ligament, and musculoskeletal healing. The evidence in favor of these techniques is still not proven, and level I studies are lacking. We performed an analysis of the therapeutic strategies and tissue engineering projects recently published in this field. Here, we try to give an insight into the current status of cell therapies and the latest techniques of bioengineering applied to the field of orthopedic surgery. The future areas for research in the management of musculoskeletal injuries are outlined. There are emerging technologies developing into substantial clinical treatment options that need to be critically evaluated. Mechanical stimulation of the constructs reproduces a more propitious environment for effective healing.
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Germann M, Snedeker JG, Stalder M, Nuss KM, Meyer DC, Farshad M. Incorporating BMP-2 and skeletal muscle to a semitendinosus autograft in an oversized tunnel yields robust bone tunnel ossification in rabbits: Toward single-step revision of failed anterior cruciate ligament reconstruction. Knee 2018; 25:765-773. [PMID: 30057249 DOI: 10.1016/j.knee.2018.07.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Revised: 05/10/2018] [Accepted: 07/12/2018] [Indexed: 02/02/2023]
Abstract
BACKGROUND Bone tunnel widening after anterior cruciate ligament (ACL) reconstruction is a known complication that can lead to graft failure. Subsequent revision surgery typically involves a two-stage procedure. The aim of this study was to test a novel autologous tendon graft retaining muscle tissue combined with Human Recombinant Bone Morphogenetic Protein-2 (rh-BMP-2) leading to rapid ossification of the muscle tissue, simultaneously replenishing bone stock and producing a mechanically stable bone-tendon insertion. METHODS In 12 skeletally mature New Zealand rabbits, the ACL was resected and oversized bone tunnels were drilled to model tunnel widening. The ipsilateral semitendinosus muscle-tendon graft was harvested and folded twice. Muscle tissue was removed in the middle third but retained at both distal ends. One side was wrapped in a collagen sponge loaded with rh-BMP-2 while the other end was used as its own control. RESULTS All animals were euthanized after six weeks. Micro-computed tomography (micro-CT) was used to analyze bone formation in 12 animals, with additional biomechanical testing to failure and histology performed for six animals each. Micro-CT showed that bone densities were higher by a factor of 2.4 in treated graft ends compared with their controls. Biomechanical testing showed a mean overall failure load of 37.5 N. Histology showed that the trabecular bone surrounding the implant was significantly (P = 0.0087) thicker on the treated (85.5 μm) compared with the control side (68.2 μm). CONCLUSIONS We conclude that a semitendinosus graft retaining the muscle tissue stimulated by recombinant Bone Morphogenetic Protein-2 (BMP-2) allows robust osseointegration of the graft within an oversized bone tunnel in an animal model.
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Affiliation(s)
- Marco Germann
- Orthopaedic Department, Balgrist University Hospital, University of Zurich, Forchstrasse 340, CH-8008 Zurich, Switzerland.
| | - Jess G Snedeker
- Orthopaedic Department, Balgrist University Hospital, University of Zurich, Forchstrasse 340, CH-8008 Zurich, Switzerland
| | - Michael Stalder
- Orthopaedic Department, Balgrist University Hospital, University of Zurich, Forchstrasse 340, CH-8008 Zurich, Switzerland
| | - Katja M Nuss
- Musculoskeletal Research Unit (MSRU), Vetsuisse Faculty, University of Zürich, Winterthurerstrasse 260, 8057 Zürich, Switzerland
| | - Dominik C Meyer
- Orthopaedic Department, Balgrist University Hospital, University of Zurich, Forchstrasse 340, CH-8008 Zurich, Switzerland
| | - Mazda Farshad
- Orthopaedic Department, Balgrist University Hospital, University of Zurich, Forchstrasse 340, CH-8008 Zurich, Switzerland
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Mahapatra P, Horriat S, Anand BS. Anterior cruciate ligament repair - past, present and future. J Exp Orthop 2018; 5:20. [PMID: 29904897 PMCID: PMC6002325 DOI: 10.1186/s40634-018-0136-6] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 05/31/2018] [Indexed: 12/14/2022] Open
Abstract
Background This article provides a detailed narrative review on the history and current concepts surrounding ligamentous repair techniques in athletic patients. In particular, we will focus on the anterior cruciate ligament (ACL) as a case study in ligament injury and ligamentous repair techniques. PubMed (MEDLINE), EMBASE and Cochrane Library databases for papers relating to primary anterior cruciate ligament reconstruction were searched by all participating authors. All relevant historical papers were included for analysis. Additional searches of the same databases were made for papers relating to biological enhancement of ligament healing. Current standard The poor capacity of the ACL to heal is one of the main reasons why the current gold standard surgical treatment for an ACL injury in an athletic patient is ACL reconstruction with autograft from either the hamstrings or patella tendon. It is hypothesised that by preserving and repairing native tissues and negating the need for autograft that primary ACL repair may represent a key step change in the treatment of ACL injuries. History of primary ACL repair The history of primary ACL repair will be discussed and the circumstances that led to the near-abandonment of primary ACL repair techniques will be reviewed. New primary repair techniques There has been a recent resurgence in interest with regards to primary ACL repair. Improvements in imaging now allow for identification of tear location, with femoral-sided injuries, being more suitable for repair. We will discuss in details strategies for improving the mechanical and biological environment in order to allow primary healing to occur. In particular, we will explain mechanical supplementation such as Internal Brace Ligament Augmentation and Dynamic Intraligamentary Stabilisation techniques. These are novel techniques that aim to protect the primary repair by providing a stabilising construct that connects the femur and the tibia, thus bridging the repair. Bio enhanced repair In addition, biological supplementation is being investigated as an adjunct and we will review the current literature with regards to bio-enhancement in the form platelet rich plasma, bio-scaffolds and stem cells. On the basis of current evidence, there appears to be a role for bio-enhancement, however, this is not yet translated into clinical practice. Conclusions Several promising avenues of further research now exist in the form of mechanical and biological augmentation techniques. Further work is clearly needed but there is renewed interest and focus for primary ACL repair that may yet prove the new frontier in ligament repair.
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Affiliation(s)
- Piyush Mahapatra
- Trauma and Orthopaedic Department, Croydon University Hospital, 530 London Road, London, CR7 7YE, UK.
| | - Saman Horriat
- Trauma and Orthopaedic Department, Croydon University Hospital, 530 London Road, London, CR7 7YE, UK
| | - Bobby S Anand
- Trauma and Orthopaedic Department, Croydon University Hospital, 530 London Road, London, CR7 7YE, UK
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Sato Y, Akagi R, Akatsu Y, Matsuura Y, Takahashi S, Yamaguchi S, Enomoto T, Nakagawa R, Hoshi H, Sasaki T, Kimura S, Ogawa Y, Sadamasu A, Ohtori S, Sasho T. The effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament reconstruction: An animal study. Bone Joint Res 2018; 7:327-335. [PMID: 29922452 PMCID: PMC5987692 DOI: 10.1302/2046-3758.75.bjr-2017-0238.r2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Objectives To compare the effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament (ACL) reconstruction animal model. Methods Anterior cruciate ligament reconstruction using the plantaris tendon as graft material was performed on both knees of 24 rabbits (48 knees) to mimic ACL reconstruction by two different suspensory fixation devices for graft fixation. For the adjustable fixation device model (Socket group; group S), a 5 mm deep socket was created in the lateral femoral condyle (LFC) of the right knee. For the fixed-loop model (Tunnel group; group T), a femoral tunnel penetrating the LFC was created in the left knee. Animals were sacrificed at four and eight weeks after surgery for histological evaluation and biomechanical testing. Results Histologically, both groups showed a mixture of direct and indirect healing patterns at four weeks, whereas only indirect healing patterns were observed in both groups at eight weeks. No significant histological differences were seen between the two groups at four and eight weeks in the roof zone (four weeks, S: mean 4.8 sd 1.7, T: mean 4.5 sd 0.5, p = 0.14; eight weeks, S: mean 5.8 sd 0.8, T: mean 4.8 sd 1.8, p = 0.88, Mann-Whitney U test) or side zone (four weeks, S: mean 5.0 sd 1.2, T: mean 4.8 sd 0.4, p = 0.43; eight weeks, S: mean 5.3 sd 0.8,T: mean 5.5 sd 0.8, p = 0.61, Mann-Whitney U test) . Similarly, no significant difference was seen in the maximum failure load between group S and group T at four (15.6 sd 9.0N and 13.1 sd 5.6N) or eight weeks (12.6 sd 3.6N and 17.1 sd 6.4N, respectively). Conclusion Regardless of bone tunnel configuration, tendon-bone healing after ACL reconstruction primarily occurred through indirect healing. No significant histological or mechanical differences were observed between adjustable and fixed-loop femoral cortical suspension methods. Cite this article: Y. Sato, R. Akagi, Y. Akatsu, Y. Matsuura, S. Takahashi, S. Yamaguchi, T. Enomoto, R. Nakagawa, H. Hoshi, T. Sasaki, S. Kimura, Y. Ogawa, A. Sadamasu, S. Ohtori, T. Sasho. The effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament reconstruction: An animal study. Bone Joint Res 2018;7:327–335. DOI: 10.1302/2046-3758.75.BJR-2017-0238.R2.
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Affiliation(s)
- Y Sato
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - R Akagi
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Y Akatsu
- Department of Orthopedic Surgery, Toho University Sakura Medical Center, Chiba, Japan
| | - Y Matsuura
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - S Takahashi
- Clinical Research Center, Chiba University Hospital, Chiba, Japan
| | - S Yamaguchi
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - T Enomoto
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - R Nakagawa
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - H Hoshi
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - T Sasaki
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - S Kimura
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Y Ogawa
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - A Sadamasu
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - S Ohtori
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - T Sasho
- Department of Orthopaedic Surgery, Graduate School of Medicine and The Center for Preventive Medicine, Chiba University, Chiba, Japan
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Tan H, Wang D, Lebaschi AH, Hutchinson ID, Ying L, Deng XH, Rodeo SA, Warren RF. Comparison of Bone Tunnel and Cortical Surface Tendon-to-Bone Healing in a Rabbit Model of Biceps Tenodesis. J Bone Joint Surg Am 2018; 100:479-486. [PMID: 29557864 PMCID: PMC6221377 DOI: 10.2106/jbjs.17.00797] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Many orthopaedic surgical procedures involve reattachment of a single tendon to bone. Whether tendon-to-bone healing is better facilitated by tendon fixation within a bone tunnel or on a cortical surface is unknown. The purpose of this study was to evaluate tendon-healing within a bone tunnel compared with that on the cortical surface in a rabbit model of biceps tenodesis. METHODS Thirty-two rabbits (24 weeks of age) underwent unilateral proximal biceps tenodesis with tendon fixation within a bone tunnel (BT group) or on the cortical surface (SA [surface attachment] group). Postoperatively, rabbits were allowed free-cage activity without immobilization. All rabbits were killed 8 weeks after surgery. Healing was assessed by biomechanical testing, microcomputed tomography (micro-CT), and histomorphometric analysis. RESULTS Biomechanical testing demonstrated no significant difference between the groups in mean failure loads (BT: 56.8 ± 28.8 N, SA: 55.8 ± 14.9 N; p = 0.92) or stiffness (BT: 26.3 ± 16.6 N/mm, SA: 32.3 ± 9.6 N/mm; p = 0.34). Micro-CT analysis demonstrated no significant difference between the groups in mean volume of newly formed bone (BT: 69.3 ± 13.9 mm, SA: 65.5 ± 21.9 mm; p = 0.70) or tissue mineral density of newly formed bone (BT: 721.4 ± 10.9 mg/cm, SA: 698.6 ± 26.2 mg/cm; p = 0.07). On average, newly formed bone within the tunnel represented only 5% of the total new bone formed in the BT specimens. Histological analysis demonstrated tendon-bone interdigitation and early fibrocartilaginous zone formation on the outer cortical surface in both groups. In contrast, minimal tendon-bone bonding was observed within the tunnel in the BT specimens. CONCLUSIONS Tendon fixation in a bone tunnel and on the cortical surface resulted in similar healing profiles. For tendons placed within a bone tunnel, intratunnel healing was minimal compared with the healing outside the tunnel on the cortical surface. CLINICAL RELEVANCE The creation of large bone tunnels, which can lead to stress risers and increase the risk of fracture, may not be necessary for biceps tenodesis procedures.
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Affiliation(s)
- Hongbo Tan
- Laboratory for Joint Tissue Repair and Regeneration, Orthopaedic Soft Tissue Research Program (H.T., D.W., A.H.L., I.D.H., L.Y., X.-H.D., S.A.R., and R.F.W.) and Sports Medicine and Shoulder Service (D.W., S.A.R., and R.F.W.), Hospital for Special Surgery, New York, NY
| | - Dean Wang
- Laboratory for Joint Tissue Repair and Regeneration, Orthopaedic Soft Tissue Research Program (H.T., D.W., A.H.L., I.D.H., L.Y., X.-H.D., S.A.R., and R.F.W.) and Sports Medicine and Shoulder Service (D.W., S.A.R., and R.F.W.), Hospital for Special Surgery, New York, NY
| | - Amir H. Lebaschi
- Laboratory for Joint Tissue Repair and Regeneration, Orthopaedic Soft Tissue Research Program (H.T., D.W., A.H.L., I.D.H., L.Y., X.-H.D., S.A.R., and R.F.W.) and Sports Medicine and Shoulder Service (D.W., S.A.R., and R.F.W.), Hospital for Special Surgery, New York, NY
| | - Ian D. Hutchinson
- Laboratory for Joint Tissue Repair and Regeneration, Orthopaedic Soft Tissue Research Program (H.T., D.W., A.H.L., I.D.H., L.Y., X.-H.D., S.A.R., and R.F.W.) and Sports Medicine and Shoulder Service (D.W., S.A.R., and R.F.W.), Hospital for Special Surgery, New York, NY
| | - Liang Ying
- Laboratory for Joint Tissue Repair and Regeneration, Orthopaedic Soft Tissue Research Program (H.T., D.W., A.H.L., I.D.H., L.Y., X.-H.D., S.A.R., and R.F.W.) and Sports Medicine and Shoulder Service (D.W., S.A.R., and R.F.W.), Hospital for Special Surgery, New York, NY
| | - Xiang-Hua Deng
- Laboratory for Joint Tissue Repair and Regeneration, Orthopaedic Soft Tissue Research Program (H.T., D.W., A.H.L., I.D.H., L.Y., X.-H.D., S.A.R., and R.F.W.) and Sports Medicine and Shoulder Service (D.W., S.A.R., and R.F.W.), Hospital for Special Surgery, New York, NY
| | - Scott A. Rodeo
- Laboratory for Joint Tissue Repair and Regeneration, Orthopaedic Soft Tissue Research Program (H.T., D.W., A.H.L., I.D.H., L.Y., X.-H.D., S.A.R., and R.F.W.) and Sports Medicine and Shoulder Service (D.W., S.A.R., and R.F.W.), Hospital for Special Surgery, New York, NY
| | - Russell F. Warren
- Laboratory for Joint Tissue Repair and Regeneration, Orthopaedic Soft Tissue Research Program (H.T., D.W., A.H.L., I.D.H., L.Y., X.-H.D., S.A.R., and R.F.W.) and Sports Medicine and Shoulder Service (D.W., S.A.R., and R.F.W.), Hospital for Special Surgery, New York, NY
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Hexter AT, Thangarajah T, Blunn G, Haddad FS. Biological augmentation of graft healing in anterior cruciate ligament reconstruction: a systematic review. Bone Joint J 2018; 100-B:271-284. [PMID: 29589505 DOI: 10.1302/0301-620x.100b3.bjj-2017-0733.r2] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Aims The success of anterior cruciate ligament reconstruction (ACLR) depends on osseointegration at the graft-tunnel interface and intra-articular ligamentization. Our aim was to conduct a systematic review of clinical and preclinical studies that evaluated biological augmentation of graft healing in ACLR. Materials and Methods In all, 1879 studies were identified across three databases. Following assessment against strict criteria, 112 studies were included (20 clinical studies; 92 animal studies). Results Seven categories of biological interventions were identified: growth factors, biomaterials, stem cells, gene therapy, autologous tissue, biophysical/environmental, and pharmaceuticals. The methodological quality of animal studies was moderate in 97%, but only 10% used clinically relevant outcome measures. The most interventions in clinical trials target the graft-tunnel interface and are applied intraoperatively. Platelet-rich plasma is the most studied intervention, but the clinical outcomes are mixed, and the methodological quality of studies was suboptimal. Other biological therapies investigated in clinical trials include: remnant-augmented ACLR; bone substitutes; calcium phosphate-hybridized grafts; extracorporeal shockwave therapy; and adult autologus non-cultivated stem cells. Conclusion There is extensive preclinical research supporting the use of biological therapies to augment ACLR. Further clinical studies that meet the minimum standards of reporting are required to determine whether emerging biological strategies will provide tangible benefits in patients undergoing ACLR. Cite this article: Bone Joint J 2018;100-B:271-84.
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Affiliation(s)
- A T Hexter
- Institute of Orthopaedics and Musculoskeletal Science, Division of Surgery and Interventional Science, University College London, and Royal National Orthopaedic Hospital Brockley Hill, Stanmore, Middlesex HA7 4LP, UK
| | - T Thangarajah
- Institute of Orthopaedics and Musculoskeletal Science, Division of Surgery and Interventional Science, University College London, and Royal National Orthopaedic Hospital Brockley Hill, Stanmore, Middlesex HA7 4LP, UK
| | - G Blunn
- Institute of Orthopaedics and Musculoskeletal Science, Division of Surgery and Interventional Science, University College London, and Royal National Orthopaedic Hospital Brockley Hill, Stanmore, Middlesex HA7 4LP, UK
| | - F S Haddad
- University College London Hospitals, 235 Euston Road, London, NW1 2BU, UK and NIHR University College London Hospitals Biomedical Research Centre, UK
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Park SH, Choi YJ, Moon SW, Lee BH, Shim JH, Cho DW, Wang JH. Three-Dimensional Bio-Printed Scaffold Sleeves With Mesenchymal Stem Cells for Enhancement of Tendon-to-Bone Healing in Anterior Cruciate Ligament Reconstruction Using Soft-Tissue Tendon Graft. Arthroscopy 2018; 34:166-179. [PMID: 28688825 DOI: 10.1016/j.arthro.2017.04.016] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Revised: 04/04/2017] [Accepted: 04/12/2017] [Indexed: 02/02/2023]
Abstract
PURPOSE To investigate the efficacy of the insertion of 3-dimensional (3D) bio-printed scaffold sleeves seeded with mesenchymal stem cells (MSCs) to enhance osteointegration between the tendon and tunnel bone in anterior cruciate ligament (ACL) reconstruction in a rabbit model. METHODS Scaffold sleeves were fabricated by 3D bio-printing. Before ACL reconstruction, MSCs were seeded into the scaffold sleeves. ACL reconstruction with hamstring tendon was performed on both legs of 15 adult rabbits (aged 12 weeks). We implanted 15 bone tunnels with scaffold sleeves with MSCs and implanted another 15 bone tunnels with scaffold sleeves without MSCs before passing the graft. The specimens were harvested at 4, 8, and 12 weeks. H&E staining, immunohistochemical staining of type II collagen, and micro-computed tomography of the tunnel cross-sectional area were evaluated. Histologic assessment was conducted with a histologic scoring system. RESULTS In the histologic assessment, a smooth bone-to-tendon transition through broad fibrocartilage formation was identified in the treatment group, and the interface zone showed abundant type II collagen production on immunohistochemical staining. Bone-tendon healing histologic scores were significantly higher in the treatment group than in the control group at all time points. Micro-computed tomography at 12 weeks showed smaller tibial (control, 9.4 ± 0.9 mm2; treatment, 5.8 ± 2.9 mm2; P = .044) and femoral (control, 9.6 ± 2.9 mm2; treatment, 6.0 ± 1.0 mm2; P = .03) bone-tunnel areas in the treated group than in the control group. CONCLUSIONS The 3D bio-printed scaffold sleeve with MSCs exhibited excellent results in osteointegration enhancement between the tendon and tunnel bone in ACL reconstruction in a rabbit model. CLINICAL RELEVANCE If secure biological healing between the tendon graft and tunnel bone can be induced in the early postoperative period, earlier, more successful rehabilitation may be facilitated. Three-dimensional bio-printed scaffold sleeves with MSCs have the potential to accelerate bone-tendon healing in ACL reconstruction.
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Affiliation(s)
- Sin Hyung Park
- Department of Orthopaedic Surgery, Soonchunhyang University School of Medicine, Bucheon Hospital, Bucheon, Republic of Korea
| | - Yeong-Jin Choi
- Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
| | - Sang Won Moon
- Department of Orthopaedic Surgery, Inje University School of Medicine, Haeundae Paik Hospital, Busan, Republic of Korea
| | - Byung Hoon Lee
- Department of Orthopaedic Surgery, Hallym University School of Medicine, Kangdong Sacred Heart Hospital, Seoul, Republic of Korea
| | - Jin-Hyung Shim
- Department of Mechanical Engineering, Korea Polytechnic University, Siheung, Republic of Korea
| | - Dong-Woo Cho
- Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
| | - Joon Ho Wang
- Department of Orthopaedic Surgery, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea.
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Guo R, Gao L, Xu B. Current Evidence of Adult Stem Cells to Enhance Anterior Cruciate Ligament Treatment: A Systematic Review of Animal Trials. Arthroscopy 2018; 34:331-340.e2. [PMID: 28967542 DOI: 10.1016/j.arthro.2017.07.010] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Revised: 07/10/2017] [Accepted: 07/13/2017] [Indexed: 02/02/2023]
Abstract
PURPOSE To systematically review the available preclinical evidence of adult stem cells as a biological augmentation in the treatment of animal anterior cruciate ligament (ACL) injury. STUDY DESIGN Systematic review. METHODS PubMed (MEDLINE) and Embase were searched for the eligible studies. The inclusion criteria were controlled animal trials of adult stem cells used in ACL treatment (repair or reconstruction). Studies of natural ACL healing without intervention, in vitro studies, ex vivo studies, and studies without controls were excluded. Evidence level, methodologic quality, and risk of bias of each included study were identified using previously established tools. RESULTS Thirteen animal studies were included. Six of 7 studies using bone marrow-derived mesenchymal stem (stromal) cells (BMSCs) reported a positive enhancement in histology, biomechanics, and biochemistry within 12 weeks postoperatively. Four studies using ACL-derived vascular stem cells showed a promoting effect in histology, biomechanics, and imaging within 8 weeks postoperatively. Two studies focusing on animal tendon-derived stem cells (TDSCs) and human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) reported promotable effects for the early healing in a small animal ACL model. CONCLUSIONS BMSCs, ACL-derived vascular stem cells, TDSCs, and hUCB-MSCs were shown to enhance the healing of ACL injury during the early phase in small animal models. CLINICAL RELEVANCE Results of clinical trials using adult stem cells in ACL treatment are conflicting, and a systematic review of the current best preclinical evidence is crucial to guide further application.
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Affiliation(s)
- Ruipeng Guo
- Department of Sports Medicine and Arthroscopic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Laboratory for Biomechanics and Biomaterials, Hannover Medical School, Hannover, Germany
| | - Liang Gao
- Center for Experimental Orthopaedics, Saarland University Medical Center, Homburg/Saar, Germany
| | - Bin Xu
- Department of Sports Medicine and Arthroscopic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
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Wang J, Xu J, Song B, Chow DH, Shu-Hang Yung P, Qin L. Magnesium (Mg) based interference screws developed for promoting tendon graft incorporation in bone tunnel in rabbits. Acta Biomater 2017; 63:393-410. [PMID: 28919510 DOI: 10.1016/j.actbio.2017.09.018] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Revised: 08/27/2017] [Accepted: 09/13/2017] [Indexed: 11/19/2022]
Abstract
How to enhance tendon graft incorporation into bone tunnels for achieving satisfactory healing outcomes in patients with anterior cruciate ligament reconstruction (ACLR) is one of the most challenging clinical problems in orthopaedic sports medicine. Several studies have recently reported the beneficial effects of Mg implants in bone fracture healing, indicating the use potential of Mg devices in promoting the tendon graft osteointegration. Here, we developed an innovative Mg-based interference screws for fixation of the tendon graft in rabbits underwent ACLR and investigated the biological role of Mg-based implants in the graft healing. The titanium (Ti) interference screw was used as the control. We demonstrated that Mg interference screw significantly accelerated the incorporation of the tendon graft into bone tunnels via multiscale analytical methods including scanning electronic microscopy/energy dispersive spectrometer (SEM/EDS), micro-hardness, micro-Fourier transform infrared spectroscopy (μFTIR), and histology. Our in vivo study showed that Mg implants enhanced the recruitment of bone marrow stromal stem cells (BMSCs) towards peri-implant bone tissue, which may be ascribed to the upregulation of local TGF-β1 and PDGF-BB. Besides, the in vitro study revealed that higher Mg ions was beneficial to the improvement of capability in cell adhesion and osteogenic differentiation of BMSCs. Thus, the enhancement in cell migration, cell adhesion and osteogenic differentiation of BMSCs may contribute to an improved tendon graft osteointegration in the Mg group. Our findings in this work may further facilitate clinical applications of Mg-based interference screws for enhancing tendon graft-bone junction healing in patients indicated for ACLR. STATEMENT OF SIGNIFICANCE How to promote tendon-bone junction healing is one of the major challenging issues for satisfactory clinical outcomes in patients after ACL reconstruction. The improvement of bony ingrowth into the tendon graft-bone interface can enhance the tendon graft osteointegration. In this study, we applied Mg based interference screws to fix the tendon graft in rabbits and found the use of Mg screws could accelerate and significantly increase mineralized matrix formation at the tendon-bone interface in animals when compared to those with Ti screws. We elucidated the mechanism behind the favorable effects of Mg screws on the graft healing in both in vitro and in vivo studies from multiscale technologies. The optimized interface structure and function in Mg group may be ascribed to the improved cell migration capability, enhanced cell adhesion strength and promoted osteogenic differentiation ability of BMSCs under the stimuli of Mg ions degraded from implanted Mg screws. Our findings may help us broaden our thinking in the application potential of Mg interference screws in future clinical trials.
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Affiliation(s)
- Jiali Wang
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Jiankun Xu
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Bin Song
- Department of Sports Medicine, Sun Yat Sen Memorial Hospital, Sun Yat Sen University, Guangzhou 510120, PR China
| | - Dick Hokiu Chow
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Patrick Shu-Hang Yung
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Ling Qin
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region; Center for Translational Medicine Research and Development, Institute of Biomedical and Health Engineering, Chinese Academy of Sciences, Shenzhen 518055, PR China.
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Zein AMN, Ali M, Zenhom Mahmoud A, Omran K. Autogenous Hamstring-Bone Graft Preparation for Anterior Cruciate Ligament Reconstruction. Arthrosc Tech 2017; 6:e1253-e1262. [PMID: 29354425 PMCID: PMC5622011 DOI: 10.1016/j.eats.2017.04.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Accepted: 04/24/2017] [Indexed: 02/03/2023] Open
Abstract
Despite the popularity of anterior cruciate ligament (ACL) reconstruction procedures, the ideal graft for reconstruction remains a matter of controversy. The ideal graft for ACL reconstruction should have histologic and biomechanical characteristics similar to those of the native ACL; should be quickly and fully incorporated within the bony tunnels; should maintain its viscoelastic properties for a long time; should have minimal donor-site morbidity; should be of sufficient length and diameter; should have minimal adverse effects on the extensor mechanism; should have no risk of rejection or disease transmission; and should be cost-effective and readily available. Synthetic grafts are not widely accepted because of their dangerous complications. The main sources of grafts for ACL reconstruction are allografts and autografts. Each type of graft has its own relative advantages and disadvantages. Allografts are not available in every country, besides being expensive, and there are many concerns regarding disease transmission. Autografts, particularly bone-patellar tendon-bone (BPTB), and hamstring tendon grafts have been the standard for ACL reconstruction. The main advantage of autogenous BPTB grafts is the direct bone-to-bone healing in the tunnel, whereas the main disadvantages of such grafts are related to donor-site morbidity, anterior knee pain, and extensor mechanism dysfunction. The popularity of autogenous hamstring tendon grafts for ACL reconstruction is increasing, but there are still concerns regarding the slow soft tissue-to-bone healing, with delayed healing and incorporation of the graft. We describe a technique for ACL reconstruction with autogenous hamstring-bone graft, aiming to produce a type of graft that combines the main advantages of BPTB and hamstring grafts, with avoidance of the main disadvantages of these 2 most commonly used graft types in ACL reconstruction.
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Affiliation(s)
- Assem Mohamed Noureldin Zein
- Address correspondence to Assem Mohamed Noureldin Zein, M.D., Department of Orthopedic Surgery, Minia University, 429 Adnan Street, Cleopatra Ceramic Building, Fifth Floor, Ard Sultan, Minia, Egypt 61111.Department of Orthopedic SurgeryMinia University429 Adnan StreetCleopatra Ceramic Building, Fifth FloorArd SultanMinia61111Egypt
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Waryasz GR, Marcaccio S, Gil JA, Owens BD, Fadale PD. Anterior Cruciate Ligament Repair and Biologic Innovations. JBJS Rev 2017; 5:e2. [DOI: 10.2106/jbjs.rvw.16.00050] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Tatu RF, Hurmuz M, Miu CA. ACL Primary Repair with Bone Marrow Stimulation and Growth Factors. A Review of Literature. JOURNAL OF INTERDISCIPLINARY MEDICINE 2017. [DOI: 10.1515/jim-2017-0036] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Abstract
Anterior cruciate ligament (ACL) ruptures represent a common pathology, especially in young and active patients. Spontaneous repair, although reported in some studies, is altered by local conditions, thus emerges the need to perform reconstruction of the ACL. It is reported that 3,430 primary reconstructions and around 267 revisions are performed yearly in Sweden. Some reconstructions result in biological failure, which represents the inability of the graft to incorporate and remodel in order to perform its role as a knee stabilizer. Orthobiology, a new concept that includes growths factors, stem cells, and different scaffolds, could represent a solution to a better outcome of this procedure. This manuscript is a review of different therapeutic strategies used for enabling ACL regeneration, including in vitro ACL-bio-enhanced repair that is currently being developed. Substantial progress is to be expected in the area of ACL surgery.
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Affiliation(s)
- Romulus Fabian Tatu
- XVth Department , “Victor Babeș” University of Medicine and Pharmacy , Timișoara , Romania
| | - Mihai Hurmuz
- XVth Department , “Victor Babeș” University of Medicine and Pharmacy , Timișoara , Romania
| | - Cătălin Adrian Miu
- XVth Department , “Victor Babeș” University of Medicine and Pharmacy , Timișoara , Romania
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Zhang P, Zhi Y, Fang H, Wu Z, Chen T, Jiang J, Chen S. Effects of polyvinylpyrrolidone-iodine on tendon-bone healing in a rabbit extra-articular model. Exp Ther Med 2017; 13:2751-2756. [PMID: 28587336 PMCID: PMC5450688 DOI: 10.3892/etm.2017.4359] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Accepted: 02/17/2017] [Indexed: 12/16/2022] Open
Abstract
Polyvinylpyrrolidone-iodine (PVP-I) is a broad-spectrum antimicrobial agent, but its effects on tendon-bone healing are unclear. The purpose of this study was to investigate the effects of PVP-I on bone marrow mesenchymal stem cells (BMSCs) in vitro and on tendon-bone healing in vivo. In this study, following investigation of the concentration-dependent effects of PVP-I on the viability and osteogenic differentiation of BMSCs, the appropriate concentration of PVP-I was selected for animal experiments. New Zealand white rabbits received autologous tendon transplantation with and without PVP-I treatment of the graft tendon. Subsequently, histological examination, biomechanical testing and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses were conducted. At 6 weeks post-surgery, connective tissue and osteogenesis was observed at the tendon-bone interface in the PVP-I group. At 12 weeks post-surgery, the interface width in the PVP-I group was much narrower compared with that of the control group. Furthermore, the biomechanical properties of the PVP-I group were significantly stronger than those in the control group (P<0.05). RT-qPCR examination revealed that the mRNA levels of bone morphogenetic protein-2 and osteopontin in the PVP-I group were higher than those in the control group at 6 weeks (P<0.05). In conclusion, these results indicated that PVP-I promoted tendon-bone healing via osteogenesis.
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Affiliation(s)
- Peng Zhang
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Yunlong Zhi
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Hongwei Fang
- Department of Anesthesiology, Bengbu Medical College, Bengbu, Anhui 233004, P.R. China
| | - Ziying Wu
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Tianwu Chen
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Jia Jiang
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Shiyi Chen
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
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Donnelly PE, Chen T, Finch A, Brial C, Maher SA, Torzilli PA. Photocrosslinked tyramine-substituted hyaluronate hydrogels with tunable mechanical properties improve immediate tissue-hydrogel interfacial strength in articular cartilage. JOURNAL OF BIOMATERIALS SCIENCE. POLYMER EDITION 2017; 28:582-600. [PMID: 28134036 PMCID: PMC5462458 DOI: 10.1080/09205063.2017.1289035] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Accepted: 01/27/2017] [Indexed: 10/20/2022]
Abstract
Articular cartilage lacks the ability to self-repair and a permanent solution for cartilage repair remains elusive. Hydrogel implantation is a promising technique for cartilage repair; however for the technique to be successful hydrogels must interface with the surrounding tissue. The objective of this study was to investigate the tunability of mechanical properties in a hydrogel system using a phenol-substituted polymer, tyramine-substituted hyaluronate (TA-HA), and to determine if the hydrogels could form an interface with cartilage. We hypothesized that tyramine moieties on hyaluronate could crosslink to aromatic amino acids in the cartilage extracellular matrix. Ultraviolet (UV) light and a riboflavin photosensitizer were used to create a hydrogel by tyramine self-crosslinking. The gel mechanical properties were tuned by varying riboflavin concentration, TA-HA concentration, and UV exposure time. Hydrogels formed with a minimum of 2.5 min of UV exposure. The compressive modulus varied from 5 to 16 kPa. Fluorescence spectroscopy analysis found differences in dityramine content. Cyanine-3 labelled tyramide reactivity at the surface of cartilage was dependent on the presence of riboflavin and UV exposure time. Hydrogels fabricated within articular cartilage defects had increasing peak interfacial shear stress at the cartilage-hydrogel interface with increasing UV exposure time, reaching a maximum shear stress 3.5× greater than a press-fit control. Our results found that phenol-substituted polymer/riboflavin systems can be used to fabricate hydrogels with tunable mechanical properties and can interface with the surface tissue, such as articular cartilage.
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Affiliation(s)
- Patrick E. Donnelly
- Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, NY 10021, USA
- Department of Biomechanics, Hospital for Special Surgery, New York, NY 10021, USA
| | - Tony Chen
- Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, NY 10021, USA
- Department of Biomechanics, Hospital for Special Surgery, New York, NY 10021, USA
| | - Anthony Finch
- Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, NY 10021, USA
| | - Caroline Brial
- Department of Biomechanics, Hospital for Special Surgery, New York, NY 10021, USA
| | - Suzanne A. Maher
- Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, NY 10021, USA
- Department of Biomechanics, Hospital for Special Surgery, New York, NY 10021, USA
| | - Peter A. Torzilli
- Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, NY 10021, USA
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Song F, Jiang D, Wang T, Wang Y, Chen F, Xu G, Kang Y, Zhang Y. Mechanical Loading Improves Tendon-Bone Healing in a Rabbit Anterior Cruciate Ligament Reconstruction Model by Promoting Proliferation and Matrix Formation of Mesenchymal Stem Cells and Tendon Cells. Cell Physiol Biochem 2017; 41:875-889. [DOI: 10.1159/000460005] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2016] [Accepted: 12/21/2016] [Indexed: 12/17/2022] Open
Abstract
Background/Aims: This study investigated the effect of mechanical stress on tendon-bone healing in a rabbit anterior cruciate ligament (ACL) reconstruction model as well as cell proliferation and matrix formation in co-culture of bone-marrow mesenchymal stem cells (BMSCs) and tendon cells (TCs). Methods: The effect of continuous passive motion (CPM) therapy on tendon-bone healing in a rabbit ACL reconstruction model was evaluated by histological analysis, biomechanical testing and gene expressions at the tendon-bone interface. Furthermore, the effect of mechanical stretch on cell proliferation and matrix synthesis in BMSC/TC co-culture was also examined. Results: Postoperative CPM therapy significantly enhanced tendon-bone healing, as evidenced by increased amount of fibrocartilage, elevated ultimate load to failure levels, and up-regulated gene expressions of Collagen I, alkaline phosphatase, osteopontin, Tenascin C and tenomodulin at the tendon-bone junction. In addition, BMSC/TC co-culture treated with mechanical stretch showed a higher rate of cell proliferation and enhanced expressions of Collagen I, Collagen III, alkaline phosphatase, osteopontin, Tenascin C and tenomodulin than that of controls. Conclusion: These results demonstrated that proliferation and differentiation of local precursor cells could be enhanced by mechanical stimulation, which results in enhanced regenerative potential of BMSCs and TCs in tendon-bone healing.
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Biodegradable Magnesium Screws Accelerate Fibrous Tissue Mineralization at the Tendon-Bone Insertion in Anterior Cruciate Ligament Reconstruction Model of Rabbit. Sci Rep 2017; 7:40369. [PMID: 28071744 PMCID: PMC5223185 DOI: 10.1038/srep40369] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Accepted: 12/06/2016] [Indexed: 01/15/2023] Open
Abstract
The incorporation of tendon graft into bone tunnel is one of the most challenging clinical issues in anterior cruciate ligament (ACL) reconstruction. As a biodegradable metal, Mg has appropriate mechanical strength and osteoinductive effects, thus may be a promising alternative to commercialized products used for graft fixation. Therefore, it was hypothesized that Mg based interference screws would promote tendon graft-bone junction healing when compared to Ti screws. Herein, we compared the effects of Mg and Ti screws on tendon graft healing in rabbits with ACL reconstruction via histological, HR-pQCT and mechanical analysis. The histological results indicated that Mg screws significantly improved the graft healing quality via promoting mineralization at the tendon graft enthesis. Besides, Mg screws significantly promoted bone formation in the peri-screw region at the early healing stage. Importantly, Mg screws exhibited excellent corrosion resistance and the degradation of Mg screws did not induce bone tunnel widening. In tensile testing, there were no significant differences in the load to failure, stress, stiffness and absorption energy between Mg and Ti groups due to the failure mode at the midsubstance. Our findings demonstrate that Mg screws can promote tendon graft healing after ACL reconstruction, implying a potential alternative to Ti screws for clinical applications.
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