Liu, Qian

Background: Healing of the tendon-bone interface (TBI) after rotator cuff injury is limited, often leading to scar-mediated repair. Decellularized tendon fibrocartilage–bone composite (dTFBC) and bone marrow mesenchymal stem cell sheets (BMSCS) improve repair in preclinical models, but full scaffold encapsulation with mechanical preconditioning remains unexplored. Purpose: To evaluate TBI regeneration using mechanically preconditioned, BMSCS-encapsulated dTFBC scaffolds in a rabbit model. Study Design: Controlled laboratory study. Methods: A total of 48 male New Zealand White rabbits were randomized into 4 groups (n = 12 each): (1) standard repair (control); (2) repair with dTFBC; (3) repair with dTFBC-BMSCS; and (4) repair with mechanically preconditioned dTFBC-BMSCS (mdTFBC-BMSCS). Healing at 12 weeks was assessed via gross observation, histomorphological and immunohistochemical analyses, and biomechanical testing. Results: The mdTFBC-BMSCS group demonstrated a higher ultimate failure load (mean, 203.9 ± 65.6 N) than both the control (118 ± 37.4 N; P = .003) and dTFBC groups (127 ± 44.1 N; P = .008), with no significant difference between the 2 BMSCS-treated groups. Histological analysis revealed enhanced fibrocartilage formation, improved collagen fiber organization, and reduced inflammation infiltration at the TBI in the mdTFBC-BMSCS group. Immunohistochemical analysis showed greater collagen type 2 alpha 1 chain-, interleukin 10-, and arginase 1-positive areas in the mdTFBC-BMSCS group than in the control and dTFBC groups. Conclusion: Mechanically preconditioned, fully BMSCS-encapsulated dTFBC scaffolds promoted TBI regeneration, with enhanced cellular integration, fibrocartilage formation, and favorable biomechanical performance. Clinical Relevance: This biomimetic scaffold strategy may enhance biological healing and reduce the risk of retear after rotator cuff repair.

The objective of this study was to examine the effect of pulling angle on time-zero mechanical properties of intact infraspinatus tendon or infraspinatus tendon repaired with the modified Mason-Allen technique in a canine model in vitro. Thirty-six canine shoulder samples were used. Twenty intact samples were randomly allocated into functional pull (135°) and anatomic pull (70°) groups (n = 10 per group). The remaining sixteen infraspinatus tendons were transected from the insertion and repaired using the modified Mason-Allen technique before being randomly allocated into functional pull or anatomic pull groups (n = 8 per group). Load to failure testing was performed on all specimens. The ultimate failure load and ultimate stress of the functional pulled intact tendons were significantly lower compared with anatomic pulled tendons (1310.2 ± 167.6 N vs. 1687.4 ± 228.2 N, p = 0.0005: 55.6 ± 8.4 MPa vs. 67.1 ± 13.3 MPa, p = 0.0334). For the tendons repaired with the modified Mason-Allen technique, no significant differences were observed in ultimate failure load, ultimate stress or stiffness between functional pull and anatomic pull groups. The variance of pulling angle had a significant influence on the biomechanical properties of the rotator cuff tendon in a canine shoulder model in vitro. Load to failure of the intact infraspinatus tendon was lower at the functional pulling position compared to the anatomic pulling position. This result indicates that uneven load distribution across tendon fibers under functional pull may predispose the tendon to tear. However, this mechanical character is not presented after rotator cuff repair using the modified Mason-Allen technique.

AbstractFlexor tendon injuries and tendinopathy are very common but remain challenging in clinical treatment. Exosomes‐based cell‐free therapy appears to be a promising strategy for tendon healing, while limited studies have evaluated its impacts on tenocyte biology. The objective of this study was to characterize a novel purified exosome product (PEP) derived from plasma, as well as to explore its cellular effects on canine tenocyte biology. The transmission electron microscope revealed that exosomes of PEP present cup‐shaped structures with the diameters ranged from 80 to 141 nm, and the NanoSight report presented that their size mainly concentrated around 100 nm. The enzyme‐linked immunosorbent assay kits analysis showed that PEP was positive for CD63 and AChE expression, and the cellular uptake of exosomes internalized into tenocyte cytoplasm was observed. The cell growth assays displayed that tenocyte proliferation ability was enhanced by PEP solution in a dose‐dependent manner. Tenogenic phenotype was preserved as is evident by that tendon‐related genes expression (SCX, COL1A, COL3A1, TNMD, DCN, and MKX) were expressed insistently in a high level, while tenocytes were treated with 5% PEP solution. Furthermore, migration capability was maintained and total collagen deposition was increased. More interesting, dexamethasone‐induced cellular apoptosis was attenuated during the incubation of tenocytes with a 5% PEP solution. These findings will provide the basic understandings about the PEP, and support the potential use of this biological strategy for tendon healing.

ABSTRACTFlexor tendon injury is often associated with suboptimal outcomes and results in substantial digit dysfunction. Stem cells have been isolated from several experimental animals for the growing interest and needs of utilizing cell‐based therapies. Recently, turkey has been developed as a new large animal model for flexor tendon research. In the present study, we reported the isolation and characterization of bone marrow‐derived mesenchymal stem cells (BMSCs) from 8‐ to 12‐month‐old heritage‐breed turkeys. The isolated cells demonstrated fibroblast‐like morphology, clonogenic capacity, and high proliferation rate. These cells were positive for surface antigens CD90, CD105, and CD44, but were negative for CD45. The multipotency of turkey BMSCs was determined by differentiating cells into osteogenic, adipogenic, chondrogenic, and tenogenic lineages. There was upregulated gene expression of tenogenic markers, including mohawk, tenomodulin, and EGR1 as well as increased collagen synthesis in BMP12 induced cells. The successful isolation and verification of bone marrow‐derived MSCs from turkey would provide opportunities of studying cell‐based therapies and developing new treatments for tendon injuries using this novel preclinical large animal model. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1419–1428, 2019.

Tendon injuries are among the most common and severe hand injuries with a high demand for functional recovery. Stem cells have been identified and isolated from different species and a variety of tissues for the sake of regenerative medicine. Recently, turkey has been suggested as a potential new large animal model for flexor tendon-related research. However, turkey tissue-specific stem cells have not been investigated. Here, we presented the isolation and verification of tendon-derived stem cells (TDSCs) from 6- to 8-month-old heritage-breed turkey. TDSCs were isolated from turkey flexor tendon by plating nucleated cells at the determined optimal density. Approximately 4% of the nucleated cells demonstrated clonogenicity, high proliferation rate, and trilineage differentiation potential after induction culturing. These cells expressed surface antigens CD90, CD105, and CD44, but did not express CD45. There was a high level of gene expression of tenogenic markers in TDSCs, including mohawk, collagen type I, tenascin C, and elastin. Turkey TDSCs also expressed transcription factorsPouV,Nanog, andSox2, which are critically involved in the regulation of stemness. The successful isolation of tendon-derived stem cells from turkey was beneficial for future studies in tendon tissue engineering and would help in the development of new treatment for tendon diseases using this novel animal model.