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Background: Poor healing of the tendon-bone interface after rotator cuff repair is one of the main causes of surgical failure. Previous studies demonstrated that demineralized cortical bone (DCB) could improve healing of the enthesis. Purpose: To evaluate the outcomes of hierarchically demineralized cortical bone (hDCB) coated with stem cell–derived extracellular matrix (hDCB-ECM) in the repair of the rotator cuff in a rabbit model. Study Design: Controlled laboratory study. Methods: Tendon-derived stem cells (TDSCs) were isolated, cultured, and identified. Then, hDCB was prepared by the graded demineralization procedure. Finally, hDCB-ECM was fabricated via 2-week cell culture and decellularization, and the morphologic features and biochemical compositions of the hDCB-ECM were evaluated. A total of 24 rabbits (48 samples) were randomly divided into 4 groups: control, DCB, hDCB, and hDCB-ECM. All rabbits underwent bilateral detachment of the infraspinatus tendon, and the tendon-bone interface was repaired with or without scaffolds. After surgery, 8 rabbits were assessed by immunofluorescence staining at 2 weeks, and the others were assessed by micro–computed tomography (CT) examination, immunohistochemical staining, histological staining, and biomechanical testing at 12 weeks. Results: TDSCs were identified to have universal stem cell characteristics including cell markers, clonogenicity, and multilineage differentiation. The hDCB-ECM contained 3 components (bone, partial DCB, and DCB coated with ECM) with a gradient of calcium and phosphorus elements, and the ECM had stromal cell-derived factor 1, biglycan, and fibromodulin. Macroscopic observations demonstrated the absence of infection and rupture around the enthesis. The results of immunofluorescence staining showed that hDCB-ECM promoted stromal cell recruitment. Results of micro-CT analysis, immunohistochemical staining, and histological staining showed that hDCB-ECM enhanced bone and fibrocartilage formation at the tendon-bone interface. Biomechanical analysis showed that the hDCB-ECM group had higher ultimate tensile stress and Young modulus than the DCB group. Conclusion: The administration of hDCB-ECM promoted healing of the tendon-bone interface. Clinical Relevance: hDCB-ECM could provide useful information for the design of scaffolds to repair the tendon-bone interface, and further studies are needed to determine its effectiveness.

It is highly desirable to develop a novel scaffold that can induce stem cell migration in tendon tissue engineering and regeneration. The objective of this study is to assess the effect of stem cell extracellular matrix-modified decellularized tendon slices (ECM-DTSs) on bone marrow mesenchymal stem cells (BMSCs) migration and explore the possible molecular mechanisms. Native ECM produced by BMSCs and tendon-derived stem cells (TDSCs) was deposited on DTSs, denoted as bECM-DTSs and tECM-DTSs, respectively, and the migration of BMSCs treated with the extracts from ECM-DTSs was studied. Almost all the seeded stem cells were removed from the stem cell-DTS composites, while ECM produced by stem cells completely covered the surface of the DTSs. Significantly higher levels of chemokines, including stromal cell-derived factor-1 (SDF-1) and monocyte chemotactic protein-1 (MCP-1) were released by ECM-DTSs than by bare DTSs (p < 0.05), according to ELISA, and tECM-DTSs exhibited the highest release within 72 h. bECM-DTSs and tECM-DTSs markedly improved BMSCs migration compared to bare DTSs, with tECM-DTSs yielding the best recruitment effects. The ECM-DTSs led to early cytoskeletal changes compared to bare DTSs (p < 0.05). Migration-related gene and protein expression was significantly upregulated in BMSCs treated with ECM-DTSs via the PI3K/AKT signaling pathway (p < 0.05), indicating that ECM-DTSs could enhance BMSCs migration via the PI3K/AKT signal pathway, and the effect of tECM-DTSs on BMSCs migration is superior to that of bECM-DTSs. This may provide the experimental and theoretical evidence for using stem cell-derived ECMmodified scaffold as a novel approach to recruit stem cells.

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Tendon regeneration highly relies on biomechanical and biochemical cues in the repair microenvironment. Herein, we combined the decellularized bovine tendon sheet (DBTS) with extracellular matrix (ECM) from tendon-derived stem cells (TDSCs) to fabricate a biomechanically and biochemically functional scaffold (tECM-DBTS), to provide a functional and stem cell ECM-based microenvironment for tendon regeneration. Our prior study showed that DBTS was biomechanically suitable to tendon repair. In this study, the biological function of tECM-DBTS was examined in vitro, and the efficiency of the scaffold for Achilles tendon repair was evaluated using immunofluorescence staining, histological staining, stem cell tracking, biomechanical and functional analyses. It was found that tECM-DBTS increased the content of bioactive factors and had a better performance for the proliferation, migration and tenogenic differentiation of bone marrow-derived stem cells (BMSCs) than DBTS. Furthermore, our results demonstrated that tECM-DBTS promoted tendon regeneration and improved the biomechanical properties of regenerated Achilles tendons in rats by recruiting endogenous stem cells and participating in the functionalization of these stem cells. As a whole, the results of this study demonstrated that the tECM-DBTS can provide a bionic microenvironment for recruiting endogenous stem cells and facilitating in situ regeneration of tendons.

ObjectiveThe aim of this study was to investigate the optimal timing for the resection of heterotopic ossification (HO) of the elbow.MethodsWe retrospectively reviewed 42 patients who were treated operatively for heterotopic ossification of the elbow from March 2010 to December 2014 at our institution. The patients were divided into early (before 12 months) and late (after 12 months) excision groups. In the early excision group (17 patients), the average time from the initial injury to HO excision was 7.4 (3–11) months, and in the late excision group (25 patients), the average time was 33.5 (12–240) months. Every patient was evaluated by range of motion (ROM), the Mayo Elbow Performance Score (MEPS), postoperative complications and HO recurrence.ResultsThe preoperative mean ROM in the late excision group was greater than that of the early excision group, suggesting that the ROM is expected to increase even without surgery. Both early and late surgery increased ROM and MEPS, but early surgery improved ROM and MEPS more than late surgery did (p < .05).ConclusionsEarly excision of HO can provide better elbow function, as indicated by ROM and MEPS. Considering that there were no notable differences in postoperative ROM and MEPS, HO recurrence, or postoperative complications, we concluded that early excision is safe and that the time from an elbow injury to surgery may be shortened.Level of EvidenceLevel III, therapeutic study.

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The associated injury of fracture may have a negative impact on the functional outcomes of elbow. And Dubberley classification is more suitable to classify this kind of fracture. Furthermore, high-quality studies are required to attain robust evidence.