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Background: Rotator cuff tendon-to-bone healing occurs by formation of a scar tissue interface after repair, which makes it prone to failure. Bone morphogenetic protein—13 (BMP-13) has been implicated in tendon and cartilage repair, and thus may augment rotator cuff repairs. The purpose of this study was to determine if the application of mesenchymal stem cells (MSCs) transduced with BMP-13 could improve regeneration of the tendon-bone insertion site in a rat rotator cuff repair model.Hypothesis: Mesenchymal stem cells genetically modified to overexpress BMP-13 will improve rotator cuff healing based on histologic and biomechanical outcomes.Study Design: Controlled laboratory study.Methods: Sixty Lewis rats underwent unilateral detachment and repair of the supraspinatus tendon and 10 rats were used for MSC harvest. Animals were randomized into 2 groups (30 animals/group). The experimental group received 106 MSCs transduced with adenoviral-mediated gene transfer of human BMP-13 (Ad-BMP-13). The second group received untransduced MSCs. Fifteen animals in each group were sacrificed at 2 and 4 weeks. At each time point, 12 animals were allocated for biomechanical testing, and 3 for histomorphometric analysis.Results: There were no differences in the amount of new cartilage formation or collagen fiber organization between groups at either time point. There were also no differences in the biomechanical strength of the repairs, the cross-sectional area, peak stress at failure, or stiffness.Conclusion: Application of MSCs genetically modified to overexpress BMP-13 did not improve healing in a rat model of rotator cuff repair.Clinical Relevance: Further studies are needed to evaluate various growth factors and combinations of growth factors to determine the optimal factor for the biologic augmentation of rotator cuff repairs. [ABSTRACT FROM AUTHOR]

Background: Rotator cuffs heal through a scar tissue interface after repair, which makes them prone to failure. Membrane type 1 matrix metalloproteinase (MT1-MMP) is upregulated during embryogenesis in areas that develop into tendon-bone insertion sites. Hypothesis: Bone marrow-derived stem cells in the presence of the developmental signal from MT1-MMP will drive the healing process toward regeneration and away from scar formation. Study Design: Controlled laboratory study. Methods: Sixty Lewis rats underwent unilateral detachment and repair of the supraspinatus tendon. Thirty animals received mesenchymal stem cells (MSCs) in a fibrin glue carrier, and 30 received adenoviral MT1-MMP (Ad-MT1-MMP)-transduced MSCs. Animals were sacrificed at 2 weeks and 4 weeks and evaluated for the presence of fibrocartilage and collagen fiber organization at the insertion. Biomechanical testing was performed to determine the structural and material properties of the repaired tissue. Statistical analysis was performed with a Wilcoxon rank-sum test with significance set at P = .05. Results: There were no differences between the Ad-MT1-MMP and MSC groups in any outcome variable at 2 weeks. At 4 weeks, the Ad-MT1-MMP group had more fibrocartilage (P = .05), higher ultimate load to failure (P = .01), higher ultimate stress to failure (P = .005), and higher stiffness values (P = .02) as compared with the MSC group. Conclusion: Mesenchymal stem cells genetically modified to overexpress the developmental gene MT1-MMP can augment rotator cuff healing at 4 weeks by the presence of more fibrocartilage at the insertion and improved biomechanical strength. Clinical Relevance: Biologic augmentation of repaired rotator cuffs with MT1-MMP-transduced MSCs may reduce the incidence of retears. However, further studies are needed to determine if this remains safe and effective in larger models. [ABSTRACT FROM AUTHOR]

Background: Rotator cuff tendons heal to bone with interposed scar tissue, which makes repairs prone to failure. The purpose of this study was to determine if the application of bone marrow-derived mesenchymal stem cells (MSCs) can improve rotator cuff healing after repair. Hypothesis: Application of MSCs to the repair site will result in superior results compared with controls on histologic and biomechanical testing. Study Design: Controlled laboratory study. Methods: Ninety-eight Lewis rats underwent unilateral detachment and repair of the supraspinatus tendon; 10 rats were used for MSC harvest. Eight animals were used for cell tracking with Ad-LacZ. The remaining animals received either 106 MSCs in a fibrin carrier, the carrier alone, or nothing at the repair site. Animals were sacrificed at 2 and 4 weeks for histologic analysis to determine the amount of fibrocartilage formation and the collagen organization at the insertion. Biomechanical testing was also performed. Results: Specimens treated with Ad-LacZ-transduced MSCs exhibited more β-galactosidase activity at the repair site compared with controls at both 2 and 4 weeks, although activity at 4 weeks was less than that at 2 weeks. There were no differences in the amount of new cartilage formation or collagen fiber organization between groups at either time point. There were also no differences in the biomechanical strength of the repairs, the cross-sectional area, peak stress to failure, or stiffness. Conclusion: The addition of MSCs to the healing rotator cuff insertion site did not improve the structure, composition, or strength of the healing tendon attachment site despite evidence that they are present and metabolically active. Clinical Relevance: A biologic solution to the problem of tendon-to-bone healing in the rotator cuff remains elusive. The repair site may lack the cellular and/or molecular signals necessary to induce appropriate differentiation of transplanted cells. Further studies are needed to determine if cell-based strategies need to be combined with growth and differentiation factors to be effective. [ABSTRACT FROM AUTHOR]

Background: Nonsteroidal anti-inflammatory drugs are commonly prescribed after rotator cuff repair. These agents can impair bone formation, but no studies have evaluated their impact on tendon-to-bone healing. Hypothesis: Traditional nonselective nonsteroidal anti-inflammatory drugs and cyclooxygenase-2-specific nonsteroidal anti-inflammatory drugs interfere with tendon-to-bone healing. Study Design: Controlled laboratory study. Methods: One hundred eighty Sprague-Dawley rats underwent acute rotator cuff repairs. Postoperatively, 60 rats received 14 days of celecoxib, a cyclooxygenase-2-specific nonsteroidal anti-inflammatory drug; 60 received indomethacin, a traditional nonselective nonsteroidal anti-inflammatory drug; and 60 received standard rat chow. Animals were sacrificed at 2, 4, and 8 weeks and evaluated by gross inspection, biomechanical testing, histologic analysis, and polarized light microscopy to quantify collagen formation and maturation. Results: Five tendons completely failed to heal (4 celecoxib, 1 indomethacin). There were significantly lower failure loads in the celecoxib and indomethacin groups compared with the control groups at 2, 4, and 8 weeks (P < .001), with no significant difference between nonsteroidal anti-inflammatory drug groups. There were significant differences in collagen organization and maturation between the controls and both nonsteroidal anti-inflammatory drug groups at 4 and 8 weeks (P < .001). Controls demonstrated progressively increasing collagen organization during the course of the study (P < .001), whereas the nonsteroidal anti-inflammatory drug groups did not. Conclusion: Traditional and cyclooxygenase-2-specific nonsteroidal anti-inflammatory drugs significantly inhibited tendon-to-bone healing. This inhibition appears linked to cyclooxygenase-2. Clinical Relevance: If the results of this study are verified in a larger animal model, the common practice of administering nonsteroidal anti-inflammatory drugs after rotator cuff repair should be reconsidered. [ABSTRACT FROM AUTHOR]