Tendon-to-Bone Healing in a Rat Extra-articular Bone Tunnel Model: A Comparison of Fresh Autologous Bone Marrow and Bone Marrow-Derived Mesenchymal Stem Cells

Jun Lu, Connie S Chamberlain, Ming-Liang Ji, Erin E Saether, Ellen M Leiferman, Wan-Ju Li, Ray Vanderby
American Journal of Sports Medicine 2019, 47 (11): 2729-2736

BACKGROUND: Despite widespread acceptance of fresh autologous bone marrow (BM) for use in clinical practice, limited information exists to analyze if tendon-to-bone healing could be accelerated with local use of fresh autologous BM.

PURPOSE: To investigate the effect of fresh autologous BM on tendon-to-bone healing with a novel rat model.

STUDY DESIGN: Controlled laboratory study.

METHODS: An extra-articular bone tunnel was created and filled with an autologous tendon graft in skeletally mature Sprague-Dawley rats (N = 60). They were then randomly divided into 3 groups: BM group (injection of fresh autologous BM into the tendon-bone interface, n = 20), BM-derived mesenchymal stem cell (BMSC) group (injection of allogenic cultured BMSCs, n = 20), and the control group (tendon-bone interface without injection of BM or BMSCs, n = 20). Biomechanical, histological, and immunohistochemical analyses were performed at 2 and 6 weeks after surgery.

RESULTS: The BM group showed a relatively well-organized and dense connective tissue interface with better orientation of collagen fibers as compared with the BMSC group. At 2 weeks, the tendon-bone interface tissue thickness of the BMSC group was 140 ± 25 μm (mean ± SEM), which was significantly greater than the BM group (58 ± 15 μm). The BM group showed fewer M1 macrophages at the tendon-bone interface at 2 and 6 weeks ( P < .001). In contrast, there were more M2 macrophages at the interface in the BM group 2 and 6 weeks postoperatively when compared with controls and the BMSC group ( P < .001). Biomechanical tests revealed significantly higher stiffness in the BM group versus the control and BMSC groups at 2 and 6 weeks after surgery ( P < .05). Load to failure showed similar trends to stiffness.

CONCLUSION: These findings indicate that local delivery of fresh autologous BM enhances tendon-to-bone healing better than the alternative treatments in this study. This effect may be partially due to the observed modulation of inflammatory processes, especially in M2 macrophage polarization.

CLINICAL RELEVANCE: Fresh autologous BM could be a treatment option for this disorder.

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