Prevascularized Bone Marrow-Derived Mesenchymal Stem Cell Sheets Promote Tendon-Bone Integration in Rotator Cuff Repair

Background: Limited vascularization at the tendon-bone interface (TBI) hinders rotator cuff (RC) healing. Although cell sheet technology has shown promise for interfacial repair, prevascularization strategies remain underexplored. Methods: Twenty female New Zealand rabbits underwent bilateral infraspinatus tendon repair and were randomized to receive either bone marrow-derived mesenchymal stem cell (BMSC) sheets or prevascularized BMSC sheets generated by coculture with endothelial cells, implanted at the TBI. An age- and weight-matched uninjured group served as a control. Healing at 6 weeks was assessed by gross observation, histology, immunohistochemistry, gene expression, and biomechanical testing. Results: Prevascularization of the BMSC sheets enhanced TBI vascularization, indicated by greater density of α-smooth muscle actin-positive vessels (16.16 ± 2.81 versus 10.63 ± 2.79/mm 2 , p = 0.0079). Immunohistochemistry demonstrated greater areas positive for collagen type II alpha 1 (86.96 ± 29.95 versus 40.25 ± 11.96 μm 2 , p = 0.0079) and interleukin 10 (14.93 ± 4.79 versus 7.43 ± 2.48 μm 2 , p = 0.0159). Biomechanically, prevascularization of the sheets yielded greater ultimate failure load (156.89 ± 51.92 versus 111.67 ± 27.51 N, p = 0.0364) and stiffness (37.27 ± 12.16 versus 27.16 ± 7.33 N/mm, p = 0.0486). Conclusions: Prevascularization of BMSC sheets was able to promote angiogenesis and improve structural and mechanical aspects of tendon-bone healing. Clinical Relevance: Prevascularized BMSC sheets may represent a biologic adjunct to enhance tendon-bone healing in RC repair.