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

Abstract

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. 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. 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/mm2, p = 0.0079). Immunohistochemistry demonstrated greater areas positive for collagen type II alpha 1 (86.96 ± 29.95 versus 40.25 ± 11.96 μm2, p = 0.0079) and interleukin 10 (14.93 ± 4.79 versus 7.43 ± 2.48 μm2, 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). Prevascularization of BMSC sheets was able to promote angiogenesis and improve structural and mechanical aspects of tendon-bone healing. Prevascularized BMSC sheets may represent a biologic adjunct to enhance tendon-bone healing in RC repair.