Tissue-engineered collagen matrix loaded with rat adipose-derived stem cells/human amniotic mesenchymal stem cells for rotator cuff tendon-bone repair

Abstract

The rotator cuff tendon-bone interface tissue exhibits high heterogeneity in its composition and structure, with collagen being its primary component. Here, we prepared tissue-engineered decellularized live hyaline cartilage grafts (dLHCG), this dLHCG scaffold's bioactive ECM mainly consists of collagen II, proteoglycans, and fibronectin, presenting a cartilage-like lacuna microstructure. The dLHCG scaffold loaded human amniotic mesenchymal stem cells (hAMSCs) and adipose stem cells (ADSCs) were implanted into the interface. The dLHCG scaffold could maintain the pluripotency of stem cells, supporting the proliferation, osteogenic differentiation, and tenogenic differentiation of the MSCs. The collagen II, through the integrin α2β1-FAK-JNK signaling axis, promotes Runx-2 activation, playing a better regulatory role in the early osteogenic differentiation of MSCs, enhancing bone defect repair through an endochondral ossification process. The in vivo rat model demonstrated that 12 weeks post-operation, the MSC-loaded dLHCG scaffold group exhibited continuous aligned collagen fibers at the tendon-bone interface, with significantly enhanced biomechanical function compared to the control group. The dLHCG scaffold create an efficient interface, which promoting the restoration of the soft-hard gradient structure tissue at the junction between the scaffold and the host tissue, thereby providing a rational and promising strategy for the rapid healing of the rotator cuff injury.