Engineering a biomimetic multiphasic suture anchor system for enhanced rotator cuff enthesis regeneration

The rotator cuff plays a vital role in shoulder movement and joint stability. Unfortunately, tears at the rotator cuff enthesis are common and frequently lead to retears after surgical intervention, particularly at the suture location and its anchor sites. These failures are typically due to the inability of current surgical treatments to mimic the native tissue complexity and provide the necessary metabolic, bioactive, and biophysical cues for effective enthesis regeneration. In this study, we engineered a biomimetic multiphasic scaffold system (BMS) to integrate with conventional suture anchor systems and deliver spatially organized structural and biological cues to enhance enthesis regeneration. The BMS consists of three distinct phases: Phase 1 features an aligned, nanofibrous decellularized tendon extracellular matrix (dECM) combined with "stiff" methacrylated hyaluronic acid (MeHA); phase 2 incorporates nonaligned, nanofibrous dECM with "soft" MeHA; and phase 3 uses a porous, bioenergetic, citrate-based composite scaffold for bone integration. In vitro, the BMS notably enhanced tenogenic, fibrochondrogenic, and chondrogenic differentiation, facilitating zone-specific rotator cuff enthesis regeneration. Further, in vivo, the BMS promoted successful integrative healing, forming distinct tendon, fibrocartilage, and bone regions at the repair site. This advanced multiphasic scaffold closely replicates native tissue properties, offering a promising strategy to improve rotator cuff repair. Its integration with conventional suture anchors provides an innovative design that enhances mechanical fixation and guides enthesis healing to reduce retear rates. Broadly, this platform offers a versatile solution for biointegrative repair strategies across complex soft-to-hard tissue interfaces.