Advanced Hydrogel/Electrospun Nanofiber Composite Scaffold With Sequential Bioactive Factor Release for Rotator Cuff Repair.

Abstract

Rotator cuff repair is a complex, multi-stage process that relies on the precise coordination of various tissue structures and healing phases. Consequently, advanced composite scaffolds with spatiotemporal drug release profiles are urgently needed to accommodate the rotator cuff's complex architecture and sequential healing demands, enabling synergistic interplay of structural cues and staged bioactivity. In this study, we design an injectable sodium alginate/bioactive glass (SA/BG) composite hydrogel loaded with stromal cell-derived factor-1α (SDF-1α), integrated with a poly (lactic-co-glycolic acid) (PLGA) electrospun membrane carrying kartogenin (KGN). This novel composite scaffold (PLGA/KGN+SA/BG/SDF-1α) addresses the biological requirements of rotator cuff repair and effectively bridges injured rotator cuff tissues. The early sustained release of bioactive glass ions and SDF-1α facilitates immunomodulation and recruits endogenous bone marrow mesenchymal stem cells (BMSCs). After eight days, the PLGA electrospun fibers release KGN to direct BMSC differentiation into chondrocytes while also providing structural support to guide fibrocartilage formation and alignment. In a rat rotator cuff injury model, this composite scaffold effectively regulates inflammation and significantly accelerates fibrocartilage regeneration, promoting targeted integration of newly formed tissues with the tendon-to-bone insertion site. With tunable bioactivity and multilayered design, this scaffold shows broad potential for regenerative medicine and complex tissue interfaces.