Injectable hydrogel scaffolds with sustained bioactive release and multilevel architecture for cartilage repair.

Abstract

Due to the extremely limited intrinsic regenerative ability of cartilage, the repair of articular cartilage defects remains a major clinical challenge at present. Here, through the Schiff-base crosslinking between chitosan and gelatin, reinforced with Sr2+, an injectable and rapidly gelling composite hydrogel - loaded coaxial electrospun staple fiber was developed. The embedded fibers bridge adjacent pores to form a layered ECM simulation structure, enhancing structural stability, cell adhesion, and local microenvironment regulation. The hydrogel exhibited rapid gelation and obvious shear thinning behavior within 30 s, realizing minimally invasive injection. The encapsulation of Sr2+ within coaxial fibers effectively suppressed initial burst release and achieved sustained ion release for 30 days, with a cumulative release of approximately 60%. In vitro, the composite hydrogel showed good biocompatibility, promoted the proliferation and migration of bone marrow mesenchymal stem cells, enhanced the early cartilage related matrix deposition, and reduced the expression of pro-inflammatory cytokines in LPS stimulated macrophages. In the rat full-thickness cartilage defect model, the sustained release hydrogel showed improved defect filling and hyaline-like cartilage repair at 8 weeks, accompanied by Safranin O staining and significantly increased COL-II and SOX-9 expression. This work may provide an effective strategy for promoting cartilage repair in vivo through the long-term release of biological factors using functional biomass materials.