Collagen–oxidized hyaluronic acid injectable self-healing hydrogel enabling sequential platelet-rich plasma release for microenvironment modulation in diabetic wound repair

Chronic wounds, characterized by persistent inflammation, impaired angiogenesis, and disrupted tissue regeneration, remain a major clinical challenge. Current therapies can alleviate symptoms but fail to achieve long-term regulation of the wound microenvironment and functional regeneration. To overcome these limitations, a self-healing collagen–oxidized hyaluronic acid hydrogel loaded with platelet-rich plasma (COL–OHA@PRP) based on dynamic covalent crosslinking was developed, integrating two clinically applied therapies—collagen (COL) and platelet-rich plasma (PRP)—into a single platform. Guided by the design concept of “sustained release–protection–synergy”, this hydrogel integrates three essential functions: self-healing ability, tissue adhesiveness, and controlled PRP release. While preserving the native triple-helix structure of COL, the hydrogel forms a stable adhesive interface with the wound surface, enabling sustained release and protection of bioactive factors in PRP, and synergistically regulating inflammation and tissue regeneration. In vivo studies demonstrated that COL–OHA@PRP hydrogel continuously released multiple bioactive factors, effectively attenuated inflammation and oxidative stress, promoted angiogenesis and COL remodeling, and accelerated wound closure and re-epithelialization. This hydrogel demonstrated sustained therapeutic efficacy following a single administration in a diabetic wound animal model, highlighting its potential as a promising biomaterial platform for further translational investigation in chronic wound treatment.