Aloe extract-loaded cationized silk fibroin/oxidized hyaluronic acid injectable self-healing hydrogel for diabetic...

Chronic wound healing in diabetes mellitus is a major clinical challenge, and its pathological microenvironment presents a vicious cycle of high glucose, hypoxia, chronic inflammation, and cellular dysfunction, which makes it difficult for a single traditional dressing to effectively promote re-epithelialization, collagen deposition, and vascular regeneration. We propose a novel injectable self-healing dual-crosslinked hydrogel integrating both "dynamic crosslinking" and "covalent binding" designed to possess multifunctionality including antibacterial, antioxidant, anti-inflammatory, and pro-healing properties. The hydrogel is formed via Schiff base reaction between aminated cationic silk fibroin (CSF) and oxidized sodium hyaluronate (OSH), further stabilized using an EDC/NHS activation system. This dual-network hydrogel platform is injectable and capable of forming in situ at specific sites, and has robust self-healing capability. Its porous structure, loaded with bioactive aloe extract (AE), imparts antibacterial, antioxidant, and anti-inflammatory properties, and significantly enhances cell adhesion and migration efficiency. Animal studies further demonstrated that this hydrogel effectively accelerates the healing of diabetic wounds by promoting re-epithelialization, accelerating angiogenesis and collagen remodeling evidenced by the upregulation of CD31 and α-SMA markers, and modulating the inflammatory response via downregulation of the pro-inflammatory cytokine IL-1β.