Bioactive injectable sulfated alginate-based hydrogels containing desferrioxamine for diabetic wound healing

Diabetic wounds are prone to bacterial infection and difficult to heal due to chronic inflammation and hyperglycemic microenvironment. Here we developed a novel bioactive hydrogel with multifunctional tunable properties, including biocompatibility, pH-response, anti-inflammatory activity, and the ability to promote diabetic wound healing. The injectable and self-healing hydrogel was prepared by cross-linking sulfated oxidized sodium alginate (S-OSA) with adipic dihydrazide (ADH) and subsequently loading with the angiogenic drug desferrioxamine (DFO). Under acidic microenvironment in diabetic wounds during the early stage, the hydrogel presented a pH-responsive and sustained release of DFO due to unstable acylhydrazone bonds. The hydrogel also exhibited good cytocompatibility and hemocompatibility. Furthermore, the in vivo experiments demonstrated that the hydrogel significantly promoted diabetic wounds healing by reducing the inflammatory response, accelerating collagen deposition, and promoting vascular regeneration. These findings suggested that sulfated alginate-based hydrogel holds considerable promise for treating diabetic wounds complicated by chronic inflammation.