pH-responsive calcium alginate hydrogel laden with protamine nanoparticles and hyaluronan oligosaccharide promotes diabetic wound healing by enhancing angiogenesis and antibacterial activity

Diabetic wounds as chronic wounds represent a severe, persistent complication of diabetes and, in the most extreme cases, can lead to amputation. Two critical and unfavorable factors affecting diabetic wound healing are sustained bacterial-induced chronic inflammation and disrupted vascularization. In this paper, we presented a novel, pH-responsive calcium alginate hydrogel laden with protamine nanoparticles and hyaluronan oligosaccharides, and explored its potential for accelerating diabetic wound healing. A thorough investigation indicated that the drug- and nanoparticle-loaded hydrogel demonstrated strong bactericidal behavior mediated by protamine nanoparticles and reduced bacterial-induced chronic inflammation at the wound site. Furthermore, it accelerated the wound-healing process by promoting angiogenesis in skin wounds with the hyaluronan oligosaccharide-mediated enhanced expression of vascular endothelial growth factor.