Several spongy wound dressings composed of various hyaluronic acid (HA) materials were developed: HA aqueous solution with cross-linking agent (epoxy compound (HAWC), without cross-linking agent (HAWOC), and combined bilayer material HAWC and HAWOC (2LHA). The microstructure, sensitivity to hyaluronidase, sensitivity to free radicals, in vitro cytotoxicity, healing potential on full-thickness defect on and diabetic ulcers were evaluated. Scanning electron micrograph views of all HA wound dressings showed an interconnected channel and high porosity structure. HAWOC was degraded rapidly in hyaluronidase and free radical solution. The in vitro cytotoxicity of HAWC was significantly (p<0.05) higher than other HA wound dressings and reduced the released amount of VEGF from human fibroblast. The HAWOC remarkably facilitated the formation of vascularized granulation tissue and provided a HA enrichment wound healing process of either a full-thickness defect or a diabetic ulcer. In contrast, the presence of un-degradable products of HAWC seemed to interfere dermal tissue restoration. Nevertheless, because of the fragile properties, rapid degradation and wound adhesion of HAWOC, the 2LHA should be developed for diabetic ulcer therapy.
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