Collagen/chitosan/genipin hydrogel loaded with phycocyanin nanoparticles and ND-336 for diabetic wound healing

Diabetic wound healing remains a healthcare challenge due to the overexpression of matrix metalloproteinase-9 (MMP-9) and the imbalance between angiogenic factors and vascular inhibitory factors. In this study, we developed a nanocomposite injectable collagen/chitosan hydrogel for the treatment of delayed diabetic wound healing, which can promote cell migration to the wound site (through the addition of phycocyanin) and reduce the expression of MMP-9 (through the use of ND-336) to improve the therapeutic effect of diabetic wound healing. Furthermore, different weight ratios of collagen and chitosan hydrogels were prepared to select the hydrogel with proper mechanical properties. In vitro experiments confirmed that all hydrogels have favorable biocompatibility and hemocompatibility. Notably, Gel 2, with a weight ratio of collagen and chitosan at 25:75, was found to have an excellent capability to facilitate cell migration and in vivo studies further proved that Gel 2 nanocomposite hydrogel had the best ability to improve diabetic wound healing by promoting cell migration and decreasing MMP-9 expression. The collagen/chitosan/genipin hydrogel loaded phycocyanin and ND-336 can be harnessed for non-toxic and efficient treatment of wound healing management of diabetes. [Display omitted] •Developed a low toxic hydrogel which has a synergistic therapeutic effect on DFU.•Genipin can reduce inflammatory reaction and is more environmentally friendly.•The addition of PCNP@ND-336 and CS improve the mechanical properties of hydrogels.