Development of nitric oxide releasing visible light crosslinked gelatin methacrylate hydrogel for rapid closure of diabetic wounds.

Management of non-healing and slow to heal diabetic wounds is a major concern in healthcare across the world. Numerous techniques have been investigated to solve the issue of delayed wound healing, though, mostly unable to promote complete healing of diabetic wounds due to the lack of proper cell proliferation, poor cell-cell communication, and higher chances of wound infections. These challenges can be minimized by using hydrogel based wound healing patches loaded with bioactive agents. Gelatin methacrylate (GelMA) has been proven to be a highly cell friendly, cell adhesive, and inexpensive biopolymer for various tissue engineering and wound healing applications. In this study, S-Nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO) donor, was incorporated in a highly porous GelMA hydrogel patch to improve cell proliferation, facilitate rapid cell migration, and enhance diabetic wound healing. We adopted a visible light crosslinking method to fabricate this highly porous biodegradable but relatively stable patch. Developed patches were characterized for morphology, NO release, cell proliferation and migration, and diabetic wound healing in a rat model. The obtained results indicate that SNAP loaded visible light crosslinked GelMA hydrogel patches can be highly effective in promoting diabetic wound healing.

Nitric oxide releasing chitosan-poly (vinyl alcohol) hydrogel promotes angiogenesis in chick embryo model.

The lack of angiogenic activity is one of the serious complications of chronic wounds associated with delayed wound closure, chronic ulceration, and subsequent limb amputation. Multiple lines of evidence suggest that nitric oxide (NO) produced endogenously by nitric oxide synthase pathway plays a significant role in angiogenic activity and accelerates wounds closure. In this work, chitosan (CS), polyvinyl alcohol (PVA) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) hydrogel was fabricated to accelerate angiogenesis and promote healing in chronic wounds due to better wound closure potential of CS-PVA hydrogel and angiogenic properties of SNAP. The developed CS-PVA hydrogels loaded with SNAP produced a continuous and sustained supply of NO. 3T3 and HaCaT cells showed a significant increase in cell proliferation with 5‰ SNAP loaded CS-PVA hydrogel compared to the control group. Wound scratch assay resulted in four-fold faster recovery of the scratched wound area and an enhanced degree of angiogenic activity was observed in the chick embryo model with the SNAP incorporated CS-PVA hydrogel compared to the control group. The results depict that the use of CS-PVA hydrogel impregnated with SNAP could be a promising material for promoting angiogenesis followed by accelerated healing of the chronic wounds in burns and diabetic patients.