# Environmentally activatable hydrogel for spatiotemporally programmed nitric oxide delivery for diabetic wound healing

## TL;DR

A smart hydrogel that releases nitric oxide on demand is developed to improve healing in diabetic wounds.

## Contribution

An environmentally activatable hydrogel for spatiotemporally controlled nitric oxide delivery is engineered for diabetic wound healing.

## Key findings

- The CS-SNAP hydrogel enables sustained nitric oxide release over 300 minutes via ambient light and temperature modulation.
- The hydrogel promotes M1-to-M2 macrophage polarization and exhibits antibacterial and angiogenic properties.
- The platform shortens the inflammatory phase and accelerates diabetic wound healing.

## Abstract

Nitric oxide (NO) plays a central role in wound healing, by regulating vascular homeostasis, inflammation, and antimicrobial effects. However, chronic diabetic wounds are difficult to heal due to the hyperglycemic microenvironment, which reduces endogenous NO production. Therefore, developing intelligent dressings capable of spatiotemporally programmed NO delivery holds great promise in promoting diabetic wound healing. Herein, we engineered an environmentally activatable hydrogel that enabled on-demand NO release for diabetic wound healing. The CS-SNAP hydrogel was achieved by covalent grafting of NO donor (S-nitroso-N-acetylpenicillamine, SNAP) onto the matrix of carboxymethyl chitosan methacryloyl (CMCSMA), and by subsequent fast photopolymerization during only 10 s. The CS-SNAP hydrogel enabled sustained release of NO over 300 min by simply modulating ambient light and temperature. When applied to diabetic wounds, not only did the CS-SNAP hydrogel exhibit effective antibacterial activity, but it also showed good angiogenic ability and promoted M1-to-M2 polarization of macrophages. Together, this environmentally activatable platform demonstrates great potential to shorten the inflammatory phase of diabetic wounds, prevent bacterial colonization, and accelerates diabetic wound healing.

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