A Self-Healing Multifunctional Hydrogel System Accelerates Diabetic Wound Healing through Orchestrating Immunoinflammatory Microenvironment

Developing an effective treatment strategy of drug delivery to improve diabetic wound healing remains a major challenge in clinical practice nowadays, due to multidrug-resistant bacterial infections, angiopathy, and oxidative damage in the wound micro environment. Herein, an effective and convenient strategy was designed through a self-healing multiple-dynamic-bond cross-linked hydrogel with interpenetrating networks, which was formed by multiple-dynamic bond cross-linking of reversible catechol-Fe3+ coordinate bonds, hydrogen bonding, and Schiff base bonds. The excellent autonomous healing of the hydrogel was initiated and accelerated by Schiff bonds with reversible breakage between 3,4-dihydroxybenzaldehyde containing catechol and aldehyde groups and chitosan chains, and further consolidated by the co-optation of other noncovalent interactions contributed of hydrogen bonding and Fe3+ coordinate bonds. Intriguingly, cathelicidin LL-37 was introduced and uniformly dispersed in the dynamic interpenetrating networks of the hydrogel as a bioactive molecular to orchestrate the diabetic wound healing microenvironment. This multifunctional wound dressing can significantly promote diabetic wound healing by antibacterial activity, immunomodulation, anti-inflammation, neovascularization, and antioxidant activity. Therefore, this study provided an effective and safe strategy for guiding the diabetic wound treatment in clinical applications.

Automated summary

Developing an effective treatment strategy for diabetic wound healing is a major challenge in clinical practice due to multidrug-resistant bacterial infections, angiopathy, and oxidative damage. This study designed a self-healing hydrogel with interpenetrating networks formed by multiple-dynamic bond cross-linking. The hydrogel showed excellent autonomous healing mediated by reversible breakage of Schiff bonds and reinforced by other noncovalent interactions. Incorporation of cathelicidin LL-37 in the hydrogel significantly promoted diabetic wound healing by various mechanisms. Therefore, this study provides an effective and safe strategy for diabetic wound treatment in clinical applications.