A pulsatile release platform based on photo-induced imine-crosslinking hydrogel promotes scarless wound healing

TLDR

Effective skin wound healing is critical, yet aberrant repair can lead to disfiguring scars driven by excessive ECM deposition, inflammation, and TGF‑β signaling, whose systemic inhibition causes adverse effects. The study aims to create a wound dressing that delivers a TGF‑β inhibitor in a pulsatile, spatiotemporally controlled manner via photo‑induced imine crosslinking and microcapsules. This platform combines photo‑crosslinkable hydrogel chemistry with microencapsulated TGF‑β inhibitor that releases the drug upon light activation, enabling precise temporal and spatial control. In murine and large animal models, the material accelerated wound closure while markedly reducing scar formation, demonstrating a promising scar‑less repair strategy.

Abstract

Effective healing of skin wounds is essential for our survival. Although skin has strong regenerative potential, dysfunctional and disfiguring scars can result from aberrant wound repair. Skin scarring involves excessive deposition and misalignment of ECM (extracellular matrix), increased cellularity, and chronic inflammation. Transforming growth factor-β (TGFβ) signaling exerts pleiotropic effects on wound healing by regulating cell proliferation, migration, ECM production, and the immune response. Although blocking TGFβ signaling can reduce tissue fibrosis and scarring, systemic inhibition of TGFβ can lead to significant side effects and inhibit wound re-epithelization. In this study, we develop a wound dressing material based on an integrated photo-crosslinking strategy and a microcapsule platform with pulsatile release of TGF-β inhibitor to achieve spatiotemporal specificity for skin wounds. The material enhances skin wound closure while effectively suppressing scar formation in murine skin wounds and large animal preclinical models. Our study presents a strategy for scarless wound repair.