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

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-beta (TGF beta) signaling exerts pleiotropic effects on wound healing by regulating cell proliferation, migration, ECM production, and the immune response. Although blocking TGF beta signaling can reduce tissue fibrosis and scarring, systemic inhibition of TGF beta 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-beta 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. Dysfunctional and disfiguring scars can result from aberrant wound repair. Here, the authors develop a wound dressing material based on an integrated photo-crosslinking strategy and a microcapsule platform with pulsatile release of TGF-beta inhibitor to achieve spatiotemporal specificity for scarless wound repair.