NIR‐Responsive Multifunctional Artificial Skin for Regenerative Wound Healing

Abstract Efficient wound repair with skin appendage regeneration following severe trauma poses a challenge due to the scarcity of skin grafts and decreased drug effectiveness in protease‐rich wound microenvironments. Here, a multifunctional artificial skin (NIR‐mFAS) with photothermal‐triggered drug delivery capabilities is designed to actively and comprehensively improve the regenerative potential of full‐thickness wounds. The antibacterial chitosan/silk fibroin hydrogel matrix of artificial skin, cross‐linked by electrostatic interactions, effectively encapsulates and sustains the release of epidermal growth factor (EGF) to accelerate re‐epithelialization and neovascularization by promoting the migration and proliferation of repair cells. Subsequently, the photothermal responsive polydopamine nanoparticles (PDA‐NPs) dispersed in the matrix enable precise control over the release of BMP4 under the irradiation of 1064 nm NIR, thereby inhibiting scarring by reducing myofibroblasts during the proliferative stage. Importantly, the concurrent controlled release of CHIR99021 can modulate cell fate by inducing the conversion of myofibroblasts into dermal papilla‐like cells, leading to hair follicle and sebaceous gland regeneration. The NIR‐mFAS functions as an advanced delivery system for achieving high‐quality wound healing with appendage regeneration and offers a smart therapeutic approach that can be applied to other treatments requiring coordinated delivery of multiple pharmacological agents.