Precision DLP Printing of Multifunctional SilMA Hydrogels Enabled by Sepia Melanin for On-Demand Wound Therapy

Chronic infected wounds present a complex healing environment characterized by excessive reactive oxygen species (ROS), persistent bacterial infection, and prolonged inflammation. While three-dimensional (3D) printing offers precision in scaffold fabrication, creating structures that combine high printing fidelity with intrinsic bioactivity and stimulus responsiveness remains a significant challenge. Here, a multifunctional and photopolymerizable silk fibroin-based scaffold augmented with Sepia-derived melanin (Mel) and N-isopropylacrylamide (NIPAM) was developed via digital light processing (DLP) printing for infected wound healing. The incorporated Mel served a dual purpose: first, as a broadband photoabsorber ensuring high-resolution printing of well-defined porous microarchitectures within a methacrylated silk fibroin (SilMA) matrix; and second, as an intrinsic bioactive component that provided potent antioxidant and antibacterial activity through redox cycling, eliminating the need for exogenous drugs or metal ions. Furthermore, the introduction of NIPAM conferred thermal sensitivity, allowing near-infrared (NIR)-triggered reversible volume contraction driven by Mel-mediated photothermal heating. This dynamic response accelerates the Mel release and locally amplifies ROS scavenging. The designed hierarchical porosity enhances molecular diffusion and surface-mediated redox interactions, leading to bioactivity superior to that of nonporous counterparts. In vivo evaluations confirmed that the scaffold effectively controls infection (nearly 98% antibacterial rate), mitigates oxidative stress, increases the polarization of M2 macrophages, and accelerates wound closure through enhanced collagen deposition and neovascularization. This work establishes a unified strategy that seamlessly integrates high-resolution printability, intrinsic bioactivity, and on-demand responsiveness into a single biocompatible platform, offering a versatile and generalizable approach for advanced tissue regeneration in infection-compromised environments.