Hydrothermal Synthesis of Light-Responsive Adhesive Protein Polymeric Dot Nanogel for Wound Healing

Most bioadhesive gels are polymeric formulations synthesized through multistep procedures and critically lack intrinsic therapeutic properties, relying on preloaded drugs or antibiotics to promote wound healing. Here, we present a novel strategy for developing next-generation smart bioadhesive gels that overcome these limitations by combining simple synthesis, built-in therapeutic functionality, and superior wound-healing performance. Our approach employs a one-step, controllable hydrothermal carbonization process, eliminating the need for photoinitiator and complex multistep methods, enhancing both cost-effectiveness and scalability. In this single-pot system, gelatin, acrylamide, and dopamine undergo hydrothermal pyrolysis in water to form a fluorescent Protein Polymer Dot (PPD) adhesive nanogel, offering a new perspective on gelatin/acrylamide-based hydrogels. Under high-pressure conditions, thermally initiated addition polymerization of gelatin and acrylamide, together with dopamine self-oxidation, balances the adhesion and cohesion strength of the nanogel. The resulting PPD nanogels mimic the multidynamic catalytic activity of natural enzymes in a completely metal-free system, while allowing precise regulation of their redox cycle. Their light-mediated nanozyme activity enables dual antioxidant and pro-oxidant functions under ambient conditions. The unique core-shell structure supports efficient free radical scavenging, protecting cells from oxidative damage and promoting scarless wound healing. Upon visible light exposure (40 W white LED), PPD exhibits photodynamic antibacterial activity, facilitating self-sterilization of wounds. By integrating intrinsic nanozyme activity with strong interfacial adhesion, PPD nanogels accelerate wound healing through early inflammation resolution, stimulation of angiogenesis, and collagen-rich extracellular matrix remodeling in rabbits. Histological, immunohistochemical, and hydroxyproline-based biochemical analyses confirmed enhanced fibroblast proliferation, organized collagen deposition, and mature vascularization. Overall, this work presents a multifunctional nanogel that outperforms traditional bioadhesives, thanks to its nanoscale design, enhanced nanozyme activity, self-sterilizing properties, and strong wound-healing efficacy.