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.
Aggarwal et al. (Thu,) studied this question.