A protein-initiated polymerization cascade enables a self-eliminating powder tissue adhesive for diabetic ulcer repair.

Abstract

Inspired by natural protein-based adhesives and protein-guided biosynthesis and assembly processes, this work proposes a strategy for constructing a bioactive dynamic adhesive through a protein-initiated polymerization cascade. In this system, ovalbumin (OVA) acts as a macromolecular director, and sodium lipoate (LANa) serves as a polymerizable bioactive monomer. The surfactant property of LANa disrupts the tertiary structure of OVA, exposing hydrophobic domains and thiol groups. LANa subsequently binds to these exposed hydrophobic microdomains to form OVA-LANa complexes, while the exposed thiols further initiate the ring-opening polymerization of LANa via thiol-disulfide exchange. This cascade proceeds rapidly and spontaneously without external energy input, complex synthetic procedures, or additional catalysts. The resulting metastable precursor solution can be lyophilized and ground into a storable powder (OPLA-P). Upon contact with body fluids, OPLA-P rapidly rehydrates and reinitiates polymerization, forming an in situ solidified adhesive hydrogel for efficient sealing. Furthermore, the sustained release of bioactive LANa helps regulate the regenerative microenvironment and accelerates wound healing. After fulfilling its functions, the hydrogel gradually dissolves spontaneously, helping alleviate the adhesion-trauma-free dilemma. When evaluated in diabetic ulcer models, including full-thickness skin defects and oral ulcers, OPLA-P exhibits superior therapeutic effects to those of the selected commercial materials.