A recombinant collagen-based nanocomposite hydrogel for programmable full-cycle intelligent management of infected wounds.

Abstract

Infected wound healing is a highly dynamic, multistage process, yet most wound dressings remain functionally static and incapable of adapting to its evolving microenvironment. Here, we develop a nanocomposite hydrogel that enables programmable, full-cycle intelligent management of infected wounds. Methacrylic anhydride-grafted recombinant collagen CF-1552 functions as a macromolecular crosslinker, overcoming the cytotoxicity and uncontrollable crosslinking associated with conventional small-molecule crosslinkers. The crosslinker copolymerizes with acrylamide monomers to form a protein-polymer hydrogel network with multiple bioactivities and tunable mechanical properties, which encapsulates electro-responsive nanoparticles self-assembled from curcumin on polydopamine-templated polypyrrole nanowires. The hydrogel employs a closed-loop therapeutic paradigm governed by a "dual sensing-precision feedback-sequential release" mechanism. Specifically, (i) Rapid hemostasis and wound closure are achieved in acute trauma phase. (ii) During the transition toward a chronic, infection-prone state, bacterial proliferation induces local alkalization, triggering endogenous-responsive curcumin release, with pH-mediated visual monitoring providing feedback for early therapeutic adjustment. (iii) In inflammatory phase, conductive nanowires endow the hydrogel with a temperature coefficient of resistance (TCR = -1.49%°C^-1), enabling real-time inflammatory monitoring and feedback-regulated exogenous drug release. (iv) During proliferation and remodeling phase, the collagen network synergizes with the electro-responsive controlled-release system to promote cell migration and angiogenesis. This nanotechnology platform is capable of achieving integrated management of the entire process of wound healing due to infection.