Synthesis of Solvent-Free Cu(I) Gel and Its Applications in Diabetic Wound Healing

The charm of small-molecules-based building blocks lies in their facile synthetic routes, programmable supramolecular interactions, and synergistic functions. Here, a solvent-free gel system constructed with thioctic acid (TA) and Cu(OAc)2·H2O is proposed, in which the ingredients were ground together and subsequently subjected to thermal polymerization under vacuum. Interestingly, Cu(II) ions from Cu(OAc)2·H2O were reduced to Cu(I); meanwhile, a small amount of TA was oxidized to thiosulfinate ester. The resulted gel exhibited a low swelling ratio (<5%), excellent self-healing (>95% recovery), high ductility (up to 2800% elongation), tissue adhesion (0.06-0.11 MPa), and photothermal performance (70 °C under 808 nm irradiation). Since sulfur-copper coordination could neutralize the adverse effects of Cu(I), this gel exhibited desirable biocompatibility, broad-spectrum antimicrobial activity, and low cellular toxicity. Furthermore, glutathione (GSH), an endogenous antioxidant, was incorporated into the gel network to synergistically enhance antioxidant capacity, copper valence stabilization, and tissue regeneration. Moreover, the gel promoted wound healing in an MRSA-infected diabetic open-wound model, achieving a 90% wound-healing rate within 15 days with 46% reduction in TNF-α and 142% increase in CD31 expression compared to the control. This work was themed on simple building blocks, facile gel preparation, and heavy-metal coordination-driven supramolecular polymer networks, which provided an approach toward reducing the toxicity of heavy-metal ions while utilizing the advantages of heavy-metal therapy for diseases.