In view of the lack of a specific drug-sustained release system that is responsive to chronic wounds of the type II diabetic foot, and the demands for frequent movement at the foot wound, pH/glucose dual-responsive metformin-released adhesion-enhanced self-healing easy-removable antibacterial antioxidant conductive hemostasis multifunctional phenylboronic acid and benzaldehyde bifunctional polyethylene glycol-co-poly­(glycerol sebacic acid)/dihydrocaffeic acid and l-arginine cografted chitosan (PEGS-PBA-BA/CS-DA-LAG, denoted as PC) hydrogel dressings were constructed based on the double dynamic bond of the Schiff-base and phenylboronate ester. It was further demonstrated that the PC hydrogel promotes wound healing by reducing inflammation and enhancing angiogenesis in a rat type II diabetic foot model. In addition, the addition of metformin (Met) and graphene oxide (GO), as well as their synergy, were confirmed to better promote wound repair in vivo. In summary, adhesion-enhanced self-healing multifunctional PC/GO/Met hydrogels with stimuli-responsive metformin release ability and easy removability have shown a promoting effect on the healing of chronic athletic diabetic wounds and provide a local-specific drug dual-response release strategy for the treatment of type II diabetic feet.

Hydrogels with multifunctionalities, including sufficient bonding strength, injectability and self-healing capacity, responsive-adhesive ability, fault-tolerant and repeated tissue adhesion, are urgently demanded for invasive wound closure and wound healing. Motivated by the adhesive mechanism of mussel and brown algae, bioinspired dynamic bonds cross-linked multifunctional hydrogel adhesive is designed based on sodium alginate (SA), gelatin (GT) and protocatechualdehyde, with ferric ions added, for sutureless post-wound-closure. The dynamic hydrogel cross-linked through Schiff base bond, catechol-Fe coordinate bond and the strong interaction between GT with temperature-dependent phase transition and SA, endows the resulting hydrogel with sufficient mechanical and adhesive strength for efficient wound closure, injectability and self-healing capacity, and repeated closure of reopened wounds. Moreover, the temperature-dependent adhesive properties endowed mispositioning hydrogel to be removed/repositioned, which is conducive for the fault-tolerant adhesion of the hydrogel adhesives during surgery. Besides, the hydrogels present good biocompatibility, near-infrared-assisted photothermal antibacterial activity, antioxidation and repeated thermo-responsive reversible adhesion and good hemostatic effect. The in vivo incision closure evaluation demonstrated their capability to promote the post-wound-closure and wound healing of the incisions, indicating that the developed reversible adhesive hydrogel dressing could serve as versatile tissue sealant.

The on-demand replacement of multifunctional hydrogel wound dressings helps to avoid bacterial colonization, and the on-demand painless peeling of tissue adhesive hydrogels on the wound site remains a major challenge to be solved. In this work, we design and develop a series of multifunctional dynamic Schiff base network hydrogels composed of cystamine-modified hyaluronic acid, benzaldehyde-functionalized poly­(ethylene glycol)-co-poly­(glycerol sebacate), and polydopamine@polypyrrole nanocomposite (PDA@PPy) with mild on-demand removability to enhance drug-resistant bacteria-infected wound healing. These hydrogels exhibited ideal injectable and self-healing properties, excellent tissue adhesion, in vivo hemostasis, good antioxidation, and conductivity. PDA@PPy inspired by melanin endows hydrogels with excellent antioxidant capacity, UV-blocking ability, and photothermal anti-infection ability. Based on the dynamic oxidation–reduction response of disulfide bonds inspired by the dissociation of the tertiary spatial structure transformation of poly-polypeptide chains, these hydrogels can achieve rapid painless on-demand removal under mild conditions by adding dithiothreitol. These multifunctional hydrogels significantly promoted collagen deposition and angiogenesis in the MRSA-infected full-thickness skin repair experiment. All the results showed that these multifunctional hydrogels with painless on-demand removal property showed great potential in clinical treatment of infected wounds.

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