The abuse of antibiotics induces the emergence of drug-resistant bacteria, which greatly increases the difficulty of clinical treatment of infected wounds. It is urgent to design a multifunctional wound dressing independent of antibiotics. In this work, we designed multifunctional hydrogels based on lignin and cellulose in natural polymers. Lignin with antioxidant properties could reduce silver nanoparticles in situ and could also be used as a crosslinking agent to construct hydrogels between hydroxypropyl cellulose modified with phenylboric acid by a dynamic borate bond. Hydrogels have excellent properties such as self-healing, shape adaptability, biocompatibility, blood compatibility, antioxidant properties, excellent broad-spectrum antimicrobial properties, good tissue adhesion, and electrical conductivity. The tissue adhesion of hydrogels endows them with an excellent hemostasis property in a rat liver injury model. In vivo experiments demonstrated that hydrogels can maintain a moist healing environment, reduce inflammatory cell infiltration, promote M2 macrophage polarization, accelerate collagen deposition, promote the regeneration of new blood vessels, and significantly speed up the wound healing of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds. Therefore, these multifunctional hydrogels are an excellent candidate to treat multiple stages of wound healing and have a broad application prospect in the medical field.

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Peripheral nerve regeneration and functional recovery is a major challenge in clinical practice. Nerve conduit is an effective treatment for peripheral nerve repair, but the traditional hollow nerve conduit is not satisfactory in peripheral nerve repair due to the limitation of cell migration and nutrient transport. Herein, the double cross-linked hydrogels with injectable, self-healing, and conductive properties are synthesized by the Schiff base reaction between polyaniline-modified carboxymethyl chitosan and aldehyde-modified Pluronic F-127 (F127-CHO), and the hydrophobic interaction of F127-CHO. The conductive hydrogel is injected into the cavity of chitosan conduit prepared by electrodeposition. The inner conductive hydrogel and the outer chitosan conduit are formed into a whole through the Schiff base reaction to obtain a double-layer composite hydrogel nerve conduit. The double-layer composite hydrogel neural conduit loaded with 7,8-dihydroxyflavone (DHF) has excellent degradability, biocompatibility, antioxidant activity, and Schwann cell proliferation activity. In the rat sciatic nerve defect model, the double-layer composite hydrogel nerve conduit significantly promotes sciatic nerve regeneration compared with the chitosan hollow conduit. Surprisingly, the repair ability of double-layered hydrogel nerve conduit loaded with DHF is comparable to that of autologous transplantation. Therefore, this multifunctional double-layer composite hydrogel conduit has great potential for peripheral nerve repairing.

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