Multifunctional Double-Layer Composite Hydrogel Conduit Based on Chitosan for Peripheral Nerve Repairing

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.