Exosomes-loaded electroconductive nerve dressing for nerve regeneration and pain relief against diabetic peripheral nerve injury

Over the years,electroconductive hydrogels(ECHs)have been extensively applied for stimulating nerve regeneration and restoring locomotor function after peripheral nerve injury(PNI)with diabetes,given their favorable mechanical and electrical properties identical to endogenous nerve tissue.Nevertheless,PNI causes the loss of locomotor function and inflammatory pain,especially in diabetic patients.It has been established that bone marrow stem cells-derived exosomes(BMSCs-Exos)have analgesic,anti-inflammatory and tissue regeneration properties.Herein,we designed an ECH loaded with BMSCs-Exos(ECH-Exos)electroconductive nerve dressing to treat diabetic PNI to achieve functional recovery and pain relief.Given its potent adhesive and self-healing properties,this laminar dressing is convenient for the treatment of damaged nerve fibers by automatically wrapping around them to form a size-matched tube-like structure,avoiding the cumbersome implantation process.Our in vitro studies showed that ECH-Exos could facilitate the attachment and migration of Schwann cells.Meanwhile,Exos in this system could modulate M2 macrophage polarization via the NF-κB pathway,thereby attenuating inflammatory pain in diabetic PNI.Additionally,ECH-Exos enhanced myelinated axonal regeneration via the MEK/ERK pathway in vitro and in vivo,consequently ameliorating muscle denervation atrophy and further promoting functional restoration.Our findings suggest that the ECH-Exos system has huge prospects for nerve regeneration,functional restoration and pain relief in patients with diabetic PNI.

Self-curling electroconductive nerve dressing for enhancing peripheral nerve regeneration in diabetic rats

Conductive scaffolds have been shown to exert a therapeutic effect on patients suffering from peripheral nerve injuries(PNIs).However,conventional conductive conduits are made of rigid structures and have limited applications for impaired diabetic patients due to their mechanical mismatch with neural tissues and poor plasticity.We propose the development of biocompatible electroconductive hydrogels(ECHs)that are identical to a surgical dressing in this study.Based on excellent adhesive and self-healing properties,the thin film-like dressing can be easily attached to the injured nerve fibers,automatically warps a tubular structure without requiring any invasive techniques.The ECH offers an intimate and stable electrical bridge coupling with the electrogenic nerve tissues.The in vitro experiments indicated that the ECH promoted the migration and adhesion of the Schwann cells.Furthermore,the ECH facilitated axonal regeneration and remyelination in vitro and in vivo through the MEK/ERK pathway,thus preventing muscle denervation atrophy while retaining functional recovery.The results of this study are likely to facilitate the development of non-invasive treatment techniques for PNIs in diabetic patients utilizing electroconductive hydrogels.