Electroceuticals for Regeneration of Long Nerve Gap Using Biodegradable Conductive Conduits and Implantable Wireless Stimulator

使用可生物降解导电导管和可植入无线刺激器进行长神经间隙再生的电疗药物

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作者:Jio Kim, Jooik Jeon, Ju-Yong Lee, Badamgarav Khoroldulam, Sung-Geun Choi, Jae-Young Bae, Jung Keun Hyun, Seung-Kyun Kang

Abstract

Regeneration of over 10 mm long peripheral nerve defects remains a challenge due to the failure of regeneration by prolonged axotomy and denervation occurring in long-term recovery. Recent studies reveal that conductive conduits and electrical stimulation accelerate the regeneration of long nerve defects. In this study, an electroceutical platform combining a fully biodegradable conductive nerve conduit and a wireless electrical stimulator is proposed to maximize the therapeutic effect on nerve regeneration. Fully biodegradable nerve conduit fabricated using molybdenum (Mo) microparticles and polycaprolactone (PCL) can eliminate the unwanted effects of non-degradable implants, which occupy nerve paths and need to be removed through surgery increasing the risk of complications. The electrical and mechanical properties of Mo/PCL conduits are optimized by controlling the amounts of Mo and tetraglycol lubricant. The dissolution behavior and electrical conductivity of biodegradable nerve conduits in the biomimetic solutions are also evaluated. In in vivo experiments, the integrated strategy of a conductive Mo/PCL conduit with controlled therapeutic electrical stimulation shows accelerated axon regeneration for long sciatic nerve defects in rats compared to the use of the Mo/PCL conduit without stimulation and has a significant therapeutic effect based on the results obtained from the functional recovery test.

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