Functional Recovery of Completely Denervated Muscle: Implica

[Chillywil91]

Functional Recovery of Completely Denervated Muscle: Implications for Tissue Engineered Muscle.

Kang SB, Olson JL, Atala A, Yoo J.


Source

Seoul National University Bundang Hospital, Department of Surgery, Bundang-gu, Korea, Republic of; kangsb@snubh.org.


Abstract

Tissue engineered muscle has been proposed as a solution to repair volumetric muscle defects and restore muscle function. To achieve functional recovery, an engineered muscle tissue, which is analogous to denervated muscle, requires integration of host nerve. In this study we investigated whether denervated muscle possesses the ability to reinnervate and recover muscle function using an in vivo model of denervation followed by neurotization. Eighty Lewis rats were classified into three groups: a normal control group (n=16); a denervated group in which sciatic innervations to the gastrocnemius muscle were disrupted (n=32); and a transplantation group in which the denervated gastrocnemius was repaired with a common peroneal nerve graft (n=32). Neurofunctional behavior, including extensor postural thrust (EPT), withdrawal reflex latency (WRL), and compound muscle action potential (CMAP), as well as histological evaluations using alpha-bungarotoxin and anti-NF-200, were performed at 2, 4, 8 and 12 weeks (n=8) after surgery. We found that EPT was improved by transplantation of the nerve grafts, but the EPT values in the transplanted animals at 12 weeks post-surgery were still significantly lower than those measured for the normal control group at 4 weeks (EPT, 155.0±38.9 vs 26.3±13.8 g, P < 0.001; WRL, 2.7±2.30 vs 8.3±5.5 sec, P = 0.027). In addition, CMAP latency and amplitude significantly improved with time after surgery in the transplantation group (P < 0.001, one-way ANOVA), and at 12 weeks post-surgery, CMAP latency and amplitude were not statistically different from normal control values (latency, 0.9±0.0 vs 1.3±0.7ms, P = 0.164; amplitude, 30.2±7.0 vs 46.4±26.9 mV, P = 0.184). Histologically, regeneration of neuromuscular junctions was seen in the transplantation group. This study indicates that transplanted nerve tissue is able to regenerate neuromuscular junctions within denervated muscle denervated muscle is able to regenerate the neuromuscular junction and thus, the muscle can recover partialits function. However, the function of the denervated muscle remains in the subnormal range even at 12 weeks after direct nerve transplantation. These results suggest that tissue engineered muscle, which is similarly denervated, could be innervated and become functional in vivo if it is properly integrated with host nerve.