Functional recovery of denervated muscle by neurotization using nerve guidance channels

Abstract

Tissue-engineered muscle has been proposed as a means of repairing volumetric muscle defects to restore anatomical and functional recovery. We have previously demonstrated that denervated muscle, which is analogous to engineered muscle construct, can be reinnervated by direct transplantation of host nerve (neurotization) in a rat model. However, the use of this approach is not possible if the length of host nerve is inadequate and cannot be mobilized to the insertion site of the engineered muscle. In this study we investigated whether neurotization coupled with nerve guidance channels would increase the regeneration of neuromuscular junctions (NMJs) in completely denervated muscle and encourage neurofunctional recovery. Seventy-two Lewis rats were evaluated in three groups, a normal control group (n = 8), a denervated group (n = 32) and a neurotization coupled with nerve guidance group (n = 32). Neurofunctional behaviour and histological evaluations were performed at 4, 8, 12 and 20 weeks postoperatively. Extensor postural thrust (EPT) and compound muscle action potential (CMAP) amplitude were significantly improved in the nerve guidance group when compared with the denervated group, even though these values were different from those of the normal control group at 20 weeks postoperation. Regeneration of axons and NMJs was demonstrated histologically in the nerve guidance group. Neurotization coupled with nerve guidance channels leads to regeneration of axons and NMJs in completely denervated muscle. To our knowledge, this is the first report to show that nerve guidance can allow re-innervation in denervated muscle containing long-gap nerve injuries.

Enhancement of primary neuronal cell proliferation using printing‐transferred carbon nanotube sheets

“…Therefore, over the last 20 years, the development of artificial NGCs as alternatives to autogenous nerve grafting has been attempted for repairing peripheral nerve injuries . An ideal guide tube for successful use in nerve grafting should possess several biological and physico‐mechanical properties, including mechanical tolerance, permeability for metabolic exchange and diffusion of growth or trophic factors, biocompatibility and absorbability, internal structure reflecting the architecture of the nerve fascicle, and the presence of Schwann cell promoting axonal extension and neural survival . CNT has been considered as a potential candidate that could offer suitable physical, chemical, and electronic advantages for neural grafting.…”

The role of peripheral nerve surgery in a tissue reinnervation

“…Histologically, in all control groups, fat infiltration and a decrease in the size of sarcomeres were observed; however, in the neurotization-conduit group, muscle fibers were restored, and the diameter of the axon increased. In conclusion, the authors of the study noted, that the presented combined technique can lead to a complete restoration of functions, but it is necessary to use a more sophisticated conduit and its inner environment [27].…”

Biomimetic Nerve Guidance Conduit Containing Intraluminal Microchannels with Aligned Nanofibers Markedly Facilitates in Nerve Regeneration

“…Neurorrhaphy is one surgical repair technique involving the direct suturing of discontinued nerve stumps. Although relatively successful at recovering nerve function, neurorrhaphy is limited to gaps no greater than 5 mm in length as excessive tension on the nerve disrupts connective tissue matrices and reduces blood flow, inducing necrosis and chronic ischemia. , The gold standard for longer nerve gaps are autografts . Although autografts offer the best nerve regenerative characteristics, they are associated with many drawbacks including a second surgical procedure, donor site morbidity, mismatch of donor nerve size, and limited donor nerve length.…”

“…5,6 The gold standard for longer nerve gaps are autografts. 7 Although autografts offer the best nerve regenerative characteristics, they are associated with many drawbacks including a second surgical procedure, donor site morbidity, mismatch of donor nerve size, and limited donor nerve length. As an alternative, allografts avoid several of the limitations of autografts, but the complexity and cost of producing allografts remains a challenge.…”