Abstract
Peripheral nerves possess the capacity of self-regeneration after traumatic injury but the extent of regeneration is often poor and may benefit from exogenous factors that enhance growth. The use of cellular systems is a rational approach for delivering neurotrophic factors at the nerve lesion site, and in the present study we investigated the effects of enwrapping the site of end-to-end rat sciatic nerve repair with an equine type III collagen membrane enriched or not with N1E-115 pre-differentiated neural cells. After neurotmesis, the sciatic nerve was repaired by end-to-end suture (End-to-End group), end-to-end suture enwrapped with an equine collagen type III membrane (End-to-EndMemb group); and end-to-end suture enwrapped with an equine collagen type III membrane previously covered with neural cells pre-differentiated in vitro from N1E-115 cells (End-to-EndMembCell group). Along the postoperative, motor and sensory functional recovery was evaluated using extensor postural thrust (EPT), withdrawal reflex latency (WRL) and ankle kinematics. After 20 weeks animals were sacrificed and the repaired sciatic nerves were processed for histological and stereological analysis. Results showed that enwrapment of the rapair site with a collagen membrane, with or without neural cell enrichment, did not lead to any significant improvement in most of functional and stereological predictors of nerve regeneration that we have assessed, with the exception of EPT which recovered significantly better after neural cell enriched membrane employment. It can thus be concluded that this particular type of nerve tissue engineering approach has very limited effects on nerve regeneration after sciatic end-to-end nerve reconstruction in the rat.
Highlights
Nerve regeneration is a complex biological phenomenon
Motor deficit and Nociception function Motor deficit (EPT) Before sciatic injury, extensor postural thrust (EPT) was similar in both hindlimbs in all experimental groups
The EPT response steadily improved during recovery but at week-20 the EPT values of the injured side were still significantly lower compared to values at week-0 (p < 0.05)
Summary
Nerve regeneration is a complex biological phenomenon. In the peripheral nervous system, nerves can spontaneously regenerate without any treatment if nerve continuity is maintained (axonotmesis) whereas more severe type of injuries must be surgically treated by direct end-to-end surgical reconnection of the damaged nerve ends [1,2,3]. Natural materials are more likely to be biocompatible than artificial materials They are less toxic and provide a good support to cell adhesion and migration due to the presence of a variety of surface molecules. ECM molecules, such as laminin, fibronectin and collagen have been shown to play a significant role in axonal development and regeneration [12,18,19,20,21,22,23,24,25,26,27]. The local presence of growth factors plays an important role in controlling survival, migration, proliferation, and differentiation of the various cell types involved in nerve regeneration [12,13,14,33]. Employment of biodegradable membranes enriched with a cellular system producing neurotrophic factors has been suggested to be a rational approach for improving nerve regeneration after neurotmesis [11]
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