In cases of complex neuromuscular defects, finding the proximal stump of a transected nerve in order to restore innervation to damaged muscle is often impossible. In this study we investigated whether a neighboring uninjured nerve could serve as a source of innervation of denervated damaged muscle through a biomaterial-based nerve conduit while preserving the uninjured nerve function. Tubular nerve conduits were fabricated by electrospinning a polymer blend consisting of poly(ε-caprolactone) (PCL) and type I collagen. Using a rat model of common peroneal injury, the proximal end of the nerve conduit was connected to the side of the adjacent uninjured tibial branch (TB) of the sciatic nerve after partial axotomy, and the distal end of the conduit was connected to the distal stump of the common peroneal nerve (CPN). The axonal continuity recovered through the nerve conduit at 8 weeks after surgery. Recovery of denervated muscle function was achieved, and simultaneously, the donor muscle, which was innervated by the axotomized TB also recovered at 20 weeks after surgery. Therefore, this end-to-side neurorrhaphy (ETS) technique using the electrospun PCL/collagen conduit appears to be clinically feasible and would be a useful alternative in instances where autologous nerve grafts or an adequate proximal nerve stump is unavailable.
"It was recently demonstrated that the use of novel electrospun PCL/collagen conduits (poly ε-caprolactone/collagen type I) may support nerve regeneration and functional recovery at 20 weeks after surgery (Lee et al 2012). However, the therapeutic usefulness of bioengineered nerve conduits remains controversial (Bell and Haycock 2012, Daly et al 2012, Kehoe et al 2012, Yao et al 2010). "
[Show abstract][Hide abstract] ABSTRACT: Objective:
The objective was to study the effectiveness of a commercially available collagen conduit filled with fibrin-agarose hydrogels alone or with fibrin-agarose hydrogels containing autologous adipose-derived mesenchymal stem cells (ADMSCs) in a rat sciatic nerve injury model.
A 10 mm gap was created in the sciatic nerve of 48 rats and repaired using saline-filled collagen conduits or collagen conduits filled with fibrin-agarose hydrogels alone (acellular conduits) or with hydrogels containing ADMSCs (ADMSC conduits). Nerve regeneration was assessed in clinical, electrophysiological and histological studies.
Clinical and electrophysiological outcomes were more favorable with ADMSC conduits than with the acellular or saline conduits, evidencing a significant recovery of sensory and motor functions. Histological analysis showed that ADMSC conduits produce more effective nerve regeneration by Schwann cells, with higher remyelination and properly oriented axonal growth that reached the distal areas of the grafted conduits, and with intensely positive expressions of S100, neurofilament and laminin. Extracellular matrix was also more abundant and better organized around regenerated nerve tissues with ADMSC conduits than those with acellular or saline conduits.
Clinical, electrophysiological and histological improvements obtained with tissue-engineered ADMSC conduits may contribute to enhancing axonal regeneration by Schwann cells.
[Show abstract][Hide abstract] ABSTRACT: Current approaches for treating peripheral nerve injury have resulted in promising, yet insufficient functional recovery compared to the clinical standard of care, autologous nerve grafts. In order to design a construct that can match the regenerative potential of the autograft, all facets of nerve tissue must be incorporated in a combinatorial therapy. Engineered biomaterial scaffolds in the future will have to promote enhanced regeneration and appropriate reinnervation by targeting the highly sensitive response of regenerating nerves to their surrounding microenvironment.
Current Opinion in Biotechnology 06/2013; 24(5). DOI:10.1016/j.copbio.2013.05.006 · 7.12 Impact Factor
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