In vivostudy of novel nanofibrous intra-luminal guidance channels to promote nerve regeneration

Abstract

A novel nanofibrous construct for promoting peripheral nerve repair was fabricated and tested in a rat sciatic nerve defect model. The conduit is made out of bilayered nanofibrous membranes with the nanofibers longitudinally aligned in the lumen and randomly oriented on the outer surface. The intra-luminal guidance channel is made out of aligned nanofibrous yarns. In addition, biomolecules such as laminin and nerve growth factor were incorporated in the nanofibrous nerve construct to determine their efficacy in in vivo nerve regeneration. Muscle reinnervation, withdrawal reflex latency, histological, axon density and electrophysiology tests were carried out to compare the efficacy of nanofibrous constructs with an autograft. Our study showed mixed results when comparing the artificial constructs with an autograft. In some cases, the nanofibrous conduit with aligned nanofibrous yarn as an intra-luminal guidance channel performs better than the autograft in muscle reinnervation and withdrawal reflex latency tests. However, the axon density count is highest in the autograft at mid-graft. Functional recovery was improved with the use of the nerve construct which suggested that this nerve implant has the potential for clinical usage in reconstructing peripheral nerve defects.

A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery

“…These intraluminal guidance channels act as a platform for SC migration and proliferation and simultaneously can provide additional topographical guidance cues to regenerating axons. Ultimately, the addition of intraluminal channels aim to recapitulate the hierarchical organization and biological function of the native ECM [13]. In early studies by Matsumoto et al [36], the addition of laminin-coated collagen fibres to a PGA NGC was shown to bridge a gap of 8 cm within a canine peroneal nerve model far exceeding that of a critical nerve gap.…”

“…To complement these luminal wall guidance features and increase regeneration across a critical nerve gap, a number of approaches need to be considered. A study by Koh et al [13] combined a number of strategies [ 40] silk fibroin poly(L-lactic acid-co-1-caprolactone) (P(LLA-CL)) fibrous NGC rat sciatic 10 mm four, eight weeks significant increase in functional nerve regeneration versus P(LLA-CL) NGCs.…”

“…It was proposed that the longitudinally aligned inner layer provided topographical cues for regenerating axons and migrating SCs, while the outer layer provided structural support to the conduit structure while maintaining the porosity of the tube. This conduit was successfully used to bridge a critical nerve gap of 15 mm and exhibited functional recovery comparable to autografts [13].…”

“…Laminin, a complex trimeric glycoprotein, is a major component of the basal lamina of SCs and has positive effects on neurite extension and SC adhesion, proliferation and migration, and overall have exhibited the ability to improve nerve regeneration [13,46,70]. This trimeric glycoprotein has been demonstrated to interact with SC integrins, which may result in activation of myelination needed for successful growth and repair [13]. Numerous studies have shown its ability to enhance Schwann proliferation and migration, as well as its direct effects on neurite outgrowth [13,36,70].…”

“…This trimeric glycoprotein has been demonstrated to interact with SC integrins, which may result in activation of myelination needed for successful growth and repair [13]. Numerous studies have shown its ability to enhance Schwann proliferation and migration, as well as its direct effects on neurite outgrowth [13,36,70]. Laminin has been used most frequently for surface modification for NGC and for their respective structural components [13,36,46,55,68,70,74,75].…”