Peripheral Nerve Repair in Rats Using Composite Hydrogel-Filled Aligned Nanofiber Conduits with Incorporated Nerve Growth Factor

Abstract

Repair of peripheral nerve defects with current synthetic, tubular nerve conduits generally shows inferior recovery when compared with using nerve autografts, the current gold standard. We tested the ability of composite collagen and hyaluronan hydrogels, with and without the nerve growth factor (NGF), to stimulate neurite extension on a promising aligned, nanofiber poly-L-lactide-co-caprolactone (PLCL) scaffold. In vitro, the hydrogels significantly increased neurite extension from dorsal root ganglia explants. Consistent with these results, the addition of hydrogels as luminal fillers within aligned, nanofiber tubular PLCL conduits led to improved sensory function compared to autograft repair in a critical-size defect in the sciatic nerve in a rat model. Sensory recovery was assessed 3 and 12 weeks after repair using a withdrawal assay from thermal stimulation. The addition of hydrogel did not enhance recovery of motor function in the rat model. The NGF led to dose-dependent improvements in neurite out-growth in vitro, but did not have a significant effect in vivo. In summary, composite collagen/hyaluronan hydrogels enhanced sensory neurite outgrowth in vitro and sensory recovery in vivo. The use of such hydrogels as luminal fillers for tubular nerve conduits may therefore be useful in assisting restoration of protective sensation following peripheral nerve injury.

Nanofiber‐Based Hydrogels: Controllable Synthesis and Multifunctional Applications

“…Kuo and co‐workers fabricated NFHGs never scaffold by compositing tubular poly‐ l ‐lactide‐ co ‐caprolactone membranes with collagen/hyaluronan mixed hydrogels. Whereas, the sensory function recovery performance of the composite NFHGs nerve conduit did not reach the effect of autograft repair . Similar research work was also carried out by Kumbar and co‐workers .…”

Evaluation of Small Intestine Submucosa and Poly(caprolactone-co-lactide) Conduits for Peripheral Nerve Regeneration

“…Several groups have reported that artificial NGCs can show comparable or even superior nerve regeneration abilities as compared with nerve autografts. [9][10][11][12][13][14]37,38 In designing the next generation of NGCs, much consideration has to be placed in the selection of an appropriate biomaterial. In addition, little previous study has examined NGCs fabricated by using a simple and versatile fabrication technique.…”

Tissue engineering of the peripheral nervous system

“…In this study, positive outcomes were obtained with the use of hydrogels containing aligned PLCL fibers, but the incorporation of NGF did not have a significant effect on nerve regeneration. This study demonstrated that the use of two combined physical fillers promotes an efficient nerve regeneration and sensory recovery [157]. Growth factors can also be used in combination providing a synergetic effect to the nerve regeneration [158][159][160].…”