Bioactive Nanofiber-based Conduits in a Peripheral Nerve Gap Management- an Animal Model Study.

Abstract

Background: Peripheral nerve injuries (PNI) are trauma with severe squeals for patients’ quality of life. Currently, the gold standard of nerve reconstruction relies on primary coaptation. However, in case of a nerve gap, a reconstructive material for bridging is needed. Nerve conduits are an increasingly popular solution alternative to autografts or processed nerved allografts. The aim of the study was to examine the efficiency of a novel bioactive nanofiber-based tubular scaffold made of poly (L-lactic acid)-co-poly(ϵ-caprolactone), collagen, polyaniline and enriched with adipose-derived stem cells (ASCs) as a nerve conduit in a rat model.Methods: Poly (L-lactic acid)-co-poly(ϵ-caprolactone) scaffold was optimized and enriched with collagen (COL) and polyaniline (PANI) to create final (P(LLA-CL)-COL-PANI), tubular-shaped scaffold, manufactured with electrospinning technology. Parallelly, adipose tissue from 10 Lewis rats was harvested for ASC culture. 28 inbred male Lewis rats were divided into four even groups. Each animal underwent sciatic nerve transection and excision of a 10 mm nerve trunk fragment. In group A, nerve gap remained untouched, in B excised trunk was rotated and used as an autograft, in C nerve stumps were secured with P(LLA-CL)-COL-PANI conduit. In the D group gap was reconstructed with P(LLA-CL)-COL-PANI conduit enriched with ASCs. After 6-months of observation rats were sacrificed. Gastrocnemius muscles (operated and non-operated side) and reconstructed sciatic nerves were harvested for analyses. Muscles were weighted and underwent histological analysis. Nerves were processed and stained immunohistochemically with NF-200 to be analyzed with dedicated software for nerve fiber count. Results: No signs of rejection or excessive fibrosis was noted. Muscle mass ratio was highest in group B (0.77±0.05), then in C (0.74±0,04) and D (0.67± 0.07). Group A showed advanced atrophy of the muscle, each intervention prevented muscle mass decrease (p<0.0001), however, ASC addition decreased efficiency vs autograft (p<0.05). Nerve fiber count revealed a superior effect in the nerve fiber density observed in the group with the use of conduit vs autograft (D vs B p<0.0001, C vs B p<0.001). ASC added to the conduit decreased perineurium hyperplasia.Conclusion: P(LLA-CL)-COL-PANI conduits with ASC showed promising results in managing nerve gap by decreasing muscle atrophy and providing a favorable environment for peripheral nerve regeneration.