Abstract

The focus of significance in neuronal repair strategies is the design of scaffold systems capable of promoting neuronal regeneration and directional guidance via provision of a biomimetic environment resemblance of native neural tissue. The purpose of this study was to synthesize triple-cue electrospun aligned nanofibrous films (physical cue) of poly(3-hyroxybutyric acid-co-3-hydroxyvaleric acid) (PHBV) blended with magnesium-oleate (MgOl) (chemical cue) and N-acetyl-L-cysteine (NAC) (therapeutic cue) with potential incorporation into hollow nerve guidance conduits for an enhanced regenerative strategy. A Box–Behnken experimental design of 15 formulations, were analysed for crystallinity, textural properties and in vitro water-uptake, erosion, NAC-release and PC12 cell viability. Nucleating effects of MgOl provided tuning of PHBV electrospinning-induced crystallinity and mechanical properties. Tensile strengths and deformation moduli of ±12 MPa and ±7 MP, respectively, were attainable, thereby matching native nerve mechanics. Crystallinity changes ascribed differing release kinetics to NAC over 30 d: diffusion-based (42%–58% crystallinity with 33%–47% fractional release) and polymer-relaxational (59%–65% crystallinity with 60%–82% fractional release). The synergistic activity of MgOl and NAC increased PC12 proliferation by 32.6% compared to the control. MgOl produced dual actions as non-toxic plasticiser and PC12 cell proliferation-promoter via nucleation and neurotrophic-like effects, respectively. Controlled release of NAC imparted neuro-protectant effects on PC12 cells and promoted neurite extension, thus, making electrospun PHBV-MgOl nanofibrous films a versatile and promising approach for axonal guidance in peripheral nerve repair strategies.

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