Biomimetic poly(serinol hexamethylene urea) for promotion of neurite outgrowth and guidance

Abstract

Nerve function recovery is a major technical challenge in the rehabilitation of patients suffering from severe neuropathies. Facilitating functional recovery requires the creation of a growth-permissive environment that directs the extension and myelination of surviving neurons. To this end, an electrospun nanofiber scaffold composed of arginine–glycine–aspartate-modified poly(serinol hexamethylene urea)-blend-poly-ε-caprolactone (PSHU-RGD/PCL) has been employed. Initially, we investigated the cytotoxicity of PSHU in PC12 cell culture. This was followed by functional examinations of PSHU-RGD for cell viability, proliferation, differentiation, and neurite outgrowth, and finally we examined electrospun scaffolds for guided neurite sprouting. MTT proliferation assays indicated no cytotoxic effects of polymer as compared to laminin-coated surfaces. Functional testing revealed PSHU-RGD surfaces to be comparable to the positive control, laminin-coated surface, in neurite outgrowth studies with average neurite lengths of 84.6 μm (laminin), 218.2 μm (PSHU-RGD), 570.2 μm (laminin + NGF), and 958.2 μm (PSHU-RGD + NGF) after two weeks on homogeneously modified surfaces, and 554.8 μm (nonwoven mats) and 1512.3 μm (uniaxially aligned mats) for PSHU-RGD/PCL + NGF scaffolds after one week. We created PSHU functionalized with the tripeptide, RGD, which provided chemical and physical cues to PC12 cell proliferation and differentiation. We expect that PSHU-RGD will be capable of directing and promoting neurite outgrowth in many neuropathy models.