(10f) Non-Covalent Surface Modification of Topologically Complex PLLA Electrospun Scaffolds with Nano-Thin Silk Fibroin Coating for Nerve Regenerative Applications.

Biodegradable synthetic polymers have found many practical uses for tissue engineering applications due to their ease of processing and uniform morphology. For nerve regenerative applications in particular, they are able to be easily aligned to promote neurite extension, and the addition of surface nanotopographies is easily achievable to help enhance a cellular response. However even with these additional modifications, they still do not promote the degree of cellular adhesion and proliferation seen with natural biopolymer materials without further surface modification. Current modification strategies utilizing covalent chemistries are limited in application due to potentially compromised biocompatibility of the device from residual cytotoxic additives. Recently, we have investigated a novel bottom-up approach for generating extremely homogeneous and conformal nano-thin coatings of silk fibroin, a biopolymer derived from Bombyx mori threads that has shown to be neurocompatible. Here we investigate the capability of these nano-thin coatings to increase the neuroregenerative properties of poly-l-lactic acid (PLLA) electrospun scaffolds while maintaining the small topography features found on the surfaces of the fibers. Prefabricated, highly aligned PLLA fiber scaffolds with smooth, pitted, or divoted nanotopographies were coated with a nano-thin coating of silk fibroin generated by leveraging the controlled self-assembly of the protein under aqueous conditions. Homogeneous coatings that completely masked the underlying surface properties of the PLLA while still maintaining the fine surface topography were verified by confocal fluorescence microscopy and scanning electron microscopy. Additionally, this alteration of surface chemistry was verified by a change in the isoelectric point of the surface close to theoretical values documented for silk fibroin. While no change in surface wettability was observed for all scaffold types, there was a significant enhancement in the adhesion of dorsal root ganglia as well as greater neurite outgrowth on fibers coated with silk fibroin. Ultimately, this work demonstrates a novel non-covalent method for functionalizing electrospun scaffolds fabricated from synthetic biodegradable polymers to enhance their neuroregenerative properties. Additionally, to our knowledge, this is the first instance of biomedical modification of topologically complex substrates using non-covalent methods.