Porous Silicon Nanoparticles Embedded in Poly(lactic- co- glycolic acid) Nanofiber Scaffolds Deliver Neurotrophic Payloads to Enhance Neuronal Growth

Abstract

Scaffolds made from biocompatible polymers provide physical cues to direct the extension of neurites and to encourage repair of damaged nerves. The inclusion of neurotrophic payloads in these scaffolds can substantially enhance regrowth and repair processes. However, many promising neurotrophic candidates are excluded from this approach due to incompatibilities with the polymer or with the polymer processing conditions. This work provides one solution to this problem by incorporating porous silicon nanoparticles (pSiNPs) that are preloaded with the therapeutic into a polymer scaffold during fabrication. The nanoparticle- drug- polymer hybrids are prepared in the form of oriented poly(lactic- co- glycolic acid) nanofiber scaffolds. Three different therapeutic payloads are tested: bpV(HOpic), a small molecule inhibitor of phosphatase and tensin homolog (PTEN); an RNA aptamer specific to tropomyosin- related kinase receptor type B (TrkB); and the protein nerve growth factor (NGF). Each therapeutic is loaded using a loading chemistry that is optimized to slow the rate of release of these water- soluble payloads. The drug- loaded pSiNP- nanofiber hybrids release approximately half of their TrkB aptamer, bpV(HOpic), or NGF payload in 2, 10, and >40 days, respectively. The nanofiber hybrids increase neurite extension relative to drug- free control nanofibers in a dorsal root ganglion explant assay.Porous silicon nanoparticles are loaded with bpV(HOpic), a tropomyosin- related kinase receptor type B RNA aptamer, or nerve growth factor using three distinct loading chemistries. They are incorporated into aligned poly(lactic- co- glycolic acid) nanofibers using an airbrush, and the nanofiber hybrids release their payloads over varying timescales. The three released payloads maintain their bioactivity as shown by enhanced neurite extension of dorsal root ganglion explants cultured on the hybrid nanofiber scaffolds.