(272g) Micropatterned Polymer Substrates for Peripheral Nerve Regeneration and Control of Neural Stem Cell Growth and Differentiation

This talk focuses on the work initially supported by Fred Heineken through a NSF CAREER award and how that provided a foundation for future work in my laboratory. Directional outgrowth is crucial for nerve regeneration. In an effort to facilitate peripheral nerve regeneration, micropatterned biodegradable polymer films were fabricated, chemically modified and preseeded with Schwann cells to furnish a combination of physical, chemical and biological cues to dorsal root ganglia. The synergistic effects caused the axons to grow along the direction of the grooves at an accelerated rate. These microgrooved substrates inserted into conduits and implanted at the site of rat sciatic nerve transections showed significantly enhanced functional recovery compared to conventional entubulization strategies. These approaches are being extended to central nervous system regeneration using a combination of astrocytes and adult neural stem cells on micropatterned substrates. Good control of neural stem cell differentiation on these substrates prior to implantation is crucial to be able to use them in a regenerative framework. Differentiation of rat adult hippocampal progenitor cells (AHPCs) into neurons, oligodendrocytes or astrocytes on these substrates was ascertained by immunocytochemistry using various markers. The synergistic combination of physical, chemical electrical and biological cues was found to promote selective neurogenesis on the micropatterned half of the substrates as opposed to smooth half of the substrates. These results provide a unique method to spatially control the differentiation of neural stem cells on different regions of the same substrate, and can be utilized in a regeneration scheme for central nervous system repair.