(36b) Supramolecular Peptide Assembly into Hydrogel Biomaterials for Neural Tissue Engineering

Neural regeneration within the central nervous system (CNS) is a critical unmet challenge as brain and spinal cord disorders continue to be the leading cause of disability nationwide. In the Lampe Group, we focus on glial cells, specifically the underappreciated oligodendrocyte which creates the essential myelin sheath that insulates axons and supports proper signal conduction. Engineering microenvironments conducive to neural stem cell guidance and differentiation in vitro and therapeutic regeneration in vivo can be addressed with hydrogel materials that mimic native neural tissue. Designer multifunctional hydrogels are well-suited as they support independent tuning of multiple biochemical and biophysical properties to create physiologically-relevant engineered extracellular matrices. We use a variety of building blocks to create tunable 3D hydrogels based on semi-synthetic polymers or engineering peptides. I will discuss our recent work designing viscoelastic networks of self-assembled short peptides. I will describe how our rapidly assembling pentapeptides for injectable delivery (RAPID) spontaneously form supramolecular structures dependent on amino acid composition, sequence, and racemic content. Coupled with all-atom molecular dynamic simulations we have been able to demonstrate the importance of hydrogen bonding and pi-interactions on peptide assembly, nanoribbon formation, and ultimately, gelation. I will further show how the RAPID system highlights the potential of peptide stereocomplexation, where combinations of l- and d-form peptides give rise to dramatically different mechanical properties due to their remarkably different nanostructure assembly. These physical hydrogels demonstrate shear-thinning, self-healing behavior conducive to minimally invasive, syringe delivery of viable neural cells. By carefully tuning material parameters in our system, such as integrin-binding peptide sequences, we engineer cell-instructive elements to directly influence stem cell differentiation and self-renewal.