(582g) Invited: Designer Protein and Peptide Hydrogels As 3D Microenvironments 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. Engineering microenvironments conducive to stem cell guidance and neural cell growth in vitro and therapeutic regeneration in vivo can be addressed with hydrogel materials that mimic native neural tissue. Designer multifunctional materials are well-suited as they support independent tuning of multiple biochemical and biophysical properties and allow three-dimensional (3D) encapsulation of neural cells to create a physiologically relevant engineered extracellular matrix. We use a variety of both recombinant protein and supramolecular peptide building blocks to create tunable 3D hydrogels. These include recombinant elastin-like proteins (ELPs) and rapidly assembling pentapeptides for injectable delivery (RAPID). By carefully tuning the degradation rate, integrin-binding ligand density, storage modulus, and viscoelastic behavior of the materials, we create designer hydrogels that highlight the utility of both covalently crosslinked proteins and physically crosslinked peptides. We engineer cell instructive and cell-responsive elements to directly influence stem cell differentiation and self-renewal. Our current work applies these concepts to the myelin-producing oligodendrocytes of the CNS, and their precursors, in an effort to enhance their maturation and therapeutic utility.