A major focus of our lab is developing strategies to regenerate brain and spinal cord tissues; for example, after injury or tumor resection. Clinically effective strategies to restore nerve tissues will require consideration multiple inherent barriers, such as formation of a chronic inflammatory microenvironment and a limited activity of endogenous stem cells. Biomaterials can be used to deliver coordinated, combinatorial therapies that include an extracellular matrix-like substrate, pro-regenerative biomolecules, electrical stimulation and cell transplants. Hydrogels are ideal biomaterials for use in the central nervous system because they can be injected and formed directly in living tissue, approximate mechanical and biochemical properties of healthy tissue and deliver regenerative therapies including cells. We are developing hydrogels based on hyaluronic acid (HA), a high molecular weight, matrix polysaccharide, reported to significantly augment wound healing, nerve regeneration and cell migration. We are working to maximize tissue regeneration by optimizing architecture, mechanical properties and biological signals of these biomaterial scaffolds.
Biomaterial-Mediated Gene Delivery
Delivery of genetic vectors from biomaterials is a powerful tool to influence the in vivo microenvironment. Lentiviral vectors enable sustained, localized protein expression and facile delivery of virtually any factor and combinations of factors simply by encapsulation of viral particles within hydrogels. We aim to engineer hydrogel scaffolds that support delivery of lentiviral vectors encoding for regenerative factors and to evaluate their effects on regeneration of the brain and spinal cord.
Stem Cell Transplants
Therapeutic delivery of neural stem and progenitor cells (NSPCs) has shown promise to treat restore neurological functions lost to injury and disease. However, low rates of survival, appropriate differentiation and functional engraftment after transplantation have been major limitations. To address these issues, we are working to develop hydrogel scaffolds that can provide NSPCs with 1) localized delivery, 2) improved survival during injection, 3) a supportive scaffolding after transplantation, 4) shielding from an inflammatory microenvironment, 5) factors that actively promote differentiation and 6) an architecture promoting integration with host tissue.