Bioactive thermoresponsive hydrogels for neural tissue engineering

Abstract

Traumatic brain injury (TBI) results in over 50,000 deaths and 80,000 disabilities each year. Current treatment strategies aim to alleviate acute disturbances, but are not able to address the chronic disorders associated with TBI. Neural transplantation is one potential treatment that will provide multifaceted sustained therapy to degenerating injured tissue. Transplantation of multipotent neural stem cells (NSCs) has been shown to enhance functional recovery in TBI models; however, poor cell survival and integration with host tissue potentially restrict the efficacy of such transplants. This limitation may be due to the absence of inherent NSC pro-survival cues (e.g., cell-ECM interactions). Furthermore, the neural injury environment presents cell death factors to transplanted NSCs. It is hypothesized that a 3-D scaffold presenting specific CNS adhesive moieties will enhance donor cell survival and promote differentiation and migration. This project encompassed material development and in vitro characterization. Results highlighted the importance of ligand tethering chemistry and density and also the mechanical integrity of cell scaffold systems. Furthermore, the developed scaffold provides a controlled microenvironment to assess the influence of LN on NSC survival, migration, and differentiation. Lastly, co-delivering NSC with the MC-LN tissue engineered scaffold into a mechanically injured neural co-culture test-bed or in vivo TBI model confirmed the importance of ECM cues for NSC survival and migration, respectively.