(52g) A Unifying Biomaterial for Constructing Chimeric Ex Vivo Neurovascular Tissue Structures
AIChE Annual Meeting
2020
2020 Virtual AIChE Annual Meeting
Materials Engineering and Sciences Division
Biomaterials: Materials for Engaging Biology
Monday, November 16, 2020 - 9:30am to 9:45am
Here, in support of the development of chimeric neurovascular tissue structures, we present a biomaterial that can: 1) mature neural cells into functional networks and 2) promote spontaneous vascular outgrowth from ex vivo brain tissue. The biomaterial consists of gelatin, a crosslinking moiety, and a peptide derived from an extracellular epitope of type 1 cadherins. A variety of polymerization regimens can produce highly porous hydrogels that are relatively soft (1-2 kPa). When human induced pluripotent stem cell (iPSC)-derived neurons are embedded in the hydrogel, they form synaptically connected networks as determined by immunostaining, electrophysiology, and viral tracing. iPSC-derived astrocytes also incorporate well into the hydrogels, with robust process extension and minimal expression of GFAP indicating suppression of a reactive phenotype. When primary mouse brain tissue is embedded in the hydrogel, robust vascular outgrowth is observed, including larger arteriole structures with proper smooth muscle organization that branch into capillary beds consisting of single endothelial cells lined by pericytes. Ongoing work is being pursued to perfuse this ex vivo vasculature and co-culture iPSC-derived astrocytes and neurons within the hydrogel to complete the full neurovascular model. Collectively, we believe this chimeric system will yield nascent, self-organizing neurovascular architectures that have been difficult to engineer and thereby represent a highly useful model for drug screening and disease modeling in the near future.