Abstract 1163: Engineering Biomaterials For Vascular Differentiation And Regeneration
The goal of our studies was to utilize engineered biomaterials to understand the mechanisms underlying microenvironment regulatory cascades during vascular differentiation and regeneration. We found that the ECM polysaccharide hyaluronic acid (HA) is a developmentally relevant material for the growth of human embryonic stem cels (hESCs). Human ESCs encapsulated in HA hydrogels in conditioned media, maintained their undifferentiated state and could be further initiate vasculogenesis within the same system by supplementation with VEGF. In a continuous study we have developed a method for introducing pores into photocurable bioelastomer while maintaining mechanical properties. Biocompatibility studies demonstrated the ability to encapsulate, grow and differentiated cells in vitro, while subcutaneous transplantation revealed inflammatory response similar to other biocompatible materials. In addition, these In vivo experiments showed that the porous bioelastomer promotes ingrowth and integration with the host circulation, suggesting that porous bioelastomer may be utilized for tissue engineering applications. Mammalian cells respond to their substrates by complex changes in gene expression profiles, morphology, proliferation and migration. We report that the nanotopography of the substrate can be used to control various cellular responses of hESCs and human endothelial progenitor cell (hEPC). Poly(dimethylsiloxane) (PDMS) films were replica-molded on passivated silicon wafers to yield line-grating (600 nm ridges with 600 nm spacing and 600 ± 150 nm feature height), coated with fibronectin or collagen, and seeded with single-cell suspensions. These nanopattered PDMS substrates induced hESC alignment and elongation, mediated the organization of cytoskeletal components, and reduced proliferation. The addition of actin disrupting agents attenuated the alignment and proliferative effects of nanotopography. Human EPCs cultured on nanotopographic substrates elongated, and aligned with the structures, while their migration was also enhanced. Long-term cultures led to the formation of band-like structures of hEPCs as their proliferation was reduced, and the addition of matrigel led to the formation of ordered tube structures.