One major challenge to creating successful tissue engineering applications is the development of a vascular supply to a newly generated or implanted tissue in order to supply oxygen and nutrients as well as to remove waste. There is a need for greater understanding of the factors influencing endothelial cell migration and capillary morphogenesis, and importantly, how to manipulate the cellular environment to optimally induce a functional blood supply in order to vasculadze engineered tissues. While numerous natural and synthetic biomatedal supports have been investigated for this purpose, there is a great interest in the use of synthetic biomatedals. One new class of materials, self-assembling oligopeptides, has shown great promise in supporting endothelial survival and capillary morphogenesis in the absence of survival factors typically necessary for cells cultured in collagen, a frequently used support. Further, these peptide gels show endothelial cell migration and little to no immunogenicity when injected in vivo.
The first aim of this proposal is to investigate the effect of peptide get stiffness on endothelial capillary morphogenesis, migration, extracellular matrix(ECM) production, and survival. The second and third aims are to further characterize the endothelial cell-peptide gel interaction and mechanisms of survival and capillary morphogenesis with a focus on the hypothesis that ECM production by the cells is responsible for both.
