This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. During embryonic development, capillary networks develop and remodel in an orderly pattern to ensure adequate blood supply to growing tissues. The architecture of developing capillary beds is tissue-specific, reflecting differences in the structure and function of the surrounding cells. This orderly process is disrupted in pathological conditions such as cancer and diabetic retinopathy. In tissue engineering, controlling vascularization of engineered constructs in a way which recapitulates developmental processes remains a desirable but elusive goal. In vivo, gradients of growth factors bound to the extracellular matrix have been implicated in directing capillary patterning in the developing mouse embryo. We are developing heparin-modified hydrogels which can present growth factors such as VEGF or FGF to endothelial cells in a well-controlled fashion, to investigate the role of matrix-bound and free cytokine gradients in controlling vascular patterning. The project involves materials synthesis and characterization as well as in vitro experiments with endothelial cells. These studies may lead to a better understanding of tissue-specific vascular patterning during embryonic development as well as to improved methods to promote functional blood vessel growth in tissue-engineered constructs.
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