UNDERSTANDING AND CONTROLLING TISSUE-SPECIFIC VASCULAR PATTERNING

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 在胚胎发育期间，毛细血管网络以有序的模式发展和重塑，以确保为生长组织提供足够的血液。发育中的毛细血管床的结构是特定于组织的，反映了周围细胞的结构和功能的差异。在癌症和糖尿病视网膜病变等病理情况下，这种有序的过程会被打乱。在组织工程学中，以一种重述发育过程的方式控制工程化结构的血管形成仍然是一个可取但难以实现的目标。在体内，与细胞外基质结合的生长因子的梯度被认为是指导发育中的小鼠胚胎毛细血管构型的因素。我们正在开发肝素修饰的水凝胶，它可以很好地控制向内皮细胞递送生长因子，如血管内皮生长因子或成纤维细胞生长因子，以研究基质结合和自由细胞因子梯度在控制血管构型中的作用。该项目包括材料合成和表征以及血管内皮细胞的体外实验。这些研究可能有助于更好地理解胚胎发育过程中组织特有的血管模式，并改进在组织工程构建中促进功能性血管生长的方法。

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.