Cell and molecular studies in cardiovascular engineering

描述（由申请人提供）：该BRP提案来自University of 宾夕法尼亚州是一个跨学科科学家的伙伴关系， 生物工程和医学研究集中在生物力学， 心血管细胞、膜和组织在特定部位的背景下 治疗和组织工程。互补的设计驱动和 假设驱动的血管细胞生理学和病理学方法是 提出了该计划的中心是医学研究所， 工程位于宾夕法尼亚大学校园的中心。有一个很大的 费城儿童医院（CHOP）和与 国家科学技术学院该伙伴关系由两个互动部分组成： 心血管基础细胞和分子研究 机械传导和（ii）工程化动脉的临床前研究， 心脏瓣膜钙化和颅内动脉瘤的微弹簧圈治疗。 基础研究的重点是 力-膜-细胞粘附和细胞外基质。实验 方法包括几何约束，空间分析，蛋白质 构象变化、变形性质和质量传递 调节血管细胞结构，基因表达， 功能，以及对血流动力学的适应不良，可能导致病理性 变化还建议开发新的材料来调节细胞 粘附（以及因此的表型），以及用于原位递送治疗剂。 平行、互补的临床前研究集中在组织工程动脉 离体、心脏瓣膜病理学（离体和体内），以及 治疗因素，以纠正颅内动脉瘤在体内。特定第一 年度目标包括细胞变形的定量空间分析， 机械诱导蛋白质构象变化的定位，分析 蛋白质磷酸化，以及细胞力学的第一次改变， 底物化学的操作。临床前短期目标是 离体维持动脉结构和功能的持续保持 以及它们在体内的重新导入，心脏瓣膜基因的阐明， 表达，并在体外和体内评价的释放， 潜在的治疗剂的涂层铂微弹簧圈。该提案 通过整合物理，化学， 和工程科学纳入血管的基础和临床前研究 机械转导，并通过开发创新的材料和设备， 包括基础研究和临床治疗。

DESCRIPTION (provided by applicant): This BRP proposal from the University of Pennnsylvania is a partnership of interdisciplinary scientists in bioengineering and medical research focused on the biomechanics of cardiovascular cells, membranes, and tissues in the context of site-specific therapy and tissue engineering. Complementary design-driven and hypothesis-driven approaches to vascular cell physiology and pathology are proposed. The center for the program is the Institute for Medicine and Engineering located centrally on the Penn campus. There is a subcontract to Childrens Hospital of Philadelphia (CHOP) and a collaborative partnership with N.I.S.T. The Partnership is composed of two interactive components: (i) fundamental cell and molecular investigations of cardiovascular mechanotransduction. and (ii) preclinical studies of engineered arteries, heart valve calcification, and microcoil treatment of intracranial aneurysms. The basic studies focus on the continuum of force-membrane-cytoskeleton-adhesion and extracellular matrix. The experimental approaches include geometric constraints, spatial analyses, protein conformational changes, deformation properties, and mass transport characteristics that regulate vascular cell structure, gene expression, function, and maladaptation to hemodynamic forces that may lead to pathological change. Also proposed are the development of new materials to regulate cell adhesion (and hence phenotype), and for the delivery of therapeutics in situ. Parallel, complementary preclinical studies focus on tissue engineered arteries ex vivo, heart valve pathology (both ex vivo and in vivo), and the delivery of therapeutic factors to correct intracranial aneurysms in vivo. Specific first year objectives include quantitative spatial analyses of cell deformation, localization of mechanically-induced protein conformational changes, analyses of protein phosphorylation, and the first alterations of cell mechanics through manipulations of substrate chemistry. The preclinical short-term objectives are sustained retention of structure and function of arteries maintained ex vivo and their reintroduction in vivo, the elucidation of heart valve gene expression, and both in vitro and in vivo evaluation of the release of potential therapeutic agents from coated platinum microcoils. The proposal addresses the objectives of the BRP program by integrating physical, chemical, and engineering sciences into fundamental and preclinical studies of vascular mechanotransduction, and by developing innovative materials and devices for both basic research and clinical therapy.