Cell and molecular studies in cardiovascular engineering

描述（由申请人提供）：来自University of University的这份BRP提案 宾夕法尼亚州是跨学科科学家的合作伙伴 生物工程和医学研究集中于生物力学 特定位点背景下的心血管细胞、膜和组织 治疗和组织工程。互补设计驱动和 血管细胞生理学和病理学的假设驱动方法是 提议。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。有一份分包合同 费城儿童医院 (CHOP) 并与以下机构建立合作伙伴关系 N.I.S.T.该伙伴关系由两个互动部分组成：(i) 心血管的基础细胞和分子研究 力传导。 (ii) 工程动脉的临床前研究， 心脏瓣膜钙化和颅内动脉瘤的微弹簧圈治疗。 基础研究侧重于连续体 力-膜-细胞骨架-粘附和细胞外基质。实验的 方法包括几何约束、空间分析、蛋白质 构象变化、变形特性和传质 调节血管细胞结构、基因表达的特征， 功能和对血流动力学的适应不良可能导致病理性的 改变。还提出了开发调节细胞的新材料 粘附（以及因此表型），以及用于原位治疗的递送。 平行、互补的临床前研究重点关注组织工程动脉 离体、心脏瓣膜病理学（离体和体内）以及 体内纠正颅内动脉瘤的治疗因素。具体先 今年的目标包括细胞变形的定量空间分析， 机械诱导的蛋白质构象变化的定位、分析 蛋白质磷酸化，以及细胞力学的首次改变 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留 及其重新引入体内，心脏瓣膜基因的阐明 表达，以及体外和体内释放的评估 来自涂层铂微线圈的潜在治疗剂。提案 通过整合物理、化学、 和工程科学融入血管的基础和临床前研究 力传导，并通过开发创新材料和设备 既包括基础研究，也包括临床治疗。

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.