ENGINEERED CARDIAC MORPHOGENESIS--STEM CELLS & SCAFFOLDS

描述：（逐字）该项目的长期目标是生产 用于心肌修复的组织工程心室壁补片，心室 辅助设备，最终替换心室。我们的学术团队 工业界在生物材料，生物反应器，组织生物力学， 胚胎和体细胞干细胞，肌肉发育，血管发生， 细胞外基质，心脏损伤和再生，动物和人类心脏 移植该团队将在三个研究领域进行合作：1） “指导性”组织支架。将使用先进的生物材料制造 为了设计具有受控孔尺寸的可生物降解的基质和网， 用受体特异性分子修饰。将对矩阵进行优化， 指导细胞附着、定向、迁移、增殖 分化和整体组织结构。2)细胞和发育 生物学原代和干细胞来源的肌肉和血管细胞将被 对改性支架进行研究，以确定制备的最佳条件 功能性肌肉组织和血管网络。工程组织将是 使其经受机械应力以引导体内成熟 表型。将开发生物反应器，以实现这些要求， 有用的规模。3)临床科学和动物模型。收缩性心室 贴片将在受伤的心脏模型中进行测试。与宿主组织整合 并评价收缩功能的恢复。管状心脏 由血管化心肌和内皮细胞组成的辅助器官也将被 开发“试管心脏”将在脉动流回路中进行调节， 在体外评估机械性能，并最终移植到 用于体内评价的同系大鼠睾丸。实现这些目标的进展 应该建立必要的设计原则， 心室器械。

DESCRIPTION: (verbatim) The long term aims of this project are to produce tissue engineered ventricular wall patches for myocardial repair, ventricular assist devices, and eventually replacement ventricles. Our team from academia and industry has expertise in biomaterials, bioreactors, tissue biomechanics, embryonic and somatic stem cells, muscle development, vasculogenesis, extracellular matrix, cardiac injury and regeneration, animal and human heart transplantation. This team will collaborate across three research foci: 1) 'Instructive' tissue scaffolds. Advanced biomaterial fabrication will be used to engineer biodegradable matrices and meshes with controlled pore dimensions, modified with receptor specific molecules. Matrices will be optimized to instruct cell attachment, orientation, migration, proliferation, differentiation, and overall tissue organization. 2) Cell and developmental biology. Primary and stem cell-derived muscle and vascular cells will be studied on modified scaffolds to determine the optimal conditions for producing functional muscle tissue and vascular networks. Engineered tissues will be subjected to mechanical stresses to direct maturation toward in vivo phenotypes. Bioreactors will be developed to implement these requirements on a useful scale. 3) Clinical science and animal models. Contractile ventricular patches will be tested in an injured heart model. Integration with host tissue and restoration of contractile function will be valuated. A tubular cardiac assist organ comprised of vascularized myocardium and endocardium will also be developed. The 'tube hearts' will be conditioned in pulsatile flow circuits, assessed for mechanical performance in vitro, and eventually grafted into aortas of syngeneic rats for in vivo evaluation. Progress toward these goals should establish design principles necessary for constructing more complex ventricular devices.