CAREER: Engineering Structural Adaptability into Biological Tissue Replacements

9984276 Barbee组织工程学的前景在于，用能够对环境刺激做出反应和适应的新组织来取代因创伤或疾病而功能失调的组织。在具有机械或结构功能的组织中，最重要的是感知和响应机械力的能力，以适应组织不断变化的物理需求。先前的体内和体外研究表明，血管壁的结构和机械性能随着组织的应力史而发展。血管内皮细胞介导血管张力和结构重塑，以响应血流的变化，而血管平滑肌(VSM)细胞则感知和响应血管壁内应力的变化。这些反应对于维持结构的完整性和血流的调节是必不可少的。本研究的中心假设是，在正常发育过程中，血管组织中的结构关系被优化，以便通过管壁细胞有效地感知和转导机械环境。为了设计一种组织结构，以获得正常组织中存在的适应性特性，我们必须首先了解细胞与其周围结构相互作用的显著特征，从而允许适当的机械转导发生。工程基质的结构和生物化学，以及生理负荷状态下的预调节，将根据初始功能特性和获得的适应性行为进行分析和优化，以允许组织的长期替换。这项职业计划的目标是发展细胞和分子力学领域的研究和教育计划。研究重点将集中在细胞对机械刺激的反应，特别强调由组织-植入物界面和工程化组织结构创造的改变的应力环境。教育的重点将是将工程力学与当前生物科学的发展相结合。这不仅需要合并课程内容，而且还需要融合物理和生物科学不同的课程形式和教学风格。将开发将细胞力学的理论和实验基础与生物学文献中的当前概念相结合的研究生课程。此外，在研究生课程中引入临床轮换将使学生接触到医疗实践和病人护理方面的最新技术。这一经历意在拓宽他们的视野，集中他们的研究目标。在本科阶段，重点将放在提供研究机会，以激发学生对工业研发或进一步学术培训等研究型职业的兴趣。

9984276BarbeeThe promise of tissue engineering lies in the prospect of replacing tissue that has become dysfunctional due to trauma or disease with new tissue capable of responding and adapting to environmental stimuli. Of primary importance in tissues that serve a mechanical or structural function is the ability to sense and respond to mechanical forces in order to adapt to the changing physical demands on the tissue. Previous in vivo and in vitro studies suggest that the structure and mechanical properties of blood vessel walls develop in response to the stress history of the tissue. The endothelium mediates vascular tone and structural remodeling in response to changes in blood flow while the vascular smooth muscle (VSM) cells sense and respond to changes in stress within the vessel wall. These responses are essential to the maintenance of structural integrity and the regulation of blood flow.The central hypothesis of this research is that in normal development, structural relationships in vascular tissue are optimized for efficient sensing and transduction of the mechanical environment by the cells of the vessel wall. To engineer a tissue structure intended to acquire the property of adaptability present in normal tissues, we must first understand the salient features of the cells' interaction with their surrounding structures that allow appropriate mechanotransduction to occur. The structure and biochemistry of engineered matrices as well as pre-conditioning with physiological loading regimes will be analyzed and optimized based on initial functional properties and the acquisition of adaptive behaviors that will allow long-term replacement of tissue.The objective of this career plan is to develop a program of research and education in the area of cellular and molecular mechanics. The research focus will be on the cellular response to mechanical stimuli with a special emphasis on the altered stress environments created by tissue-implant interfaces and engineered tissue constructs. The educational emphasis will be on the integration of engineering mechanics with current developments in the biological sciences. This will require not only a merging of course content but also a blending of the disparate course formats and teaching styles from the physical and biological sciences. Graduate courses that integrate theoretical and experimental foundations of cell mechanics with current concepts in the biological literature will be developed. In addition, the introduction of clinical rotations into the graduate curriculum will expose students to the state of the art in medical practice and patient care. This experience is intended to broaden their perspective and to focus their research objectives. At the undergraduate level, emphasis will be placed on providing research opportunities to stimulate students' interest in research-oriented careers either in industrial R&D or in further academic training.