CAREER: Engineering Structural Adaptability into Biological Tissue Replacements

Drexel University, Philadelphia PA

Investigators

Abstract

9984276 Barbee The 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.