1992 ALZA Distinguished Lecture: bioengineering and vascular biology.

The vascular system is naturally dynamic; fluid mechanics and mass transfer are closely integrated with blood and vascular cell function. We are beginning to understand how local wall shear stress and strain modulate endothelial cell metabolism at the gene level. This knowledge may help explain the focal nature of many vascular pathologies, including atherosclerosis. Understanding mechanical control of gene regulation at the level of specific promoter elements and transcription factors involved will lead to development of novel constructs for localized delivery of specific gene products in regions of high or low shear stress or strain in the vascular system. In addition, recent research has shown how local fluid mechanics can alter receptor specificity in cell-to-cell and cell-to-matrix protein adhesion and aggregation. Knowledge of the specific molecular sequences involved in cell-to-cell recognition will allow development of targeted therapeutics, with applications in thrombosis, inflammation, cancer metastasis, and sickle-cell anemia. Bioengineers are uniquely qualified to be leaders in this field, because advances require a synthesis of cell and molecular biology with systems analysis, transport phenomena, and quantitative modeling. Rapid progress in tissue engineering applications will require this new kind of biomedical engineer, which represents both a challenge and an opportunity for our profession.