Cellular engineering involves the analysis and modification of cell function in order to achieve a set of desired characteristics for a system. One approach has been the use of genetic manipulation to alter cell regulatory processes. The research objective of this project is to utilize RNA interference to engineer mechanotransduction processes for the purposes of enhancing efforts in cell-based therapies, such as tissue engineering. Such applications often involve spatially heterogeneous cells and matrix, and sites that possess an adverse mechanical environment. The incorporation of intrinsic control over cellular mechanobiologic function, in addition to current strategies, may enhance the performance of cellular constructs. This project investigates the modification of mechanotransduction at different levels. Pericellular regulation will be studied by individually silencing types II and VI collagen and small leucine-rich proteoglycans, decorin and biglycan, and assessing their contributions to cell mechanics and mechanobiologic response. Altering transmembrane and intracellular mechanosignaling will be investigated through interference of stretch activated channel KCNK2, actin bridging protein á-actinin, and G-protein signaling molecules RhoA and Rock1. The impact of using engineered cells for generating stratified tissue constructs will be determined by fabricating dual population hydrogels that are maintained in long-term co-culture and co-stimulation.
The educational objectives that are integrated with cellular engineering include the introduction of new classroom and research opportunities at both undergraduate and graduate levels. Students will learn how cellular engineering can serve as a tool in bioengineering and as a novel approach in biomechanics. More broadly relevant educational objectives are to generate greater awareness of the bioengineering field, and to provide current bioengineers with a competitive advantage in the job market. To promote awareness, the PI plans to expand his current outreach program, which involves both giving demonstrations at high schools and bringing high school student groups to the University of Maryland. To enhance bioengineering design experience, a pilot program will be tested wherein multidisciplinary teams of engineers will be formed. This will allow bioengineering students to leverage their cross-disciplinary skills, and provide opportunities for other engineering students to learn how their skills can be applied to bio-related designs.
