Despite significant advances in medicine and biology, the lack of precisely defined in vitro systems has hindered our ability to understand cell function and to regulate its behavior for tissue engineering. In addition, our inability to miniaturize experiments and to perform high-throughput cell-based experiments has limited our ability to define optimized culture conditions. Therefore, it is important to control cell microenvironment in a manner that is tightly controlled, reproducible and scalable. Using innovative approaches at the interface of biology, engineering, medicine and materials science, we aim to address this challenge. Our goal is to develop micro- and nanoengineering approaches for controlling cell microenvironment and to use these techniques to regulate stem cell fate decisions. To control cell microenvironment we develop novel micro- and nanoscale technologies to regulate cell-cell contact (using patterned co-cultures), cell-ECM interactions (using novel biomaterials), cell-soluble factor components (using microfluidics) and cell shape (using micropatterning) . In addition, we have developed microfluidic and microarray methods to perform high-throughput experiments, in order to facilitate systematic testing of various environmental conditions on cell fate. Equipped with these tools we study various aspects of stem cell self-renewal and differentiation and develop microreactors that facilitate directed differentiation of stem cells to therapeutic cells.
Tissue engineering is an emerging field that aims at regeneration of natural tissues and the creation of new tissues using biological cells, biomaterials, biotechnology, and clinical medicine. According to Eugene Bell, author of Tissue Engineering: Current Perspectives, the main goals of tissue engineering include providing cellular replacement parts, providing formed acellular parts capable of inducing regeneration, providing cell populated tissue models for research, providing vehicles for delivering engineered cells to an organism, and surfacing non-biological devices with cultured cells.
Microelectromechanical systems, or MEMS, is a technology developed by the microelectronics industry for the microfabrication and micromachining of ever faster, more powerful, and less expensive integrated microelectronics chips. These technologies have recently been adopted for use in bioengineering applications and have collectively become known as BioMEMS. The techniques originally developed to enable the deployment of airbags and ink jet printing have now enabled bioengineers to apply previously developed and extremely well-defined techniques to interesting biological and medical problems.
In our lab, we have primarily used BioMEMS approaches in the service of developing technologies for controlling the cellular microenvironment. Within these disciplines, we have developed a wide range of techniques such as the patterning of cells on surfaces to facilitate co-cultures of different cell types, the generation of gradients within hydrogels, and the isolation of cells in wells within microfluidic channels. We are currently running many projects in this area as it continues to be a major focus of the lab.
Stem Cell Bioengineering
Stem cells have the unique ability of self-renewal as well as being able to give rise to differentiated cell types. Because stem cells can differentiate into diverse cell types, they have the potential to provide treatment for a wide variety of human diseases by providing functional tissues for therapy. The ability to control differentiation of stem cells can generate a renewable source of cells for regenerative medicine and be utilized in a wide array of applications including use as models of human disease. Stem cell differentiation is affected by a myriad of microenvironmental factors such as soluble growth factors, matrix components, and cell-cell contact molecules. One of the major challenges to using stem cell derived tissues is the ability to homogenously direct stem cell differentiation in a scalable manner. In our lab, a variety of BioMEMS techniques and materials are applied in order to control the cellular microenvironment. By regulating factors such as cell-cell interactions we are working to develop methods of creating controlled microenvironmental systems in which homogeneous differentiation of stem cells can occur.