Functional Tissue Engineering
Functional tissue engineering involves the study of the structure and the function of living tissues, with the aim of recreating these tissues in the laboratory. Such engineered tissues could then be used to replace damaged body parts, or to study complex biological problems in a controlled environment. The field is highly multidisciplinary, drawing on expertise in the areas of biology, physiology, computational modeling, transport phenomena, mechanics, and many others.

A key issue in functional tissue engineering is the ability to control cell function in three-dimensional engineered tissues. This is a requirement in order to promote appropriate tissue development in vitro, as well as to ensure physiological tissue function in vivo. A variety of strategies have been developed to achieve these ends, including the application of biochemical and mechanical stimulation, as well as the use of genetic modification to control cell function.

Current research in our laboratory focuses on the use of extracellular environments to control cell function and the development of engineered tissues. In particular, we are interested in naturally-derived hydrogels for use as scaffolds in tissue engineering, and their effects on cell phenotype and function. One focus of this work is to create better matrices for vascular tissue engineering applications, and to study vascular biology. Knowledge of how engineered extracellular environments can affect cell function can also be extended to the field of biotechnology, for example in the optimization of protein production in mammalian cell bioreactors. Each of these areas is discussed briefly below.

Matrix Biology and Engineering
Naturally derived polymers such as agarose, alginate, collagen and fibrin have been used widely in tissue engineering applications. However, a more complete understanding of the structure of these different matrices, how they interact with cells and how they affect cell function would be of great benefit to a variety of fields. Thorough characterization of the properties of these different matrices includes chemical characterization, structural analysis, mass transfer evaluation as well as testing of mechanical properties. The primary goal of this research is to understand how each of these properties affects tissue-specific cell functions, and how matrix properties can then be tailored to direct these functions.

Vascular Biology and Tissue Engineering
Diseases of the heart and blood vessels are among the most costly health problems in modern society, and there is an urgent need for both an improved understanding of the disease process as well as improved treatments for affected patients. We are developing an engineered blood vessel composed of isolated vascular smooth muscle cells embedded in a matrix of collagen and fibrin. A key issue is the change in cell function that is observed when smooth muscle cells are removed from their native environment. Our research aims to understand this change, and to define extracellular environments that can prevent or reverse this shift. This work is also relevant to understanding the mechanisms of certain vascular diseases, such as atherosclerosis and hypertension, in which phenotype shifts are implicated. In addition, we are interested in improving the mechanical properties of the engineered construct in order to allow its use as a vascular replacement.

Control of Cell Function in Biotechnology
Mammalian cell bioreactor cultures have the potential to produce fully functional complex proteins that bacterial or insect cells are unable to produce. We are studying how mammalian cell function can be better controlled in bioreactor systems, in order to maximize the efficiency of therapeutic protein production. Live mammalian cells are embedded in beads formed from a variety of hydrogel matrices, and the effect of the matrix on cell function is assessed. Use of more physiologically appropriate extracellular matrices in a spherical geometry may enhance cell function while improving mass transfer characteristics. Potential applications of this technology are to enhance transfection of target cells by non-viral vectors, or to grow and maintain stem cells in bioreactor systems, since the properties of the matrix could be tailored to promote cell proliferation or desired differentiated functions.

Douglas B Chrisey
Professor

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