ORTHOPEDIC AND SOFT TISSUE ENGINEERING

The typical mammalian response to chronic and acute injuries is characterized by a complex inflammatory response, cell-mediated wound contraction, and scar tissue synthesis (repair). However, introduction of a suitable biomaterial such as a scaffold into the wound can block cell-mediated contraction and induce regeneration of physiological tissue. Specific projects include the use of uniform/monolithic, gradient, and layered scaffolds technologies to induce regeneration of a wide range of orthopedic and soft tissues, such as cartilage, bone, tendon, ligament, and peripheral nerves, following injury.

CELL BEHAVIORAL CLUES

Cell motility, contraction, proliferation, and extracellular matrix protein biosynthesis are critical components of many physiological and pathological processes as well as in tissue engineering applications. These behaviors are modulated by a complex, spatio-temporally integrated set of biophysical mechanisms influenced not only by the biochemistry of extracellular and intracellular signaling, but also by the biophysics of the surrounding extracellular environment and of cell-cell interactions. In our research, we use a series of highly porous collagen-based scaffolds as a model extracellular matrix (ECM) system to study how distinct extrinsic factors within the local microenvironment of a cell influences its motility.

STEM CELL NICHE ENGINEERING

Adult stem cells have the capacity to remain quiescent for long periods of time, produce more stem cells of the same type, or give rise to a defined set of mature differentiated progeny. The stem cell niche is the local microenvironment surrounding a stem cell, consisting of multiple cells, mechanical influences, as well as soluble and insoluble regulators, that modulates stem cell behavior. We use hematopoietic and mesenchymal stem cells in concert with imaging and scaffold technologies as a platform for studying microenvironmental cues on stem cell behavior and for optimizing porous biomaterials and in vitro culture systems for stem cell engineering. We are interested in understanding how synthetic materials can be used to take a single stem cell and turn it into thousands of stem cells, or to take that stem cell and turn it into a specific adult cell we can then use to treat injuries and diseases. We are also interested in using materials to study how stem cells can turn bad, such as in diseases like leukemia, lymphoma, and other cancers.

MODELING CELLULAR MATERIALS

Cellular solids include engineering materials such as foams for structural and biomedical purposes and porous scaffolds for tissue engineering applications, as well as natural materials like wood and coral. The porous (cellular) structure of these materials gives rise to many distinct mechanical and material properties such as exceptional mechanical efficiency on a per weight basis. The complex geometry and behavior of these porous materials are difficult to describe exactly, however. In our research, we use cellular solids and poroelastic modeling techniques as analytical tools to describe mechanical and microstructural features of biological tissues, tissue engineering scaffolds and gels, and intracellular features of individual cells such as the cytoskeleton.