Botchwey, Edward A.
P O Box 800759
Tissue engineering has long held the promise of providing newer, more innovative clinical alternatives for organ and tissue repair. Despite intense research effort, investigators have faced significant challenges for the repair of musculoskeletal tissues that require an initial biomechanical function, such as articular cartilage, ligaments, tendons, and bone. The classic paradigm for tissue engineering of musculoskeletal tissues ex vivo involves the isolation and culture of patient donor cells within three-dimensional (3-D) scaffold biomaterials under conditions that support tissue growth and maturation. By combining appropriately engineered biomaterials, culture conditions and cells, strategies may ultimately be found to produce tissue-equivalent graft materials capable of providing both initial biomechanical support and complete re-integration and regeneration of damaged tissues.
Our laboratory is interested in the development of new tissue engineering approaches for bone repair using bioreactors. These bioreactor technologies provide a well-mixed environment and culture medium flow within scaffold constructs during cultivation. Our studies involve measurement of cellular and tissue synthetic parameters as a function of time and bioreactor cultivation conditions. However, multiple operative factors can affect measured outcomes during cultivation in rotating bioreactors and other systems of dynamic culture are complex, and encompass a broad range of scaffold materials and designs, scaffold porosity and size, cell types, initial cell plating densities and methods, and experimental fluid flow conditions. This complexity presents a significant challenge to tissue engineers in attempting to quantify the temporal sequence of downstream cell signaling events and possible dose response relationships to physicochemical factors that are modulated by dynamic culture. We work to rigorously quantify the chemical and mechanical stimuli present during dynamic culture in order to selectively engineer culture conditions to enhance tissue growth.
Our laboratory is also interested in the processes of angiogenesis and vascular remodeling to maintain nutrient supply within implanted tissue-engineered constructs. We are developing new methods of vascular endothelial cell co-culture with osteoblastic cells on 3-D scaffolds and working to quantify the effects of physicochemical factors in dynamic co-cultivation, as well as the effects of angiogenic growth factor overexpression on measured outcomes. Our studies will lead to more fundamental understanding of the interaction of these two cell types in a physiologically relevant 3-D environment, and the development of new strategies to improve neoangiogenesis and bony repair potential on implanted bone grafts