The purpose of this research is to test the global hypothesis that the incorporation and function of a tissue engineered construct for bone regeneration is significantly influenced by the transmission of physical forces through its extracellular matrix. Utilizing a series of in vivo rat models, the investigators will test for the synergistic affects of device mediated mechanical forces and local delivery of biologic factors in stimulating the repair and incorporation of tissue engineered bone substitutes. The models in both a cranial-facial and long bone site utilize specifically designed external fixators which enable the implementation of experimentally controlled mechanical loading conditions across surgically created osteotomy gaps. Local biologic factors will be produced by placing DNA-delivering matrices within these fracture gaps. The effects of the mechanical and biologic factors on tissue repair and regeneration will be assayed by documenting the spatial patterns of gene expression, matrix synthesis, and bone morphology as a function of time and anatomic location. This information is fundamental to the development of strategies to replace or augment bony defects in the cranial-facial or appendicular skeleton. Identification of factors which influences the incorporation and remodeling of tissue engineered transplants will lead to significantly improved and more reliable biomimetic therapies.
