Tracking Cell Fate during Mechanically Directed Bone Regeneration In Vivo

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The research objective of this award is to quantify the mechanical environment of a bone injury and its association with the response of skeletal progenitor cells at the injury site. Skeletal progenitor cells play a principal role in healing of bone fractures and other skeletal injuries and can differentiate into one of multiple, committed cell types depending on stimuli in their local environment. The planned studies will apply a combination of experimental and computational tools from engineering and biology to label progenitor cells at the injury site, to quantify the mechanical environment of the tissues in which these cells reside, and to identify the specific mechanical stimuli (e.g., shear strain, pressure, etc.) associated with the recruitment of these cells and their various fates. These studies will define the mechanical conditions highly favorable to formation of a given type of skeletal tissue, such as bone, cartilage, and fibrous tissue.These studies will accelerate the pace of discovery in several areas of basic and clinical research, including defining mechanical environments that can promote bone healing, uncovering the mechanisms by which mechanical stimuli can influence cell differentiation, and identifying new classes of molecular targets for enhancing bone formation. Each of these avenues is directed towards alleviating the personal and economic costs arising from bone injuries, and in particular, from poor healing of these injuries. The educational components of the project consist of training of junior scientists and engineers-two graduate students and three undergraduate students will be mentored on this research project-and on enhancing a successful, residential summer program for low-income, high-school girls interested in scientific and quantitative fields of study. Content for the program is supplied by university faculty and staff, industry partnerships, and outreach modules designed by undergraduate and graduate students enrolled in courses in engineering mechanics and biomechanics.