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Integrated approach to designing growth factor delivery systems

Ruth R. Chen^*,, Eduardo A. Silva, William W. Yuen, Andrea A. Brock, Claudia Fischbach, Angela S. Lin, Robert E. Guldberg and David J. Mooney^,1

^* Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA;

Division of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA;

Department of Biomedical Engineering, Saint Louis University, St. Louis, Missouri, USA; and

School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA

¹Correspondence: Harvard University, 319 Pierce Hall, Cambridge, MA 02138, USA. E-mail: mooneyd{at}deas.harvard.edu

Growth factors have been widely used in strategies to regenerate and repair diseased tissues, but current therapies that go directly from bench to bedside have had limited clinical success. We hypothesize that engineering successful therapies with recombinant proteins will often require specific quantitative information of the spatiotemporal role of the factors and the development of sophisticated delivery approaches that provide appropriate tissue exposures. This hypothesis was tested in the context of therapeutic angiogenesis. An in vitro model of angiogenesis was adapted to quantify the role of the concentration/gradient of vascular endothelial growth factor [VEGF(165)] on microvascular endothelial cells, and a delivery system was then designed, based on a mathematical model, to provide the desired profile in ischemic mice hindlimbs. This system significantly enhanced blood vessel formation, and perfusion and recovery from severe ischemia. This general approach may be broadly applicable to growth factor therapies. Chen, R. R., Silva, E. A., Yuen, W. W., Brock, A. A., Fischbach, C., Lin, A. S., Guldberg, R. E., Mooney, D. J. Integrated approach to designing growth factor delivery systems.

Key Words: tissue engineering • in vitro models • angiogenesis