Integrated approach to designing growth factor delivery systems.
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
Ruth R
RR
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Silva
Eduardo A
EA
Yuen
William W
WW
Brock
Andrea A
AA
Fischbach
Claudia
C
Lin
Angela S
AS
Guldberg
Robert E
RE
Mooney
David J
DJ
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D018919:Neovascularization, Physiologic / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000627:therapeutic use
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A