A significant hurdle in tissue engineering is adequate perfusion of donor tissue. Since the diffusion limit of oxygen is <200um (Carmeliet and Jain, 2000), even fairly simple tissue constructs require rapid perfusion following transplantation. Thus, successfully engineered tissues are restricted to thin or a vascular tissues such as skin, cartilage, bladder etc (Rouwkema et al., 2008). Interestingly, a related problem plagues therapeutic angiogenesis approaches to treat ischemic disease. Despite the discovery of numerous pro-angiogenic factors, clinical therapeutic strategies based on single factors have been wholly unsuccessful (Henry et al., 2003;Molin and Post, 2007;Simons, 2005);however, combinations of growth factors are beginning to show great promise in promoting stable angiogenesis and improving damaged circulation, inspiring new designs of pro-angiogenic tissue scaffolds. Here we will use multiple transgenic fluorescent reporter lines in a novel strategy to optimize hydrogel scaffolds for tissue engineering and for use in treating ischemic disease. Research goals include the optimization of hydrogel scaffold design to deliver growth factors and cells and the characterization of the host response to guide new scaffold designs.
Current strategies to repair damaged tissues are limited by the lack of efficient methods to improve circulation and rebuild tissues in damaged areas. In this proposal we will design and test whether custom engineered scaffolds can aid in vessel infiltration and can deliver donor cells that can participate in repair.
|Culver, James C; Vadakkan, Tegy J; Dickinson, Mary E (2013) A specialized microvascular domain in the mouse neural stem cell niche. PLoS One 8:e53546|
|Udan, Ryan S; Vadakkan, Tegy J; Dickinson, Mary E (2013) Dynamic responses of endothelial cells to changes in blood flow during vascular remodeling of the mouse yolk sac. Development 140:4041-50|
|Hoffmann, Joseph C; West, Jennifer L (2013) Three-dimensional photolithographic micropatterning: a novel tool to probe the complexities of cell migration. Integr Biol (Camb) 5:817-27|
|Goldberg, Joshua S; Vadakkan, Tegy J; Hirschi, Karen K et al. (2013) A computational approach to detect gap junction plaques and associate them with cells in fluorescent images. J Histochem Cytochem 61:283-93|
|Culver, James C; Hoffmann, Joseph C; Poche, Ross A et al. (2012) Three-dimensional biomimetic patterning in hydrogels to guide cellular organization. Adv Mater 24:2344-8|
|Saik, Jennifer E; Gould, Daniel J; Watkins, Emily M et al. (2011) Covalently immobilized platelet-derived growth factor-BB promotes angiogenesis in biomimetic poly(ethylene glycol) hydrogels. Acta Biomater 7:133-43|
|Gould, Daniel J; Vadakkan, Tegy J; Poche, Ross A et al. (2011) Multifractal and lacunarity analysis of microvascular morphology and remodeling. Microcirculation 18:136-51|
|Saik, Jennifer E; Gould, Daniel J; Keswani, Aakash H et al. (2011) Biomimetic hydrogels with immobilized ephrinA1 for therapeutic angiogenesis. Biomacromolecules 12:2715-22|