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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL097520-01A1
Application #
7987506
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Lundberg, Martha
Project Start
2010-08-01
Project End
2014-04-30
Budget Start
2010-08-01
Budget End
2011-04-30
Support Year
1
Fiscal Year
2010
Total Cost
$495,368
Indirect Cost
Name
Baylor College of Medicine
Department
Physiology
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Peters, Erica B; Christoforou, Nicolas; Leong, Kam W et al. (2016) Poly(ethylene glycol) Hydrogel Scaffolds Containing Cell-Adhesive and Protease-Sensitive Peptides Support Microvessel Formation by Endothelial Progenitor Cells. Cell Mol Bioeng 9:38-54
Roudsari, Laila C; Jeffs, Sydney E; Witt, Amber S et al. (2016) A 3D Poly(ethylene glycol)-based Tumor Angiogenesis Model to Study the Influence of Vascular Cells on Lung Tumor Cell Behavior. Sci Rep 6:32726
Shukla, Anita; Slater, John H; Culver, James C et al. (2016) Biomimetic Surface Patterning Promotes Mesenchymal Stem Cell Differentiation. ACS Appl Mater Interfaces 8:21883-92
Slater, John H; Culver, James C; Long, Byron L et al. (2015) Recapitulation and Modulation of the Cellular Architecture of a User-Chosen Cell of Interest Using Cell-Derived, Biomimetic Patterning. ACS Nano 9:6128-38
Peters, Erica B; Liu, Betty; Christoforou, Nicolas et al. (2015) Umbilical Cord Blood-Derived Mononuclear Cells Exhibit Pericyte-Like Phenotype and Support Network Formation of Endothelial Progenitor Cells In Vitro. Ann Biomed Eng 43:2552-68
Hsu, Chih-Wei; Poché, Ross A; Saik, Jennifer E et al. (2015) Improved Angiogenesis in Response to Localized Delivery of Macrophage-Recruiting Molecules. PLoS One 10:e0131643
Udan, Ryan S; Culver, James C; Dickinson, Mary E (2013) Understanding vascular development. Wiley Interdiscip Rev Dev Biol 2:327-46
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

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