Tissues engineered in vitro can be used to restore and repair human organs, potentially saving the lives of some patients waiting for organ donation. To engineer tissues in vitro, cells are attached to a network of adhesive proteins, the extracellular matrix, on biodegradable scaffolds. One major challenge in developing viable tissues is the need to control the spatial distribution of blood vessels to supply adequate oxygen and nutrients. Previous work in developing vascularized tissues has only been successful in forming vascularized skin. Engineering vascularized tissues that have more complex structures has not been achieved. The key to this problem lies in the development of technologies to precisely organize the spatial arrangement of various cell types to mimic the structure of living tissues. The proposed research is a venture into new strategies for inducing and spatially guiding endothelial cells to assemble into vascular networks through control of surface topography, spatial and temporal distribution of cell adhesive/resistant molecules, and microscale cell-cell interactions on implantable biomaterials. The immediate focus of this research is to establish the knowledge and technology for creating capillary networks that can be used for future effort for designing and fabricating vascularized tissues at a commercially and clinically relevant scale. The key innovation of this research lies in the formation of microscale topological and chemical patterns to control cell-cell interactions and induce endothelial cells to form functional capillary networks next to liver cells. Our preliminary investigations with these microfabrication techniques have convinced us of the utility of these tools for precisely defining cellular microenvironments and controlling cell behaviors. We will use these tools to achieve the following specific objectives that altogether lead us towards our project goal of creating vascular networks next to liver cells: 1. Explore the use of a novel polyelectrolyte patterning method for creating a network of capillaries on biodegradable scaffolds. 2. Structure multiple cell types using a novel """"""""Cell Photolithography"""""""" method and ascertain the effects of microscale endothelium-hepatocyte interactions on the endothelial phenotype. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HL084648-02
Application #
7230191
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Lundberg, Martha
Project Start
2006-03-01
Project End
2009-02-28
Budget Start
2007-03-01
Budget End
2009-02-28
Support Year
2
Fiscal Year
2007
Total Cost
$180,160
Indirect Cost
Name
University of Cincinnati
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Gao, Dahai; Kumar, Girish; Co, Carlos et al. (2008) Formation of capillary tube-like structures on micropatterned biomaterials. Adv Exp Med Biol 614:199-205