While current understanding of growth factor biology has been incorporated into the design of tissue-engineered products, little is known about how the architecture and composition of the adhesive matrix regulates angiogenesis. It is proposed that changes in cell shape, as governed by the architecture of the extracellular matrix (ECM), act as a distinct signal to regulate capillary endothelial cell proliferation, apoptosis and differentiation in angiogenesis. To test this hypothesis, we will probe how cells respond to changes in cell shape and structure as controlled by the geometry of microfabricated islands of ECM. Preliminary findings suggest that the degree of cell spreading regulates a switch between cell proliferation and apoptosis.
In Specific Aim 1, geometric parameters controlling this switch will be identified by using multiple series of geometric islands to specifically vary projected cell area, perimeter, length, aspect ratio, cell height, membrane surface area or volume. The P.I. will determine whether an island size exists where cells neither grow nor die, and therefore can be effectively maintained for long periods in vitro without passage to a new substrate.
In Aim 2, he will explore the ability of integrins and growth factors to modulate the degree to which changes in cell shape regulate cell proliferation and apoptosis.
In Aim 3, he will determine the geometric requirements for ECM-induced capillary differentiation and tube formation. In this manner, he will seek to determine the ability of matrix architecture to regulate capillary cell behavior and, thus, provide a rational basis for the design of the engineered matrices to promote tissue vascularization.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB000262-05
Application #
6701803
Study Section
Special Emphasis Panel (ZRG1-SSS-M (01))
Program Officer
Wang, Fei
Project Start
2000-02-01
Project End
2004-11-30
Budget Start
2004-02-01
Budget End
2004-11-30
Support Year
5
Fiscal Year
2004
Total Cost
$210,172
Indirect Cost
Name
Johns Hopkins University
Department
Biomedical Engineering
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Greco Song, H-H; Rumma, Rowza T; Ozaki, C Keith et al. (2018) Vascular Tissue Engineering: Progress, Challenges, and Clinical Promise. Cell Stem Cell 22:608
Song, H-H Greco; Rumma, Rowza T; Ozaki, C Keith et al. (2018) Vascular Tissue Engineering: Progress, Challenges, and Clinical Promise. Cell Stem Cell 22:340-354
Longchamp, Alban; Mirabella, Teodelinda; Arduini, Alessandro et al. (2018) Amino Acid Restriction Triggers Angiogenesis via GCN2/ATF4 Regulation of VEGF and H2S Production. Cell 173:117-129.e14
Polacheck, William J; Kutys, Matthew L; Yang, Jinling et al. (2017) A non-canonical Notch complex regulates adherens junctions and vascular barrier function. Nature 552:258-262
Trappmann, Britta; Baker, Brendon M; Polacheck, William J et al. (2017) Matrix degradability controls multicellularity of 3D cell migration. Nat Commun 8:371
Choi, Dongwon; Park, Eunkyung; Jung, Eunson et al. (2017) Laminar flow downregulates Notch activity to promote lymphatic sprouting. J Clin Invest 127:1225-1240
Stevens, Kelly R; Scull, Margaret A; Ramanan, Vyas et al. (2017) In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease. Sci Transl Med 9:
Mirabella, T; MacArthur, J W; Cheng, D et al. (2017) 3D-printed vascular networks direct therapeutic angiogenesis in ischaemia. Nat Biomed Eng 1:
Nguyen, Duc-Huy T; Gao, Lin; Wong, Alec et al. (2017) Cdc42 regulates branching in angiogenic sprouting in vitro. Microcirculation 24:
Alimperti, Stella; Mirabella, Teodelinda; Bajaj, Varnica et al. (2017) Three-dimensional biomimetic vascular model reveals a RhoA, Rac1, and N-cadherin balance in mural cell-endothelial cell-regulated barrier function. Proc Natl Acad Sci U S A 114:8758-8763

Showing the most recent 10 out of 93 publications