The candidate, Dr. Edward Botchwey, is experienced in orthopaedic biomaterials and tissue engineering. His long term career goal is to establish an independent research laboratory to pursue his interests in the development of experimental and computational methods to study the role of angiogenesis and microvascular remodeling in bone tissue engineering. His intermediate term objective is to work together with mentor Dr. Thomas Skalak, chair of biomedical engineering at the University of Virginia, to leverage the tremendous resources available at UVA to achieve this goal. This proposal outlines a career development plan to design and build new enabling technologies capable of co-cultivating osteoblastic cells and vascular endothelial cells within tissue engineered scaffolds, and varying the geometric arrangement of cells so that optimization of both bone remodeling and neo-vascularization can be explored. In vivo experimental assessment and novel computational modeling approaches will be developed to identify the geometries of combined cell distribution that are most conducive to bone healing and vascular remodeling. The specific objectives of the proposal are 1) to quantify the effects of perfusion flow velocity and internal pore network geometry on rMSC proliferation, gene expression, and mineralized deposition within 3-D microsphere based scaffolds in a customized perfusion. 2) to develop new experimental methods to co-culture rat microvascular endothelial cells (rVECs) within mineralized rMSC constructs formed in Aim1. Specifically, rVECs will be cultivated according to two predetermined geometric configurations, (a) uniformly dispersed network within the scaffolds, and (b) externally laminated layer around the scaffolds. 3) to combine experimental and computational methods to determine whether the geometric distribution of vascular endothelial cells within mineralized bone tissue engineered scaffolds developed in Aim 2 enhance microvascular network remodeling and ectopic bone formation in a customized rat window chamber model in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AR052352-04
Application #
7568206
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Wang, Fei
Project Start
2006-03-05
Project End
2010-12-31
Budget Start
2009-01-01
Budget End
2009-12-31
Support Year
4
Fiscal Year
2009
Total Cost
$127,650
Indirect Cost
Name
University of Virginia
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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Sok, Mary Caitlin P; Tria, Maxianne C; Olingy, Claire E et al. (2017) Aspirin-Triggered Resolvin D1-modified materials promote the accumulation of pro-regenerative immune cell subsets and enhance vascular remodeling. Acta Biomater 53:109-122
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Ogle, Molly E; Sefcik, Lauren S; Awojoodu, Anthony O et al. (2014) Engineering in vivo gradients of sphingosine-1-phosphate receptor ligands for localized microvascular remodeling and inflammatory cell positioning. Acta Biomater 10:4704-4714
Huang, Cynthia; Das, Anusuya; Barker, Daniel et al. (2012) Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation. Cell Tissue Res 347:553-66
Sefcik, Lauren S; Aronin, Caren E Petrie; Awojoodu, Anthony O et al. (2011) Selective activation of sphingosine 1-phosphate receptors 1 and 3 promotes local microvascular network growth. Tissue Eng Part A 17:617-29
Cui, Quanjun; Botchwey, Edward A (2011) Emerging ideas: treatment of precollapse osteonecrosis using stem cells and growth factors. Clin Orthop Relat Res 469:2665-9
Stephan, Scott J; Tholpady, Sunil S; Gross, Brian et al. (2010) Injectable tissue-engineered bone repair of a rat calvarial defect. Laryngoscope 120:895-901
Petrie Aronin, Caren E; Sefcik, Lauren S; Tholpady, Sunil S et al. (2010) FTY720 promotes local microvascular network formation and regeneration of cranial bone defects. Tissue Eng Part A 16:1801-9
Petrie Aronin, Caren E; Shin, Soo J; Naden, Kimberly B et al. (2010) The enhancement of bone allograft incorporation by the local delivery of the sphingosine 1-phosphate receptor targeted drug FTY720. Biomaterials 31:6417-24

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