? Spatial concentration gradients of endogenous soluble growth factors play critical roles directing cell migration, proliferation, and differentiation during development, homeostasis, and wound healing. This grant application addresses the question: Could an exogenous solid-phase growth factor immobilized in specified directional gradients within an engineered biomimetic extracellular matrix (bECM) be an effective approach to recruit and guide surrounding host cells into a bECM and promote a desired biological outcome? The goal is to determine if this growth factor delivery paradigm would be relevant for future therapy development in tissue engineering applications. The paradigm in vitro models will include human microvascular endothelial cell, MG-63 human preosteoblastic cell, and human adult mesenchymal stem cell responses to solid-phase human fibroblast growth factor-2 (FGF-2) in fibrin bECMs. The in vivo model will be a chicken embryo chorioallantoic membrane (CAM) assay to assess directed angiogenic response within fibrin bECM/FGF-2 structures placed on the CAM. The research will systematically progress from two-dimensional patterns of FGF-2 on fibrin films to three-dimensional (3D) patterns of FGF-2 within fibrin bECMs, and from isolated cell responses in vitro to angiogenic responses in vivo. The overall hypotheses are spatial gradients of solid phase FGF-2 in a fibrin bECM will direct cell migration in vitro in register with gradient directionality, and cell migrational flux will be greater in response to gradient patterns than patterns with uniform distributions. And in vivo, a directed angiogenic response will be greater in designs with gradients in comparison with uniform distributions. The bECM/FGF-2 structures will be fabricated with a solid freeform fabrication printing process that produces specified 3D spatial patterns of growth factors within 3D fibrin bECMs. Fluorescent based quantum dot imaging technology and fluorescence optical sectioning microscopy will be used to validate printed structures and assess cell and CAM responses. The research will be carried out by multidisciplinary bioengineering with expertise in endocrinology, advanced manufacturing, and biophysical imaging. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB004343-04
Application #
7367807
Study Section
Special Emphasis Panel (ZRG1-MOSS-G (01))
Program Officer
Hunziker, Rosemarie
Project Start
2005-05-01
Project End
2009-05-31
Budget Start
2008-03-01
Budget End
2009-05-31
Support Year
4
Fiscal Year
2008
Total Cost
$307,004
Indirect Cost
Name
Carnegie-Mellon University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
052184116
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Ker, Dai Fei Elmer; Eom, Sungeun; Sanami, Sho et al. (2018) Phase contrast time-lapse microscopy datasets with automated and manual cell tracking annotations. Sci Data 5:180237
Yin, Zhaozheng; Ker, Dai Fei; Junkers, Silvina et al. (2011) Data-driven prediction of stem cell expansion cultures. Conf Proc IEEE Eng Med Biol Soc 2011:3577-80
Ker, Elmer D F; Nain, Amrinder S; Weiss, Lee E et al. (2011) Bioprinting of growth factors onto aligned sub-micron fibrous scaffolds for simultaneous control of cell differentiation and alignment. Biomaterials 32:8097-107
Huh, Seungil; Ker, Dai Fei Elmer; Bise, Ryoma et al. (2011) Automated mitosis detection of stem cell populations in phase-contrast microscopy images. IEEE Trans Med Imaging 30:586-96
Yin, Zhaozheng; Ker, Dai Fei Elmer; Kanade, Takeo (2011) Restoring DIC microscopy images from multiple shear directions. Inf Process Med Imaging 22:384-97
Ker, Dai Fei Elmer; Weiss, Lee E; Junkers, Silvina N et al. (2011) An engineered approach to stem cell culture: automating the decision process for real-time adaptive subculture of stem cells. PLoS One 6:e27672
Ker, Elmer D F; Chu, Bur; Phillippi, Julie A et al. (2011) Engineering spatial control of multiple differentiation fates within a stem cell population. Biomaterials 32:3413-22
Miller, Eric D; Li, Kang; Kanade, Takeo et al. (2011) Spatially directed guidance of stem cell population migration by immobilized patterns of growth factors. Biomaterials 32:2775-85
Cooper, Gregory M; Miller, Eric D; Decesare, Gary E et al. (2010) Inkjet-based biopatterning of bone morphogenetic protein-2 to spatially control calvarial bone formation. Tissue Eng Part A 16:1749-59
Smith, J D; Melhem, M E; Magge, K T et al. (2007) Improved growth factor directed vascularization into fibrin constructs through inclusion of additional extracellular molecules. Microvasc Res 73:84-94

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