It is well accepted that synthetic microenvironments can be engineered to promote the formation of blood vessels within tissue-engineered constructs, but that these synthetic microenvironments do not result in stable vascular networks that are long lasting. This has been a particular problem with presentation of the most well characterized angiogenic growth factor, vascular endothelial growth factor (VEGF). Our long-term goal is to gain a molecular understanding of engineered vascular microenvironments and to use this information to better design scaffolds for therapeutic angiogenesis. Based on published and preliminary data we have found that the method of VEGF ligand presentation in tissue engineering scaffolds affects not only the physical stability and release kinetics of the growth factor, but also the molecular signals conveyed to the residing cells and ultimately the morphology and maturity of the resulting vascular network formed. In this proposal, we want to further investigate how VEGF ligand presentation affects VR-2 phosphorylation and the resulting cellular outcomes (phenotype and vessel morphology) in vitro and in vivo.
Aim 1 and Aim 2 investigate how VEGF ligand presentation and synergistic signaling between VEGF and integrin ligands modulate activation of VEGF receptor-2 (VR-2), downstream signaling and endothelial cell branching.
Aim 3 uses the knowledge gained from Aims 1 and 2 to design hydrogel scaffolds for revascularization of the brain after stroke. !

Public Health Relevance

Therapeutic angiogenesis aims to repair damaged tissue that lacks a normal blood supply. This proposal aims to better understand how vascular endothelial growth factor (VEGF) and extracellular matrix proteins are able to induce blood vessel formation to better design scaffolds for therapeutic angiogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS079691-03
Application #
8658865
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Koenig, James I
Project Start
2012-05-01
Project End
2017-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Nih, Lina Ratiba; Carmichael, Stanley Thomas; Segura, Tatiana (2016) Hydrogels for brain repair after stroke: an emerging treatment option. Curr Opin Biotechnol 40:155-63
Zhu, Suwei; Segura, Tatiana (2016) Cell-Demanded VEGF Release via Nanocapsules Elicits Different Receptor Activation Dynamics and Enhanced Angiogenesis. Ann Biomed Eng 44:1983-92
Moshayedi, Pouria; Nih, Lina R; Llorente, Irene L et al. (2016) Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain. Biomaterials 105:145-55
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Zhu, Suwei; Segura, Tatiana (2014) HYDROGEL-BASED NANOCOMPOSITES OF THERAPEUTIC PROTEINS FOR TISSUE REPAIR. Curr Opin Chem Eng 4:128-136
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Griffin, Donald R; Borrajo, Jacob; Soon, Allyson et al. (2014) Hybrid photopatterned enzymatic reaction (HyPER) for in situ cell manipulation. Chembiochem 15:233-42

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