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.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Biomaterials and Biointerfaces Study Section (BMBI)
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Koenig, James I
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University of California Los Angeles
Engineering (All Types)
Schools of Engineering
Los Angeles
United States
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Dimatteo, Robert; Darling, Nicole J; Segura, Tatiana (2018) In situ forming injectable hydrogels for drug delivery and wound repair. Adv Drug Deliv Rev 127:167-184
Nih, Lina R; Gojgini, Shiva; Carmichael, S Thomas et al. (2018) Dual-function injectable angiogenic biomaterial for the repair of brain tissue following stroke. Nat Mater 17:642-651
Zhu, Suwei; Li, Shuoran; Escuin-Ordinas, Helena et al. (2018) Accelerated wound healing by injectable star poly(ethylene glycol)-b-poly(propylene sulfide) scaffolds loaded with poorly water-soluble drugs. J Control Release 282:156-165
Li, Shuoran; Nih, Lina R; Bachman, Haylee et al. (2017) Hydrogels with precisely controlled integrin activation dictate vascular patterning and permeability. Nat Mater 16:953-961
Nih, Lina R; Moshayedi, Pouria; Llorente, Irene L et al. (2017) Engineered HA hydrogel for stem cell transplantation in the brain: Biocompatibility data using a design of experiment approach. Data Brief 10:202-209
Nih, Lina Ratiba; Carmichael, Stanley Thomas; Segura, Tatiana (2016) Hydrogels for brain repair after stroke: an emerging treatment option. Curr Opin Biotechnol 40:155-163
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 105:145-155
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
Griffin, Donald R; Weaver, Westbrook M; Scumpia, Philip O et al. (2015) Accelerated wound healing by injectable microporous gel scaffolds assembled from annealed building blocks. Nat Mater 14:737-44
Lam, Jonathan; Carmichael, S Thomas; Lowry, William E et al. (2015) Hydrogel design of experiments methodology to optimize hydrogel for iPSC-NPC culture. Adv Healthc Mater 4:534-9

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