Title:
INTEGRIN STIMULATING MATERIALS FOR THE NORMALIZATION OF DISEASED VASCULATURE
Document Type and Number:
WIPO Patent Application WO/2018/053166
Kind Code:
A3
Abstract:
Integrin binding to bioengineered hydrogel scaffolds is essential for tissue regrowth and regeneration, yet not all integrin binding can lead to tissue repair. Here we show that through engineering hydrogel materials to promote α3/α5β1 integrin binding, we can promote the formation of a space filling and mature vasculature compared to hydrogel materials that promote a αvβ3 integrin binding (e.g. RGD). In vivo, α3/α5β1 scaffolds delivering vascular endothelial growth factor (VEGF) promoted non-tortuous blood vessel infiltration and non-leaky blood vessels by 10 days post stroke. In contrast, materials that promote αvβ3 integrin binding promoted endothelial sprout clumping in vitro and leaky vessels in vivo. This work shows for the first time that precisely controlled integrin activation from a biomaterial can be harnessed to direct therapeutic vessel regeneration and reduce VEGF induced vascular permeability in vivo.
Inventors:
SEGURA TATIANA (US)
BARKER THOMAS H (US)
LI SHUORAN (US)
BARKER THOMAS H (US)
LI SHUORAN (US)
Application Number:
PCT/US2017/051616
Publication Date:
May 23, 2019
Filing Date:
September 14, 2017
Export Citation:
Assignee:
UNIV CALIFORNIA (US)
International Classes:
G01N33/567; A61F2/10; A61K38/18; A61K38/39; C07K14/435; C07K14/475; G01N33/53; G01N33/574
Foreign References:
| US20140010832A1 | 2014-01-09 | |||
| US20150283210A1 | 2015-10-08 | |||
| US20050118661A1 | 2005-06-02 | |||
| US20140010757A1 | 2014-01-09 |
Other References:
STUPACK, DG: "Integrins as a distinct subtype of dependence receptors", CELL DEATH AND DIFFERENTIATION, vol. 12, no. 8, 6 March 2005 (2005-03-06), pages 1021 - 1030, XP055614204
FRANCIS, SE ET AL.: "Central Roles of alpha5beta1 Integrin and Fibronectin in Vascular Development in Mouse Embryos and Embryoid Bodies", ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY, vol. 22, no. 6, 21 March 2002 (2002-03-21) - June 2002 (2002-06-01), pages 927 - 933, XP055614206
FRANCIS, SE ET AL.: "Central Roles of alpha5beta1 Integrin and Fibronectin in Vascular Development in Mouse Embryos and Embryoid Bodies", ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY, vol. 22, no. 6, 21 March 2002 (2002-03-21) - June 2002 (2002-06-01), pages 927 - 933, XP055614206
Attorney, Agent or Firm:
WOOD, William J. et al. (US)
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