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Scaffold Composition Determines the Angiogenic Outcome of Cell-Based Vascular Endothelial Growth Factor Expression by Modulating Its Microenvironmental Distribution

Gaudiello, Emanuele and Melly, Ludovic and Cerino, Giulia and Boccardo, Stefano and Jalili-Firoozinezhad, Sasan and Xu, Lifen and Eckstein, Friedrich and Martin, Ivan and Kaufmann, Beat A. and Banfi, Andrea and Marsano, Anna. (2017) Scaffold Composition Determines the Angiogenic Outcome of Cell-Based Vascular Endothelial Growth Factor Expression by Modulating Its Microenvironmental Distribution. Advanced healthcare materials, 6 (24). p. 1700600.

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Abstract

Delivery of genetically modified cells overexpressing Vascular Endothelial Growth Factor (VEGF) is a promising approach to induce therapeutic angiogenesis in ischemic tissues. The effect of the protein is strictly modulated by its interaction with the components of the extracellular matrix. Its therapeutic potential depends on a sustained but controlled release at the microenvironmental level in order to avoid the formation of abnormal blood vessels. In this study, it is hypothesized that the composition of the scaffold plays a key role in modulating the binding, hence the therapeutic effect, of the VEGF released by 3D-cell constructs. It is found that collagen sponges, which poorly bind VEGF, prevent the formation of localized hot spots of excessive concentration, therefore, precluding the development of aberrant angiogenesis despite uncontrolled expression by a genetically engineered population of adipose tissue-derived stromal cells. On the contrary, after seeding on VEGF-binding egg-white scaffolds, the same cell population caused aberrantly enlarged vascular structures after 14 d. Collagen-based engineered tissues also induced a safe and efficient angiogenesis in both the patch itself and the underlying myocardium in rat models. These findings open new perspectives on the control and the delivery of proangiogenic stimuli, and are fundamental for the vascularization of engineered tissues/organs.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Cell and Gene Therapy (Banfi)
UniBasel Contributors:Banfi, Andrea
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley
ISSN:2192-2640
e-ISSN:2192-2659
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:10 Oct 2018 08:38
Deposited On:19 Mar 2018 14:44

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