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Engineered full-length Fibronectin-based hydrogels sequester and present growth factors to promote regenerative responses in vitro and in vivo

View ORCID ProfileSara Trujillo, Cristina Gonzalez-Garcia, View ORCID ProfilePatricia Rico, Andrew Reid, View ORCID ProfileJames Windmill, View ORCID ProfileMatthew J. Dalby, View ORCID ProfileManuel Salmeron-Sanchez
doi: https://doi.org/10.1101/687244
Sara Trujillo
Centre for the Cellular Microenvironment, University of Glasgow, Glasgow, United Kingdom
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Cristina Gonzalez-Garcia
Centre for the Cellular Microenvironment, University of Glasgow, Glasgow, United Kingdom
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Patricia Rico
Biomedical Research Networking Centre in Bioengineering biomaterials and Nanomedicine, Universitat Politècnica de València, Valencia, Spain
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Andrew Reid
Centre for Ultrasonic Engineering, Department of Electronic and Electrical Engineering, University of Strathclyde, Glasgow, United Kingdom
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James Windmill
Centre for Ultrasonic Engineering, Department of Electronic and Electrical Engineering, University of Strathclyde, Glasgow, United Kingdom
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Matthew J. Dalby
Centre for the Cellular Microenvironment, University of Glasgow, Glasgow, United Kingdom
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Manuel Salmeron-Sanchez
Centre for the Cellular Microenvironment, University of Glasgow, Glasgow, United Kingdom
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  • ORCID record for Manuel Salmeron-Sanchez
  • For correspondence: Manuel.Salmeron-Sanchez@glasgow.ac.uk
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Abstract

Extracellular matrix (ECM)-derived matrices such as Matrigel are used to culture numerous cell types in vitro and can recapitulate certain ECM functions that support cell growth and differentiation. However, ECM-derived matrices suffer lot-to-lot variability, undefined composition and lack of controlled physical properties. There is a need to develop rationally designed synthetic matrices that can also recapitulate ECM roles. Synthetic matrices have certain limitation as normally used synthetic peptides or fragments whereas the ECM consists of full proteins. Here, we report the development of degradable, PEG-based hydrogels of controlled stiffness that incorporate full-length fibronectin (FN) to enable solid-phase presentation of growth factors in a physiological manner. We demonstrate, in vitro and in vivo, the effect of incorporating vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2), in these hydrogels to enhance angiogenesis and bone regeneration, respectively. We show that the solid-state presentation of growth factors enables very low growth factor doses to achieve regenerative effects.

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Posted June 29, 2019.
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Engineered full-length Fibronectin-based hydrogels sequester and present growth factors to promote regenerative responses in vitro and in vivo
Sara Trujillo, Cristina Gonzalez-Garcia, Patricia Rico, Andrew Reid, James Windmill, Matthew J. Dalby, Manuel Salmeron-Sanchez
bioRxiv 687244; doi: https://doi.org/10.1101/687244
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Engineered full-length Fibronectin-based hydrogels sequester and present growth factors to promote regenerative responses in vitro and in vivo
Sara Trujillo, Cristina Gonzalez-Garcia, Patricia Rico, Andrew Reid, James Windmill, Matthew J. Dalby, Manuel Salmeron-Sanchez
bioRxiv 687244; doi: https://doi.org/10.1101/687244

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