Engineered 3D hydrogels with full-length fibronectin that sequester and present growth factors

Trujillo Munoz, S. , Gonzalez Garcia, C., Rico Tortosa, P., Reid, A., Windmill, J., Dalby, M. J. and Salmeron-Sanchez, M. (2020) Engineered 3D hydrogels with full-length fibronectin that sequester and present growth factors. Biomaterials, 252, 120104. (doi: 10.1016/j.biomaterials.2020.120104)

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Abstract

Extracellular matrix (ECM)-derived matrices such as Matrigel are used to culture numerous cell types in vitro as they recapitulate ECM properties that support cell growth, organisation, migration and differentiation. These ECM-derived matrices contain various growth factors which make them highly bioactive. However, they suffer lot-to-lot variability, undefined composition and lack of controlled physical properties. There is a need to develop rationally designed biomaterials that can also recapitulate ECM roles. Here, we report the development of Fibronectin (FN)-based 3D hydrogels of controlled stiffness and degradability that incorporate full-length 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. These hydrogels represent a step-change in the design of well-defined, reproducible, synthetic microenvironments for 3D cell culture that incorporate growth factors to achieve functional effects.

Item Type:Articles
Additional Information:This study was supported by the UK Regenerative Medicine Platform (MRC grant MR/L022710/1), the UK Engineering and Physical Sciences Research Council (EPSRC EP/P001114/1) and a programme grant from the Sir Bobby Charlton Foundation. μCT work was supported by the European Research Council (ERC) under the European Union's Seventh Framework Programme (FP7/2007-2013) (grant agreement No. [615030]). S.T. acknowledges support from the University of Glasgow through their internal scholarship funding program.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Salmeron-Sanchez, Professor Manuel and Windmill, Professor James and Trujillo Munoz, Dr Sara and Rico Tortosa, Dr Patricia and Dalby, Professor Matthew and Gonzalez Garcia, Dr Cristina
Creator Roles:
Trujillo Munoz, S.Conceptualization, Methodology, Investigation, Writing – original draft
Dalby, M.Conceptualization, Methodology, Writing – original draft, Supervision
Salmeron-Sanchez, M.Conceptualization, Methodology, Writing – original draft, Supervision, Funding acquisition
Gonzalez Garcia, C.Methodology, Investigation
Rico Tortosa, P.Methodology, Investigation
Windmill, J.Methodology, Supervision
Authors: Trujillo Munoz, S., Gonzalez Garcia, C., Rico Tortosa, P., Reid, A., Windmill, J., Dalby, M. J., and Salmeron-Sanchez, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Science and Engineering > School of Engineering
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Biomaterials
Publisher:Elsevier
ISSN:0142-9612
ISSN (Online):1878-5905
Published Online:07 May 2020

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173192Engineering growth factor microenvironments- a new therapeutic paradigm for regenerative medicineManuel Salmeron-SanchezEngineering and Physical Sciences Research Council (EPSRC)EP/P001114/1ENG - Biomedical Engineering