Engineered full-length fibronectin-hyaluronic acid hydrogels for stem cell engineering

Trujillo, S. , Vega, S. L., Song, K. H., San Félix, A., Dalby, M. J. , Burdick, J. A. and Salmeron-Sanchez, M. (2020) Engineered full-length fibronectin-hyaluronic acid hydrogels for stem cell engineering. Advanced Healthcare Materials, (doi: 10.1002/adhm.202000989) (Early Online Publication)

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Abstract

Mechanical cues induce a variety of downstream effects on cells, including the regulation of stem cell behavior. Cell fate is typically characterized on biomaterial substrates where mechanical and chemical properties can be precisely tuned; however, most of these substrates do not recapitulate the biological complexity of the extracellular matrix (ECM). Here, hydrogels are engineered for mechanobiological studies using two major components of the ECM: hyaluronic acid (HA) and fibronectin (FN). Rather than typical surface chemisorption of FN to substrates, the system contains full‐length FN covalently crosslinked to HA throughout the hydrogel. The control over the mechanical properties of the hydrogel independent of the concentration of FN and the ability to culture viable cells either on top or encapsulated within the hydrogels are shown. Interestingly, human mesenchymal stem cells (MSCs) experience an increase in nuclear translocation of the yes‐associated protein (YAP) to the nucleus when cultured on (2D) substrates with increasing amounts of FN while maintaining constant hydrogel stiffness. However, this FN dependence on nuclear YAP translocation is not observed for MSCs encapsulated in (3D) hydrogels. This work develops complex hydrogels that recapitulate features of the ECM for the control of stem cells in both 2D and 3D environments.

Item Type:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Salmeron-Sanchez, Professor Manuel and San Felix Garcia-Obregon, Ms Ana and Trujillo Munoz, Dr Sara and Dalby, Professor Matthew
Authors: Trujillo, S., Vega, S. L., Song, K. H., San Félix, A., Dalby, M. J., Burdick, J. A., 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 > Biomedical Engineering
Journal Name:Advanced Healthcare Materials
Publisher:Wiley
ISSN:2192-2640
ISSN (Online):2192-2659
Published Online:01 October 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Advanced Healthcare Materials 2020
Publisher Policy:Reproduced under a Creative Commons licence

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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
301095UKRMP2 Acellular/Smart Materials 3D Architecture HubManuel Salmeron-SanchezMedical Research Council (MRC)MMRE_P75176 (MR/R015651/1ENG - Biomedical Engineering