Engineered surfaces that promote capture of latent proteins to facilitate integrin-mediated mechanical activation of growth factors

Dhawan, U. , Williams, J. A., Windmill, J. F.C., Childs, P., Gonzalez-Garcia, C., Dalby, M. J. and Salmeron-Sanchez, M. (2024) Engineered surfaces that promote capture of latent proteins to facilitate integrin-mediated mechanical activation of growth factors. Advanced Materials, (doi: 10.1002/adma.202310789) (PMID:38253339) (Early Online Publication)

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Abstract

Conventional osteogenic platforms utilize active growth factors to repair bone defects that are extensive in size, but they can adversely affect patient health. Here, an unconventional osteogenic platform is reported that functions by promoting capture of inactive osteogenic growth factor molecules to the site of cell growth for subsequent integrin-mediated activation, using a recombinant fragment of latent transforming growth factor beta-binding protein-1 (rLTBP1). It is shown that rLTBP1 binds to the growth-factor- and integrin-binding domains of fibronectin on poly(ethyl acrylate) surfaces, which immobilizes rLTBP1 and promotes the binding of latency associated peptide (LAP), within which inactive transforming growth factor beta 1 (TGF-β1) is bound. rLTBP1 facilitates the interaction of LAP with integrin β1 and the subsequent mechanically driven release of TGF-β1 to stimulate canonical TGF-β1 signaling, activating osteogenic marker expression in vitro and complete regeneration of a critical-sized bone defect in vivo.

Item Type:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Salmeron-Sanchez, Professor Manuel and Childs, Dr Peter and Dalby, Professor Matthew and Windmill, Professor James and Dhawan, Dr Udesh and Gonzalez Garcia, Dr Cristina
Authors: Dhawan, U., Williams, J. A., Windmill, J. F.C., Childs, P., Gonzalez-Garcia, C., Dalby, M. J., and Salmeron-Sanchez, M.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Advanced Materials
Publisher:Wiley
ISSN:0935-9648
ISSN (Online):1521-4095
Published Online:22 January 2024
Copyright Holders:Copyright © 2024 The Authors
First Published:First published in Advanced Materials 2024
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
307621HEALIKICKManuel Salmeron-SanchezEuropean Commission (EC)874889School of Molecular Biosciences
315918DEVISE - Engineered viscoelasticity in regenerative microenvironmentsManuel Salmeron-SanchezEPSRC EU Guarantee (EPSRCEU)101054728ENG - Biomedical Engineering
304627Bioactive polysaccharide-based hydrogels for growth factors delivery during tissue repair.Cristina Gonzalez GarciaEngineering and Physical Sciences Research Council (EPSRC)EP/T000457/1ENG - Biomedical Engineering