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

Udesh Dhawan, Jonathan A. Williams, James F. C. Windmill, Peter Childs, Cristina Gonzalez-Garcia, Matthew J. Dalby, Manuel Salmeron-Sanchez

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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.
Original languageEnglish
Article number2310789
Number of pages15
JournalAdvanced Materials
Early online date22 Jan 2024
DOIs
Publication statusE-pub ahead of print - 22 Jan 2024

Keywords

  • bone regeneration
  • fibronectin
  • growth factors
  • LTBP1

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