Engineered Surfaces that Promote Capture of Latent Proteins to Facilitate Integrin-Mediated Mechanical Activation of Growth Factors.

Conventional osteogenic platforms utilize active growth factors to repair bone defects that are extensive in size, but they can adversely affect patient health. Here, we report an unconventional osteogenic platform 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). We show that rLTBP1 binds to the growth factor- and integrin-binding domains of fibronectin on poly(ethyl acrylate) surfaces, which immobilises rLTBP1 and promotes the binding of latency associated peptide (LAP), within which inactive 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 signalling, activating osteogenic marker expression in-vitro and complete regeneration of a critical-sized bone defect in-vivo. This article is protected by copyright. All rights reserved.