Engineered Surfaces That Promote Capture of Latent Proteins to Facilitate Integrin‐Mediated Mechanical Activation of Growth Factors

• Published in: Advanced materials (Weinheim) 2024-06, Vol.36 (23), p.e2310789-n/a
• Main Authors: Dhawan, Udesh, Williams, Jonathan A., Windmill, James F. C., Childs, Peter, Gonzalez‐Garcia, Cristina, Dalby, Matthew J., Salmeron‐Sanchez, Manuel
• Format: Article
• Language: English
• Subjects: Animals; Bone Regeneration; Defects; Fibronectin; Fibronectins - chemistry; Fibronectins - metabolism; Growth factors; Humans; Integrin beta1 - metabolism; Integrins - metabolism; Latent TGF-beta Binding Proteins - chemistry; Latent TGF-beta Binding Proteins - metabolism; LTBP1; Osteogenesis; Protein Binding; Proteins; Signal Transduction; Surface Properties; Transforming Growth Factor beta1 - metabolism
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202310789

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. An osteogenic platform that functions by capturing inactive growth factor molecules is engineered to overcome conventional challenges associated with the use of active growth factors. The platform triggers capture of inactive transforming growth factor beta‐1 for its subsequent integrin‐mediated activation which activates osteogenic downstream signaling in vitro and fully repairs critical‐sized bone defect in vivo.