title: Material-driven fibronectin assembly for high-efficiency presentation of growth factors.
abstract: Growth factors (GFs) are powerful signaling molecules with the potential to drive regenerative strategies, including bone repair and vascularization. However, GFs are typically delivered in soluble format at supraphysiological doses because of rapid clearance and limited therapeutic impact. These high doses have serious side effects and are expensive. Although it is well established that GF interactions with extracellular matrix proteins such as fibronectin control GF presentation and activity, a translation-ready approach to unlocking GF potential has not been realized. We demonstrate a simple, robust, and controlled material-based approach to enhance the activity of GFs during tissue healing. The underlying mechanism is based on spontaneous fibrillar organization of fibronectin driven by adsorption onto the polymer poly(ethyl acrylate). Fibrillar fibronectin on this polymer, but not a globular conformation obtained on control polymers, promotes synergistic presentation of integrin-binding sites and bound bone morphogenetic protein 2 (BMP-2), which enhances mesenchymal stem cell osteogenesis in vitro and drives full regeneration of a nonhealing bone defect in vivo at low GF concentrations. This simple and translatable technology could unlock the full regenerative potential of GF therapies while improving safety and cost-effectiveness.
authors: Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow G12 8LT, UK.
authors: Virginia
authors: V
authors: Llopis-Hernández
authors: Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow G12 8LT, UK.
authors: Marco
authors: M
authors: Cantini
authors: Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow G12 8LT, UK.
authors: Cristina
authors: C
authors: González-García
authors: Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow G12 8LT, UK.
authors: Zhe A
authors: ZA
authors: Cheng
authors: Center for Cell Engineering, Institute of Molecular Cell and Systems Biology, University of Glasgow, Joseph Black Building, University Avenue, Glasgow G12 8QQ, UK.
authors: Jingli
authors: J
authors: Yang
authors: Center for Cell Engineering, Institute of Molecular Cell and Systems Biology, University of Glasgow, Joseph Black Building, University Avenue, Glasgow G12 8QQ, UK.
authors: Penelope M
authors: PM
authors: Tsimbouri
authors: Woodruff School of Mechanical Engineering, Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 First Drive, Atlanta, GA 30332, USA.
authors: Andrés J
authors: AJ
authors: García
authors: Center for Cell Engineering, Institute of Molecular Cell and Systems Biology, University of Glasgow, Joseph Black Building, University Avenue, Glasgow G12 8QQ, UK.
authors: Matthew J
authors: MJ
authors: Dalby
authors: Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow G12 8LT, UK.
authors: Manuel
authors: M
authors: Salmerón-Sánchez
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry / Q000627:therapeutic use; D001665:Binding Sites; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000235:genetics*; D001861:Bone Regeneration / Q000187:drug effects; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics; D005353:Fibronectins / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D011108:Polymers / Q000627:therapeutic use; D044968:Regenerative Medicine
chemical_list: D000180:Acrylic Resins; C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D005353:Fibronectins; D016023:Integrins; D036341:Intercellular Signaling Peptides and Proteins; D011108:Polymers; C478961:poly(ethylacrylate)
keywords: BMP-2; Bone Regeneration; biomaterials; fibronectin; growth factors