TY - JOUR
T1 - Material-driven fibronectin assembly for high-efficiency presentation of growth factors
AU - Llopis-Hernández, Virginia
AU - Cantini, Marco
AU - González-García, Cristina
AU - Cheng, Zhe A.
AU - Yang, Jingli
AU - Tsimbouri, Penelope M.
AU - García, Andrés J.
AU - Dalby, Matthew J.
AU - Salmerón-Sánchez, Manuel
N1 - Funding Information:
We acknowledge the advice of A. Clark and J. Garcia (Georgia Institute of Technology) on the in vivo experiments and D. Russell (School of Life Sciences, University of Glasgow) on the histological analysis. This study was supported by the European Research Council (ERC HealInSynergy, 306990), the UK Medical Research Council (MR/L022710/ 1), the Marie Curie International Outgoing Fellowship program (Protdel 331655), and the NIH (R01 AR062368 and R01 AR062920).
Publisher Copyright:
© 2016 The Authors.
PY - 2016/8
Y1 - 2016/8
N2 - 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.
AB - 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.
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U2 - 10.1126/sciadv.1600188
DO - 10.1126/sciadv.1600188
M3 - Article
C2 - 27574702
AN - SCOPUS:84994051654
VL - 2
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 8
M1 - e1600188
ER -