Material-driven fibronectin assembly for high-efficiency presentation of growth factors

Virginia Llopis-Hernández, Marco Cantini, Cristina González-García, Zhe A. Cheng, Jingli Yang, Penelope M. Tsimbouri, Andrés J. García, Matthew J. Dalby, Manuel Salmerón-Sánchez

研究成果: Contribution to journalArticle査読

68 被引用数 (Scopus)

抄録

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.

本文言語英語
論文番号e1600188
ジャーナルScience Advances
2
8
DOI
出版ステータス出版済み - 8 2016

All Science Journal Classification (ASJC) codes

  • 一般

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