Material-driven fibronectin assembly for high-efficiency presentation of growth factors.
Material-driven fibronectin assembly for high-efficiency presentation of growth factors.
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DOI：
10.1126/sciadv.1600188
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发表时间：
2016-08
期刊：
影响因子：
13.6
通讯作者：
Salmerón-Sánchez M
中科院分区：
文献类型：
--
作者：
Llopis-Hernández V;Cantini M;González-García C;Cheng ZA;Yang J;Tsimbouri PM;García AJ;Dalby MJ;Salmerón-Sánchez M
研究人员开发了一种简单的技术来增强组织愈合过程中生长因子的活性。生长因子 (GF) 是强大的信号分子，具有推动再生策略的潜力，包括骨修复和血管形成。然而，由于快速清除和有限的治疗影响，GF 通常以超生理剂量以可溶形式递送。这些高剂量具有严重的副作用并且价格昂贵。尽管众所周知，GF 与细胞外基质蛋白（如纤连蛋白）的相互作用控制 GF 的表达和活性，但尚未实现释放 GF 潜力的翻译就绪方法。我们展示了一种简单、稳健且受控的基于材料的方法来增强组织愈合过程中 GF 的活性。其基本机制是基于纤连蛋白的自发纤维组织，该组织是由聚合物聚丙烯酸乙酯吸附驱动的。该聚合物上的纤维状纤连蛋白（而非对照聚合物上获得的球状构象）促进整合素结合位点和结合骨形态发生蛋白 2 (BMP-2) 的协同呈现，从而增强体外间充质干细胞成骨作用，并在低 GF 浓度下驱动体内不愈合骨缺损的完全再生。这种简单且可转化的技术可以释放 GF 疗法的全部再生潜力，同时提高安全性和成本效益。
Researchers develop a simple technique to enhance the activity of growth factors during tissue healing. 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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影响因子：
2.5
作者：
Hudalla, Gregory A.;Kouris, Nicholas A.;Murphy, William L.
通讯作者：
Murphy, William L.
影响因子：
3.4
作者：
Carlos Rodriguez Hernandez, Jose;Salmeron Sanchez, Manuel;Monleon Pradas, Manuel
通讯作者：
Monleon Pradas, Manuel
影响因子：
41.2
作者：
Chaudhuri O;Gu L;Klumpers D;Darnell M;Bencherif SA;Weaver JC;Huebsch N;Lee HP;Lippens E;Duda GN;Mooney DJ
通讯作者：
Mooney DJ
影响因子：
3.4
作者：
Brizuela Guerra, Nayrim;Gonzalez-Garcia, Cristina;Salmeron-Sanchez, Manuel
通讯作者：
Salmeron-Sanchez, Manuel
通过生物启发的相互作用调节生长因子活性的生物材料。
影响因子：
19
作者：
Hudalla, Gregory A.;Murphy, William L.
通讯作者：
Murphy, William L.