Design of hydrogels to stabilize and enhance bone morphogenetic protein activity by heparin mimetics.
Design of hydrogels to stabilize and enhance bone morphogenetic protein activity by heparin mimetics.
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通过类肝素设计水凝胶以稳定并增强骨形态发生蛋白活性
DOI：
10.1016/j.actbio.2018.03.034
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发表时间：
2018-05
影响因子：
9.7
通讯作者：
Lee M
中科院分区：
文献类型：
--
作者：
Kim S;Cui ZK;Kim PJ;Jung LY;Lee M
尽管骨形态发生蛋白-2 (BMP-2) 被认为是可用于骨形成的最有效的刺激剂，但广泛临床使用的主要障碍是其固有的不稳定性和缺乏足够的输送系统。肝素因其强大的结合能力和对许多生长因子蛋白的保护作用而被广泛应用于控释系统。在这项工作中，我们开发了一种水凝胶表面，可以模仿肝素来稳定BMP-2，并通过将模仿肝素的磺化分子（例如聚乙烯磺酸（PVSA）或聚4-苯乙烯磺酸（PSS））引入光交联水凝胶中来增强成骨。在暴露于各种治疗相关应激源期间，在存在多磺酸盐的情况下，BMP-2 的生物活性得到了很好的保留。与未修饰的 MeGC 水凝胶相比，模拟肝素的磺化水凝胶可有效结合 BMP-2，并且在不添加外源 BMP-2 的情况下显着增强封装的骨髓基质细胞 (BMSC) 的成骨分化。磺化水凝胶可有效递送外源 BMP-2，并减少 BMP-2 诱导的初始爆发并增加 BMSC 成骨作用。这些发现提出了一种新型水凝胶平台，用于隔离和稳定 BMP-2，以增强骨组织工程中的骨诱导活性。
Although bone morphogenetic protein-2 (BMP-2) is known to be the most potent stimulator available for bone formation, a major barrier to widespread clinical use is its inherent instability and absence of an adequate delivery system. Heparin is being widely used in controlled release systems due to its strong binding ability and protective effect for many growth factor proteins. In this work, we developed a hydrogel surface that can mimic heparin to stabilize BMP-2 and to enhance osteogenesis by introducing heparin-mimicking sulfonated molecules such as poly-vinylsulfonic acid (PVSA) or poly-4-styrenesulfonic acid (PSS), into photo-crosslinkable hydrogel. Bioactivity of BMP-2 was well preserved in the presence of polysulfonates during exposure to various therapeutically relevant stressors. The heparin-mimicking sulfonated hydrogels were effective to bind BMP-2 compared to unmodified MeGC hydrogel and significantly enhanced osteogenic differentiation of encapsulated bone marrow stromal cells (BMSCs) without the addition of exogenous BMP-2. The sulfonated hydrogels were effective in delivering exogenous BMP-2 with reduced initial burst and increased BMSCs osteogenesis induced by BMP-2. These findings suggest a novel hydrogel platform for sequestering and stabilizing BMP-2 to enhance osteoinductive activity in bone tissue engineering.
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DOI：
10.1039/c6tb01154c
发表时间：
2016-08-21
期刊：
Journal of materials chemistry. B
影响因子：
--
作者：
Kim S;Cui ZK;Fan J;Fartash A;Aghaloo TL;Lee M
通讯作者：
Lee M
影响因子：
3.3
作者：
Kuo WJ;Digman MA;Lander AD
通讯作者：
Lander AD
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：
3.7
作者：
El Bialy I;Jiskoot W;Reza Nejadnik M
通讯作者：
Reza Nejadnik M
影响因子：
41.2
作者：
Huebsch N;Lippens E;Lee K;Mehta M;Koshy ST;Darnell MC;Desai RM;Madl CM;Xu M;Zhao X;Chaudhuri O;Verbeke C;Kim WS;Alim K;Mammoto A;Ingber DE;Duda GN;Mooney DJ
通讯作者：
Mooney DJ