Self-gelling hydrogels based on oppositely charged dextran microspheres
Self-gelling hydrogels based on oppositely charged dextran microspheres
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DOI：
10.1016/j.biomaterials.2004.05.035
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发表时间：
2005-05-01
期刊：
影响因子：
14
通讯作者：
Hennink, WE
中科院分区：
文献类型：
--
作者：
Van Tomme, SR;van Steenbergen, MJ;Hennink, WE
本文介绍了一种新型的自凝胶水凝胶，可能适用于药物控制释放和组织工程。宏观凝胶通过混合带相反电荷的交联葡聚糖微球的分散体获得。这些微球又通过交联在聚（乙二醇）水溶液中乳化的甲基丙烯酸羟乙酯衍生的葡聚糖来制备。通过向聚合混合物中加入甲基丙烯酸（MAA）或甲基丙烯酸二甲氨基乙酯（DMAEMA），得到带负电荷或正电荷的微球。流变学分析表明，当等体积的带相反电荷的微球，分散在pH 7的缓冲溶液中，混合时，发生瞬时凝胶化。通过改变体系的含水量，可以在30 ~ 6500 Pa范围内调节网络的剪切模量。此外，控制应变和蠕变实验表明，所形成的网络主要是弹性的。对于这些系统的应用，例如作为药物活性蛋白质的受控基质，重要的是，证明了水凝胶系统具有可逆的屈服点，这意味着在一定的施加应力以上，系统开始流动，而当应力去除时，发生凝胶形成。此外，它表明，网络结构可以通过介质的低pH值或高离子强度来破坏。这表明网络在pH 7和低离子强度下形成。通过带相反电荷的葡聚糖微球之间的离子相互作用保持在一起。该系统有望成为适用于药物递送和组织工程应用的可注射凝胶。(C)2004爱思唯尔有限公司保留所有权利。
This paper presents a novel self-gelling hydrogel potentially suitable for controlled drug delivery and tissue engineering. The macroscopic gels are obtained by mixing dispersions of oppositely charged crosslinked dextran microspheres. These microspheres in turn were prepared by crosslinking of dextran derivatized with hydroxyethyl methacrylate emulsified in an aqueous poly(ethylene glycol) solution. Negatively or positively charged microspheres were obtained by addition of methacrylic acid (MAA) or dimethylaminoethyl methacrylate (DMAEMA) to the polymerization mixture. Rheological analysis showed that instantaneous gelation occurred when equal volumes of oppositely charged microspheres, dispersed in buffer solutions of pH 7, were mixed. The shear modulus of the networks could be tailored from 30 to 6500Pa by varying the water content of the system. Moreover, controlled strain and creep experiments showed that the formed networks were mainly elastic. Importantly for application of these systems, e.g. as controlled matrix of pharmaceutically active proteins, it was demonstrated that the hydrogel system has a reversible yield point, meaning that above a certain applied stress, the system starts to flow, whereas when the stress is removed, gel formation occurred. Further it was shown that the network structure could be broken by either a low pH or a high ionic strength of the medium. This demonstrates that the networks, formed at pH 7 and at low ionic strength. are held together by ionic interactions between the oppositely charged dextran microspheres. This system holds promise as injectable gels that are suitable for drug delivery and tissue engineering applications. (C) 2004 Elsevier Ltd. All rights reserved.