酶促自由基聚合制备纳米复合凝胶的研究及生物应用

The organic-inorganic nanocomposite hydrogels expand the application of hydrogels in materials, especially as biomaterials. Enzyme catalyzed free radical polymerization is advantageous over other polymerization mathods due to its mild reaction condition, high efficiency, low energy consumption and facile operation . Our project applys the enzymatic polymerization to the mild preparation of nanocomposite hydrogels. Firstly, serveral oxidordeuctases/substrates reaction systems are screened by the formation of free radical and the initiation of polymerization with monomer. Secondly, the biocompatible inorganic nanoparticles are modified by the substrates to form the inorgnaic initiator. At last, the reaction between oxidordeuctases and inorgnaic initiator can form radical on the surface of nanoparticles, which initiate the polymerization of monomers from the surface and the crosslinking between organic and inorganic components to form three dimensional nanocomposite gel. In this research, the modified inorganic nanoparticles act as both the initiator and the crosslinking point, which endow the gel with high mechanical property. The enzyme immobilized into the gel can remain its biological properties. Integrated with strength and bioactive enzyme, this kind of soft-wet hydrogel platform can be applied in tissue engineering and hydrogel-immobilized enzyme electrode.

有机无机纳米复合凝胶因高的强度拓展了在材料领域，特别是生物材料相关领域的应用。相对于其它引发途径，酶促自由基聚合具有反应条件温和、高效、低能耗、操作简便的特点。本课题将酶促自由基聚合的方法应用到纳米复合凝胶的温和制备研究中。研究的基础是筛选氧化还原酶和底物分子的反应体系来产生自由基并验证它的单体引发能力。接下来的工作是将底物分子修饰到生物相容性的无机纳米颗粒表面来构建无机引发点。最终的工作是应用氧化还原酶来催化无机表面的底物产生自由基，进而引发单体在无机颗粒表面聚合并最后三维交联无机组分制备复合凝胶。本研究中修饰后的无机纳米颗粒作为成胶的引发点和交联点能有效赋予复合凝胶高的强度。生物酶分子在催化自由基聚合后被负载在复合凝胶中依然保持一定的生物性能。因此集成上述力学和生物性能于一体的复合凝胶可望应用为组织工程和生物电极等领域。

在项目51473123的资助下，课题组利用氧化还原酶调控的自由基聚合和氧化交联来进行高分子复合凝胶的制备和打印成型。这种生物氧化成胶技术适合于不同聚合物种类和不同尺寸的复合水凝胶体系。我们发现氧气作为氧化酶催化单体聚合及交联的底物能影响凝胶成型速度和交联密度的梯度分布。结合生物氧化成胶方法与3D生物打印技术，我们可以获得强度可调的生物医用凝胶支架，用于脊髓损伤修复和其它组织工程领域。负载于纳米凝胶/可注射凝胶载体中的氧化还原酶能够维持高的催化能力，在肿瘤显影和氧化治疗等领域也展现了优异的应用前景。近4年来，课题组在生物氧化成胶、仿生材料构建和肿瘤酶动力治疗等领域开展了卓有成效的工作，累计发表SCI收录论文21篇，相关研究成果获得国际国内同行的认可。