酶氧化代谢用于多糖复合凝胶的制备及生物应用

Strategies for building biomedical injectable gels have proceeded in two main directions: structure units building and polymer crosslinking methods. Biocompatible macromolecules, such as polysaccharide, collagen, polyethylene glycol (PEG) or their derivates are usually used as building blocks to synthesize injectable ges by thiol-double bond or Schiff base reaction. The characteristic of this crosslinking process is mild and rapid condition, but poor mechanical performance due to insufficient mixing. Macromolecular oxidative crosslinking and free radical polymerization are simultaneously realized by mild oxidative enzyme catalysis oxidation in this project. The first step of macromolecules oxidative cross-linking gives the gel ability to be injected and printed and further radical polymerization which optimizes mechanical properties meets the actual demand of tissue engineering. In addition enzymes in-situ loaded in the final gel can retain high biological oxidation activity. This soft and moist hydrogels platform contained active enzymes has a promising prospect for the recovery of spinal cord injury and enzymatic oxidative treatment of the tumor.

为构建可注射成型的生物医用凝胶，研究者们从凝胶构建单元和聚合交联方法两个方向着手进行材料设计。所用的凝胶构建单元通常都是多糖、胶原蛋白、聚乙二醇等生物相容性组分或者它们的修饰物，然后通过巯基-双键或希夫碱等化学反应来交联大分子单元形成凝胶。这些凝胶的交联过程温和快速，但力学性能常因不均匀的混合过程而非常弱。本项目利用酶催化的温和氧化代谢同步实现大分子成胶单元的氧化交联成型和单体自由基聚合强化，得到得到强度可调的复合凝胶。第一步的大分子单元的氧化交联赋予该凝胶的可注射和可打印性，进一步的自由基聚合优化了生物医用凝胶的强度达到实际组织工程的需求。同时最后的复合凝胶中原位负载的酶分子，能保留非常高的生物氧化活性。含活性酶的软湿水凝胶平台可望应用于脊髓损伤修复和肿瘤酶氧化治疗等。

在项目51873156的资助下，课题组利用多酶催化氧化聚合与交联构筑生物医用凝胶与纳米凝胶。我们发展了超分子共组装设计和级联酶聚合的遴选来实现多酶在凝胶网络中的最优化固定。我们进一步实现了体内多酶促聚合成胶，探索构筑各类智能组织工程支架。最后我们设计并应用纳米凝胶整合的多酶用于活性氧调控的肿瘤治疗与联合治疗。近4年来，课题组在多酶级联催化成胶、体内原位构筑凝胶组织工程支架和肿瘤酶催化动力学治疗等领域开展了卓有成效的工作，累计发表SCI收录论文23篇，相关研究成果获得国际国内同行的认可。