Department of Molecular Science and Technology, Ajou University, 5 Woncheon, Yeongtong, Suwon 443-749, Republic of Korea.
Biomacromolecules. 2010 Mar 8;11(3):706-12. doi: 10.1021/bm9012875.
Over the past decades, hydrogels have been widely studied as biomaterials for various biomedical applications like implants, drugs and cell delivery carriers because of their high biocompatibility, high water contents and excellent permeability for nutrients and metabolites. Especially, in situ forming hydrogel systems have received much attention because of their easy application based on minimal invasive techniques. Chemical cross-linking systems fabricated using enzymatic reactions have various advantages, such as high biocompatibility and easy control of reaction rates under mild condition. In this study, we report enzyme-triggered injectable and biodegradable hydrogels composed of Tetronic-tyramine conjugates. The Tetronic-tyramine conjugates were synthesized by first reacting Tetronic with succinic anhydride and subsequent conjugation with tyramine using DCC/NHS as coupling reagents. The chemical structure of Tetronic-succinic anhydride-tyramine (Tet-SA-TA) copolymer was characterized by (1)H NMR and FTIR. The hydrogels were prepared from a Tet-SA-TA solution above 3 wt % in the presence of horseradish peroxidase (HRP) and H(2)O(2) under physiological conditions. Their mechanical property, gelation time, swelling ratio and degradation time were evaluated at different polymer, HRP, and H(2)O(2) concentrations. In addition, a cyto-compatibility study was performed using the MC3T3-E1 cell line. In the cytotoxicity test, it was clear that the Tet-SA-TA hydrogel had no apparent cytotoxicity except for the hydrogel formed with 0.25 wt % H(2)O(2) due to the cytotoxicity of residual H(2)O(2). In conclusion, the obtained results demonstrated that the Tet-SA-TA hydrogel has great potential for use as an injectable scaffold for tissue engineering and as a drug carrier for controlled drug delivery systems.
在过去的几十年中，水凝胶因其高生物相容性、高含水量以及对营养物和代谢物的优异渗透性而被广泛研究作为各种生物医学应用的生物材料，如植入物、药物和细胞输送载体。特别是，原位形成的水凝胶系统因其基于微创技术的简单应用而受到广泛关注。使用酶反应制造的化学交联系统具有各种优点，例如高生物相容性和在温和条件下容易控制反应速率。在这项研究中，我们报告了由 Tetronic-酪胺缀合物组成的酶触发可注射和可生物降解的水凝胶。Tetronic-酪胺缀合物通过首先用琥珀酸酐反应 Tetronic，然后使用 DCC/NHS 作为偶联试剂与酪胺进行缀合来合成。Tetronic-琥珀酸酐-酪胺（Tet-SA-TA）共聚物的化学结构通过 1H NMR 和 FTIR 进行了表征。在生理条件下，Tet-SA-TA 溶液的浓度高于 3wt%，在辣根过氧化物酶（HRP）和 H2O2 的存在下制备水凝胶。在不同的聚合物、HRP 和 H2O2 浓度下，评估了它们的机械性能、凝胶时间、溶胀比和降解时间。此外，还使用 MC3T3-E1 细胞系进行了细胞相容性研究。在细胞毒性试验中，除了由于残留 H2O2 的细胞毒性而形成的 0.25wt%H2O2 的水凝胶外，很明显 Tet-SA-TA 水凝胶没有明显的细胞毒性。总之，研究结果表明，Tet-SA-TA 水凝胶具有作为组织工程可注射支架和作为控制药物释放系统的药物载体的巨大潜力。
