Gopinathan Janarthanan, Noh Insup
1Department of Chemical and Biomolecular Engineering, Seoul National University of Science and Technology (Seoul Tech), 232 Gongneung-ro, Nowon-Gu, Seoul, 01811 Republic of Korea.
2Convergence Institute of Biomedical Engineering and Biomaterials, Seoul National University of Science and Technology (Seoul Tech), 232 Gongneung-ro, Nowon-Gu, Seoul, 01811 Republic of Korea.
Tissue Eng Regen Med. 2018 Aug 16;15(5):531-546. doi: 10.1007/s13770-018-0152-8. eCollection 2018 Oct.
The tissue engineering and regenerative medicine approach require biomaterials which are biocompatible, easily reproducible in less time, biodegradable and should be able to generate complex three-dimensional (3D) structures to mimic the native tissue structures. Click chemistry offers the much-needed multifunctional hydrogel materials which are interesting biomaterials for the tissue engineering and bioprinting inks applications owing to their excellent ability to form hydrogels with printability instantly and to retain the live cells in their 3D network without losing the mechanical integrity even under swollen state.
In this review, we present the recent developments of hydrogel in the field of click chemistry reported for the tissue engineering and 3D bioinks applications, by mainly covering the diverse types of click chemistry methods such as Diels-Alder reaction, strain-promoted azide-alkyne cycloaddition reactions, thiol-ene reactions, oxime reactions and other interrelated reactions, excluding enzyme-based reactions.
The click chemistry-based hydrogels are formed spontaneously on mixing of reactive compounds and can encapsulate live cells with high viability for a long time. The recent works reported by combining the advantages of click chemistry and 3D bioprinting technology have shown to produce 3D tissue constructs with high resolution using biocompatible hydrogels as bioinks and injectable forms.
Interestingly, the emergence of click chemistry reactions in bioink synthesis for 3D bioprinting have shown the massive potential of these reaction methods in creating 3D tissue constructs. However, the limitations and challenges involved in the click chemistry reactions should be analyzed and bettered to be applied to tissue engineering and 3D bioinks. The future scope of these materials is promising, including their applications in 3D bioprinting for tissue or organ regeneration.
组织工程和再生医学方法需要生物相容性好、能在更短时间内轻松重现、可生物降解且应能够生成复杂三维（3D）结构以模拟天然组织结构的生物材料。点击化学提供了急需的多功能水凝胶材料，由于其具有出色的即时形成具有可印刷性的水凝胶以及在3D网络中保留活细胞的能力，即使在肿胀状态下也不会失去机械完整性，因此是组织工程和生物打印墨水应用中有趣的生物材料。
在本综述中，我们介绍了点击化学领域中用于组织工程和3D生物墨水应用的水凝胶的最新进展，主要涵盖了不同类型的点击化学方法，如狄尔斯-阿尔德反应、应变促进的叠氮化物-炔烃环加成反应、硫醇-烯反应、肟反应及其他相关反应，但不包括基于酶的反应。
基于点击化学的水凝胶在反应性化合物混合时自发形成，并且可以长时间高活力地封装活细胞。最近结合点击化学和3D生物打印技术优势的研究表明，使用生物相容性水凝胶作为生物墨水和可注射形式能够生产出高分辨率的3D组织构建体。
有趣的是，点击化学反应在用于3D生物打印的生物墨水合成中的出现，显示了这些反应方法在创建3D组织构建体方面的巨大潜力。然而，应分析并改进点击化学反应中涉及的局限性和挑战，以便应用于组织工程和3D生物墨水。这些材料的未来前景广阔，包括它们在用于组织或器官再生的3D生物打印中的应用。
