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透明质酸和硫酸软骨素(甲基)丙烯酰胺基水凝胶在组织工程中的应用:合成、特性和临床前评价。

Hyaluronic acid and chondroitin sulfate (meth)acrylate-based hydrogels for tissue engineering: Synthesis, characteristics and pre-clinical evaluation.

机构信息

Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Science for Life, Utrecht University, 3508 TB, Utrecht, the Netherlands.

Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Science for Life, Utrecht University, 3508 TB, Utrecht, the Netherlands; Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB, Eindhoven, the Netherlands.

出版信息

Biomaterials. 2021 Jan;268:120602. doi: 10.1016/j.biomaterials.2020.120602. Epub 2020 Dec 22.

Abstract

Hydrogels based on photocrosslinkable Hyaluronic Acid Methacrylate (HAMA) and Chondroitin Sulfate Methacrylate (CSMA) are presently under investigation for tissue engineering applications. HAMA and CSMA gels offer tunable characteristics such as tailorable mechanical properties, swelling characteristics, and enzymatic degradability. This review gives an overview of the scientific literature published regarding the pre-clinical development of covalently crosslinked hydrogels that (partially) are based on HAMA and/or CSMA. Throughout the review, recommendations for the next steps in clinical translation of hydrogels based on HAMA or CSMA are made and potential pitfalls are defined. Specifically, a myriad of different synthetic routes to obtain polymerizable hyaluronic acid and chondroitin sulfate derivatives are described. The effects of important parameters such as degree of (meth)acrylation and molecular weight of the synthesized polymers on the formed hydrogels are discussed and useful analytical techniques for their characterization are summarized. Furthermore, the characteristics of the formed hydrogels including their enzymatic degradability are discussed. Finally, a summary of several recent applications of these hydrogels in applied fields such as cartilage and cardiac regeneration and advanced tissue modelling is presented.

摘要

基于光交联透明质酸甲基丙烯酸酯(HAMA)和硫酸软骨素甲基丙烯酸酯(CSMA)的水凝胶目前正在研究用于组织工程应用。HAMA 和 CSMA 凝胶具有可调节的特性,如可调节的机械性能、溶胀特性和酶降解性。本文综述了关于部分基于 HAMA 和/或 CSMA 的共价交联水凝胶的临床前开发的科学文献。在综述过程中,对基于 HAMA 或 CSMA 的水凝胶临床转化的下一步提出了建议,并定义了潜在的陷阱。具体来说,描述了获得可聚合透明质酸和硫酸软骨素衍生物的多种不同合成途径。讨论了合成聚合物的(甲基)丙烯酰化程度和分子量等重要参数对形成水凝胶的影响,并总结了用于其表征的有用分析技术。此外,还讨论了形成的水凝胶的特性,包括其酶降解性。最后,总结了这些水凝胶在软骨和心脏再生以及高级组织建模等应用领域的一些最新应用。

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