制备脱细胞基质生物墨水在心血管疾病领域中的应用  

Preparation and applications of decellularized extracellular matrix bioink in cardiovascular fields

作　　者：蒋鸿辉 孔媛媛 刘婧 王志红 Jiang Honghui;Kong Yuanyuan;Liu Jing;Wang Zhihong(Institute of Biomedical Engineering,Chinese Academy of Medical Sciences,Tianjin 300192,China)

机构地区：[1]中国医学科学院生物医学工程研究所,天津市300192

出　　处：《中国组织工程研究》2023年第30期4904-4911,共8页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金面上项目(32071356),项目负责人:王志红;国家自然科学基金面上项目(82272158),项目负责人:刘婧;中央高校基本科研业务费专项资金(3332022069),项目负责人:刘婧;中国医学科学院医学与健康科技创新工程(2022-I2M-1-023),项目负责人:王志红。

摘　　要：背景:借助计算机辅助,3D生物打印技术利用负载活细胞的生物墨水实现组织器官的构建,这种技术设计自由度高、可个性化定制且制造灵活,为心血管组织工程构建带来了新希望。生物墨水是3D生物打印技术的关键,是生物材料与组织再生领域近年来的研究热点。脱细胞基质材料具有低免疫原性、维持原有细胞外基质组分与纤维结构以及利于组织特异性细胞的存活与扩增的特点,是一种具有潜力的生物墨水。目的:总结了脱细胞基质生物墨水的制备与性能表征方法及其在心血管领域中的应用,为脱细胞基质生物墨水在心血管领域中的应用研究提供重要参考。方法:在中国知网和PubMed数据库中进行相关文献检索,中文检索词为“3D打印、脱细胞、生物墨水、血管、心脏”,英文检索词为“decellularization,bioink,3D print,vessel,cardiac”,最终纳入82篇文献进行分析。结果与结论:①脱细胞基质生物墨水的基本制备步骤包括生物材料脱细胞处理获得脱细胞基质,酶解消化脱细胞基质,调节消化液pH值和渗透压以及脱细胞基质混合细胞;②脱细胞基质生物墨水的基本性能表征主要包括脱细胞基质组分、流变性能、微观结构、生物活性、力学性能以及生物降解性;③在血管方面,研究者们通过使用先进打印技术、材料复合以及牺牲层等策略,制备出的脱细胞基质血管的力学性能可得到提升,并得到多层小口径血管,但这些打印过程较复杂,血管性能缺乏动物实验验证,多层血管的培养条件未经优化,且未进行缝合强度和爆破压等重要测试,无法满足医疗器械所需的性能;④在心肌修复方面,研究者证实与胶原及GelMA等相比,脱细胞基质生物墨水在心肌修复中更有优势。同时研究者集中于通过提升材料力学强度和导电性能,并构建微血管网络,进行脱细胞基质心肌补片的设计,这些补片在治�BACKGROUND:With the aid of computer-assisted technology,3D bioprinting technology uses bioink loaded with living cells to achieve tissue organ construction,which brings new hope for cardiovascular tissue engineering construction with its high freedom of design,personalization and manufacturing flexibility.Bioinks are the key to 3D bioprinting technology and have been a hot research topic in the field of biomaterials and tissue regeneration in recent years.Decellularized matrix materials are a promising bioink with low immunogenicity,maintaining the original extracellular matrix components and fibrous structure,and facilitating the survival and expansion of tissue-specific cells.OBJECTIVE:To summarize the preparation and performance characterization methods of decellularized extracellular matrix bioink and its application in cardiovascular field,which is an important reference for the study of decellularized extracellular matrix bioink application in cardiovascular field.METHODS:The Chinese and English search terms“decellularization,bioink,3D print,vessel,cardiac”were used in the CNKI and PubMed databases,respectively,and 82 articles were finally included for analysis.RESULTS AND CONCLUSION:(1)The basic preparation steps of decellularized extracellular matrix bioink include decellularization of biomaterials to obtain decellularized extracellular matrix,enzymatic digestion of decellularized extracellular matrix,adjustment of pH and osmotic pressure of digesting solution,and mixture with decellularized extracellular matrix pregel with cells.(2)The basic performance characterization of decellularized extracellular matrix bioink mainly includes decellularized matrix components,rheological properties,microstructure,bioactivity,mechanical properties,and biodegradability.(3)In terms of blood vessels,researchers have prepared decellularized extracellular matrix vessels with improved mechanical properties and obtained multilayer smalldiameter vessels by using advanced printing techniques,material composites,and sacrifi

关 键 词：心血管疾病 3D生物打印 细胞外基质 脱细胞基质 低免疫原性 生物墨水 血管 心肌组织 心肌补片 心肌梗死 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学] R741