制备细胞外基质材料组织脱细胞方法的研究与热点

doi:10.3969/j.issn.2095-4344.2331

中国组织工程研究 ›› 2020, Vol. 24 ›› Issue (34): 5413-5420.doi: 10.3969/j.issn.2095-4344.2331

• 生物材料综述 biomaterial review • 下一篇

制备细胞外基质材料组织脱细胞方法的研究与热点

何晶^1，2，敖强^2，3

¹中国医科大学口腔医学院•附属口腔医院，辽宁省口腔疾病重点实验室；²中国医科大学组织工程教研室；³国家药监局医疗器械监管科学研究基地，四川大学医疗器械监管科学研究院

收稿日期:2020-01-20 修回日期:2020-01-21 接受日期:2020-03-13 出版日期:2020-11-08 发布日期:2020-09-11
通讯作者: 敖强，教授，博士生导师，中国医科大学组织工程教研室，辽宁省沈阳市 110122；国家药监局医疗器械监管科学研究基地，四川大学医疗器械监管科学研究院，四川省成都市 610064
作者简介:何晶，女，1988年生，辽宁省沈阳市人，汉族，中国医科大学在读博士，讲师，主治医师，主要从事脱细胞基质材料的制备与应用方面的研究。
基金资助:
国家重点研发项目(2017YFA0105802)；国家自然科学基金(81771351)

Research hotspots in tissue decellularization method for manufacturing extracellular matrices

He Jing^{1, 2}, Ao Qiang^{2, 3}

¹School and Hospital of Stomatology, China Medical University, Liaoning Province Key Laboratory of Oral Diseases; ²Department of Tissue Engineering, China Medical University; ³Institute of Regulatory Science for Medical Device, Engineering Research Center in Biomaterial, Sichuan University

Received:2020-01-20 Revised:2020-01-21 Accepted:2020-03-13 Online:2020-11-08 Published:2020-09-11
Contact: Ao Qiang, Professor, Doctoral supervisor, Department of Tissue Engineering, China Medical University, Shenyang 110122, Liaoning Province, China; Institute of Regulatory Science for Medical Device, Engineering Research Center in Biomaterial, Sichuan University, Chengdu 610064, Sichuan Province, China
About author:He Jing, Doctoral candidate, Lecturer, Attending physician, School and Hospital of Stomatology, China Medical University, Liaoning Province Key Laboratory of Oral Diseases, Shenyang 110002, Liaoning Province, China; Department of Tissue Engineering, China Medical University, Shenyang 110122, Liaoning Province, China
Supported by:
the National Key Research &Development Program of China, No. 2017YFA0105802; the National Natural Science Foundation of China, No. 81771351

摘要/Abstract

摘要：

文题释义：

细胞外基质：是由大分子构成的错综复杂网络，为细胞的生存及活动提供适宜的场所，并通过信号转导系统影响细胞的形状、代谢、功能、迁移、增殖和分化。

组织脱细胞：在组织工程学范畴中，应用物理、化学、生物等方法将同种异体或异种组织中的细胞裂解、洗脱，从而获得无细胞的细胞外基质支架材料的过程。

背景：细胞外基质构成的生物支架材料目前已被广泛应用于临床治疗和体内外基础研究中，该种材料脱细胞技术的质量至关重要，不彻底的脱细胞效果会导致生物支架材料植入体内后，诱发一系列免疫排斥反应，最终导致治疗的失败。

目的：介绍制备细胞外基质材料组织脱细胞方法的研究进展。

方法：以“extracellular matrix，tissue decellularization，decellularized method，tissue engineering”为检索词，应用计算机检索PubMed数据库检索2005年1月至2019年12月的相关文章；以“acellular tissue，enzymatic modification”为检索词，应用计算机检索Google Patent数据库2014年1月至2019年12月的相关专利。纳入与组织细胞外基质材料脱细胞方法密切相关的文献，排除重复性研究。

结果与结论：脱细胞基质材料的制备方法纷繁复杂，主要包括物理法、化学法和生物法3大类。根据不同的组织类型而选择恰当的脱细胞方法可以在完全去除细胞的同时，最大限度地保留细胞外基质的结构和成分。如果脱细胞的效果不充分，则会造成严重的免疫炎症反应。脱细胞组织的酶修饰方法可以不同程度改善组织的柔韧性、弹性、耐摩擦性等，并可以进一步去除组织的免疫原性。另外，正确选择恰当的灭菌方法有助于更好地保留细胞外基质材料的超微结构与机械性能。同时，异种来源的脱细胞生物支架作为植入性医疗器械，应严格遵循食品药品监督管理办法的规定，规定中要求对于细胞外基质产品的最终灭菌方法的选择要根据不同细菌接种量的指导方针。

ORCID: 0000-0002-1309-1971(敖强)

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

关键词: 材料, 细胞外基质, 脱细胞, 酶修饰, 灭菌方法, 医疗器械, 综述

Abstract:

BACKGROUND: Biological scaffold materials made of extracellular matrix are currently widely used in clinical treatment and basic studies in vivo and in vitro. The quality of decellularization technique is of great importance since unsuccessful decellularized effects will lead to a series of immunological rejection after implantation, which would finally result in treatment failure.

OBJECTIVE: To introduce the research advancement of tissue decellularized method of extracellular matrix materials.

METHODS: The articles published from January 2005 to December 2019 were retrieved from PubMed database. The key words were “extracellular matrix, tissue decellularization, decellularized method, tissue engineering”. The articles published from January 2014 to December 2019 were retrieved from Google Patent database; the key words were “acellular tissue, enzymatic modification”. References closely related to the decellularized method of extracellular matrix materials were included and repetitive studies were excluded.

RESULTS AND CONCLUSION: Preparation methods of acellular matrix materials vary widely, which mainly include physical, chemical and biological methods. Selecting appropriate decellularized method according to different tissue types is vital for thoroughly removing cell components and retaining the structure and constituent of extracellular matrix to the fullest extent. Severe immunoinflammatory responses can occur under the condition of insufficient decellularized effects. Enzymatic modification of acellular tissue can improve tissue flexibility, elasticity and resistance to friction, and further remove tissue immunogenicity. Additionally, proper selection of sterilization method can help to better preserve the ultrastructural and mechanical properties of extracellular matrix materials. Simultaneously, acellular biological scaffolds of xenogenic sources should strictly comply with the provisions of the food and drug supervision and administration measures, which require that the final method of sterilization for extracellular matrix products is selected according to the guidelines for different bacterial inoculations.

Key words: materials, extracellular matrix, acellularization, enzyme modification, sterilization methods, medical devices, review

中图分类号:

何晶, 敖强. 制备细胞外基质材料组织脱细胞方法的研究与热点[J]. 中国组织工程研究, 2020, 24(34): 5413-5420.

He Jing, Ao Qiang. Research hotspots in tissue decellularization method for manufacturing extracellular matrices[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(34): 5413-5420.

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引言

材料方法

讨论

脱细胞组织材料的临床应用目前仍是一个相对较新的课题，但其在临床上的关注度与医生对此种材料的应用兴趣却日渐高涨。比如一种叫做Alloderm的异体脱细胞真皮产品，已在临床上应用了20年，可以应用于烧伤治疗、乳房重建、疝修补等^[27]。然而，近年来提出恢复脱细胞基质材料内的细胞活力同样重要，为脱细胞基质材料后期的自体细胞再植研究(如在脱细胞真皮组织中植入自体成纤维细胞和角质形成细胞)提供了方向。随着脱细胞技术的不断创新和推进，应用人类诱导多功能干细胞或非自体组织和器官的治疗策略会逐渐完善，从而有助于消除医疗界对器官或组织移植治疗日益增长的需求。

综上，脱细胞基质材料的制备方法纷繁复杂，根据不同的组织类型而选择恰当的脱细胞方法可以在完全去除细胞的同时，最大限度地保留细胞外基质的结构和成分。如果脱细胞的效果不充分会造成严重的免疫炎症反应。脱细胞组织的酶修饰方法可不同程度地改善组织的柔韧性、弹性、耐摩擦性等，并可以进一步去除组织的免疫原性，为将来脱细胞组织产品在临床中广泛应用提供了较理想的优化方案。另外，正确选择恰当的灭菌方法至关重要，不当的灭菌方法则有可能会显著影响细胞外基质材料的超微结构与机械性能。同时，异种来源的脱细胞生物支架作为植入性医疗器械，应严格遵循食品药品监督管理办法的规定，规定中要求对于细胞外基质产品的最终灭菌方法的选择要根据不同细菌接种量的指导方针。中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

制备细胞外基质材料组织脱细胞方法的研究与热点

Research hotspots in tissue decellularization method for manufacturing extracellular matrices

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