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J Zhejiang Univ (Med Sci)  2021, Vol. 50 Issue (2): 212-221    DOI: 10.3724/zdxbyxb-2021-0118
    
Research progress on tissue engineering in repairing temporo-mandibular joint
WANG Chenyu1(),WANG Yingnan2,WANG Cunyi1,SHI Jiejun2,WANG Huiming2,*()
1. Zhejiang University School of Medicine, Hangzhou 310058, China;
2.
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou 310006, China
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Abstract  

Temporomandibular joint osteoarthritis (TMJOA) is mainly manifested as perforation of temporomandibular joint disc (TMJD) and destruction of condylar osteochondral complex (COCC). In recent years, tissue engineering technology has become one of the effective strategies in repairing this damage. With the development of scaffold material technology, composite scaffolds have become an important means to optimize the performance of scaffolds with the combined advantages of natural materials and synthetic materials. The in situ gelling method with the minimally invasive concept can greatly solve the problems of surgical trauma and material anastomosis, which is beneficial to the clinical transformation of temporomandibular joint tissue engineering. Extracellular matrix scaffolds technology can solve the problem of scaffold source and maximize the simulation of the extracellular environment, which provides an important means for the transformation of temporomandibular joint tissue engineering to animal level. Due to the limitation of the source and amplification of costal chondrocytes, the use of mesenchymal stem cells from different sources has been widely used for temporomandibular joint tissue engineering. The fibrochondral stem cells isolated from surface layer of articular cartilage may provide one more suitable cell source. Transforming growth factor β superfamily, due to its osteochondrogenesis activity has been widely used in tissue engineering, and platelet-rich derivative as a convenient preparation of compound biological factor, gradually get used in temporomandibular joint tissue engineering. With the deepening of research on extracellular microenvironment and mechanical stimulation, mesenchymal stem cells, exosomes and stress stimulation are increasingly being used to regulate the extracellular microenvironment. In the future, the combination of complex bioactive factors and certain stress stimulation may become a trend in the temporomandibular joint tissue engineering research. In this article, the progress on tissue engineering in repairing COCC and TMJD, especially in scaffold materials, seed cells and bioactive factors, are reviewed, so as to provide information for future research design and clinical intervention.



Key wordsTemporomandibular joint      Osteoarthritis      Tissue engineering      Temporomandibular joint disc      Osteochondral complex      Review     
Received: 05 December 2020      Published: 18 June 2021
CLC:  Q819  
  R782.6  
Corresponding Authors: WANG Huiming     E-mail: 21818694@zju.edu.cn;whmwhm@zju.edu.cn
Cite this article:

WANG Chenyu,WANG Yingnan,WANG Cunyi,SHI Jiejun,WANG Huiming. Research progress on tissue engineering in repairing temporo-mandibular joint. J Zhejiang Univ (Med Sci), 2021, 50(2): 212-221.

URL:

http://www.zjujournals.com/med/10.3724/zdxbyxb-2021-0118     OR     http://www.zjujournals.com/med/Y2021/V50/I2/212


组织工程修复颞下颌关节的关键因素研究进展

颞下颌关节骨关节炎(TMJOA)主要表现为颞下颌关节盘(TMJD)穿孔以及髁突骨软骨复合体(COCC)破坏。近年来,组织工程技术成为修复颞下颌关节的有效策略之一。随着支架材料技术的不断进步,结合天然材料与人工合成材料优势的复合支架成为优化支架性能的重要手段。近年来,微创理念下的原位成胶方法极大地解决了手术创伤以及材料吻合的问题,有利于组织工程向临床转化。细胞外基质支架技术在解决支架来源问题的同时最大程度地模拟了细胞外环境,为颞下颌关节组织工程向动物水平的转化提供了重要的手段。由于肋软骨细胞来源与扩增的限制,采用不同来源的间充质干细胞成为颞下颌关节组织工程的广泛选择,其中从关节软骨表面分离得到的纤维软骨干细胞可能更为合适。转化生长因子β超家族由于其明确的骨软骨活性,富血小板衍生物作为一种制备便捷的复合生物因子,同时结合间充质干细胞外泌体和应力刺激的形式调控细胞外微环境等方法均在颞下颌关节组织工程中得到运用。未来,通过复合生物活性因子并结合一定的应力刺激可能成为颞下颌关节组织工程研究的重要趋势之一。本文就组织工程技术修复颞下颌关节骨软骨复合体及关节盘的进展,尤其是在支架材料、种子细胞以及刺激因子方面的研究进展作一综述,以期为未来的研究设计和临床干预提供指导。


关键词: 颞下颌关节,  骨关节炎,  组织工程,  颞下颌关节盘,  骨软骨复合体,  综述 
Figure 1 Anatomical structure of temporomandibular joint (frontal plane)

作者(发表年)

研究对象

材料种类

支架材料

细胞来源

生物因子

Kalpakci 等(2011)[10]

细胞

天然高分子材料

琼脂糖

纤维软骨细胞、

关节软骨细胞

转化生长因子β1

MacBarb 等(2013)[28]

细胞

天然高分子材料

琼脂糖

纤维软骨细胞、

关节软骨细胞

软骨素酶 ABC、转化生长因子β1

Wang 等(2017)[8]

天然高分子材料

重组胶原

Vapniarsky 等(2018)[29]

天然高分子材料

琼脂糖

肋软骨细胞

转化生长因子β1、软骨素酶 ABC、赖氨酰氧化酶样蛋白 2

Ahtiainen 等(2013)[30]

人工合成材料

聚乳酸

脂肪来源干细胞

转化生长因子β1

Legemate 等(2016)[13]

细胞

人工合成材料

聚己内酯

骨髓间充质干细胞

结缔组织生长因子、转化生长因子β1

Ronald 等(2016)[15]

细胞

人工合成材料

二氧化钛纳米薄膜

纤维软骨细胞

Wang 等(2018)[11]

细胞

人工合成材料

聚乳酸–羟基乙酸共聚物

纤维软骨细胞、

滑膜间充质干细胞

转化生长因子β3

Wu 等(2014)[7]

裸鼠*

复合材料

纤维蛋白–壳聚糖

滑膜间充质干细胞

Tarafder 等(2016)[14]

复合材料

聚乳酸–羟基乙酸微球–聚己内酯

骨髓间充质干细胞

结缔组织生长因子、转化生长因子β3

Bousnaki 等(2018)[31]

细胞

复合材料

壳聚糖–海藻酸钠

牙髓干细胞

Moura 等(2020)[17]

材料

复合材料

聚乙二醇丙烯酸酯水凝胶为核的聚己内酯

Brown 等(2012)[26]

组织支架材料

脱细胞膀胱组织

Juran 等(2015)[27]

细胞

组织支架材料

脱细胞颞下颌关节盘

脐带间充质干细胞

Table 1 Researches on tissue engineering scaffold materials of articular disc

作者(发表年)

研究对象

材料种类

支架材料

细胞来源

刺激因子

Zheng 等(2011)[32]

裸鼠*

天然高分子材料

珊瑚

骨髓间充质干细胞

碱性成纤维生长因子(转染)

Liu 等(2011)[9]

天然高分子材料

透明质酸水凝胶

胰岛素生长因子-1

沈佩等(2019)[33]

大鼠

天然高分子材料

胶原蛋白

软骨干细胞

Dormer 等(2011)[12]

人工合成材料

聚乳酸–羟基乙酸共聚物微球梯度

骨形态发生蛋白-2、

转化生长因子β1

张广德等(2017)[24]

人工合成材料

聚乳酸–羟基乙酸共聚物–聚乙二醇–聚乳酸–羟基乙酸共聚物嵌段共聚物

脂肪间充质干细胞

肝细胞生长因子(转染)

Sun 等(2018)[34]

山羊

人工合成材料

聚氧乙烯–聚氧丙烯醚嵌段共聚物

关节软骨细胞骨髓间充质干细胞

李祥等(2010)[35]

复合材料

梯度磷酸三钙–胶原

刘春栋等(2012)[18]

*

复合材料

透明质酸–聚乳酸

关节软骨细胞

石磊等(2015)[36]

复合材料

细胞膜片/PRF 双膜

骨髓间充质干细胞

富血小板纤维蛋白

Wei 等(2016)[37]

山羊

复合材料

羟基磷灰石、脱细胞肋骨

郭延伟等(2018)[23]

复合材料

成骨多肽–透明质酸–硫酸软骨素

脂肪间充质干细胞

转化生长因子β3(转染)

Chin 等(2018)[38]

山羊

复合材料

聚癸二酸丙三醇酯/明胶

镁离子

Wang 等(2018)[39]

*

复合材料

骨相:聚己内酯–羟基磷灰石

软骨相:细胞膜片/聚乳酸–聚羟基乙酸

骨髓间充质干细胞

关节软骨细胞

Table 2 Researches on tissue engineering scaffold materials of condylar osteochondral complex
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