中国组织工程研究

中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (35): 5714-5720.doi: 10.12307/2023.852

• 组织构建综述 tissue construction review • 上一篇    下一篇

临界骨缺损动物模型评估骨组织工程支架成骨效能的价值

熊  伟1，袁灵梅2，钱国文3，黄锦阳1，潘  斌1，郭  灵1，曾志奎2，4   

  1. 1江西中医药大学，江西省南昌市  330004；2江西中医药大学附属医院，江西省南昌市  330006；3江西理工大学，江西省南昌市  330013；4江西中医药大学中药固体制剂制造技术国家工程研究中心，江西省南昌市  330004
  • 收稿日期:2022-10-31 接受日期:2023-01-10 出版日期:2023-12-18 发布日期:2023-06-05
  • 通讯作者: 曾志奎，博士，博士生导师，江西中医药大学附属医院创伤骨科，江西省南昌市 330006；江西中医药大学中药固体制剂制造技术国家工程研究中心，江西省南昌市 330004
  • 作者简介:熊伟，男，1998年生，江西省瑞昌市人，汉族，江西中医药大学临床医学院在读硕士，主要从事中医药修复骨缺损研究。
  • 基金资助:
    国家自然科学基金项目(81960880)，项目负责人：曾志奎；江西中医药大学科技创新团队(CXTD22009)；江西省临床医学中心(20212BCG74004)

Value of a critical bone defect animal model in evaluating osteogenic efficacy of bone tissue engineering scaffold

Xiong Wei1, Yuan Lingmei2, Qian Guowen3, Huang Jinyang1, Pan Bin1, Guo Ling1, Zeng Zhikui2, 4   

  1. 1Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; 2Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang 330006, Jiangxi Province, China; 3Jiangxi University of Science and Technology, Nanchang 330013, Jiangxi Province, China; 4National Engineering Research Center for Manufacturing Technology of Traditional Chinese Medicine Solid Preparations, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
  • Received:2022-10-31 Accepted:2023-01-10 Online:2023-12-18 Published:2023-06-05
  • Contact: Zeng Zhikui, MD, Doctoral supervisor, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang 330006, Jiangxi Province, China
  • About author:Xiong Wei, MD, Doctoral supervisor, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
  • Supported by:
    the National Natural Science Foundation of China, No. 81960880 (to ZZK); Scientific Research Innovation Team Project of Jiangxi University of Chinese Medicine, No. CXTD22009; a grant from Jiangxi Clinical Medical Center, No. 20212BCG74004

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摘要：


文题释义：

临界骨缺损：又称极限骨缺损，是指由创伤、骨肿瘤、骨感染和先天发育缺陷等原因造成的骨质缺损，缺损范围超出机体自行修复的阈值，在不进行外界干预的情况下无法自我修复，需采用骨移植、骨搬移、诱导膜技术或骨组织工程材料等方法进行骨修复。
骨组织工程支架：利用组织工程技术设计生产出具有生物相容性、骨传导及骨诱导等特性的支架，将其植入到骨缺损部位，以促进成骨细胞增殖、诱导成骨分化和加快血管形成从而修复骨缺损。


背景：临界骨缺损的修复一直是创伤骨科医师面临的临床难题。随着临床技术与生物材料的发展，Ilizarov，Masquelet以及骨组织工程等技术正逐步取代传统自体骨及同种异体骨移植术成为骨修复领域的研究热点。其中尤以骨组织工程支架最具发展潜力，但在骨组织工程支架正式应用于临床前，进行大量基础研究必不可少，而动物实验意义最大，因此选择合适的临界骨缺损动物实验模型对验证骨组织工程支架成骨效能非常重要。

目的：系统总结不同种类临界骨缺损动物模型的优缺点，评估各类骨组织工程支架在临界骨缺损动物模型中的成骨效能。
方法：检索中国知网、万方、Web of Science、Cochrane Library和PubMed数据库，中文检索词为“骨缺损，动物模型，骨组织工程，支架，骨修复，骨再生”，英文检索词为“Bone defects，Animal models，Bone tissue engineering，scaffolds，Bone repair，Bone regeneration”，最终将临界骨缺损动物模型和其应用于评估骨组织工程支架成骨效能的相关实验研究文献62篇进行综述。

结果与结论：①目前关于临界骨缺损的具体定义仍不明确，各类骨缺损动物模型如何建立临界缺损尚未取得共识。②检索迄今发表建立的小鼠、大鼠、兔、猪、犬和羊临界骨缺损动物模型文章，发现国内外学者在建立临界骨缺损模型时基本遵循骨缺损大小为实验期间内无法自愈的原则，但在具体数值上则存在不一。③大鼠颅骨、股骨和兔股骨髁为较合适的临界骨缺损模型部位选择，二者具有来源广泛、实验环境要求低、容易饲养、造模成本低和可操作性强等优点，适合大规模造模。但与绵羊和猪等大动物相比，存在骨骼偏小、骨组织成分与人体骨存在一定差异性、难以完全模拟人体骨愈合过程的缺点。④骨组织工程支架在进行细胞实验评估生物相容性及成骨活性后，可借助稳定的临界骨缺损动物模型证实其体内成骨效能及生物安全性，大鼠颅骨、股骨和兔股骨髁临界骨缺损模型分别适合于膜内成骨和软骨内成骨的初步评估，而绵羊、猪胫骨临界骨缺损为较理想的大动物模型，推荐用于临床前评价。⑤未来研究将深入探讨骨组织工程支架成骨的分子机制，有望帮助研发出可媲美自体骨成骨效能的人工支架材料，对攻克大段骨缺损这一临床棘手问题具有重要意义。

https://orcid.org/0000-0002-9318-0244(熊伟)

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: 骨缺损, 动物模型, 评估, 骨组织工程, 支架, 骨移植物, 骨修复, 骨再生, 成骨效能, 综述

Abstract: BACKGROUND: The repair of critical size bone defects has always been a challenge clinical problem for trauma orthopedic surgeons. With the development of clinical techniques and biomaterials, Ilizarov, Masquelet and bone tissue engineering techniques are gradually replacing the traditional autologous and allogeneic bone transplantation to become the research hotspots in the field of bone repair. Among them, bone tissue engineering scaffolds have the greatest potential for development. But a lot of basic research is necessary before the formal clinical application of bone tissue engineering scaffolds, and animal experiments are the most important. Therefore, it is very important to select an appropriate animal model of critical bone defects for testing the osteogenic efficacy of bone tissue engineering scaffolds.
OBJECTIVE: To systematically summarize the advantages and disadvantages of different types of animal models of critical bone defects and to evaluate the osteogenic efficacy of various types of bone tissue engineering scaffolds in the animal models of critical bone defects.
METHODS: CNKI, WanFang, Web of Science, Cochrane Library, and PubMed were searched for relevant literature. Search terms included “bone defects, animal models, bone tissue engineering, scaffolds, bone repair, bone regeneration” in Chinese and English. A total of 62 articles addressing the animal models of critical bone defects and their application to evaluate the osteogenic efficacy of bone tissue engineering scaffolds were included for further review. 
RESULTS AND CONCLUSION: The specific definition of critical bone defects is still unclear and there is no consensus on how to establish critical defects in various animal models of bone defects. By searching the published articles about the establishment of critical bone defect animal models in mice, rats, rabbits, pigs, dogs and sheep, we found that domestic and foreign scholars basically followed the principle that the size of the bone defect that could be not self-healing during the experimental period is selected when establishing the critical bone defect model, but there were differences in the specific values. In general, rat skull, femur and rabbit femoral condyles are the more suitable sites for critical bone defect models, which are suitable for large-scale modeling because of their wide sources, low requirement of experimental environment, easy breeding, low modeling cost, and high operability. However, compared with large animals such as sheep and pigs, they have the disadvantages of small bones and the composition of bone tissue is different from that of human, which makes it difficult to fully simulate the human bone healing process. After the biocompatibility and osteogenic activity of the bone tissue engineering scaffolds are evaluated by cytological experiments, its osteogenic efficiency and biological safety in vivo can be confirmed with the help of the stable animal model of critical bone defects. The critical bone defect models of rat skull and femur and rabbit femoral condyle are respectively suitable for the preliminary evaluation of intramembranous osteogenesis and endochondral osteogenesis, while the critical bone defect models of sheep and pig tibia are ideal animal models that are recommended for preclinical evaluation. Further research on the molecular mechanism of bone tissue engineering scaffold osteogenesis is expected to help develop artificial scaffold materials that can match the osteogenesis efficiency of autogenous bone, which is of great significance for overcoming the difficult clinical problem of segmental bone defects.

Key words: bone defect, animal model, evaluation, bone tissue engineering, scaffold, bone graft, bone repair, bone regeneration, osteogenic efficacy, review

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