中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (31): 5071-5077.doi: 10.12307/2023.676

• 骨与关节综述 bone and joint review • 上一篇    下一篇

骨三维药物筛选模型的特性、功能及应用

黄  淼1,巫谢生2,黄文诗2,黄海纳1,陈龙云1,彭维杰1   

  1. 1赣南医学院,江西省赣州市   341000;2南昌大学药学院,江西省南昌市   330006
  • 收稿日期:2022-09-09 接受日期:2022-10-18 出版日期:2023-11-08 发布日期:2023-01-31
  • 通讯作者: 彭维杰,博士,教授,博士生导师,赣南医学院,江西省赣州市 341000
  • 作者简介:黄淼,男,1998年生,江西省赣州市人,汉族,赣南医学院在读硕士,主要从事干细胞与组织工程相关研究工作。
  • 基金资助:
    国家自然科学基金 (81860327),项目负责人:彭维杰

Properties, functions and applications of three-dimensional models of bone for drug screening

Huang Miao1, Wu Xiesheng2, Huang Wenshi2, Huang Haina1, Chen Longyun1, Peng Weijie1   

  1. 1Gannan Medical University, Ganzhou 341000, Jiangxi Province, China; 2School of Pharmacy, Nanchang University, Nanchang 330006, Jiangxi Province, China
  • Received:2022-09-09 Accepted:2022-10-18 Online:2023-11-08 Published:2023-01-31
  • Contact: Peng Weijie, PhD, Professor, Doctoral supervisor, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
  • About author:Huang Miao, Master candidate, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 81860327 (to PWJ)

摘要:


文题释义:

药物筛选:是指测试和优化来自化学品库的化合物,再选择候选药物的过程,包括临床前和临床筛选过程。
骨三维模型:是在传统的二维模型上进行优化升级的技术产品,可以模拟骨组织的基本结构和特征,还能模拟骨骼相关的疾病,对于研究骨骼系统相关的疾病以及相关药物的开发至关重要,可为个人和社会减少经济负担。

背景:临床上骨骼相关疾病药物的开发是个漫长的过程,传统的二维模型药物筛选的效果已经不能满足需求,改进研发的各种三维模型均有其优缺点和相关应用,但到目前为止还没有一个理想的实验模型可以用于所有骨骼相关疾病的药物筛选。
目的:综述近几年相关文献,总结骨二维模型和三维模型的基本特性以及对细胞功能的可能影响,重点综述目前常见的骨三维模型以及其在实际骨骼系统疾病中的药物筛选应用,以期为将来骨三维模型在药物筛选中的应用和改进提供一定帮助。
方法检索PubMed数据库中的相关英文文章,英文检索词为“bone,skeleton, three-dimensional models, models,drug screening, drug selection”;检索中国知网及万方数据库相关中文文献,中文检索词为“骨、骨骼、模型、三维模型、药物筛选”,并结合文献追溯法查找部分文献进行综述分析。

结果与结论:①骨二维模型和三维模型的物理特性不同,二维模型基质一般是固定的,三维模型基质则是可调节的,二者对细胞的功能方面影响不同。②骨二维模型的构建和生产较为容易,但其缺乏典型的三维微观结构,缺少与周围细胞及细胞外基质的相互联系,因此只能适应于细胞水平研究。③骨二维模型和三维模型培养的骨组织有生物学差异,二维状态下骨细胞或者诱导成骨细胞都是扁平状的,而三维模型更接近骨组织的自然细胞外基质的结构,能更准确地表现药物反应。④目前常见的骨三维模型包括细胞球、水凝胶、生物反应器和微流体芯片等,它们的构建方法不同,在药物筛选方面各有优势。⑤目前常见的骨三维模型已经应用于骨骼相关疾病的药物筛选,不同疾病对不同三维模型的需求不同,例如在骨质疏松症的药物筛选中,支架和水凝胶的可降解和可持续性更能达到药物筛选的效果。

https://orcid.org/0000-0002-7912-916X(黄淼);https://orcid.org/0000-0003-0019-010X(彭维杰)

中国组织工程研究杂志出版内容重点:人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程

关键词: 干细胞, 三维培养, 骨骼疾病, 三维模型, 药物筛选, 细胞球, 水凝胶, 生物打印, 组织工程, 综述

Abstract: BACKGROUND: The development of drugs for skeletal-related diseases in clinical settings is a lengthy process, and the effectiveness of traditional two-dimensional models for drug screening no longer meets the needs. Various modified 3D models have their advantages and disadvantages and related applications, but so far there is no ideal experimental model that can be utilized for drug screening of all bone related diseases.  
OBJECTIVE: To review relevant literature in recent years, to summarize the basic characteristics of two-dimensional and three-dimensional models of bone and their possible effects on cellular function, and to focus on a review of the current common three-dimensional models of bone and their application for drug screening in actual skeletal system diseases, with a view to providing ideas for future applications and improvements of three-dimensional models of bone in drug screening.
METHODS: Relevant English articles were searched on PubMed database with English search terms of “bone, skeleton, three-dimensional models, models, drug screening, drug selection”. Related Chinese articles were searched on Wanfang and CNKI databases, and the Chinese search terms were “bone, skeleton, models, three-dimensional models, drug screening, drug selection”. Some articles were searched with literature retrospective method for review analysis.  
RESULTS AND CONCLUSION: (1) The physical properties of the two-dimensional model of bone are different from those of the three-dimensional model of bone; the matrix is generally fixed in the two-dimensional model, whereas the three-dimensional model matrix is adjustable, and the two have different effects on the functional aspects of the cells. (2) Two-dimensional models of bone are easier to construct and produce, but they lack the typical three-dimensional microstructure and interconnections with surrounding cells and the extracellular matrix, and are therefore only suitable for cellular level studies. (3) There are biological differences between two-dimensional and three-dimensional models of cultured bone tissue. In the two-dimensional state, osteocytes or induced osteoblasts are flattened, whereas the three-dimensional model is closer to the natural extracellular matrix of bone tissue and more accurately represents the drug response. (4) Commonly used three-dimensional models of bone include cell spheres, hydrogels, bioreactors and microfluidic chips, which are constructed in different ways and have their own advantages in drug screening. (5) Common three-dimensional models of bone have been used for drug screening in skeletal-related diseases, and the need for different three-dimensional models of bone varies from disease to disease, for example, in the case of osteoporosis, a degenerative disease, where the degradability and sustainability of scaffolds and hydrogels are more effective for drug screening.

Key words: stem cell, three-dimensional culture, skeletal disease, three-dimensional model, drug screening, cell sphere, hydrogel, bioprinting, tissue engineering, review

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