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
1Gannan Medical University, Ganzhou 341000, Jiangxi Province, China; 2School of Pharmacy, Nanchang University, Nanchang 330006, Jiangxi Province, China
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