한빛사논문
Kyurim Paek1,2, Seulha Kim3, Sungho Tak4, Min Kyeong Kim1, Jubin Park1,2, Seok Chung2,5, Tai Hyun Park3, Jeong Ah Kim1,6
1Center for Scientific Instrumentation, Korea Basic Science Institute, Daejeon, South Korea
2Program in Micro/Nano System, Korea University, Seoul, South Korea
3School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul, South Korea
4Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju, Chungbuk, South Korea
5School of Mechanical Engineering, KoreaUniversity, Seoul, South Korea
6Department of Bio-Analytical Science, University of Science and Technology, Daejeon, South Korea
CORRESPONDING AUTHOR : Jeong Ah Kim
Abstract
Although numerous organ-on-a-chips have been developed, bone-on-a-chip platforms have rarely been reported because of the high complexity of the bone microenvironment. With an increase in the elderly population, a high-risk group for bone-related diseases such as osteoporosis, it is essential to develop a precise bone-mimicking model for efficient drug screening and accurate evaluation in preclinical studies. Here, we developed a high-throughput biomimetic bone-on-a-chip platform combined with an artificial intelligence (AI)-based image analysis system. To recapitulate the key aspects of natural bone microenvironment, mouse osteocytes (IDG-SW3) and osteoblasts (MC3T3-E1) were cocultured within the osteoblast-derived decellularized extracellular matrix (OB-dECM) built in a well plate-based three-dimensional gel unit. This platform spatiotemporally and configurationally mimics the characteristics of the structural bone unit, known as the osteon. Combinations of native and bioactive ingredients obtained from the OB-dECM and coculture of two types of bone cells synergistically enhanced osteogenic functions such as osteocyte differentiation and osteoblast maturation. This platform provides a uniform and transparent imaging window that facilitates the observation of cell-cell interactions and features high-throughput bone units in a well plate that is compatible with a high-content screening system, enabling fast and easy drug tests. The drug efficacy of anti-SOST antibody, which is a newly developed osteoporosis drug for bone formation, was tested via β-catenin translocation analysis, and the performance of the platform was evaluated using AI-based deep learning analysis. This platform could be a cutting-edge translational tool for bone-related diseases and an efficient alternative to bone models for the development of promising drugs.
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