Microfluidic nutrient gradient–based three-dimensional chondrocyte culture-on-a-chip as an in vitro equine arthritis model

作者：Julie Rosser, Barbara Bachmann, Christian Jordan, Iris Ribitsch, Eva Haltmayer, Sinan Gueltekin, Sini Junttila, Bence Gálik, Attila Gyenesei, Bahram Haddadi, Michael Harasek, Monika Egerbacher, Peter Ertl, Florien Jenner · 发表于：Materials Today Bio · 年份：2019 · DOI：10.1016/j.mtbio.2019.100023 · 被引用次数：83 · 研究领域：Osteoarthritis Treatment and Mechanisms、3D Printing in Biomedical Research、Knee injuries and reconstruction techniques

In this work, we describe a microfluidic three-dimensional (3D) chondrocyte culture mimicking in vivo articular chondrocyte morphology, cell distribution, metabolism, and gene expression. This has been accomplished by establishing a physiologic nutrient diffusion gradient across the simulated matrix, while geometric design constraints of the microchambers drive native-like cellular behavior. Primary equine chondrocytes remained viable for the extended culture time of 3 weeks and maintained the low metabolic activity and high Sox9, aggrecan, and Col2 expression typical of articular chondrocytes. Our microfluidic 3D chondrocyte microtissues were further exposed to inflammatory cytokines to establish an animal-free, in vitro osteoarthritis model. Results of our study indicate that our microtissue model emulates the basic characteristics of native cartilage and responds to biochemical injury, thus providing a new foundation for exploration of osteoarthritis pathophysiology in both human and veterinary patients.