Microfluidic nutrient gradient-based three-dimensional chondrocyte culture-on-a-chip as an in vitro equine arthritis model.
Abstract: 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.
© 2019 The Authors.
Publication Date: 2019-08-19 PubMed ID: 32159153PubMed Central: PMC7061638DOI: 10.1016/j.mtbio.2019.100023Google Scholar: Lookup
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Summary
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This research details the creation and use of a microfluidic 3D model that recreates the environment of horse cartilage cells. The study is centered on the mimicry of articular chondrocyte context and response to inflammatory stimuli, thereby providing an animal-free model for studying equine joint disease.
Microfluidic 3D Chondrocyte Culture
- This study presents a microfluidic three-dimensional (3D) chondrocyte culture that imitates the shape, distribution, metabolism, and gene expression of articular chondrocytes, which are cells found in the cartilage of joints.
- The imitation of these conditions was executed by setting up a physiologic nutrient diffusion gradient throughout the simulated matrix. The geometric design constraints of the microchambers steered the cells to behave like those in their natural environment.
- The primary chondrocytes – isolated from horses in this study – remained viable for an extended culture duration of 3 weeks. During this time, they exhibited low metabolic activity and high expression of Sox9, aggrecan, and Col2, typical markers of articular chondrocytes.
Create an Animal-Free Arthritis Model
- The researchers further subjected microfluidic 3D chondrocyte microtissues to inflammatory cytokines, proteins involved in cell signaling during immune responses. This was done to simulate conditions under osteoarthritis – a common form of arthritis caused by inflammation and wear and tear of the joint’s cartilage.
- This process enabled the establishment of an animal-free model to study osteoarthritis, reducing the need for animal experimentation which often entails ethical and logistical hurdles.
Research Findings and Implication
- Findings of the study confirmed that the microtissue model reproduced the basic characteristics of native cartilage and accurately responded to biochemical injury, bringing about conditions similar to those in osteoarthritis.
- These results pave the way for exploring the pathophysiology of osteoarthritis in both human and veterinary patients. It provides a means to understand and investigate the progression and mechanisms of joint disease, thus serving as a foundation for the development of better diagnosis, prevention, and treatment strategies.
Cite This Article
APA
Rosser J, Bachmann B, Jordan C, Ribitsch I, Haltmayer E, Gueltekin S, Junttila S, Galik B, Gyenesei A, Haddadi B, Harasek M, Egerbacher M, Ertl P, Jenner F.
(2019).
Microfluidic nutrient gradient-based three-dimensional chondrocyte culture-on-a-chip as an in vitro equine arthritis model.
Mater Today Bio, 4, 100023.
https://doi.org/10.1016/j.mtbio.2019.100023 Publication
Researcher Affiliations
- Faculty of Technical Chemistry, Vienna University of Technology, Getreidemarkt 9, 1060 Vienna, Austria.
- Faculty of Technical Chemistry, Vienna University of Technology, Getreidemarkt 9, 1060 Vienna, Austria.
- Faculty of Technical Chemistry, Vienna University of Technology, Getreidemarkt 9, 1060 Vienna, Austria.
- Department of Equine Surgery, University of Veterinary Medicine, Veterinärplatz 1, 1210 Vienna, Austria.
- Department of Equine Surgery, University of Veterinary Medicine, Veterinärplatz 1, 1210 Vienna, Austria.
- Department of Equine Surgery, University of Veterinary Medicine, Veterinärplatz 1, 1210 Vienna, Austria.
- BIOCOMP, Bioinformatics & Scientific Computing VBCF, Vienna Biocenter Core Facilities GmbH, GmbH, Dr. Bohr Gasse 3, 1030 Vienna, Austria.
- BIOCOMP, Bioinformatics & Scientific Computing VBCF, Vienna Biocenter Core Facilities GmbH, GmbH, Dr. Bohr Gasse 3, 1030 Vienna, Austria.
- BIOCOMP, Bioinformatics & Scientific Computing VBCF, Vienna Biocenter Core Facilities GmbH, GmbH, Dr. Bohr Gasse 3, 1030 Vienna, Austria.
- Faculty of Technical Chemistry, Vienna University of Technology, Getreidemarkt 9, 1060 Vienna, Austria.
- Faculty of Technical Chemistry, Vienna University of Technology, Getreidemarkt 9, 1060 Vienna, Austria.
- Department of Equine Surgery, University of Veterinary Medicine, Veterinärplatz 1, 1210 Vienna, Austria.
- Faculty of Technical Chemistry, Vienna University of Technology, Getreidemarkt 9, 1060 Vienna, Austria.
- Department of Equine Surgery, University of Veterinary Medicine, Veterinärplatz 1, 1210 Vienna, Austria.
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