In Vitro Human Joint Models Combining Advanced 3D Cell Culture and Cutting-Edge 3D Bioprinting Technologies

Abstract

Joint-on-a-chip is a new technology able to replicate the joint functions into microscale systems close to pathophysiological conditions. Recent advances in 3D printing techniques allow the precise control of the architecture of the cellular compartments (including chondrocytes, stromal cells, osteocytes and synoviocytes). These tools integrate fluid circulation, the delivery of growth factors, physical stimulation including oxygen level, external pressure, and mobility. All of these structures must be able to mimic the specific functions of the diarthrodial joint: mobility, biomechanical aspects and cellular interactions. All the elements must be grouped together in space and reorganized in a manner close to the joint organ. This will allow the study of rheumatic disease physiopathology, the development of biomarkers and the screening of new drugs.

Keywords: microspheres; musculoskeletal progenitor/stromal cells; organoids.

Figure 1

Overview of the biological models commonly used: (top) animals, 2D and 3D cell cultures and (bottom) emerging: joint-on-a-chip and 3D bioprinting to study human articulation and its related diseases. Organoids are complex clusters of organ-specific cells, microspheres refer to shape-specific, macroporous scaffolds seeded with cells and micromass corresponds to high-density 3D cell cultures with multilayered organization. Top left, a schematic representation of the whole knee articulation, bones are in light brown, synovial cavity in light blue, articular cartilage in red and meniscus in orange, this color code was used for all the figures. Parts of the figure were created using biorender.com.