Design and development of a multi-layered osteochondral unit-on-chip to study osteoarthritis initiation

Osteoarthritis (OA) is a degenerative joint disease affecting millions of people worldwide, leading to pain, decreased mobility, and joint function impairment. Current in vitro models fail to replicate the complex 3D architecture and inter-tissue communication of the osteochondral unit, a key tissue in the knee joint and pathology. Consequently, this limitation results in our failure to understand mechanisms related to disease initiation and progression.

In this project, the student will design, fabricate and test a multi-layered osteochondral unit-on-chip that mimics the native spatial organization of the articular cartilage and subchondral bone. Unlike existing planar designs, this innovative chip with stacked tissues, in the form of pre-designed cell-embedded hydrogels, enabling biochemical crosstalk while maintaining distinct environments.

The main challenges to address include:

• Hydrogel injection: ensuring the hydrogels are in contact without mixing
• Leakage prevention: developing robust sealing strategies for multilayered structures
• Imaging feasibility: designing the chip for compatibility with high-resolution imaging (e.g. confocal microscopy)

The device will be fabricated using advanced 3D printing techniques. The student will then perform imaging and preliminary biological assessments to confirm functionality.

The student will learn techniques such as: CAD design, 3D printing, cell culture in BSL2, hydrogel handling, immunohistochemistry, fluorescence and confocal microscopy.

Required background: interest in tissue engineering and microfluidics, experience with CAD software, knowledge of 3D printing and/or biomaterials is a plus.

The internship is a non-paid position and requires a minimum commitment of 6 months to ensure sufficient time for design, fabrication, and validation of the system.