Due to its poor innate healing capacity, focal defects in articular cartilage often lead to degeneration and eventually osteoarthritis. To prevent this, tissue engineering approaches are developed to regain the biological and mechanical function of the tissue. For articular cartilage tissue engineering, mainly combinations of articular chondrocytes (ACs) and hydrogels are used. The cell microenvironment is essential for successful outcomes, since it largely determines the cell phenotype. In the native tissue, ACs are enveloped in a thin layer of highly specialized pericellular matrix (PCM). The cell and PCM together are called a chondron. The PCM is relatively soft when compared to the bulk extracellular matrix (ECM), which can be up to 30x stiffer. This creates a mismatch between the scaffold properties needed for proper function of the cells and the full construct.
The use of chondrons for articular cartilage tissue engineering is considered to be beneficial, however the current methods to isolated chondrons results in a heterogeneous mixture of ACs and chondrons. Additionally, from a clinical perspective, using ACs is not ideal since the chondrogenic phenotype is lost during in vitro expansion. Therefore articular chondroprogenitor cells (ACPCs) are explored as an alternative cell source.
Within this project, micro-scale hydrogels produced using microfluidics are used to study the early synthesis of PCM and ECM components by ACs and ACPCs to gain more insight in the process and explore the potential use of ACPCs. Additionally, microgels will be used to create an artificial microenvironment favorable to the chondrogenic phenotype. As a proof of concept, these “artificial chondrons” will be embedded in a construct with mechanical properties sufficient to withstand joint loading. The full construct will be tested in a dynamically loaded ex vivo chondral defect model.