Researchers have developed a 3D organ-on-a-chip, complete with blood vessels, that mimics the human joint. The discovery will help researchers understand the pathology of joint diseases better and assist with the identification and testing of new treatments for arthritis.
Arthritic joint diseases, such as rheumatoid arthritis and osteoarthritis, are characterized by inflammation of the synovium, the membrane that lines joint cavities and produces viscous fluid that lubricates the joint, preventing wear while it’s in motion. Other than treating the pain and swelling associated with the debilitating condition, there’s no cure.
Synovium-targeted therapies hold great potential for the treatment of arthritic joint disease but require a model that accurately replicates complex human physiology. Now, researchers at the Queen Mary University of London have done that, creating a 3D organ-on-a-chip that contains human synovial cells and blood vessel cells.
“Our model is the first human, vascularized, synovium-on-a-chip with applied mechanical loading and successfully replicates a number of key features of native synovium biology,” said Timothy Hopkins, one of the study’s co-authors.
A number of 2D cell culture experiments were conducted first to optimize culture and experimental conditions that were subsequently applied to the organ-on-a-chip model. The model comprised primary human fibroblast-like synoviocytes (hFLS), specialized synovial cells, and human umbilical vein endothelial cells (HUVECs), which can develop into functional vascular networks.
The researchers observed that hFLS exhibited behavior characteristic of the intima, or lining layer, of native human synovium. In humans, the synovium is highly vascularized, with capillaries commonly located just below the intima. The hFLS also secreted the major constituents of synovial fluid and responded to inflammation and mechanical stretch testing.
The researchers say their findings suggest that the synovium-on-a-chip has the potential to understand disease mechanisms better and identify and test new therapies for arthritic diseases, including personalized organ-on-a-chip models of synovium and associated tissues.
“We believe that our synovium-on-a-chip model, and related models of human joints currently under development in our lab, have the potential to transform preclinical testing, streamlining delivery of new therapeutics for treatment of arthritis,” said Martin Knight, another of the study’s co-authors. “We are excited to share this model with the scientific community and to work with industry partners to bring new treatments to patients as quickly as possible.”
Moreover, the model was developed using a commercially available platform that doesn’t require specialist knowledge of device design and fabrication, making it suitable for widespread use.
The study was published in the journal Biomedical Materials.
Source: Queen Mary University of London