Researchers have developed a 3D organ-on-a-chip with blood vessels that mimic human joints. The discovery will help researchers better understand the pathology of joint disease and assist in 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 in the joint cavity that produces viscous fluid to lubricate the joint and prevent wear and tear during joint movement. There is no cure other than treating the pain and swelling associated with the debilitating condition.
Synovial-targeted therapies have great potential to treat arthritic joint disease, but a model that accurately replicates complex human physiology is needed. Now, researchers at Queen Mary University of London have done just that, creating a 3D organ-on-a-chip containing human synoviocytes and blood vessel cells.
"Our model is the first human vascularized synovial chip to employ mechanical loading and successfully replicates many key features of native synovial biology," said Timothy Hopkins, one of the study's co-authors.
A number of 2D cell culture experiments were first performed to optimize culture and experimental conditions that were subsequently applied to the organ-on-a-chip model. The model consists of primary human fibroblast-like synovial cells (hFLS), specialized synoviocytes, and human umbilical vein endothelial cells (HUVEC), which can develop into a functional vascular network.
The researchers observed that hFLS exhibited behavioral characteristics of the native human synovium lining, or lining. In humans, the synovium is highly vascularized, and capillaries are often located beneath the intima. hFLS also secretes a major component of synovial fluid and responds to inflammation and mechanical stretch testing.
The researchers say their findings demonstrate the potential of synovium-on-a-chip to better understand disease mechanisms and identify and test new treatments for arthritic disease, including personalized organ-on-a-chip models of synovium and related tissues.
"We believe our synovial-on-a-chip model, and the related human joint models currently being developed in our laboratory, have the potential to transform preclinical testing and streamline the delivery of new treatments for arthritis," said Martin Knight, another co-author of the study. "We are excited to share this model with the scientific community and work with industry partners to bring new treatments to patients as quickly as possible."
Furthermore, the model was developed using a commercially available platform and does not require expertise in device design and manufacturing, making it suitable for widespread use.
The research was published in the journal Biomedical Materials.