Human vascularised synovium-on-a-chip: a mechanically stimulated, microfluidic model to investigate synovial inflammation and monocyte recruitment

作者：Clare L. Thompson, Timothy Hopkins, Catrin Bevan, Hazel R. C. Screen, Karina T. Wright, Martin M. Knight · 发表于：Biomedical Materials · 年份：2023 · DOI：10.1088/1748-605x/acf976 · 被引用次数：36 · 研究领域：Cell Adhesion Molecules Research、Osteoarthritis Treatment and Mechanisms、Platelet Disorders and Treatments

Abstract Healthy synovium is critical for joint homeostasis. Synovial inflammation (synovitis) is implicated in the onset, progression and symptomatic presentation of arthritic joint diseases such as rheumatoid arthritis and osteoarthritis. Thus, the synovium is a promising target for the development of novel, disease-modifying therapeutics. However, target exploration is hampered by a lack of good pre-clinical models that accurately replicate human physiology and that are developed in a way that allows for widespread uptake. The current study presents a multi-channel, microfluidic, organ-on-a-chip (OOAC) model, comprising a 3D configuration of the human synovium and its associated vasculature, with biomechanical and inflammatory stimulation, built upon a commercially available OOAC platform. Healthy human fibroblast-like synoviocytes (hFLS) were co-cultured with human umbilical vein endothelial cells (HUVECs) with appropriate matrix proteins, separated by a flexible, porous membrane. The model was developed within the Emulate organ-chip platform enabling the application of physiological biomechanical stimulation in the form of fluid shear and cyclic tensile strain. The hFLS exhibited characteristic morphology, cytoskeletal architecture and matrix protein deposition. Synovial inflammation was initiated through the addition of interleukin−1 β (IL−1 β ) into the synovium channel resulting in the increased secretion of inflammatory and catabolic mediators, interleukin-6 (IL−6), ...