The promise of Synovial Joint-on-a-Chip in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) affects millions of people worldwide, but there are limited drugs available to treat it, so acquiring a more comprehensive comprehension of the underlying reasons and mechanisms behind inflammation is crucial, as well as developing novel therapeutic approaches to manage it and mitigate or forestall associated harm. It is evident that current in vitro models cannot faithfully replicate all aspects of joint diseases, which makes them ineffective as tools for disease research and drug testing. Organ-on-a-chip (OoC) technology is an innovative platform that can mimic the microenvironment and physiological state of living tissues more realistically than traditional methods by simulating the spatial arrangement of cells and interorgan communication. This technology allows for the precise control of fluid flow, nutrient exchange, and the transmission of physicochemical signals, such as bioelectrical, mechanical stimulation and shear force. In addition, the integration of cutting-edge technologies like sensors, 3D printing, and artificial intelligence enhances the capabilities of these models. Here, we delve into OoC models with a particular focus on Synovial Joints-on-a-Chip, where we outline their structure and function, highlighting the potential of the model to advance our understanding of RA. We integrate the actual evidence regarding various OoC models and their possible integration for multisystem disease study in RA research for the first time and introduce the prospects and opportunities of the chip in RA etiology and pathological mechanism research, drug research, disease prevention and human precision medicine. Although many challenges remain, OoC holds great promise as an in vitro model that approaches physiology and dynamics.

Keywords: Organ-on-a-Chip; Synovial Joint-on-a-Chip; disease models; microphysiological systems; precision medicine; rheumatoid arthritis.

Figure 1

Joint characteristics of health and RA. During RA, the synovial membrane undergoes the following changes: infiltration of immune cells, new angiogenesis, uncontrolled proliferation of FLS, and the intima thickens and develops an aggressive pannus (6). Pannus tissue invades and destroys the underlying cartilage and bone (7), resulting in cartilage degeneration, bone destruction, and joint space narrowing.

Figure 2

(Part A) Extra-Articular Manifestations (EMs) and comorbidities of RA. While synovitis serves as the pathological hallmark of RA, the intricate and persistent inflammatory and autoimmune nature of this disease gives rise to various Ems and comorbidities. These complications and comorbidities lead to increased morbidity and mortality. Among patients with RA, cardiovascular disease emerges as the primary cause of death, followed closely by respiratory ailments. (Part B) Multi-Organ-on-Chip (Multi-OoC) or Body-on-a-chip (BoC). OoC platforms can be interconnected to form more complex multi-OoC models or even BoC models, which can generalize interactions between various organs in the body, making it possible to study multi-tissue and even systemic diseases. Because intertissue crosstalk holds a pivotal position in the emergence and advancement of human, a common shared medium is often required for recycling that allows organ components to communicate with each other, while allowing them to retain their identity.

Figure 3

Synovial Joint-on-a-Chip. The multi-tissue characteristic of joint determines the complexity of synovial joint-on-a-chip. When making JoC, the usual method is to separate each joint tissue into a single chip module, and then connect the required part appropriately according to their own research purposes.