A Progress Report and Roadmap for Microphysiological Systems and Organ-On-A-Chip Technologies to Be More Predictive Models in Human (Knee) Osteoarthritis

Abstract

Osteoarthritis (OA), a chronic debilitating joint disease affecting hundreds of million people globally, is associated with significant pain and socioeconomic costs. Current treatment modalities are palliative and unable to stop the progressive degeneration of articular cartilage in OA. Scientific attention has shifted from the historical view of OA as a wear-and-tear cartilage disorder to its recognition as a whole-joint disease, highlighting the contribution of other knee joint tissues in OA pathogenesis. Despite much progress in the field of microfluidic systems/organs-on-a-chip in other research fields, current in vitro models in use do not yet accurately reflect the complexity of the OA pathophenotype. In this review, we provide: 1) a detailed overview of the most significant recent developments in the field of microsystems approaches for OA modeling, and 2) an OA-pathophysiology-based bioengineering roadmap for the requirements of the next generation of more predictive and authentic microscale systems fit for the purpose of not only disease modeling but also of drug screening to potentially allow OA animal model reduction and replacement in the near future.

Osteoarthritis models: From animals to tissue engineering

“… 103 These benefits are mainly related to the characteristics of controllable fluid flow in organs-on-chips and the stable delivery of specific nutrients to cells or tissues, which enhance the differentiation, function, and long-term survival of chondrocytes. 154 , 155 However, there are still limitations to the microphysiological system, including the amount of biological replication and the lack of appropriate biomechanical stimuli, which will require further research. 128 , 156 For instance, the presence of air bubbles in microfluidic channels may harm cells, hinder the fabrication and control of chips, and make it difficult to completely remove them.…”

A Comprehensive Review of Biosensor Integration in Microphysiological Systems for Online Monitoring: Current Challenges and Future Advancements

“…Continuous real time monitoring of multiple physical, biological, and electrochemical parameters [42] Gradient generators Optically clear: Polystyrene (PS), glass, PDMS Fluorescent microscope, camera (life cell imaging), and magnetic separator [43] Perfusion circuit Elasticity: Polycarbonate (PC), cyclic olefin copolymer (COC), silicon Electrical sensors, optical sensors, bio/ chemical sensors [44] Inter-compartment communication barriers Microfabrication: Si, PMMA, cyclic olefin copolymer (COC) Automated reproducible multisampling analysis, comparable and compatible with R&D robotics [35] Dosing(injection) sampling and gas regulator Sensor integration: Si, polyimide (PI) Recapitulation of dynamic mechano-biological properties and stimuli response of organs [17] For example, the analyte of interest may go through an enzyme activity that changes the ionic composition as detected by conductometric sensors. Voltammetric sensors assess the change in electric current between a working and reference electrode as a function of applied voltage.…”

“…The first publications on amperometric biosensors were published in the 1960s. Since then, this sensing modality has been employed to quickly identify biomarkers in environmental and physiological samples [43]. Amperometric biosensors were designed to detect glucose and lactate in liver-on-a-chip mitochondrial stress (Fig.…”

A personalized osteoarthritic joint-on-a-chip as a screening platform for biological treatments

“…Besides being characterized by ethical issues, animal models cannot always be considered fully reliable, due to differences in pathological mechanisms and drug responses, particularly for inflammatory diseases [ 6 ]. On the other hand, currently available in vitro models fail to recapitulate the complexity of articular joints since they generally focus only on cartilage, neglecting the contribution of other joint elements [ 7 ]. Thus, complex in vitro models, mimicking the joint microenvironment, represent a possible solution to accelerate the development of new OA treatments.…”