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Updated: Jun 12, 2025
Creation of a Knee Joint-on-a-Chip for Modeling Joint Diseases and Testing Drugs
Published on: January 27, 2023
An Advanced Mechanically Active Osteoarthritis-on-Chip Model to Test Injectable Therapeutic Formulations: The SYN321
Cecilia Palma1, Stefano Piazza2, Roberta Visone2
1Department of Electronics, Information and Bioengineering, Politecnico di Milano, Via Ponzio 34/5, Milan, 20133, Italy.
Abstract:
Current treatments for osteoarthritis (OA) often fail to address the underlying pathophysiology and may have systemic side effects, particularly associated with long-term use of non-steroidal anti-inflammatory drugs (NSAIDs). Thus, researchers are currently directing their efforts toward innovative polymer-drug combinations, such as mixtures of hyaluronic acid viscoelastic hydrogels and NSAIDs like diclofenac, to ensure sustained release of the NSAID within the joint following intra-articular injection. However, the progress of novel injectable therapies for OA is hindered by the absence of preclinical models that accurately represent the pathology of the disease. The uBeat® MultiCompress platform is here presented as a novel approach for studying anti-OA injectable therapeutics on human mechanically-damaged OA cartilage microtissues, in a physiologically relevant environment. This platform can accommodate injectable therapeutic formulations and is successfully tested with SYN321, a novel diclofenac-sodium hyaluronate conjugate under development as a treatment for knee OA. Results indicate the platform's effectiveness in evaluating therapeutic potential, showing downregulation of inflammatory markers and reduction in matrix degradation in OA cartilage micro-tissues treated with SYN321. The uBeat® MultiCompress platform thus represents a valuable tool for OA research, offering a bridge between traditional in vitro studies and potential clinical applications, with implications for future drug discovery.
Insights
A new uBeat® MultiCompress platform effectively tests injectable osteoarthritis (OA) therapies on human cartilage microtissues. It demonstrated SYN321
Area of Science:
- Biomedical Engineering
- Orthopedics
- Pharmacology
Background:
- Current osteoarthritis (OA) treatments often lack efficacy and can cause systemic side effects, especially with long-term non-steroidal anti-inflammatory drug (NSAID) use.
- Injectable therapies combining polymers and NSAIDs, like diclofenac, aim for sustained intra-articular drug release but require better preclinical models.
- Developing accurate preclinical models is crucial for advancing novel OA injectable therapeutics.
Purpose of the Study:
- To introduce the uBeat® MultiCompress platform as a novel preclinical model for evaluating injectable OA therapeutics.
- To assess the platform's capability in testing human mechanically-damaged OA cartilage microtissues in a physiologically relevant manner.
- To evaluate the therapeutic potential of SYN321, a diclofenac-sodium hyaluronate conjugate, using the uBeat® platform.
Main Methods:
- Utilizing the uBeat® MultiCompress platform to test injectable formulations on human OA cartilage microtissues.
- Employing mechanically-damaged OA cartilage microtissues to simulate disease pathology.
- Treating microtissues with SYN321, a novel diclofenac-sodium hyaluronate conjugate, and analyzing outcomes.
Main Results:
- The uBeat® platform successfully accommodated and tested injectable therapeutic formulations.
- SYN321 treatment of OA cartilage microtissues led to the downregulation of inflammatory markers.
- SYN321 demonstrated a reduction in matrix degradation within the treated OA cartilage microtissues.
Conclusions:
- The uBeat® MultiCompress platform is an effective tool for studying injectable OA therapeutics on human cartilage microtissues.
- The platform provides a physiologically relevant environment for evaluating drug efficacy, including anti-inflammatory and anti-degradative effects.
- This technology serves as a vital bridge between in vitro research and clinical applications for osteoarthritis drug discovery.
