An Advanced Mechanically Active Osteoarthritis-on-Chip Model to Test Injectable Therapeutic Formulations: The SYN321 Case Study

Adv Healthc Mater. 2024 Dec;13(32):e2401187. doi: 10.1002/adhm.202401187. Epub 2024 Sep 24.

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.

Keywords: cartilage; organ‐on‐chip; osteoarthritis; therapy.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal* / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal* / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal* / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal* / therapeutic use
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology
  • Diclofenac* / administration & dosage
  • Diclofenac* / chemistry
  • Diclofenac* / pharmacology
  • Humans
  • Hyaluronic Acid* / chemistry
  • Hydrogels / chemistry
  • Injections, Intra-Articular
  • Lab-On-A-Chip Devices
  • Osteoarthritis* / drug therapy
  • Osteoarthritis* / pathology

Substances

  • Diclofenac
  • Hyaluronic Acid
  • Anti-Inflammatory Agents, Non-Steroidal
  • Hydrogels