Effect of hyaluronic acid-based viscosupplementation on cartilage
material properties - Patois et al.
Clinical benefits observed in osteoarthritis patients treated with hyaluronic acid (HA) are commonly accepted to result from restored viscoelastic properties of the synovial fluid. However, although HA remains in the joint for only a few days, viscosupplementation is known to provide long-term pain relief, and the underlying mechanism behind this prolonged effect is not well understood.
TRB Chemedica's R&D team, under the supervision of Emilie Patois and in close collaboration with the University of Geneva (Prof. Ammann and colleagues), recently published new data focusing on the modulation of cartilage properties induced by the penetration of HA into the cartilage. They hypothesized that HA might penetrate the cartilage and improve its mechanical properties, which could explain the sustained therapeutic benefits observed in OA patients. To test this hypothesis, they conducted experiments on rat femurs, exposing the cartilage to different HA-based products, including both linear and crosslinked HA. Using techniques such as bio-indentation and confocal microscopy, the study assessed how HA affected the properties of the cartilage, particularly changes in its elastic modulus, which measures how the material responds to applied force.
The findings revealed that HA does indeed penetrate the cartilage and leads to an improvement in its mechanical behaviour. For example, after exposure to Ostenil, cartilage exhibited a higher elastic modulus, meaning it became more resistant to deformation under load. This suggests that HA could help cartilage maintain its structural integrity under the pressures experienced in joint movement, which may contribute to the long-term reduction in pain seen in patients after viscosupplementation.
The study also compared the effects of different HA products with varying molecular weights (MW). It found that mid-range MW HA (0.25–1 MDa) had the most significant impact on improving cartilage properties, while products with higher MW were less effective. These findings suggest that the molecular size of HA plays a crucial role in its ability to penetrate cartilage and improve its mechanical properties. The authors propose that the 3D conformation of large HA molecules prevents them from penetrating the cartilage as the size of the molecule would be larger than that of cartilage pores.
In summary, the study offers new insights into how HA injections can improve the material properties of cartilage, potentially explaining the extended pain relief observed in osteoarthritis treatments. The results highlight the importance of choosing HA formulations based on MW to maximize therapeutic outcomes.
Notable Key Points:
• Not all HA-based viscosupplements are the same: the HA MW might directly impact the cartilage penetration and the modulation of cartilage properties.
• New data obtained by size exclusion chromatography reveal that the HA present in Ostenil (final product) has a mean MW of 1.3 MDa, with a dispersion between 0.5 and 2 MDa. This should not be mixed with the molecular weight of the API used to prepared Ostenil (mean 1.6 MDa, range between 1 and 2 MDa).
• It is well accepted that the ideal HA viscosupplement should contain high MW HA to ensure a good viscosity and support the shear-thinning properties of the synovial fluid. These new data however support the hypothesis that short chains should also be present in order to maximize cartilage penetration, while keeping in mind that chains below 500 kDa have pro-inflammatory properties. In this context, Ostenil is ideal as it contains linear, high MW HA which spontaneously degrades to generate an interesting proportion of 0.5-1.0 MDa fragments.
• HA can remain in the cartilage even after washout, which might possibly explain the long-term clinical benefits reported even once exogenous HA has been cleared from the synovial fluid. As the model used in this publication is free from cellular activity, the effects of HA on cartilage are proposed to be mainly physicochemical. Our current hypothesis is that HA modify the environment of chondrocytes and promote anabolic mechanisms.
Access to the paper:
https://www.sciencedirect.com/science/article/pii/S2589152924002151