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Advances in viscosupplementation and tribosupplementation for early-stage osteoarthritis therapy

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From Nature Reviews Rheumatology

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Abstract

Joint kinematic instability, arising from congenital or acquired musculoskeletal pathoanatomy or from imbalances in anabolism and catabolism induced by pathophysiological factors, leads to deterioration of the composition, structure and function of cartilage and, ultimately, progression to osteoarthritis (OA). Alongside articular cartilage degeneration, synovial fluid lubricity decreases in OA owing to a reduction in the concentration and molecular weight of hyaluronic acid and surface-active mucinous glycoproteins that form a lubricating film over the articulating joint surfaces. Minimizing friction between articulating joint surfaces by lubrication is fundamental for decreasing hyaline cartilage wear and for maintaining the function of synovial joints. Augmentation with highly viscous supplements (that is, viscosupplementation) offers one approach to re-establishing the rheological and tribological properties of synovial fluid in OA. However, this approach has varied clinical outcomes owing to limited intra-articular residence time and ineffective mechanisms of chondroprotection. This Review discusses normal hyaline cartilage function and lubrication and examines the advantages and disadvantages of various strategies for restoring normal joint lubrication. These strategies include contemporary viscosupplements that contain antioxidants, anti-inflammatory drugs or platelet-rich plasma and new synthetic synovial fluid additives and cartilage matrix enhancers. Advanced biomimetic tribosupplements offer promise for mitigating cartilage wear, restoring joint function and, ultimately, improving patient care.

Key points

  • In osteoarthritis, compositional changes to the synovial fluid reduce the lubricating ability of the joint and can lead to propagation of cartilage wear.

  • Clinically approved viscosupplements are aimed at restoring synovial fluid lubricity and reducing the inflammatory response, but their efficacy remains nebulous.

  • Enhanced viscosupplements combine sodium hyaluronate with additional materials (such as glucocorticoids and antioxidants) that target specific aspects of osteoarthritis, but the benefits of these additions seem minimal.

  • Tribosupplementation, the delivery of non-hyaluronan-based lubricants to the joint, shows some promise but is largely in the preclinical stages of development; this approach includes fluid additives and matrix enhancers.

  • Fluid additives are cartilage lubricants (with a linear, hydrogel or particle structure) that remain suspended in the synovial fluid following intraarticular injection and comprise linear, hydrogel and particle structures.

  • Matrix enhancers are cartilage lubricants (with a linear, hydrogel or particle structure) that, in addition to containing a lubricious domain, contain a domain that binds to the cartilage surface.

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Fig. 1: Types of viscosupplementation and tribosupplementation.
Fig. 2: The composition, morphology and biomechanics of cartilage and synovial fluid in the healthy and osteoarthritic states.
Fig. 3: Clinical results for several clinically approved viscosupplements.
Fig. 4: Structures of various linear tribosupplements.

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Acknowledgements

C.D.D.M. acknowledges support from the National Science Foundation Graduate Research Fellowship Program (DGE-1840990). T.B.L. acknowledges support from the National Institutes of Health (NIH; F31 AR075386). J.M. acknowledges support from the Academy of Finland (348410, 357787), Instrumentarium Science Foundation (190021) and the Orion Research Foundation sr. B.D.S. acknowledges support from the Harvard Catalyst Foundation. A.J., D.T.F., T.P.S., M.B., M.B.A. and M.W.G. acknowledge support from Boston University and the Wallace H. Coulter Foundation.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Boston University, Boston, MA, USA

    Christian D. DeMoya & Mark W. Grinstaff

  2. Division of Materials Science and Engineering, Boston University, Boston, MA, USA

    Anisha Joenathan & Mark W. Grinstaff

  3. Department of Mechanical Engineering, Boston University, Boston, MA, USA

    Taylor B. Lawson & Michael B. Albro

  4. Section of Rheumatology, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, USA

    David T. Felson

  5. PENN VET Institute for Medical Translation, University of Pennsylvania School of Veterinary Medicine New Bolton Center, Kennett Square, PA, USA

    Thomas P. Schaer

  6. Boston University, Henry M. Goldman School of Dental Medicine, Boston, MA, USA

    Manish Bais

  7. Department of Technical Physics, University of Eastern Finland, Kuopio, Finland

    Janne Mäkelä

  8. Department of Orthopaedic Surgery, Boston Children’s Hospital Boston, Boston, MA, USA

    Brian D. Snyder

  9. Department of Chemistry, Boston University, Boston, MA, USA

    Mark W. Grinstaff

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Contributions

M.W.G., C.D.D.M. and A.J. researched data for the article. M.W.G., C.D.D.M., A.J., T.B.L., T.P.S., M.B., M.B.A., J.M. and B.D.S. contributed substantially to discussion of the content. All authors wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Brian D. Snyder or Mark W. Grinstaff.

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Competing interests

A patent was filed and is owned by Boston University on poly(7-oxanorbornene-2-carboxylate), a tribosupplement formulation described in the Review, and the patent is available for licensing (US8378064B2). M.W.G. is an inventor listed on the patent. No IP has been licensed to the author. All other authors declare no competing interests.

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Glossary

Boundary lubrication

The mode of lubrication in which the two sliding surfaces are only separated by a thin film of lubricant, such that imperfections along the surfaces can come into contact with each other.

Fluid-film lubrication

The mode of lubrication in which two sliding surfaces are completely separated by a film of lubricant.

Hydration lubrication

The phenomenon of water molecules clustering around charged groups to form hydration layers that maintain extremely low coefficients of friction.

Interstitial fluid load support

The proportion of an applied load that is supported by pressurized fluid entrapped within the cartilage matrix.

Non-Newtonian fluid

A fluid that has a variable viscosity depending on the stress applied to it.

Rheological properties

The deformation properties of a material, often described in terms of viscosity, storage modulus and loss modulus.

Shear-thinning

A rheological behaviour in which the viscosity of a fluid decreases with increasing shear strain.

Tribological properties

The frictional properties of a material during rubbing; lubricants are intended to affect tribological properties by decreasing friction between two rubbing surfaces.

Tribosupplementation

Delivery of a material, other than an exogenous hyaluronic acid solution, to a synovial joint, with the intention of improving cartilage lubrication as a treatment for osteoarthritis.

Viscosupplementation

Delivery of an exogenous hyaluronic acid solution, often formulated as sodium hyaluronate, to an osteoarthritic joint, to restore the lubricity of the synovial fluid.

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DeMoya, C.D., Joenathan, A., Lawson, T.B. et al. Advances in viscosupplementation and tribosupplementation for early-stage osteoarthritis therapy. Nat Rev Rheumatol 20, 432–451 (2024). https://doi.org/10.1038/s41584-024-01125-5

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