The Evolving Role of Hyaluronic Acid in Osteoarthritis and Rheumatology

Current Landscape of HA and Osteoarthritis

Among the most widely established applications of HA is viscosupplementation or intra-articular injections in osteoarthritis treatment for the knees. By delivering HA precisely into the synovial fluid of affected joints, this treatment helps reduce pain, restore lubrication and cushioning, and improve mobility.^1,2

HA is also believed to have anti-inflammatory properties by modulating the activity of cytokines and reducing the degradation of cartilage.^3,4,5,6  These properties alleviates symptoms while slowing the progression of the disease.⁷

Beyond providing symptomatic relief leading to better quality of life, receiving intra-articular HA injections also helps in preserving joint cartilage.⁸

Patient testimonials and outcome studies have reinforced the role of HA in osteoarthritis and rheumatology, with patients reporting reduction in pain and improved joint function.^4,9 Comparative studies have also shown that repeated intra-articular HA treatments could deliver sustained benefits with respect to pain relief and functional benefits. These outcomes highlight HA’s role as a reliable, long-term strategy in osteoarthritis management.¹⁰

Emerging Applications: Expanding HA’s Role in Rheumatology

In the broader field of rheumatology, HA’s anti-inflammatory and immunomodulatory properties are being explored in conditions attributed to joint pain and inflammation.

While HA’s benefits in osteoarthritis are well established, its potential applications are expanding into the broader field of rheumatology, for example in ankle osteoarthritis.

A randomized, double-blind study on efficacy of HA in ankle osteoarthritis showed encouraging results, suggesting that HA can improve pain and function across multiple joints, not just the knee. This underscores HA’s potential as a versatile therapy for various inflammatory and degenerative joint conditions.¹¹

Recent developments are propelling HA based therapies into an exciting new phase, that is, combining HA with other therapeutic agents, such as corticosteroids or other anti-inflammatory compounds, to enhance its efficacy.⁵

Pursuit of improved efficacy and patient compliance have resulted in the development of novel HA formulations.^5,12 This includes combining HA with agents targeting specific inflammatory pathways that address symptoms and causes of joint diseases, as well as sustained release HA formulations.^5,12,16 These next generation formulations not only improve patient convenience but also ensure a more consistent therapeutic outcome.

Novel delivery systems are also being developed with the aim of enhancing bioavailability, duration of action, and patient experience leading to the integration of HA in the nanotechnology and target delivery field.^5,13,14,15 Engineered nanoparticles can deliver HA directly to affected tissues, maximizing their therapeutic concentration while minimizing systemic exposure or potential side-effects.

Looking Ahead: The Future of HA in Rheumatology

The evolution of hyaluronic acid from a naturally occurring biopolymer to an important therapy option for joint disease highlights its transformative impact in biomedical science. As innovation drives new delivery systems and broader applications, HA continues to stand at the forefront of osteoarthritis and rheumatology treatment as well as across other medical fields, from ophthalmology to regenerative medicine, improving lives worldwide.

References

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2. Dougados M, Nguyen M, Listrat V, Amor B. High molecular weight sodium hyaluronate (hyalectin) in osteoarthritis of the knee: a 1 year placebo-controlled trial. Osteoarthritis Cartilage. 1993;1(2):97-103. doi: 10.1016/s1063-4584(05)80024-x.
3. Kuo JW, Prestwich GD. Hyaluronic Acid. In: Ducheyne P, Healy KE, Hutmacher DW, Grainger DW, Kirkpatrick CJ. Comprehensive Biomaterials. 2011;2:239-259. Elsevier.
4. Marinho A, Nunes C, Reis S .Hyaluronic Acid: A Key Ingredient in the Therapy of Inflammation. Biomolecules. 2021;11(10):1518. doi:10.3390/biom11101518
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6. Castro KC, Campos MGN, Mei LHI. Hyaluronic acid electrospinning: Challenges, applications in wound dressings and new perspectives. Int J Biol Macromol. 2021;173:251–66. doi:10.1016/j.ijbiomac.2021.01.100
7. Kuppa SS, Kang JY, Yang HY, Lee SC, Sankaranarayanan J, Kim HK, Seon JK. Hyaluronic Acid Viscosupplement Modulates Inflammatory Mediators in Chondrocyte and Macrophage Coculture via MAPK and NF-κB Signaling Pathways. ACS Omega. 2024; 9(19):21467–83 doi:10.1021/acsomega.4c01911
8. Avenoso A, D’Ascola A, Scuruchi M, Mandraffino G, Calatroni A, Saitta A, Campo S, Campo GM. Hyaluronan in experimental injured/inflamed cartilage: In vivo studies. Life Sci 2018;193:132-40. doi:10.1016/j.lfs.2017.11.006.
9. Brophy RH, Fillingham YA. AAOS Clinical Practice Guideline Summary: Management of Osteoarthritis of the Knee (Nonarthroplasty), Third Edition. J Am Acad Orthop Surg. 2022;30(9):e721-e729. doi:10.5435/JAAOS-D-21-0123.
10. Navarro-Sarabia F, Coronel P, Collantes E, Navarro FJ, de la Serna AR, Naranjo A, Gimeno M, Herrero-Beaumont G; AMELIA study group. A 40-month multicentre, randomised placebo-controlled study to assess the efficacy and carry-over effect of repeated intra-articular injections of hyaluronic acid in knee osteoarthritis: the AMELIA project. Ann Rheum Dis. 2011;70(11):1957–62doi:10.1136/ard.2011.152017.
11. Salk RS, Chang TJ, D’Costa WF, Soomekh DJ, Grogan KA. Sodium hyaluronate in the treatment of osteoarthritis of the ankle: a controlled, randomized, double-blind pilot study. J Bone Joint Surg Am. 2006;88(2):295–302. doi:10.2106/JBJS.E.00193.
12. Chavda S, Rabbani SA, Wadhwa T. Role and Effectiveness of Intra-articular Injection of Hyaluronic Acid in the Treatment of Knee Osteoarthritis: A Systematic Review. Cureus. 2022;14(4):e24503. doi:10.7759/cureus.2450
13. Vasvani S, Kulkarni P, Rawtani D. Hyaluronic acid: A review on its biology, aspects of drug delivery, route of administrations and a special emphasis on its approved marketed products and recent clinical studies. Int J Biol Macromol. 2020;151:1012-1029. doi:10.1016/j.ijbiomac.2019.11.066.
14. Fallacara A, Baldini E, Manfredini S, Vertuani S. Hyaluronic Acid in the Third Millennium. 2018;10:701. doi:10.3390/polym10070701.
15. Yasin A, Ren Y, Li J, Sheng Y, Cao C, Zhang K. Advances in Hyaluronic Acid for Biomedical Applications. Front Bioeng Biotechnol. 2022;10:910290. doi:10.3389/fbioe.2022.910290.
16. Lee S, Seo J, Kim YH, Ju HJ, Kim S, Ji YB, Lee HB, Kim HS, Choi S, Kim MS. Enhanced intra-articular therapy for rheumatoid arthritis using click-crosslinked hyaluronic acid hydrogels loaded with toll-like receptor antagonizing peptides. Acta Biomater. 2023;172:188-205. doi:10.1016/j.actbio.2023.10.023.