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Intra-articular Hyaluronic Acid Injections

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Orthobiologics

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Abstract

Intra-articular hyaluronic acid (HA) viscosupplementation has been a mainstay of osteoarthritis treatment for many decades. Viscosupplementation as the name suggests involves the restoration of the viscosity and the lubricating ability of injured or inflamed synovial fluid. While the lubricating ability of HA injections has been well characterized, recent studies have demonstrated that the anti-inflammatory, anti-catabolic, and chondroprotective actions of HA reduce pain and improve patient function. This chapter details some of these biologic effects of intra-articular HA. The key mechanical properties that contribute to joint lubrication and can predict clinical outcomes in patients have also been described. Additionally, future directions for the characterization and application of synthetic HA-derived viscosupplements are discussed.

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References

  1. Fallacara A, Baldini E, Manfredini S, Vertuani S. Hyaluronic acid in the third millennium. Polymers. 2018;10(7):701.

    Article  Google Scholar 

  2. Gupta R, Lall R, Srivastava A, Sinha A. Hyaluronic acid: molecular mechanisms and therapeutic trajectory. Front Vet Sci. 2019;6:192.

    Article  Google Scholar 

  3. Dicker K, Gurski L, Pradhan-Bhatt S, Witt R, Farach-Carson M, Jia X. Hyaluronan: a simple polysaccharide with diverse biological functions. Acta Biomater. 2014;10(4):1558–70.

    Article  CAS  Google Scholar 

  4. Nicholls M, Manjoo A, Shaw P, Niazi F, Rosen J. A comparison between rheological properties of intra-articular hyaluronic acid preparations and reported human synovial fluid. Adv Ther. 2018;35(4):523–30.

    Article  CAS  Google Scholar 

  5. Bellamy N, Campbell J, Welch V, Gee T, Bourne R, Wells G. Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006;(2):CD005321.

    Google Scholar 

  6. Moskowitz R. Hyaluronic acid supplementation. Curr Rheumatol Rep. 2000;2(6):466–71.

    Article  CAS  Google Scholar 

  7. Hochberg M, Altman R, April K, Benkhalti M, Guyatt G, McGowan J, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res. 2012;64(4):465–74.

    Article  CAS  Google Scholar 

  8. Trojian T, Concoff A, Joy S, Hatzenbuehler J, Saulsberry W, Coleman C. AMSSM scientific statement concerning viscosupplementation injections for knee osteoarthritis: importance for individual patient outcomes. Br J Sports Med. 2016;50(2):84–92.

    Article  Google Scholar 

  9. Jevsevar D. Treatment of osteoarthritis of the knee: evidence-based guideline, 2nd edition. J Am Acad Orthop Surg. 2013;21(9):571–6.

    PubMed  Google Scholar 

  10. Viscosupplementation Market Size, trends, Outlook 2020–25 [Internet]. Mordorintelligence.com. 2020 [cited 22 December 2020].

  11. Ghosh P, Guidolin D. Potential mechanism of action of intra-articular hyaluronan therapy in osteoarthritis: are the effects molecular weight dependent? Semin Arthritis Rheum. 2002;32(1):10–37.

    Article  CAS  Google Scholar 

  12. Altman R, Bedi A, Manjoo A, Niazi F, Shaw P, Mease P. Anti-inflammatory effects of intra-articular hyaluronic acid: a systematic review. CARTILAGE. 2018;10(1):43–52.

    Article  Google Scholar 

  13. Dunn S, Kolomytkin O, Waddell D, Marino A. Hyaluronan-binding receptors: possible involvement in osteoarthritis. Mod Rheumatol. 2009;19(2):151–5.

    Article  CAS  Google Scholar 

  14. Hashizume M, Koike N, Yoshida H, Suzuki M, Mihara M. High molecular weight hyaluronic acid relieved joint pain and prevented the progression of cartilage degeneration in a rabbit osteoarthritis model after onset of arthritis. Mod Rheumatol. 2010;20(5):432–8.

    Article  CAS  Google Scholar 

  15. Kikuchi T, Yamada H, Shimmei M. Effect of high molecular weight hyaluronan on cartilage degeneration in a rabbit model of osteoarthritis. Osteoarthr Cartil. 1996;4(2):99–110.

    Article  CAS  Google Scholar 

  16. Wang C, Lin Y, Chiang B, Lin Y, Hou S. High molecular weight hyaluronic acid down-regulates the gene expression of osteoarthritis-associated cytokines and enzymes in fibroblast-like synoviocytes from patients with early osteoarthritis. Osteoarthr Cartil. 2006;14(12):1237–47.

    Article  Google Scholar 

  17. Campo G, Avenoso A, D’Ascola A, Scuruchi M, Prestipino V, Nastasi G, et al. The inhibition of hyaluronan degradation reduced pro-inflammatory cytokines in mouse synovial fibroblasts subjected to collagen-induced arthritis. J Cell Biochem. 2012;113(6):1852–67.

    Article  CAS  Google Scholar 

  18. Kawana H, Karaki H, Higashi M, Miyazaki M, Hilberg F, Kitagawa M, et al. CD44 suppresses TLR-mediated inflammation. J Immunol. 2008;180(6):4235–45.

    Article  CAS  Google Scholar 

  19. Campo G, Avenoso A, Nastasi G, Micali A, Prestipino V, Vaccaro M, et al. Hyaluronan reduces inflammation in experimental arthritis by modulating TLR-2 and TLR-4 cartilage expression. Biochim Biophys Acta Mol basis Dis. 2011;1812(9):1170–81.

    Article  CAS  Google Scholar 

  20. McCourt P, Ek B, Forsberg N, Gustafson S. Intercellular adhesion molecule-1 is a cell surface receptor for hyaluronan. J Biol Chem. 1994;269(48):30081–4.

    Article  CAS  Google Scholar 

  21. Noble P, McKee C, Cowman M, Shin H. Hyaluronan fragments activate an NF-kappa B/I-kappa B alpha autoregulatory loop in murine macrophages. J Exp Med. 1996;183(5):2373–8.

    Article  CAS  Google Scholar 

  22. Yasuda T. Hyaluronan inhibits cytokine production by lipopolysaccharide-stimulated U937 macrophages through down-regulation of NF-κB via ICAM-1. Inflamm Res. 2007;56(6):246–53.

    Article  CAS  Google Scholar 

  23. Balazs E, Denlinger J. Sodium hyaluronate and joint function. J Equine Vet. 1985;5(4):217–28.

    Article  Google Scholar 

  24. Braithwaite G, Daley M, Toledo-Velasquez D. Rheological and molecular weight comparisons of approved hyaluronic acid products—preliminary standards for establishing class III medical device equivalence. J Biomater Sci Polym Ed. 2015;27(3):235–46.

    Article  Google Scholar 

  25. Bonnevie E, Galesso D, Secchieri C, Bonassar L. Frictional characterization of injectable hyaluronic acids is more predictive of clinical outcomes than traditional rheological or viscoelastic characterization. PLoS One. 2019;14(5):e0216702.

    Article  Google Scholar 

  26. Bonnevie E, Bonassar L. A Century of Cartilage Tribology Research Is Informing Lubrication Therapies. J Biomech Eng. 2020;142(3).

    Google Scholar 

  27. Gleghorn J, Bonassar L. Lubrication mode analysis of articular cartilage using Stribeck surfaces. J Biomech. 2008;41(9):1910–8.

    Article  Google Scholar 

  28. Ateshian G. The role of interstitial fluid pressurization in articular cartilage lubrication. J Biomech. 2009;42(9):1163–76.

    Article  Google Scholar 

  29. Moore A, Burris D. Tribological rehydration of cartilage and its potential role in preserving joint health. Osteoarthr Cartil. 2017;25(1):99–107.

    Article  CAS  Google Scholar 

  30. Cook S, Bonassar L. Interaction with cartilage increases the viscosity of hyaluronic acid solutions. ACS Biomater Sci Eng. 2020;6(5):2787–95.

    Article  CAS  Google Scholar 

  31. Bonnevie E, Galesso D, Secchieri C, Cohen I, Bonassar L. Elastoviscous transitions of articular cartilage reveal a mechanism of synergy between lubricin and hyaluronic acid. PLoS One. 2015;10(11):e0143415.

    Article  Google Scholar 

  32. Feeney E, Peal B, Inglis J, Su J, Nixon A, Bonassar L, et al. Temporal changes in synovial fluid composition and elastoviscous lubrication in the equine carpal fracture model. J Orthop Res. 2019;37(5):1071–9.

    Article  CAS  Google Scholar 

  33. Irwin R, Feeney E, Galesso D, Secchieri C, Ramonda R, Cohen I, et al. Distinct tribological phenotypes of arthritic synovial fluid reveal differences in viscosupplementation efficacy. Osteoarthr Cartil. 2019;27:S165–6.

    Article  Google Scholar 

  34. Brown T, Laurent U. Fraser. Turnover of hyaluronan in synovial joints: elimination of labelled hyaluronan from the knee joint of the rabbit. Exp Physiol. 1991;76(1):125–34.

    Article  CAS  Google Scholar 

  35. Wathier M, Lakin B, Cooper B, Bansal P, Bendele A, Entezari V, et al. A synthetic polymeric biolubricant imparts chondroprotection in a rat meniscal tear model. Biomaterials. 2018;182:13–20.

    Article  CAS  Google Scholar 

  36. Faust H, Sommerfeld S, Rathod S, Rittenbach A, Ray Banerjee S, Tsui B, et al. A hyaluronic acid binding peptide-polymer system for treating osteoarthritis. Biomaterials. 2018;183:93–101.

    Article  CAS  Google Scholar 

  37. Singh A, Corvelli M, Unterman S, Wepasnick K, McDonnell P, Elisseeff J. Enhanced lubrication on tissue and biomaterial surfaces through peptide-mediated binding of hyaluronic acid. Nat Mater. 2014;13(10):988–95.

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Materials Science and Engineering, Cornell University, Ithaca, NY, USA

    Karan Vishwanath

  2. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA

    Lawrence J. Bonassar

  3. Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA

    Lawrence J. Bonassar

Authors
  1. Karan Vishwanath
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  2. Lawrence J. Bonassar
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Corresponding author

Correspondence to Lawrence J. Bonassar .

Editor information

Editors and Affiliations

  1. Rizzoli Orthopaedic Institute, Bologna, Italy

    Giuseppe Filardo

  2. Orthopaedic & Sports Medicine Group, Santa Monica Orthopaedic & Sports Medicine, Santa Monica, CA, USA

    Bert R. Mandelbaum

  3. Orthopaedic Surgery and Biomedical Engineering, Cleveland Clinic, Cleveland, OH, USA

    George F. Muschler

  4. Hospital for Special Surgery, New York, NY, USA

    Scott A. Rodeo

  5. Institute for Medical Science in Sports, Osaka Health Science University, Osaka, Japan

    Norimasa Nakamura

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Vishwanath, K., Bonassar, L.J. (2022). Intra-articular Hyaluronic Acid Injections. In: Filardo, G., Mandelbaum, B.R., Muschler, G.F., Rodeo, S.A., Nakamura, N. (eds) Orthobiologics. Springer, Cham. https://doi.org/10.1007/978-3-030-84744-9_8

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  • DOI: https://doi.org/10.1007/978-3-030-84744-9_8

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-84743-2

  • Online ISBN: 978-3-030-84744-9

  • eBook Packages: MedicineMedicine (R0)

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