Hyaluronic acid (HA) injections represent one of the most common methods for the treatment of osteoarthritis. However, the clinical results of this method are unambiguous mainly because the mechanism of action has not been clearly clarified yet. Viscosupplementation consists, inter alia, of the improvement of synovial fluid rheological properties by injected solution. The present paper deals with the effect of HA molecular weight on the rheological properties of its solutions and also on friction in the articular cartilage model. Viscosity and viscoelastic properties of HA solutions were analyzed with a rotational rheometer in a cone-plate and plate-plate configuration. In total, four HA solutions with molecular weights between 77 kDa and 2010 kDa were tested. The frictional measurements were realized on a commercial tribometer Bruker UMT TriboLab, while the coefficient of friction (CoF) dependency on time was measured. The contact couple consisted of the articular cartilage pin and the plate made from optical glass. The contact was fully flooded with tested HA solutions. Results showed a strong dependency between HA molecular weight and its rheological properties. However, no clear dependence between HA molecular weight and CoF was revealed from the frictional measurements. This study presents new insight into the dependence between rheological and frictional behavior of the articular cartilage, while such an extensive investigation has not been presented before.

Contipro a s Dolní Dobrouč 401 561 02 Dolní Dobrouč Czech Republic

Faculty of Mechanical Engineering Brno University of Technology 616 69 Brno Czech Republic

See more in PubMed

Lees D., Partington P. Articular cartilage. Orthop. Trauma. 2016;30:265–272. doi: 10.1016/j.mporth.2016.04.007. DOI

Goldring M.B. Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis. Ther. Adv. Musculoskelet. Dis. 2012;4:269–285. doi: 10.1177/1759720X12448454. PubMed DOI PMC

Ateshian G.A. The role of interstitial fluid pressurization in articular cartilage lubrication. J. Biomech. 2009;42:1163–1176. doi: 10.1016/j.jbiomech.2009.04.040. PubMed DOI PMC

Forsey R., Fisher J., Thompson J., Stone M., Bell C., Ingham E. The effect of hyaluronic acid and phospholipid-based lubricants on friction within a human cartilage damage model. Biomaterials. 2006;27:4581–4590. doi: 10.1016/j.biomaterials.2006.04.018. PubMed DOI

Galandáková A., Ulrichová J., Langová K., Hanáková A., Vrbka M., Hartl M., Gallo J. Characteristics of synovial fluid required for optimization of lubrication fluid for biotribological experiments. J. Biomed. Mater. Res. B Appl. Biomater. 2017;105:1422–1431. doi: 10.1002/jbm.b.33663. PubMed DOI

Balazs E.A., Denlinger J.L. Viscosupplementation: A new concept in the treatment of osteoarthritis. J. Rheumatol. Suppl. 1993;39:3–9. PubMed

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;32:10–37. doi: 10.1053/sarh.2002.33720. PubMed DOI

Altman R.D., Manjoo A., Fierlinger A., Niazi F., Nicholls M. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: A systematic review. BMC Musculoskelet. Disord. 2015;16:321. doi: 10.1186/s12891-015-0775-z. PubMed DOI PMC

Watterson J.R., Esdaile J.M. Viscosupplementation: Therapeutic Mechanisms and clinical potential in osteoarthritis of the knee. J. Am. Acad. Orthop. Surg. 2000;8:277–284. doi: 10.5435/00124635-200009000-00001. PubMed DOI

Mazzucco D., Scott R., Spector M. Composition of joint fluid in patients undergoing total knee replacement and revision arthroplasty: Correlation with flow properties. Biomaterials. 2004;25:4433–4445. doi: 10.1016/j.biomaterials.2003.11.023. PubMed DOI

Ghosh P. The role of hyaluronic acid (hyaluronan) in health and disease: Interactions with cells, cartilage and components of synovial fluid. Clin. Exp. Rheumatol. 1994;12:75–82. PubMed

Zhang Z., Barman S., Christopher G.F. The role of protein content on the steady and oscillatory shear rheology of model synovial fluids. Soft Matter. 2014;10:5965–5973. doi: 10.1039/C4SM00716F. PubMed DOI

Balazs E.A. Viscoelastic properties of hyaluronan and its therapeutic use. In: Garg G.G., Hales C.A., editors. Chemistry and Biology of Hyaluronan. 1st ed. Volume 1. Elsevier Ltd.; Amsterdam, The Netherlands: 2004. pp. 415–455.

Falcone S.J., Palmeri D.M., Berg R.A. Rheological and cohesive properties of hyaluronic acid. J. Biomed. Mater. Res. A. 2006;76A:721–728. doi: 10.1002/jbm.a.30623. PubMed DOI

Bhuanantanondh P., Grecov D., Kwok E. Rheological Study of viscosupplements and synovial fluid in patients with osteoarthritis. J. Med. Biol. Eng. 2010;32:12–16. doi: 10.5405/jmbe.834. DOI

Altman R.D. Status of hyaluronan supplementation therapy in osteoarthritis. Curr. Rheumatol. Rep. 2003;5:7–14. doi: 10.1007/s11926-003-0077-6. PubMed DOI

Mathieu P., Conrozier T., Vignon E., Rozand Y., Rinaudo M. Rheologic behavior of osteoarthritic synovial fluid after addition of hyaluronic acid: A pilot study. Clin. Orthop. Relat. Res. 2009;467:3002–3009. doi: 10.1007/s11999-009-0867-x. PubMed DOI PMC

Bhuanantanondh P., Grecov D., Kwok E., Guy P. Rheology of osteoarthritic synovial fluid mixed with viscosupplements: A pilot study. Biomed. Eng. Lett. 2011;1:213–219. doi: 10.1007/s13534-011-0034-7. DOI

Dowson D. Modes of lubrication in human joints. Proc. Inst. Mech. Eng. 1996;181:45–54.

McCutchen C.W. The frictional properties of animal joints. Wear. 1962;5:1–17. doi: 10.1016/0043-1648(62)90176-X. DOI

Dowson D., Jin Z.-M. Micro-elastohydrodynamic lubrication of synovial joints. Eng. Med. 1986;15:63–65. doi: 10.1243/EMED_JOUR_1986_015_019_02. PubMed DOI

Murakami T. The lubrication in natural synovial joints and joint prostheses. JSME Int. J. Ser. III Vib. Control Eng. Eng. Ind. 1990;33:465–474. doi: 10.1299/jsmec1988.33.465. DOI

Murakami T., Higaki H., Sawae Y., Ohtsuki N., Moriyama S., Nakanishi Y. Adaptive multimode lubrication in natural synovial joints and artificial joints. Proc. Inst. Mech. Eng. H. 2006;212:23–35. doi: 10.1243/0954411981533791. PubMed DOI

Ateshian G.A. A theoretical formulation for boundary friction in articular cartilage. J. Biomech. Eng. 1997;119:81–86. doi: 10.1115/1.2796069. PubMed DOI

Ikeuchi K. Origin and future of hydration lubrication. Proc. Inst. Mech. Eng. J. 2007;221:301–305. doi: 10.1243/13506501JET214. DOI

Bell C.J., Ingham E., Fisher J. Influence of hyaluronic acid on the time-dependent friction response of articular cartilage under different conditions. Proc. Inst. Mech. Eng. H. 2006;220:23–31. doi: 10.1243/095441105X69060. PubMed DOI

Murakami T., Yarimitsu S., Nakashima K., Sawae Y., Sakai N. Influence of synovia constituents on tribological behaviors of articular cartilage. Friction. 2013;1:150–162. doi: 10.1007/s40544-013-0010-6. DOI

Seror J., Zhu L., Goldberg R., Day A.J., Klein J. Supramolecular synergy in the boundary lubrication of synovial joints. Nat. Commun. 2015;6:6497. doi: 10.1038/ncomms7497. PubMed DOI PMC

Yarimitsu S., Sasaki S., Murakami T., Suzuki A. Evaluation of lubrication properties of hydrogel artificial cartilage materials for joint prosthesis. Biosurf. Biotribol. 2016;2:40–47. doi: 10.1016/j.bsbt.2016.02.005. DOI

Murakami T., Nakashima K., Yarimitsu S., Sawae Y., Sakai N. Effectiveness of adsorbed film and gel layer in hydration lubrication as adaptive multimode lubrication mechanism for articular cartilage. Proc. Inst. Mech. Eng. J. 2011;225:1174–1185. doi: 10.1177/1350650111415756. DOI

Szarko M., Muldrew K., Bertram J.E.A. Freeze-thaw treatment effects on the dynamic mechanical properties of articular cartilage. BMC Musculoskelet. Disord. 2010;11:281. doi: 10.1186/1471-2474-11-231. PubMed DOI PMC

Fam H., Bryant J.T., Kontopoulou M. Rheological properties of synovial fluids. Biorheology. 2007;44:59–74. PubMed

Mazzucco D., McKinley G., Scott R.D., Spector M. Rheology of joint fluid in total knee arthroplasty patients. J. Orthop. Res. 2002;20:1157–1163. doi: 10.1016/S0736-0266(02)00050-5. PubMed DOI

Lapasin R. Rheological Studies Dedicated to the Development of a Novel Injectable Polymeric Blend for Viscosupplementation Treatment. Chem. Biochem. Eng. Q. 2016;29:511–518. doi: 10.15255/CABEQ.2014.2148. DOI

Bonnevie E.D., Galesso D., Secchieri C., Bonassar L.J., Awad H.A. Frictional characterization of injectable hyaluronic acids is more predictive of clinical outcomes than traditional rheological or viscoelastic characterization. PLoS ONE. 2019;14:e0216702. doi: 10.1371/journal.pone.0216702. PubMed DOI PMC

Rainer F., Ribitsch V. Viscoelastic properties of normal human synovia and their relation to biomechanics. Zeitschrift fur Rheumatologie. 1985;44:114–119. PubMed

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;35:523–530. doi: 10.1007/s12325-018-0688-y. PubMed DOI PMC

Borzacchiello A., Mayol L., Schiavinato A., Ambrosio L. Effect of hyaluronic acid amide derivative on equine synovial fluid viscoelasticity. J. Biomed. Mater. Res. A. 2009;92A:1162–1170. doi: 10.1002/jbm.a.32455. PubMed DOI

Balazs E.A. The physical properties of synovial fluid and the special role of hyaluronic acid. In: Helfet A.J., editor. Disorders of the Knee. 1st ed. Vol. 2. JB Lippincott & Co.; Philadelphia, PA, USA: 1974. pp. 63–75.

Finelli I., Chiessi E., Galesso D., Renier D., Paradossi G. A new viscosupplement based on partially hydrophobic hyaluronic acid: A comparative study. Biorheology. 2011;48:263–275. doi: 10.3233/BIR-2011-0596. PubMed DOI

Krishnan R., Kopacz M., Ateshian G.A. Experimental verification of the role of interstitial fluid pressurization in cartilage lubrication. J. Orthop. Res. 2004;22:565–570. doi: 10.1016/j.orthres.2003.07.002. PubMed DOI PMC

Bonnevie E.D., Galesso D., Secchieri C., Cohen I., Bonassar L.J., Awad H.A. Elastoviscous transitions of articular cartilage reveal a mechanism of synergy between lubricin and hyaluronic acid. PLoS ONE. 2015;10:e0143415. doi: 10.1371/journal.pone.0143415. PubMed DOI PMC

Kwiecinski J.J., Dorosz S.G., Ludwig T.E., Abubacker S., Cowman M.K., Schmidt T.A. The effect of molecular weight on hyaluronan’s cartilage boundary lubricating ability—Alone and in combination with proteoglycan 4. Osteoarthr. Cartil. 2011;19:1356–1362. doi: 10.1016/j.joca.2011.07.019. PubMed DOI

Appleyard R.C., Burkhardt D., Ghosh P., Read R., Cake M., Swain M.V., Murrell G.A.C. Topographical analysis of the structural, biochemical and dynamic biomechanical properties of cartilage in an ovine model of osteoarthritis. Osteoarthr. Cartil. 2003;11:65–77. doi: 10.1053/joca.2002.0867. PubMed DOI

Kiviranta P., Lammentausta E., Töyräs J., Kiviranta I., Jurvelin J.S. Indentation diagnostics of cartilage degeneration. Osteoarthr. Cartil. 2008;16:796–804. doi: 10.1016/j.joca.2007.10.016. PubMed DOI

Richard F., Villars M., Thibaud S. Viscoelastic modeling and quantitative experimental characterization of normal and osteoarthritic human articular cartilage using indentation. J. Mech. Behav. Biomed. Mater. 2013;24:41–52. doi: 10.1016/j.jmbbm.2013.04.012. PubMed DOI

DuRaine G., Neu C.P., Chan S.M.T., Komvopoulos K., June R.K., Reddi A.H. Regulation of the friction coefficient of articular cartilage by TGF-β1 and IL-1β. J. Orthop. Res. 2009;27:249–256. doi: 10.1002/jor.20713. PubMed DOI

Chan S.M.T., Neu C.P., Komvopoulos K., Reddi A.H. The role of lubricant entrapment at biological interfaces: Reduction of friction and adhesion in articular cartilage. J. Biomech. 2011;44:2015–2020. doi: 10.1016/j.jbiomech.2011.04.015. PubMed DOI

Nečas D., Vrbka M., Urban F., Křupka I., Hartl M. The effect of lubricant constituents on lubrication mechanisms in hip joint replacements. J. Mech. Behav. Biomed. Mater. 2016;55:295–307. doi: 10.1016/j.jmbbm.2015.11.006. PubMed DOI

Myant C.W., Cann P. The effect of transient conditions on synovial fluid protein aggregation lubrication. J. Mech. Behav. Biomed. Mater. 2014;34:349–357. doi: 10.1016/j.jmbbm.2014.02.005. PubMed DOI

Ma L., Rainforth W.M. The effect of lubrication on the friction and wear of Biolox®delta. Acta Biomater. 2012;8:2348–2359. doi: 10.1016/j.actbio.2011.12.037. PubMed DOI

Schmidt T.A., Gastelum N.S., Nguyen Q.T., Schumacher B.L., Sah R.L. Boundary lubrication of articular cartilage: Role of synovial fluid constituents. Arthritis Rheum. 2007;56:882–891. doi: 10.1002/art.22446. PubMed DOI

Seror J., Sorkin R., Klein J. Boundary lubrication by macromolecular layers and its relevance to synovial joints. Polym. Adv. Technol. 2014;25:468–477. doi: 10.1002/pat.3295. DOI

Klein J. Hydration lubrication. Friction. 2013;1:1–23. doi: 10.1007/s40544-013-0001-7. DOI

Jahn S., Klein J. Lubrication of articular cartilage. Physics Today. 2018;71:48–54. doi: 10.1063/PT.3.3898. DOI

Maheu E., Rannou F., Reginster J.-Y. Efficacy and safety of hyaluronic acid in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin. Arthritis Rheum. 2016;45:S28–S33. doi: 10.1016/j.semarthrit.2015.11.008. PubMed DOI

Tıkız C., Ünlü Z., Şener A., Efe M., Tüzün Ç. Comparison of the efficacy of lower and higher molecular weight viscosupplementation in the treatment of hip osteoarthritis. Clin. Rheum. 2005;24:244–250. doi: 10.1007/s10067-004-1013-5. PubMed DOI

Bannuru R.R., Vaysbrot E.E., Sullivan M.C., McAlindon T.E. Relative efficacy of hyaluronic acid in comparison with NSAIDs for knee osteoarthritis: A systematic review and meta-analysis. Semin. Arthritis Rheum. 2014;43:593–599. doi: 10.1016/j.semarthrit.2013.10.002. PubMed DOI

Jevsevar D., Donnelly P., Brown G.A., Cummins D.S. Viscosupplementation for osteoarthritis of the knee. J. Bone Jt. Surg. Am. 2015;97:2047–2060. doi: 10.2106/JBJS.N.00743. PubMed DOI

Rutjes A.W.S., Jüni P., da Costa B.R., Trelle S., Nüesch E., Reichenbach S. Viscosupplementation for osteoarthritis of the knee. Ann. Intern. Med. 2012;157:180–191. doi: 10.7326/0003-4819-157-3-201208070-00473. PubMed DOI

Arrich J. Intra-articular hyaluronic acid for the treatment of osteoarthritis of the knee: Systematic review and meta-analysis. Can. Med. Assoc. J. 2005;172:1039–1043. doi: 10.1503/cmaj.1041203. PubMed DOI PMC

Bruyère O., Cooper C., Pelletier J.-P., Branco J., Luisa Brandi M., Guillemin F., Hochberg M.C., Kanis J.A., Kvien T.K., Martel-Pelletier J., et al. An algorithm recommendation for the management of knee osteoarthritis in Europe and internationally: A report from a task force of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) Semin. Arthritis Rheum. 2014;44:253–263. doi: 10.1016/j.semarthrit.2014.05.014. PubMed DOI

McAlindon T.E., Bannuru R.R., Sullivan M.C., Arden N.K., Berenbaum F., Bierma-Zeinstra S.M., Hawker G.A., Henrotin Y., Hunter D.J., Kawaguchi H., et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr. Cartil. 2014;22:363–388. doi: 10.1016/j.joca.2014.01.003. PubMed DOI

Pan Y.-S., Xiong D.-S., Ma R.-Y. A study on the friction properties of poly (vinyl alcohol) hydrogel as articular cartilage against titanium alloy. Wear. 2007;262:1021–1025. doi: 10.1016/j.wear.2006.10.005. DOI

Katta J.K., Marcolongo M., Lowman A., Mansmann K.A. Friction and wear behavior of poly (vinyl alcohol)/poly (vinyl pyrrolidone) hydrogels for articular cartilage replacement. J. Biomed. Mater. Res. A. 2007;83A:471–479. doi: 10.1002/jbm.a.31238. PubMed DOI

Murakami T., Sakai N., Yamaguchi T., Yarimitsu S., Nakashima K., Sawae Y., Suzuki A. Evaluation of a superior lubrication mechanism with biphasic hydrogels for artificial cartilage. Tribol. Int. 2015;89:19–26. doi: 10.1016/j.triboint.2014.12.013. DOI

Murakami T., Yarimitsu S., Nakashima K., Yamaguchi T., Sawae Y., Sakai N., Suzuki A. Superior lubricity in articular cartilage and artificial hydrogel cartilage. Proc. Inst. Mech. Eng. J. 2014;228:1099–1111. doi: 10.1177/1350650114530273. PubMed DOI

Murakami T., Yarimitsu S., Sakai N., Nakashima K., Yamaguchi T., Sawae Y., Suzuki A. Superior lubrication mechanism in poly (vinyl alcohol) hybrid gel as artificial cartilage. Proc. Inst. Mech. Eng. J. 2017;231:1160–1170. doi: 10.1177/1350650117712881. DOI

Nečas D., Vrbka M., Galandáková A., Křupka I., Hartl M. On the observation of lubrication mechanisms within hip joint replacements. Part I: Hard-on-soft bearing pairs. J. Mech. Behav. Biomed. Mater. 2019;89:237–248. PubMed

Čípek P., Rebenda D., Nečas D., Vrbka M., Křupka I., Hartl M. Visualization of lubrication film in model of synovial joint. Tribol. Ind. 2019;41:387–393. doi: 10.24874/ti.2019.41.03.08. DOI

Size Matters: Rethinking Hertz Model Interpretation for Cell Mechanics Using AFM

Analysis of Chemisorbed Tribo-Film for Ceramic-on-Ceramic Hip Joint Prostheses by Raman Spectroscopy