Rheologica Acta

, Volume 55, Issue 3, pp 223–233 | Cite as

The rheological characterisation of typical injection implants based on hyaluronic acid for contour correction

  • Sergey O. Ilyin
  • Valery G. Kulichikhin
  • Alexander Ya. Malkin
Original Contribution


Systematic rheological characterisation of several injection implants based on hyaluronic acid (Belotero®, Teosyal®, Glytone® and Juvéderm® brands) has been carried out. All these dermal fillers are viscoelastic media with the storage modulus exceeding the loss modulus. So at low deformations, they are gel-like materials, but at increasing shear stress, they can flow demonstrating typical non-Newtonian behaviour. In some cases, though not always, the yield stress is expressed rather clearly. The application of the technique of large amplitude oscillation shear (LAOS) allowed us to distinguish two groups of rheological behaviour characterised by shear thinning or strain overshoot. The Belotero® fillers belong to the first group. Similar strong changes in the storage and loss moduli as a function of frequency and fuzzy yielding are characteristic of these materials. The Teosyal® and Juvéderm® Voluma filler belong to the second group. Their typical rheological features are existence of the minimum for the frequency dependence of the loss modulus and clearly expressed the yield stress. The Glytone® and Juvéderm® Ultra fillers occupy the intermediate position. When the dermal fillers of the second group were diluted, they demonstrated effects similar to the phase separation. As a result of the rheological characterisation, some assumptions have been advanced regarding correlations between the objective rheological parameters of dermal fillers and conditions of their application.


Injection implants Dermal fillers Viscoelasticity Viscosity yielding Hyaluronic acid 



The authors are grateful to Dr. Alexey Terekhov (Merz Aesthetics, Russia) for submission of the dermal filler samples for research and for discussing the results.

This work was partially supported by the Russian Science Foundation (agreement no. 14-23-00003, 7 August 2014).


  1. Baumann LS, Shamban AT, Mary Y, Lupo P, Gary Z, Monheit D, Thomas JY, Murphy JDK, Walker PS (2007) Comparison of smooth-gel hyaluronic acid dermal fillers with cross-linked bovine collagen: a multicenter, double-masked, randomized, within-subject study. Dermatol Surg 33:128–135. doi: 10.1111/j.1524-4725.2007.33352.x Google Scholar
  2. Borrell M, Leslie DB, Tezel A (2011) Lift capabilities of hyaluronic acid fillers. J Cosmet Laser Ther 13:21–27. doi: 10.3109/14764172.2011.552609 CrossRefGoogle Scholar
  3. de Maio M, Rzany B (2014) Injectable fillers in aesthetic medicine. Springer, Berlin doi: 10.1007/978-3-642-45125-6
  4. Edsman K, Nord LI, Ohrlund A, Lärkner H, Kenne AH (2012) Gel properties of hyaluronic acid dermal fillers. Dermatol Surg 38:1170–1179. doi: 10.1111/j.1524-4725.2012.02472.x CrossRefGoogle Scholar
  5. Edwards PC, Fantasia JE (2007) Review of long-term adverse effects associated with the use of chemically-modified animal and nonanimal source hyaluronic acid dermal fillers. Clin Interv Aging 2:509–519. doi: 10.2147/CIA.S382 Google Scholar
  6. Fakhari A, Berkland C (2013) Applications and emerging trends of hyaluronic acid in tissue engineering, as a dermal filler and in osteoarthritis treatment. Acta Biomater 9:7081–7092. doi: 10.1016/j.actbio.2013.03.005 CrossRefGoogle Scholar
  7. Fakhari A, Phan Q, Berkland C (2014) Hyaluronic acid colloidal gels as self-assembling elastic biomaterials. J Biomed Mater Res B Appl Biomater 102:612–618. doi: 10.1002/jbm.b.33041 CrossRefGoogle Scholar
  8. Falcone SJ, Berg RA (2008) Crosslinked hyaluronic acid dermal fillers: a comparison of rheological properties. J Biomed Mater Res A 87:264–271. doi: 10.1002/jbm.a.31675 CrossRefGoogle Scholar
  9. Falcone SJ, Palmeri DM, Berg RA (2006) Rheological and cohesive properties of hyaluronic acid. J Biomed Mater Res A 76:721–728. doi: 10.1002/jbm.a.30623 CrossRefGoogle Scholar
  10. Heden P, Sellman G, von Wachenfeldt M, Olenius M, Fagrell D (2009) Body shaping and volume restoration: the role of hyaluronic acid. Aesthet Plast Surg 33:274–282. doi: 10.1007/s00266-008-9303-y CrossRefGoogle Scholar
  11. Hee CK, Shumate GT, Narurkar V, Bernardin A, Messina DJ (2015) Rheological properties and in vivo performance characteristics of soft tissue fillers. Dermatol Surg 41:S373–S381. doi: 10.1097/DSS.0000000000000536 CrossRefGoogle Scholar
  12. Hyun K, Kim SH, Ahn KH, Lee SJ (2002) Large amplitude oscillatory shear as a way to classify the complex fluids. J Non-Newton Fluid Mech 107:51–65. doi: 10.1016/S0377-0257(02)00141-6 CrossRefGoogle Scholar
  13. Iannitti T, Palmieri B (2011) Inflammation and genetics: an insight in the centenarian model. Hum Biol 83:531–559. doi: 10.3378/027.083.0407 CrossRefGoogle Scholar
  14. Iannitti T, Bingöl AÖ, Rottigni V, Palmieri B (2013) A new highly viscoelastic hyaluronic acid gel: rheological properties, biocompatibility and clinical investigation in esthetic and restorative surgery. Int J Pharm 456:583–592. doi: 10.1016/j.ijpharm.2013.06.066 CrossRefGoogle Scholar
  15. Iannitti T, Rottigni V, Torricelli F, Palmieri B (2014) Combination therapy of hyaluronic acid mesotherapic injections and sclerotherapy for treatment of lower leg telangiectasia without major venous insufficiency: a preliminary clinical study. Clin Appl Thromb Hemost 20:326–330. doi: 10.1177/1076029612461844 CrossRefGoogle Scholar
  16. Ilyin SO (2015) Non-linearity in rheological properties of polymers and composites under large amplitude oscillatory shear. Polym Sci Ser A 57:910–923. doi: 10.1134/S0965545X15060103 CrossRefGoogle Scholar
  17. Ilyin S, Roumyantseva T, Spiridonova V, Semakov A, Frenkin E, Malkin A, Kulichikhin V (2011) Gels of cysteine/Ag-based dilute colloid systems and their rheological properties. Soft Matter 7:9090–9103. doi: 10.1039/C1SM06007D CrossRefGoogle Scholar
  18. Ilyin S, Kulichikhin V, Malkin A (2014) Characterization of material viscoelasticity at large deformations. Appl Rheol 24:13653. doi: 10.3933/ApplRheol-24-13653 Google Scholar
  19. Kablik J, Monheit GD, Yu L, Chang G, Gershkovich J (2009) Comparative physical properties of hyaluronic acid dermal fillers. Dermatol Surg 35:302–312. doi: 10.1111/j.1524-4725.2008.01046.x CrossRefGoogle Scholar
  20. La Gatta A, Schiraldi C, Papa A, De Rosa M (2011) Comparative analysis of commercial dermal fillers based on crosslinked hyaluronan: physical characterization and in vitro enzymatic degradation. Polym Degrad Stabil 96:630–636. doi: 10.1016/j.polymdegradstab.2010.12.025 CrossRefGoogle Scholar
  21. Littara A, Palmieri B, Rottigni V, Iannitti T (2013) A clinical study to assess the effectiveness of a hyaluronic acid-based procedure for treatment of premature ejaculation. Int J Impot Res 25:117–120. doi: 10.1038/ijir.2013.13 CrossRefGoogle Scholar
  22. Malkin A, Ilyin S, Roumyantseva T, Kulichikhin V (2013) Rheological evidence of gel formation in dilute poly(acrylonitrile) solutions. Macromolecules 46:257–266. doi: 10.1021/ma301423u CrossRefGoogle Scholar
  23. Monheit GD, Coleman KM (2006) Hyaluronic acid fillers. Derm Ther 19:141–150. doi: 10.1111/j.1529-8019.2006.00068.x CrossRefGoogle Scholar
  24. Nast A, Reytan N, Hartmann V, Pathirana D, Bachmann F, Erdmann R, Rzany B (2011) Efficacy and durability of two hyaluronic acid–based fillers in the correction of nasolabial folds: results of a prospective, randomized, double-blind, actively controlled clinical pilot study. Dermatol Surg 37:768–775. doi: 10.1111/j.1524-4725.2011.01993.x Google Scholar
  25. Öhrlund JÅ, Edsman KL (2014) The myth of the “biphasic” hyaluronic acid filler. Dermatol Surg 41:S358–S364. doi: 10.1097/DSS.0000000000000545 CrossRefGoogle Scholar
  26. Park KY, Kim HK, Kim BJ (2014) Comparative study of hyaluronic acid fillers by in vitro and in vivo testing. J Eur Acad Dermatol Venereol 28:565–568. doi: 10.1111/jdv.12135 CrossRefGoogle Scholar
  27. Pierre S, Liew S, Bernardin A (2015) Basics of dermal filler rheology. Dermatol Surg 41:S120–S126. doi: 10.1097/DSS.0000000000000334 CrossRefGoogle Scholar
  28. Ramos-e-Silva М, Fonteles LA, Lagalhard CSX, Fucci-da-Costa APC (2013) STYLAGE®: a range of hyaluronic acid dermal fillers containing mannitol. Phys Prop Rev Lit Clin Cosmet Investig Dermatol 6:257–261. doi: 10.2147/CCID.S35251 CrossRefGoogle Scholar
  29. Shramm C, Spitzer MS, Henke-Fahle S, Steinmetz G, Januschowski K, Heiduschka P, Geis-Gerstorfer J, Biedermann T, Bartz-Schmidt KU, Szurman P (2012) The cross-linked biopolymer hyaluronic acid as an artificial vitreous substitute. Invest Ophthalmol Vis Sci 53:613–621. doi: 10.1167/iovs.11-7322 CrossRefGoogle Scholar
  30. Tezel A, Fredrickson GH (2008) The science of hyaluronic acid dermal fillers. J Cosmet Laser Ther 10:35–42. doi: 10.1080/14764170701774901 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Sergey O. Ilyin
    • 1
  • Valery G. Kulichikhin
    • 1
  • Alexander Ya. Malkin
    • 1
  1. 1.A.V. Topchiev Institute of Petrochemical SynthesisRussian Academy of SciencesMoscowRussia

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