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CC BY-NC-ND 4.0 · Facial Plast Surg 2022; 38(02): 116-123
DOI: 10.1055/s-0041-1741560
Original Article

Rheologic and Physicochemical Characteristics of Hyaluronic Acid Fillers: Overview and Relationship to Product Performance

Carola de la Guardia
1   Medical Affairs, Allergan Aesthetics, an AbbVie company, Marlow, United Kingdom of Great Britain and Northern Ireland
,
Ada Virno
2   Clinical Development, Allergan Aesthetics, an AbbVie company, Rome, Italy
,
Maria Musumeci
1   Medical Affairs, Allergan Aesthetics, an AbbVie company, Marlow, United Kingdom of Great Britain and Northern Ireland
,
Aude Bernardin
3   Allergan Aesthetics, an AbbVie company, Pringy, France
,
Michael B. Silberberg
1   Medical Affairs, Allergan Aesthetics, an AbbVie company, Marlow, United Kingdom of Great Britain and Northern Ireland
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Abstract

Injections with hyaluronic acid (HA) fillers for facial rejuvenation and soft-tissue augmentation are among the most popular aesthetic procedures worldwide. Many HA fillers are available with unique manufacturing processes and distinct in vitro physicochemical and rheologic properties, which result in important differences in the fillers' clinical performance. The aim of this paper is to provide an overview of the properties most widely used to characterize HA fillers and to report their rheologic and physicochemical values obtained using standardized methodology to allow scientifically based comparisons. Understanding rheologic and physicochemical properties will guide clinicians in aligning HA characteristics to the facial area being treated for optimal clinical performance.

Keywords

aesthetics - hyaluronic acid fillers - elastic modulus - rheology

Note

Medical writing and editorial assistance were provided to the authors by Mayuri Kerr, PhD of Allergan Aesthetics and Regina Kelly of Peloton Advantage, LLC, an OPEN Health company, and funded by Allergan Aesthetics. All authors met the ICMJE authorship criteria. No honoraria were paid for authorship.




Publication History

Article published online:
03 February 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 International Society of Aesthetic Plastic Surgery. ISAPS international survey on aesthetic/cosmetic procedures performed in 2019. 2020 Accessed October 14, 2021 at: https://www.isaps.org/wp-content/uploads/2020/12/Global-Survey-2019.pdf
    PubMedSearch in Google Scholar
  • 2 Humphrey S, Carruthers J, Carruthers A. Clinical experience with 11,460 mL of a 20-mg/mL, smooth, highly cohesive, viscous hyaluronic acid filler. Dermatol Surg 2015; 41 (09) 1060-1067
    CrossrefPubMedSearch in Google Scholar
  • 3 Philipp-Dormston WG, Bergfeld D, Sommer BM. et al. Consensus statement on prevention and management of adverse effects following rejuvenation procedures with hyaluronic acid-based fillers. J Eur Acad Dermatol Venereol 2017; 31 (07) 1088-1095
    CrossrefPubMedSearch in Google Scholar
  • 4 Snozzi P, van Loghem JAJ. Complication management following rejuvenation procedures with hyaluronic acid fillers—an algorithm-based approach. Plast Reconstr Surg Glob Open 2018; 6 (12) e2061
    CrossrefPubMedSearch in Google Scholar
  • 5 Matarasso SL. Understanding and using hyaluronic acid. Aesthet Surg J 2004; 24 (04) 361-364
    CrossrefPubMedSearch in Google Scholar
  • 6 Salwowska NM, Bebenek KA, Żądło DA, Wcisło-Dziadecka DL. Physiochemical properties and application of hyaluronic acid: a systematic review. J Cosmet Dermatol 2016; 15 (04) 520-526
    CrossrefPubMedSearch in Google Scholar
  • 7 Kablik J, Monheit GD, Yu L, Chang G, Gershkovich J. Comparative physical properties of hyaluronic acid dermal fillers. Dermatol Surg 2009; 35 (Suppl. 01) 302-312
    CrossrefPubMedSearch in Google Scholar
  • 8 Bacos JT, Dayan SH. Superficial dermal fillers with hyaluronic acid. Facial Plast Surg 2019; 35 (03) 219-223
    Thieme ConnectPubMedSearch in Google Scholar
  • 9 Faivre J, Gallet M, Tremblais E, Trévidic P, Bourdon F. Advanced concepts in rheology for the evaluation of hyaluronic acid-based soft tissue fillers. Dermatol Surg 2021; 47 (05) e159-e167
    CrossrefPubMedSearch in Google Scholar
  • 10 Edsman K, Nord LI, Ohrlund A, Lärkner H, Kenne AH. Gel properties of hyaluronic acid dermal fillers. Dermatol Surg 2012; 38 (7 Pt 2): 1170-1179
    CrossrefPubMedSearch in Google Scholar
  • 11 Fagien S, Bertucci V, von Grote E, Mashburn JH. Rheologic and physicochemical properties used to differentiate injectable hyaluronic acid filler products. Plast Reconstr Surg 2019; 143 (04) 707e-720e
    CrossrefPubMedSearch in Google Scholar
  • 12 Sundaram H, Cassuto D. Biophysical characteristics of hyaluronic acid soft-tissue fillers and their relevance to aesthetic applications. Plast Reconstr Surg 2013; 132 (4, suppl 2): 5S-21S
    CrossrefPubMedSearch in Google Scholar
  • 13 Hee CK, Shumate GT, Narurkar V, Bernardin A, Messina DJ. Rheological properties and in vivo performance characteristics of soft tissue fillers. Dermatol Surg 2015; 41 (Suppl. 01) S373-S381
    CrossrefPubMedSearch in Google Scholar
  • 14 Kapoor KM, Saputra DI, Porter CE. et al. Treating aging changes of facial anatomical layers with hyaluronic acid fillers. Clin Cosmet Investig Dermatol 2021; 14: 1105-1118
    CrossrefPubMedSearch in Google Scholar
  • 15 Michaud T. Rheology of hyaluronic acid and dynamic facial rejuvenation: topographical specificities. J Cosmet Dermatol 2018; 17 (05) 736-743
    CrossrefPubMedSearch in Google Scholar
  • 16 Edsman KL, Wiebensjö AM, Risberg AM, Öhrlund JA. Is there a method that can measure cohesivity? Cohesion by sensory evaluation compared with other test methods. Dermatol Surg 2015; 41 (Suppl. 01) S365-S372
    CrossrefPubMedSearch in Google Scholar
  • 17 Pierre S, Liew S, Bernardin A. Basics of dermal filler rheology. Dermatol Surg 2015; 41 (Suppl. 01) S120-S126
    CrossrefPubMedSearch in Google Scholar
  • 18 Heitmiller K, Ring C, Saedi N. Rheologic properties of soft tissue fillers and implications for clinical use. J Cosmet Dermatol 2021; 20 (01) 28-34
    CrossrefPubMedSearch in Google Scholar
  • 19 Goldman MP, Few J, Binauld S, Nuñez I, Hee CK, Bernardin A. Evaluation of physicochemical properties following syringe-to-syringe mixing of hyaluronic acid dermal fillers. Dermatol Surg 2020; 46 (12) 1606-1612
    CrossrefPubMedSearch in Google Scholar
  • 20 Lorenc ZP, Öhrlund Å, Edsman K. Factors affecting the rheological measurement of hyaluronic acid gel fillers. J Drugs Dermatol 2017; 16 (09) 876-882
    PubMedSearch in Google Scholar
  • 21 Micheels P, Besse S, Sarazin D, Obamba M. Hyaluronic acid gel based on CPM® technology with and without lidocaine: is there a difference?. J Cosmet Dermatol 2019; 18 (01) 36-44
    CrossrefPubMedSearch in Google Scholar
  • 22 Zerbinati N, Esposito C, Cipolla G. et al. Chemical and mechanical characterization of hyaluronic acid hydrogel cross-linked with polyethylene glycol and its use in dermatology. Dermatol Ther (Heidelb) 2020; 33 (04) e13747
    PubMedSearch in Google Scholar
  • 23 Sundaram H, Voigts B, Beer K, Meland M. Comparison of the rheological properties of viscosity and elasticity in two categories of soft tissue fillers: calcium hydroxylapatite and hyaluronic acid. Dermatol Surg 2010; 36 (Suppl. 03) 1859-1865
    CrossrefPubMedSearch in Google Scholar
  • 24 Falcone SJ, Berg RA. Temporary polysaccharide dermal fillers: a model for persistence based on physical properties. Dermatol Surg 2009; 35 (08) 1238-1243
    CrossrefPubMedSearch in Google Scholar
  • 25 Lee W, Hwang SG, Oh W, Kim CY, Lee JL, Yang EJ. Practical guidelines for hyaluronic acid soft-tissue filler use in facial rejuvenation. Dermatol Surg 2020; 46 (01) 41-49
    CrossrefPubMedSearch in Google Scholar
  • 26 Falcone SJ, Doerfler AM, Berg RA. Novel synthetic dermal fillers based on sodium carboxymethylcellulose: comparison with crosslinked hyaluronic acid-based dermal fillers. Dermatol Surg 2007; 33 (Suppl. 02) S136-S143 , discussion S143
    PubMedSearch in Google Scholar
  • 27 Lundgren B, Sandkvist U, Bordier N, Gauthier B. Using a new photo scale to compare product integration of different hyaluronan-based fillers after injection in human ex vivo skin. J Drugs Dermatol 2018; 17 (09) 982-986
    PubMedSearch in Google Scholar
  • 28 Gold M. The science and art of hyaluronic acid dermal filler use in esthetic applications. J Cosmet Dermatol 2009; 8 (04) 301-307
    CrossrefPubMedSearch in Google Scholar
  • 29 Dugaret AS, Bertino B, Gauthier B. et al. An innovative method to quantitate tissue integration of hyaluronic acid-based dermal fillers. Skin Res Technol 2018; 24 (03) 423-431
    CrossrefPubMedSearch in Google Scholar
  • 30 Stocks D, Sundaram H, Michaels J, Durrani MJ, Wortzman MS, Nelson DB. Rheological evaluation of the physical properties of hyaluronic acid dermal fillers. J Drugs Dermatol 2011; 10 (09) 974-980
    PubMedSearch in Google Scholar
  • 31 Carruthers J, Cohen SR, Joseph JH, Narins RS, Rubin M. The science and art of dermal fillers for soft-tissue augmentation. J Drugs Dermatol 2009; 8 (04) 335-350
    PubMedSearch in Google Scholar
  • 32 La Gatta A, Schiraldi C, Zaccaria G, Cassuto D. Hyaluronan dermal fillers: efforts towards a wider biophysical characterization and the correlation of the biophysical parameters to the clinical outcome. Clin Cosmet Investig Dermatol 2020; 13: 87-97
    CrossrefPubMedSearch in Google Scholar
  • 33 Sundaram H, Rohrich RJ, Liew S. et al. Cohesivity of hyaluronic acid fillers: development and clinical implications of a novel assay, pilot validation with a five-point grading scale, and evaluation of six U.S. Food and Drug Administration-approved fillers. Plast Reconstr Surg 2015; 136 (04) 678-686
    CrossrefPubMedSearch in Google Scholar
  • 34 Edsman KLM, Öhrlund Å. Cohesion of hyaluronic acid fillers: correlation between cohesion and other physicochemical properties. Dermatol Surg 2018; 44 (04) 557-562
    CrossrefPubMedSearch in Google Scholar
  • 35 Cho SY, Park JW, An H. et al. Physical properties of a novel small-particle hyaluronic acid filler: In vitro, in vivo, and clinical studies. J Cosmet Dermatol 2018; 17 (03) 347-354
    CrossrefPubMedSearch in Google Scholar
  • 36 Baek J, Fan Y, Jeong SH. et al. Facile strategy involving low-temperature chemical cross-linking to enhance the physical and biological properties of hyaluronic acid hydrogel. Carbohydr Polym 2018; 202: 545-553
    CrossrefPubMedSearch in Google Scholar
  • 37 Tezel A, Fredrickson GH. The science of hyaluronic acid dermal fillers. J Cosmet Laser Ther 2008; 10 (01) 35-42
    CrossrefPubMedSearch in Google Scholar
  • 38 Baumann LS, Weisberg EM, Mayans M, Arcuri E. Open label study evaluating efficacy, safety, and effects on perception of age after injectable 20 mg/mL hyaluronic acid gel for volumization of facial temples. J Drugs Dermatol 2019; 18 (01) 67-74
    PubMedSearch in Google Scholar
  • 39 Wollina U, Goldman A. Correction of tear trough deformity by hyaluronic acid soft tissue filler placement inferior to the lateral orbital thickening. Dermatol Ther (Heidelb) 2021; 34 (05) e15045
    PubMedSearch in Google Scholar
  • 40 Niforos F, Acquilla R, Ogilvie P. et al. A prospective, open-label study of hyaluronic acid-based filler with lidocaine (VYC-15L) treatment for the correction of infraorbital skin depressions. Dermatol Surg 2017; 43 (10) 1271-1280
    CrossrefPubMedSearch in Google Scholar
  • 41 Hevia O, Cohen BH, Howell DJ. Safety and efficacy of a cohesive polydensified matrix hyaluronic acid for the correction of infraorbital hollow: an observational study with results at 40 weeks. J Drugs Dermatol 2014; 13 (09) 1030-1036
    PubMedSearch in Google Scholar
  • 42 Bertossi D, Lanaro L, Dell'Acqua I, Albanese M, Malchiodi L, Nocini PF. Injectable profiloplasty: forehead, nose, lips, and chin filler treatment. J Cosmet Dermatol 2019; 18 (04) 976-984
    Search in Google Scholar
  • 43 Sharad J. Dermal fillers for the treatment of tear trough deformity: a review of anatomy, treatment techniques, and their outcomes. J Cutan Aesthet Surg 2012; 5 (04) 229-238
    CrossrefPubMedSearch in Google Scholar
  • 44 Jones D, Murphy DK. Volumizing hyaluronic acid filler for midface volume deficit: 2-year results from a pivotal single-blind randomized controlled study. Dermatol Surg 2013; 39 (11) 1602-1612
    CrossrefPubMedSearch in Google Scholar
  • 45 Kerscher M, Agsten K, Kravtsov M, Prager W. Effectiveness evaluation of two volumizing hyaluronic acid dermal fillers in a controlled, randomized, double-blind, split-face clinical study. Clin Cosmet Investig Dermatol 2017; 10: 239-247
    CrossrefPubMedSearch in Google Scholar
  • 46 Wilson AJ, Taglienti AJ, Chang CS, Low DW, Percec I. Current applications of facial volumization with fillers. Plast Reconstr Surg 2016; 137 (05) 872e-889e
    CrossrefPubMedSearch in Google Scholar
  • 47 Monheit G, Beer K, Hardas B. et al. Safety and effectiveness of the hyaluronic acid dermal filler VYC-17.5L for nasolabial folds: results of a randomized, controlled study. Dermatol Surg 2018; 44 (05) 670-678
    CrossrefPubMedSearch in Google Scholar
  • 48 Monheit G, Kaufman-Janette J, Joseph JH, Shamban A, Dover JS, Smith S. Efficacy and safety of two resilient hyaluronic acid fillers in the treatment of moderate-to-severe nasolabial folds: a 64-week, prospective, multicenter, controlled, randomized, double-blinded, and within-subject study. Dermatol Surg 2020; 46 (12) 1521-1529
    CrossrefPubMedSearch in Google Scholar
  • 49 Eccleston D, Murphy DK. Juvéderm(®) Volbella™ in the perioral area: a 12-month prospective, multicenter, open-label study. Clin Cosmet Investig Dermatol 2012; 5: 167-172
    PubMedSearch in Google Scholar
  • 50 Geronemus RG, Bank DE, Hardas B, Shamban A, Weichman BM, Murphy DK. Safety and effectiveness of VYC-15L, a hyaluronic acid filler for lip and perioral enhancement: one-year results from a randomized, controlled study. Dermatol Surg 2017; 43 (03) 396-404
    CrossrefPubMedSearch in Google Scholar
  • 51 Fischer TC, Sattler G, Gauglitz GG. Hyaluron filler containing lidocaine on a CPM basis for lip augmentation: reports from practical experience. Facial Plast Surg 2016; 32 (03) 283-288
    Thieme ConnectPubMedSearch in Google Scholar
  • 52 Wende FJ, Gohil S, Nord LI, Helander Kenne A, Sandström C. 1D NMR methods for determination of degree of cross-linking and BDDE substitution positions in HA hydrogels. Carbohydr Polym 2017; 157: 1525-1530
    CrossrefPubMedSearch in Google Scholar
  • 53 Niforos F, Ogilvie P, Cavallini M. et al. VYC-12 injectable gel is safe and effective for improvement of facial skin topography: a prospective study. Clin Cosmet Investig Dermatol 2019; 12: 791-798
    CrossrefPubMedSearch in Google Scholar
  • 54 Black JM, Gross TM, Murcia CL, Jones DH. Cohesive polydensified matrix hyaluronic acid for the treatment of etched-in fine facial lines: a 6-month, open-label clinical trial. Dermatol Surg 2018; 44 (07) 1002-1011
    CrossrefPubMedSearch in Google Scholar