Skip to main content
Top
Published in: European Journal of Medical Research 1/2018

Open Access 01-12-2018 | Research

Standardized in vitro analysis of the degradability of hyaluronic acid fillers by hyaluronidase

Authors: Bettina Alexandra Buhren, Holger Schrumpf, Edwin Bölke, Kai Kammers, Peter Arne Gerber

Published in: European Journal of Medical Research | Issue 1/2018

Login to get access

Abstract

Background

Hyaluronidase is a hyaluronic acid (HA) metabolizing enzyme, which is approved as an adjuvant for infiltration anesthesia. The “off-label” use of hyaluronidase is regarded as gold standard for the management of HA-filler-associated complications. Yet, up to date there are only few studies that have systematically assessed the degradability of different HA-fillers by hyaluronidase.

Objective

To analyze the interactions of HA-fillers and hyaluronidase in a time-dependent manner using a novel standardized in vitro approach.

Methods

Comparable HA-fillers, Belotero Balance Lidocaine (BEL; Merz), Emervel classic (EMV; Galderma) and Juvederm Ultra 3 (JUV; Allergan), were incubated with a fluorescent dye and bovine hyaluronidase (HYAL; Hylase “Dessau”, Riemser) or control (NaCl) and monitored by time-lapse videomicroscopy. The degradation of HA-fillers was assessed as decrease in fluorescence intensity of HA-filler plus hyaluronidase vs. HA-filler plus control, quantified by computer-assisted image analysis (ImageJ).

Results

Hyaluronidase showed a significant degradation of the HA-fillers BEL and EMV. Degradation was measurable at 5 h (BEL) and 7 h (EMV), respectively; significance was reached at 14 h (BEL) and 13 h (EMV). No effect of hyaluronidase was observed for JUV.

Conclusion

Time-lapse microscopy enables systematically, standardized, comparative in vitro analyses of the interactions of hyaluronidase and HA-fillers.
Literature
1.
go back to reference Buhren BA, Schrumpf H, Hoff NP, Bolke E, Hilton S, Gerber PA. Hyaluronidase: from clinical applications to molecular and cellular mechanisms. Eur J Med Res. 2016;21:5.CrossRefPubMedPubMedCentral Buhren BA, Schrumpf H, Hoff NP, Bolke E, Hilton S, Gerber PA. Hyaluronidase: from clinical applications to molecular and cellular mechanisms. Eur J Med Res. 2016;21:5.CrossRefPubMedPubMedCentral
4.
go back to reference Meyer LJ, Stern R. Age-dependent changes of hyaluronan in human skin. J Invest Dermatol. 1994;102:385–9.CrossRefPubMed Meyer LJ, Stern R. Age-dependent changes of hyaluronan in human skin. J Invest Dermatol. 1994;102:385–9.CrossRefPubMed
5.
go back to reference Narins RS, Brandt FS, Dayan SH, Hornfeldt CS. Persistence of nasolabial fold correction with a hyaluronic acid dermal filler with retreatment: results of an 18-month extension study. Dermatol Surg. 2011;37:644–50.CrossRefPubMed Narins RS, Brandt FS, Dayan SH, Hornfeldt CS. Persistence of nasolabial fold correction with a hyaluronic acid dermal filler with retreatment: results of an 18-month extension study. Dermatol Surg. 2011;37:644–50.CrossRefPubMed
6.
go back to reference Narins RS, Coleman WP 3rd, Donofrio LM, et al. Improvement in nasolabial folds with a hyaluronic acid filler using a cohesive polydensified matrix technology: results from an 18-month open-label extension trial. Dermatol Surg. 2010;36(Suppl 3):1800–8.CrossRefPubMed Narins RS, Coleman WP 3rd, Donofrio LM, et al. Improvement in nasolabial folds with a hyaluronic acid filler using a cohesive polydensified matrix technology: results from an 18-month open-label extension trial. Dermatol Surg. 2010;36(Suppl 3):1800–8.CrossRefPubMed
7.
go back to reference Hilton S, Schrumpf H, Buhren BA, Bolke E, Gerber PA. Hyaluronidase injection for the treatment of eyelid edema: a retrospective analysis of 20 patients. Eur J Med Res. 2014;19:30.CrossRefPubMedPubMedCentral Hilton S, Schrumpf H, Buhren BA, Bolke E, Gerber PA. Hyaluronidase injection for the treatment of eyelid edema: a retrospective analysis of 20 patients. Eur J Med Res. 2014;19:30.CrossRefPubMedPubMedCentral
8.
go back to reference Hirsch RJ, Brody HJ, Carruthers JD. Hyaluronidase in the office: a necessity for every dermasurgeon that injects hyaluronic acid. J Cosmet Laser Ther. 2007;9:182–5.CrossRefPubMed Hirsch RJ, Brody HJ, Carruthers JD. Hyaluronidase in the office: a necessity for every dermasurgeon that injects hyaluronic acid. J Cosmet Laser Ther. 2007;9:182–5.CrossRefPubMed
9.
go back to reference Hirsch RJ, Cohen JL, Carruthers JD. Successful management of an unusual presentation of impending necrosis following a hyaluronic acid injection embolus and a proposed algorithm for management with hyaluronidase. Dermatol Surg. 2007;33:357–60.PubMed Hirsch RJ, Cohen JL, Carruthers JD. Successful management of an unusual presentation of impending necrosis following a hyaluronic acid injection embolus and a proposed algorithm for management with hyaluronidase. Dermatol Surg. 2007;33:357–60.PubMed
10.
go back to reference Kim DW, Yoon ES, Ji YH, Park SH, Lee BI, Dhong ES. Vascular complications of hyaluronic acid fillers and the role of hyaluronidase in management. J Plast Reconstr Aesthet Surg. 2011;64:1590–5.CrossRefPubMed Kim DW, Yoon ES, Ji YH, Park SH, Lee BI, Dhong ES. Vascular complications of hyaluronic acid fillers and the role of hyaluronidase in management. J Plast Reconstr Aesthet Surg. 2011;64:1590–5.CrossRefPubMed
11.
go back to reference Jahn K, Homey B. Gerber PA [Management of complications after aesthetic hyaluronic acid injections]. Hautarzt. 2014;65:851–3.CrossRefPubMed Jahn K, Homey B. Gerber PA [Management of complications after aesthetic hyaluronic acid injections]. Hautarzt. 2014;65:851–3.CrossRefPubMed
12.
go back to reference Jones D, Tezel A, Borrell M. In vitro resistance to degradation of hyaluronic acid dermal fillers by ovine testicular hyaluronidase. Dermatol Surg. 2010;36:804–9.CrossRef Jones D, Tezel A, Borrell M. In vitro resistance to degradation of hyaluronic acid dermal fillers by ovine testicular hyaluronidase. Dermatol Surg. 2010;36:804–9.CrossRef
13.
go back to reference Rao V, Chi S, Woodward J. Reversing facial fillers: interactions between hyaluronidase and commercially available hyaluronic-acid based fillers. J Drugs Dermatol. 2014;13:1053–6.PubMed Rao V, Chi S, Woodward J. Reversing facial fillers: interactions between hyaluronidase and commercially available hyaluronic-acid based fillers. J Drugs Dermatol. 2014;13:1053–6.PubMed
14.
go back to reference Juhasz MLW, Levin MK, Marmur ES. The kinetics of reversible hyaluronic acid filler injection treated with hyaluronidase. Dermatol Surg. 2017;43:841–7.CrossRefPubMed Juhasz MLW, Levin MK, Marmur ES. The kinetics of reversible hyaluronic acid filler injection treated with hyaluronidase. Dermatol Surg. 2017;43:841–7.CrossRefPubMed
15.
go back to reference Hwang E, Song YS. Quantitative correlation between hyaluronic acid filler and hyaluronidase. J Craniofac Surg. 2017;28:838–41.CrossRefPubMed Hwang E, Song YS. Quantitative correlation between hyaluronic acid filler and hyaluronidase. J Craniofac Surg. 2017;28:838–41.CrossRefPubMed
16.
go back to reference Sall I, Ferard G. Comparison of the sensitivity of 11 crosslinked hyaluronic acid gels to bovine testis hyaluronidase. Polym Degrad Stabil. 2007;92:915–9.CrossRef Sall I, Ferard G. Comparison of the sensitivity of 11 crosslinked hyaluronic acid gels to bovine testis hyaluronidase. Polym Degrad Stabil. 2007;92:915–9.CrossRef
17.
go back to reference Wang M, Li W, Zhang Y, Tian W, Wang H. Comparison of intra-arterial and subcutaneous testicular hyaluronidase injection treatments and the vascular complications of hyaluronic acid filler. Dermatol Surg. 2017;43:246–54.CrossRefPubMed Wang M, Li W, Zhang Y, Tian W, Wang H. Comparison of intra-arterial and subcutaneous testicular hyaluronidase injection treatments and the vascular complications of hyaluronic acid filler. Dermatol Surg. 2017;43:246–54.CrossRefPubMed
18.
go back to reference Menzinger S, Kaya A, Saurat JH, Kaya G. Injected hyaluronidase reduces the volume of exogenous hyaluronate fillers in mice and results in clinical improvement in a patient with pretibial myxedema. Dermatopathology (Basel). 2016;3:61–7.CrossRef Menzinger S, Kaya A, Saurat JH, Kaya G. Injected hyaluronidase reduces the volume of exogenous hyaluronate fillers in mice and results in clinical improvement in a patient with pretibial myxedema. Dermatopathology (Basel). 2016;3:61–7.CrossRef
19.
go back to reference Bohaumilitzky L, Huber AK, Stork EM, Wengert S, Woelfl F, Boehm H. A trickster in disguise: Hyaluronan’s ambivalent roles in the matrix. Front Oncol. 2017;7:242.CrossRefPubMedPubMedCentral Bohaumilitzky L, Huber AK, Stork EM, Wengert S, Woelfl F, Boehm H. A trickster in disguise: Hyaluronan’s ambivalent roles in the matrix. Front Oncol. 2017;7:242.CrossRefPubMedPubMedCentral
Metadata
Title
Standardized in vitro analysis of the degradability of hyaluronic acid fillers by hyaluronidase
Authors
Bettina Alexandra Buhren
Holger Schrumpf
Edwin Bölke
Kai Kammers
Peter Arne Gerber
Publication date
01-12-2018
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2018
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-018-0334-9

Other articles of this Issue 1/2018

European Journal of Medical Research 1/2018 Go to the issue