Abstract
Hyaluronic acid hydrogels (HAHs) were synthesized by immersing HA microbeads crosslinked with divinyl sulfone in a phosphate buffered saline solution to evaluate the biocompatibility of the gels by means of cytotoxicity, genotoxicity (in vitro chromosome aberration test, reverse mutation assay, and in vivo micronucleus test), skin sensitization, and intradermal reactivity. The HAHs induced no cytotoxicity or genotoxicity. In guinea pigs treated with grafts and prostheses, no animals died and there were no abnormal clinical signs. The sensitization scores were zero in all guinea pigs after 24 h and 48 h challenge, suggesting that the HAHs had no contact allergic sensitization in the guinea pig maximization test. No abnormal signs were found in New Zealand White rabbits during the 72 h observation period after the injection. There was no difference between the HAHs and negative control mean scores because skin reaction such as erythema or oedema was not observed after injection. Experimental results suggest that the HAHs would be suitable for soft tissue augmentation due to the absence of cytotoxicity, genotoxicity, skin sensitization, and intradermal reactivity.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
G. D. Monheit and K. M. Comeman, Dermatol. Therapy 19, 141 (2006).
R. S. Narins, F. Brandt, J. Leyden, and Z. P. Lorene, Dermatol. Surg. 29, 588 (2003).
S. Fernandez-Cossio and M. T. Castano-Oreja, Plast. Reconstr. Surg. 117, 1789 (2006).
A. Pourjavadi and M. Kurdtabar, Eur. Polym. J. 43, 877 (2007).
Y. Hong, H. Song, Y. Gong, Z. Mao, C. Gao, and J. Shen, Acta Biomater. 3, 23 (2007).
P. A. Ramires, M. A. Miccoli, L. Dini, and C. Protopapa, J. Biomed. Mater. Res. Part B:Appl. Biomater. 72B, 230 (2005).
H. Omidian, J. G. Rocca, and K. Park, J. Control. Release 102, 3 (2005).
J. T. Kim, D. Y. Lee, and J. H. Choi, Biomater. Res. 14, 157 (2010).
D. H. Shin, S. S. Chun, M. W. Ahn, I. H. Song, and S. K. Kim, Korean J. Met. Mater. 50, 338 (2012).
S. K. Kim and V. H. Pham, Korean J. Met. Mater. 51, 907 (2013).
J. Kopecek and J. Yang, Polymer Int. 56, 1078 (2007).
A. C. Jen, M. C. Wake, and A. G. Mikos, Biotech, Bioeng. 50, 357 (1996).
W. E. Hennink and C. F. Van Nostrum, Adv. Drug Deliver. Rev. 54, 13 (2002).
A. S. Hoffman, Adv. Drug Deliver. Rev. 54, 3 (2002).
J. T. Kim, D. Y. Lee, and J. H. Choi, Biomater. Res. 15, 125 (2011).
ISO 10993-3:2003, Biological evaluation of medical devices-Part3: Tests for genotoxicity, carcinogenicity and reproductive toxicity.
OECD Guideline for the Testing of Chemicals TG No. 473, In vitro Mammalian Chromosome Aberration Test (1997).
OECD Guideline for the Testing of Chemicals TG No. 471, Genetic Toxicology: Salmonella typhimurium, Reverse Mutation Assay (1997).
OECD Guideline for the Testing of Chemicals TG No. 472, Genetic Toxicology: Escherichia coli, Reverse Mutation Assay (1997).
D. M. Maron and B. N. Ames, Revised methods of the Salmonella Mutagenicity Test. Mutat. Res. 113, 173 (1983).
OECD Guideline for the Testing of Chemicals TG No. 474, Genetic Toxicology: Micronucleus Test.
ISO 10993-10:2002, Biological evaluation of medical devices-Part10: Tests for irritation and delayed-type hypersensitivity: Maximization test for delayed hypersensitivity.
ISO 10993-10:2002, Biological evaluation of medical devices-Part10: Tests for irritation and delayed-type hypersensitivity: Intracutaneous (intradermal) reactivity test.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kim, JT., Lee, D.Y., Kim, TH. et al. Biocompatibility of hyaluronic acid hydrogels prepared by porous hyaluronic acid microbeads. Met. Mater. Int. 20, 555–563 (2014). https://doi.org/10.1007/s12540-014-3022-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12540-014-3022-5