Pyrogenicity of hyaluronic acid hydrogel crosslinked by divinyl sulfone for soft tissue augmentation

Abstract

Hyaluronic acid hydrogels (HAHs) were synthesized by immersing the microbeads in phosphate buffered saline solution to assess short term biocompatibility of the gels by means of the rabbit pyrogen test and the bacterial endotoxin test. The rise in body temperature of 3 male New Zealand white rabbits weighing about 2~3 kg (12~16 weeks old) following intravenous injection of the test article (10 mL/kg) was mo nitored at 30 min intervals in 3 h to examine the pyrogenicity. No rabbits showed an individual rise in temperature of 0.5oC or more above its respective control temperature. The temperature rises of the rabbits after injection were 0.12oC, 0.13oC, and 0.18oC, respectively, sugge sting that HAH meets the requirements for the absence of pyrogens. The bacterial endotoxin test revealed that the concentration of endoto xins required to cause the lysate to clot under standard conditions was < 0.125 EU/mL. Comparing the HAHs that was synthesized in this experiment to the ones approved by FDA, the amount of < 0.125 EU/mL endotoxins is relatively safe and effective. The test solution did not contain any interfering factors under the ex perimental conditions used. It is conceivable that the HAHs are likely to be suitable injectable dermal filler for facial soft tissue augmentation due to the absence of pyrogens