Hyaluronic acid hydrogels (HAHs) were synthesized by immersing the micro-beads in phosphate buffered saline solution to assess shortterm 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 monitored at 30 min intervals in 3 h to examine the pyrogenicity. No rabbits showed an individual rise in temperature of 0.5 o C or more above its respective control temperature. The temperature rises of the rabbits after injection were 0.12 o C, 0.13 o C, and 0.18 o C, respectively, suggesting that HAH meets the requirements for the absence of pyrogens. The bacterial endotoxin test revealed that the concentration of endotoxins 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 experimental 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.
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