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

Abstract

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.

Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity

“…DVS is known to be toxic because of the reactivity of its vinyl groups [45,46], so its use implies a risk of toxicity if remnants of this molecule are not completely washed from the material. However, once reacted with the OH groups of the HA molecule these double bonds disappear, and, if non-reacted molecules are thoroughly removed, the resulting HA-DVS networks are devoid of inflammatory, pyrogenic or cytotoxic effects [47][48][49][50]. HA-based materials employed in clinic for several uses in humans contain HA-DVS networks and count with FDA approval [51,52].…”

Effect of pH on Swelling Property of Hyaluronic Acid Hydrogels for Smart Drug Delivery Systems

“…Since the hydrogels have structural similarities to body tissue, they can be used as biomaterial for defected tissue regeneration by replacing water with biological body fluid, cell, and/or medicine [1][2][3][4][5][6][7][8][9][10][11]. Recently, natural polymer hydrogels such as hyaluronic acid(HA), collagen, gelatin, fibrin, alginic acid, and chitosan are gaining tremendous attention in a wide variety of applications in medical, pharmaceutical and related fields [12][13][14][15][16].…”

“…Among natural polymers, the HA molecule is stabilized in order to produce a crosslinked gel suitable for soft tissue implantation, resulting in improving its resistance to enzymatic degradation within the dermis without compromising its biocompatibility [13]. Our previous studies revealed that porous polymer networks of the hydrogels are a prerequisite to tissue regeneration as a scaffold because of their good mechanical properties and cell proliferation [4,12,13,16].…”

“…Our previous studies revealed that porous polymer networks of the hydrogels are a prerequisite to tissue regeneration as a scaffold because of their good mechanical properties and cell proliferation [4,12,13,16]. HA is a linear polysaccharide formed from the disaccharide units of Dglucuronic acid and N-acetyl-glucosamine linked by (1,4) and (1,3) glucosidic bonds, as shown in Fig.…”

“…HA is a linear polysaccharide formed from the disaccharide units of Dglucuronic acid and N-acetyl-glucosamine linked by (1,4) and (1,3) glucosidic bonds, as shown in Fig. 1 [12,13,16,20,21]. Water-soluble polymers owe their solubility properties to the presence of functional groups(mainly OH, COOH, NH 2 ) [7].…”