酰肼交联透明质酸衍生物的生物相容性研究

The biocompatibility of the hyaluronan derivatives cross-linked by adipic dihydrazide

目的评价酰肼交联透明质酸衍生物(HA-ADH)的生物相容性。方法采用咔唑法测定HA-ADH在体外对透明质酸酶(HAse)的抗酶解性;HA-ADH植入大鼠皮下,间隔5d或10d处死,测定植入物重量,观察HA-ADH在体内的存留时间和局部刺激。结果体外酶降解实验结果表明,HAse的浓度与降解产物之间呈线性关系;HA-ADH在体外的抗酶解性与其交联度密切相关,交联度大的样品抗酶性强;HA-ADH在体内的降解曲线显示植入物降解速度先快后慢,植入样品在大鼠体内存留15d以上,交联度大的样品存留时间长;试验期间未发现局部刺激反应。结论HA-ADH具有抗酶解性和较好的生物相容性,是一种具有开发潜力的可降解性植入材料。

Objective To evaluate the biocompatibility of the hyaluronan derivatives cross-linked by adipic dihydrazide （HADH）. Methods The resistance to hyaluronidase （HAase） degradation of the derivatives of HA-ADH in vitro was measured by carbazole method. The derivatives of HA-ADH were implanted subcutaneously in rats and Weighed aider the rats were executed in batches aider or at an interval of 5 or 10 days. The turnover and its localirritation of the derivatives were examined, Results The result of in vitro degradation demonstrated a linear relationship between the concentration of HAase and the products of degradation. The resistance to HAase of the derivatives was correlated with its cross-linking degree intimately. The derivatives with high cross-linking degree was more resistant to enzymatic degradation than those with low cross-linking degree. The plot of in vivo degradation of the derivatives indicated the turnover rate of the implant was quick in the earlier period, then stepped down in the later period. The turnovers of all derivatives was over 15 days. The derivatives with high cross-linking degree were more persistent. No local stimulation on rats was observed during the experiment. Conclusion The derivatives of HA-ADH are resistant to enzymatic degradation and biocompatible. They have excellent potentials as degradable and implantable materials.