强化交联促进透明质酸凝胶的抗酶解能力

Promote the Anti-Enzymatic Degradation Stability of Hyaluronic Acid Hydrogel Using Enhanced-Crosslinking

DOI：10.3969/j.issn.1673-1689.2019.07.003

中文关键词: 透明质酸凝胶 强化交联 酶解

英文关键词: hyaluronic acid hydrogel,enhanced-crosslinking,enzymatic degradation

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中文摘要:

为了强化透明质酸凝胶抗酶解能力，开发了初次交联-强化交联的偶联制备模式，并通过正交试验来确定最佳的交联条件。通过化学发光法测定透明质酸酶降解透明质酸凝胶后得到的产物，并由此计算凝胶的降解率。通过气相色谱法测定凝胶酸解后甘油含量并计算交联度。此外，检测了强化交联对透明质酸凝胶细胞毒性、遗传毒性以及溶血毒性的影响。结果表明，经过强化交联后（最优条件：35 ℃，0.05 mol/L NaOH，1.5 h，透明质酸单体/交联剂比例8∶1）。此后24、48、72 h降解率分别由初次交联后的9.76%、16.79%、20.45%到降低至强化交联后的6.85%、7.56%、12.4%；交联度由初次交联后的16.53%上升到强化交联后的54.52%。此外，强化交联后的凝胶在毒性检测中细胞毒性维持在1级，无明显致突变性，溶血度符合一般生物材料安全要求。

英文摘要:

To promote the anti-enzymatic degradation stability of hyaluronic acid hydrogel，an enhanced-crosslinking strategy was employed，and the most appropriate model was confirmed in orthogonal test. The degradation ratio was determined using a chromogenic reaction with released hyaluronic acid monomer. The cross-linking ration was calculated according to the content of glycerin detected with gas chromatography. In addition，the cytotoxicity，mutagenicity and hemolytic toxicity of the enhanced gel were also carefully checked. After an optimized strengthen cross-linking（35 ℃，0.05 mol/L NaOH，reaction for 1.5 h，BDDE/HA at 1∶8），the anti-enzymatic degradation stability was dramatically decreased compared that of first crosslinked gel；the degradation ratios were decreased from 9.76% to 6.85%，16.79% to 7.65% and 20.45% to 12.4% at 24，48 and 72 h respectively；and the crosslinking degree was increased from 16.53% to 54.52%. Additionally，after the enhanced-crosslinking，the cytotoxicity，mutagenicity and hemolytic toxicity of the gel were detected as in the safety scale of biomaterials.

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