Institute of Chemistry Far Eastern Branch of the Russian Academy of Sciences , 159, prosp.100-letiya Vladivostoka , 690022 Vladivostok , Russia.
I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences , 20, S. Kovalevskoy str. , Yekaterinburg 620990 , Russia.
Biomacromolecules. 2019 Apr 8;20(4):1635-1643. doi: 10.1021/acs.biomac.8b01817. Epub 2019 Mar 1.
Here we show that the efficacy of the chitosan interaction with diglycidyl ethers of glycols significantly depends on pH and the nature of acid used to dissolve chitosan. In solutions of hydrochloric acid, cross-linking with diglycidyl ethers of ethylene glycol (EGDGE) and polyethylene glycol (PEGDGE) at room and subzero temperatures yields mechanically stable chitosan gels and cryogels, while in acetic acid solutions only weak chitosan gels can be formed under the same conditions. A combination of elemental analysis, FT-IR spectroscopy, and solid state C and N NMR spectroscopy was used to elucidate possible differences in the mechanism of chitosan cross-linking in alkaline and acidic media at room and subzero temperatures. We have proved that in acidic media diglycidyl ethers of glycols interacted with chitosan mainly via hydroxyl groups at the C6 position of the glucosamine unit. Besides, not only cross-linkages but also grafts were formed at room temperature. The cryo-concentration effect facilitates cross-linkages formation at -10 °C and, despite lower modification degrees compared to those of gels obtained at room temperature, supermacroporous chitosan cryogels with Young's moduli up to 90 kPa can be fabricated in one step. Investigations of chitosan cryogels biocompatibility in a mouse model have shown that a moderate inflammatory reaction around the implants is accompanied by formation of a normal granulation tissue. No toxic, immunosuppressive, and sensitizing effects on the recipient's tissues have been observed.
在这里，我们表明壳聚糖与二醇的缩水甘油醚的相互作用的功效显著依赖于 pH 值和用于溶解壳聚糖的酸的性质。在盐酸溶液中，在室温及亚低温下用乙二醇（EGDGE）和聚乙二醇（PEGDGE）的二缩水甘油醚交联，可以得到机械稳定的壳聚糖凝胶和冷冻凝胶，而在醋酸溶液中，只有在相同条件下才能形成弱的壳聚糖凝胶。采用元素分析、傅里叶变换红外光谱和固态 C 和 N 核磁共振光谱相结合的方法，阐明了在室温及亚低温碱性和酸性介质中壳聚糖交联的可能的机制差异。我们已经证明，在酸性介质中，二醇的缩水甘油醚主要通过氨基葡萄糖单元的 C6 位上的羟基与壳聚糖相互作用。此外，不仅形成了交联，而且在室温下也形成了接枝。在-10°C 时，冷冻浓缩效应有利于交联的形成，尽管与在室温下获得的凝胶相比，修饰程度较低，但仍可一步制备出杨氏模量高达 90kPa 的超大孔壳聚糖冷冻凝胶。对小鼠模型中壳聚糖冷冻凝胶生物相容性的研究表明，植入物周围存在适度的炎症反应，同时形成正常的肉芽组织。未观察到对受体组织的毒性、免疫抑制和致敏作用。
