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采用无溶剂法交联透明质酸水凝胶的合成与表征及其在潜在生物医学中的应用。

Synthesis and characterization of hyaluronic acid hydrogels crosslinked using a solvent-free process for potential biomedical applications.

机构信息

School of Pharmacy, Queens University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.

School of Pharmacy, Queens University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.

出版信息

Carbohydr Polym. 2018 Feb 1;181:1194-1205. doi: 10.1016/j.carbpol.2017.12.015. Epub 2017 Dec 7.

Abstract

Hyaluronic acid (HA) is a natural linear polysaccharide that has been used extensively in the biomedical field as it is a biocompatible, biodegradable, nontoxic and non-immunogenic polymer with high water affinity. Besides, the presence of multiple acid and hydroxyl groups in the HA molecule makes it an ideal candidate for chemical modification. The present paper describes the synthesis and characterization of HA-based hydrogels. For this purpose, aqueous mixtures containing 5% (w/w) of HA and different concentrations of Gantrez S97 (GAN) (1, 3 and 5% w/w) were used to prepare HA-based hydrogels. The mixtures were dried and the hydrogels were obtained after heating the solid material at 80°C for 24h. GAN is the acid form of an methylvinylether and maleic anhydride copolymer and contains multiple acid groups that can form ester bonds when reacting with the multiple hydroxyl groups present in HA chains. The method described here present potential to be applied for the preparation of HA-based biomaterials with a defined form as the crosslinking reaction between HA and the crosslinker takes place in solid phase. Besides, the method can be considered an environmental-friendly process as no organic solvents or potentially toxic substances were used. The esterification reaction was confirmed by infrared spectroscopy and dynamic scanning calorimetry measurements. The loading and release capabilities of the hydrogels were evaluating by using methylene blue (MB) as a model molecule. The hydrogels showed a high affinity for MB showing loadings up to 0.35mg MB per mg of hydrogel. Moreover, the hydrogels were capable of sustaining the MB release over two days. The use of microwave radiation was evaluated to reduce the crosslinking time from 24h to 1h, but this procedure needs to be optimized in future studies. As the crosslinking procedure takes place in solid state, the HA/GAN hydrogels were used to prepare micro-engineered device, microneedle arrays. Finally, the antimicrobial properties of the hydrogels were evaluated. The results showed that the hydrogels presented anti-infective properties.

摘要

透明质酸(HA)是一种天然线性多糖,由于其具有生物相容性、可生物降解、无毒和非免疫原性等特点,同时还具有高亲水性,因此已被广泛应用于生物医学领域。此外,HA 分子中存在多个酸和羟基,使其成为化学修饰的理想候选物。本文描述了基于 HA 的水凝胶的合成与表征。为此,使用含有 5%(w/w)HA 和不同浓度 Gantrez S97(GAN)(1、3 和 5% w/w)的水相混合物来制备基于 HA 的水凝胶。将混合物干燥,并将固体材料在 80°C 下加热 24h 后获得水凝胶。GAN 是甲基乙烯基醚和马来酸酐共聚物的酸形式,含有多个酸基,当与 HA 链中存在的多个羟基反应时,可以形成酯键。这里描述的方法具有潜在的应用前景,可以制备具有特定形状的基于 HA 的生物材料,因为 HA 与交联剂之间的交联反应发生在固相。此外,该方法可以被认为是一种环保的工艺,因为没有使用有机溶剂或潜在有毒物质。通过红外光谱和动态扫描量热法测量证实了酯化反应。通过使用亚甲蓝(MB)作为模型分子来评估水凝胶的负载和释放能力。水凝胶对 MB 具有高亲和力,表现出高达 0.35mg MB 每毫克水凝胶的负载量。此外,水凝胶能够在两天内持续释放 MB。评估了微波辐射的使用,以将交联时间从 24h 缩短至 1h,但在未来的研究中需要对此程序进行优化。由于交联过程发生在固态,因此使用 HA/GAN 水凝胶制备了微工程器件,即微针阵列。最后,评估了水凝胶的抗菌性能。结果表明,水凝胶具有抗感染性能。

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