【作者】 毋中明； 张新歌； 张绍敏； 董荣娜； 李朝兴； 于德民；

【Author】 Wu Zhong-ming;Zhang Xinge;Zhang Shao-min;Dong Rong-na;Li Chao-xing;Yu De-min;Metabolic Diseases Hospital,Key Lab of Hormones and Development,Ministry of Health China.Tianjin Medical University;The Key Laboratory of Functional Polymer Materials of Ministry Education,Institute of Polymer Chemistry,Nankai University;

【机构】 天津医科大学代谢病医院,卫生部激素与发育重点实验室； 南开大学高分子化学研究所,功能高分子材料教育部重点实验室；

【摘要】 目的:本研究采用一种新型的生理相容性策略制备壳聚糖水凝胶,通过控制其交联的密度和性质以寻找适合种子细胞生长的支架材料,为构建治疗糖尿病足溃疡的组织工程皮肤奠定基础。方法:本研究通过使用N-乙酰-L-半胱氨酸（NCS）对生物可降解壳聚糖修饰得到巯基化壳聚糖（CSSH）,将此聚合物溶液在空气中氧化生成二硫键水凝胶（CSS-S）;并对该水凝胶的结构、形态、溶胀性、热稳定性、流变学性能进行表征,进一步评价其作为细胞支架材料的生物相容性及其细胞黏附性能。结果:CSSH在pH 7.4通过空气氧化便可生成CSS-S,经冷冻干燥后扫描电镜观察具有均匀的多孔网络结构,孔径在10₂0_m之间;该水凝胶材料具有良好溶胀性、稳定不易解离,与巯基化壳聚糖中巯基含量无明显关系;流变学性能显示,水凝胶的交联密度和弹性与制备水凝胶的CSSH中巯基含量呈正相关关系;与壳聚糖相比,该水凝胶材料具有良好的热稳定和生物相容性;NIH 3T3细胞能很好在该水凝胶材料网络空间结构黏附生长。结论:本研究所制备的CSS-S水凝胶作为一种具有良好生物相容性和生物可降解的功能材料,有望应用于治疗糖尿病足溃疡的组织工程皮肤构建。更多还原

【Abstract】 Objective:A new disulfide cross-linking method was developed for the preparation of chitosan hydrogels(CSS-S) to form a synthetic,covalently linked mimic of the extracellular matrix(ECM) for application in the diabetic foot ulcers.Methods:N-acetyl-L-cysteine was coupled to chitosan with carbodiimide chemistry.The pendant thiol groups of polymer could be oxidized in air to reform disulfide linkages to form gel.Moreover,the suitability of the hydrogel as a novel injectable cellular scaffold for tissue regeneration is demonstrated by a preliminary investigation of gelation time,mechanical and thermal stability and swelling properties of the hydrogels,and in vitro cell compatibility on NIH-3T3 cells,and cell culture on the hydrogels are evaluated.Results:Disulfide crosslinked chitosan hydrogel exhibited rapidly swelling at 30 min,but the swelling ratio decreased with delaying the incubated time.Thermogravimetric analysis showed disulfide crosslinked chitosan hydrogel possessed the thermal stabilities of hydrogels.Rheological studies showed that the cross-linking density and elasticity of hydrogel has a correlation to the contents of free thiol on CSSH copolymer.The cultured NIH 3T3 cell viability and cell adhesion were confirmed by culture tests.The obtained hydrogel,due to its swelling,the thermal stabilities,elasticity and enzymatic degradability,together with cell adhesion and compatibility,could be potentially useful for tissue engineering.Conclusion:These results demonstrate that disulfide-crosslinked chitosan hydrogels,a new type of covalent synthetic ECM,constitute biocompatible and biodegradable substrate for application of scaffold materials of tissue-engineered skin.更多还原