中国组织工程研究 ›› 2012, Vol. 16 ›› Issue (51): 9600-9606.doi: 10.3969/j.issn.2095-4344.2012.51.019

• 药物控释材料 drug delivery materials • 上一篇    下一篇

温敏性羟丁基几丁糖凝胶防治猕猴脑脊液漏

周  霖1,魏长征2,侯春林1,林浩东1,刘  勇1   

  • 出版日期:2012-12-16 发布日期:2012-12-16

Prevention of cerebrospinal fluid leakage by using temperature-responsive hydroxybutyl chitosan

Zhou Lin1, Wei Chang-zheng2, Hou Chun-lin1, Lin Hao-dong1, Liu Yong1   

  • Online:2012-12-16 Published:2012-12-16

摘要:

背景:前期研究表明羟丁基几丁糖具有良好的生物相容性及极低的细胞毒性,同时具有良好的生物降解性。
目的:探讨羟丁基几丁糖凝胶防止术后脑脊液漏的可行性。
方法:首先利用流变仪和动态力学实验仪检测1.5%,2.0%,3.0%温敏性羟丁基几丁糖凝胶的力学强度及耐疲劳性质,同时测定各浓度温敏性羟丁基几丁糖的凝胶时间。将10只猕猴随机分为实验组与对照组,均制作脑脊液渗漏模型,实验组采用1.5%温敏性羟丁基几丁糖凝胶封堵,对照组未采用任何材料封堵。
结果与结论:1.5%温敏性羟丁基几丁糖的凝胶时间为(70±4) s,承受的最大压力为50.3-60.1 kPa,并且在疲劳实验和频率扫描实验中呈现出良好的稳定性;2.0%温敏性羟丁基几丁糖凝胶的凝胶时间为(45±3) s,承受的最大压力为70.6-122.5 kPa,在频率扫描中呈现了较好的稳定性;3.0%温敏性羟丁基几丁糖凝胶的凝胶时间为(26±2) s,承受的最大压力为77.8-104.7 kPa,频率扫描呈现了较好的稳定性。但后两者的疲劳实验未达实验要求。脑脊液渗漏封堵实验中,实验组封堵率为100%,对照组无封堵效果,表明1.5%温敏性羟丁基几丁糖凝胶可防止猕猴脑脊液漏。

Abstract:

BACKGROUND: Previous studies have showed that temperature-responsive hydroxybutyl chitosan has a good biocompatibility, extremely low toxicity, and good biodegradability.
OBJECTIVE: To evaluate the efficacy of a novel biomaterial, temperature-responsive hydroxybutyl chitosan, in the prevention of postoperative cerebrospinal fluid leakage.
METHODS: The basic mechanical properties of temperature-responsive hydroxybutyl chitosan at 1.5%, 2.0%, 3.0% were measured by rheometer and dynamic mechanical instrument, including gelation time, mechanical strength, and anti-fatigue property. Ten macaques were selected to prepare animal models of cerebrospinal fluid leakage, and then randomly divided into experimental and control groups. Temperature-responsive hydroxybutyl chitosan at 1.5% was used in the experimental group and nothing in the control group.
RESULTS AND CONCLUSION: The gelation time of temperature-responsive hydroxybutyl chitosan at 1.5% was (70±4) seconds, and the max sustainable pressure was 50.3-60.1 kPa, which showed excellent stability in the fatigue tests and frequency scanning. The gelation time of samples at 2% was (45±3) seconds, and the max sustainable pressure was 70.6-122.5 kPa, which failed to pass the fatigue test, but showed excellent stability in frequency scanning. The gelation time of temperature-responsive hydroxybutyl chitosan at 3% was (26±2) seconds, and the max sustainable pressure was 77.8-104.7 kPa. Likewise, the temperature-responsive hydroxybutyl chitosan at 3% with excellent stability in frequency scanning also failed to pass the fatigue test. The plugging rate was 100% in the experimental group, but 0 in the control group. Therefore, the temperature-responsive hydroxybutyl chitosan at 1.5% is most suitable for clinical application that confirmed by the animal studies of macaques in prevention of cerebrospinal fluid leakage.