生物医学工程学杂志

生物医学工程学杂志

超亲水性医用导管的制备及其动物体内组织相容性研究

查看全文

利用天然高分子葡聚糖(Dextran)和烯丙基异氰酸酯(AI)反应,首先合成了预聚物 Dex-AI,然后预聚物 Dex-AI 再与聚乙二醇二丙烯酸酯(PEGDA)反应,制备了具有良好亲水性和生物相容性的水凝胶(DP)。同时探索了反应物比例对最终产物的影响,结果是在 Dex-AI∶PEGDA 为 4∶6(质量比)时,所制得的水凝胶 DP 的吸水率最大,可达 810%。将此水凝胶接枝于经二苯甲酮在紫外光下处理的临床用导管表面,经静态和动态表面接触角测试,接枝有水凝胶的导管其表面亲水性显著提高,如静态表面接触角由水凝胶接枝前的(97 ± 6.1)° 下降到了接枝后的(25 ± 4.2)°。另一方面,以小鼠(ICR,30 只)为实验动物,将接枝前后的导管植入小鼠背部皮下,观察时间为 30 d。发现导管经 DP 接枝后,反映急性炎症情况的白细胞水平始终低于未接枝的样本;大体观察和组织学检测也发现,与未接枝的导管相比,在相同的时间点接枝 DP 的导管其炎性程度明显下降,导管与周边组织相容性提高。本研究证实了接枝水凝胶的技术可以提高目前临床用的 PE 导管的组织相容性,这对改善因治疗需要导管较长时间置留于体内而对患者带来的不良影响是非常有利的。

The biocompatible hydrogel was fabricated under suitable conditions with natural dextran and poly(ethylene glycol) (PEG) as the reaction materials. The oligomer (Dex-AI) was firstly synthesized with dextran and allylisocyanate (AI). This Dex-AI was then reacted with poly (ethyleneglycoldiacrylate) (PEGDA) under the mass ratio of 4∶6 to get hydrogel (DP) with the maximum water absorption of 810%. This hydrogel was grafted onto the surface of medical catheter via diphenyl ketone treatment under ultraviolet (UV) initiator. The surface contact angle became lower from (97 ± 6.1)° to (25 ± 4.2)° after the catheter surface was grafted with hydrogel DP, which suggests that the catheter possessed super hydrophilicity with hydrogel grafting. The in vivo evaluation after they were implanted into ICR rats subcutaneously verified that this catheter had less serious inflammation and possessed better histocompatibility comparing with the untreated medical catheter. Therefore, it could be concluded that hydrogel grafting is a good technology for patients to reduce inflammation due to catheter implantation, esp. for the case of retention in body for a relative long time.

关键词: 水凝胶; 医用导管; 亲水性; 组织相容性

Key words: hydrogel; medical catheter; hydrophilicity; histocompatibility

登录后 ,请手动点击刷新查看全文内容。 没有账号,
登录后 ,请手动点击刷新查看图表内容。 没有账号,
1. Salem S A, Hwei N M, Bin Saim A, et al. Polylactic-co-glycolic acid mesh coated with fibrin or collagen and biological adhesive substance as a prefabricated, degradable, biocompatible, and functional scaffold for regeneration of the urinary bladder wall. J Biomed Mater Res A, 2013, 101(8): 2237-2247.
2. Hoffman A S. Hydrogels for biomedical applications. Adv Drug Deliv Rev, 2012, 64(Suppl): 18-23.
3. 姚康德, 彭涛, 高伟, 等. 智能水凝胶. 高分子通报, 1994, (2): 103-111.
4. 卓仁禧, 张先正. 温度及 pH 敏感聚(丙烯酸)/聚(N-异丙基丙烯酰胺)互穿聚合物网络水凝胶的合成及性能研究. 高分子学报, 1998, (1): 39-42.
5. Sheridan M H, Shea L D, Peters M C, et al. Bioabsorbable polymer scaffolds for tissue engineering capable of sustained growth factor delivery. J Control Release, 2000, 64(1/3): 91-102.
6. Peppas N A, Hilt J Z, Khademhosseini A, et al. Hydrogels in biology and medicine: From molecular principles to bionanotechnology. Adv Mater, 2006, 18(11): 1345-1360.
7. Sun Guoming, Zhang Xianzheng, Chu C C. Formulation and characterization of chitosan-based hydrogel films having both temperature and pH sensitivity. J Mater Sci Mater Med, 2007, 18(8): 1563-1577.
8. Jeong B, Kim S W, Bae Y H. Thermosensitive sol-gel reversible hydrogels. Adv Drug Deliv Rev, 2002, 54(1): 37-51.
9. Li Jun, Li Xu, Ni Xiping, et al. Self-assembled supramolecular hydrogels formed by biodegradable PEO-PHB-PEO triblock copolymers and α-cyclodextrin for controlled drug delivery. Biomaterials, 2006, 27(4): 4132-4140.
10. Patel A, Mequanint K. Novel physically crosslinked polyurethane-block-poly(viny1 pyrrolidone)hydrogel biomaterials. Macromol Biosci, 2007, 7(5): 727-737.
11. Prabaharan M, Mano J F. Stimuli-responsive hydrogels based on polysaccharides incorporated with thermo-responsive polymers as novel biomaterials. Macromol Biosci, 2006, 6(12): 991-1008.
12. Kwon J S, Yoon S M, Kwon D Y, et al. Injectable in situ-forming hydrogel for cartilage tissue engineering. J Mater Chem B, 2013, 1(26): 3314-3321.
13. Kopecek J, Yang Jiyuan. Hydrogels as smart biomaterials. Polym Int, 2007, 56(9): 1078-1098.
14. Kopeček J, Yang Jiyuan. Smart self-assembled hybrid hydrogel biomaterials. Angew Chem Int Ed Engl, 2012, 51(30): 7396-7417.
15. Samchenko Y, Ulberg Z, Korotych O. Multipurpose smart hydrogel systems. Adv Colloid Interface Sci, 2011, 168(1/2): 247-262.
16. 侯雷, 徐择贤, 竺亚斌, 等. 水凝胶的制备及其在工程化组织和器官构建中的应用. 航天医学与医学工程, 2014, 27(4): 307-312.
17. Zhang Miao, Li Xunhu, Gong Yandao, et al. Properties and biocompatibility of chitosan films modified by blending with PEG. Biomaterials, 2002, 23(13): 2641-2648.
18. Muslim T, Morimoto M, Saimoto H, et al. Synthesis and bioactivities of poly(ethylene glycol)-chitosan hybrids. Carbohydr Polym, 2001, 46(4): 323-330.
19. Hu Ronggui, Zhai Qiwei, He Wenjun, et al. Bioactivities of ricin retained and its immunoreactivity to anti-ricin polyclonal antibodies alleviated through pegylation. Int J Biochem Cell Biol, 2002, 34(4): 396-402.
20. Lee M Y, Tsai W W, Chen H J, et al. Laser sintered porous polycaprolacone scaffolds loaded with hyaluronic acid and gelatin-grafted thermoresponsive hydrogel for cartilage tissue engineering. Biomed Mater Eng, 2013, 23(6): 533-543.
21. Sheu S Y, CHEN Wenshan, Sun J S, et al. Biological characterization of oxidized hyaluronic acid/resveratrol hydrogel for cartilage tissue engineering. J Biomed Mater Res A, 2013, 101(12): 3457-3466.
22. Balakrishnan B, Kumard D S, Yoshida Y, et al. Chemical modification of poly(vinyl chloride) resin using poly(ethylene glycol) to improve blood compatibility. Biomaterials, 2005, 26(17): 3495-3502.
23. Zhu A P, Zhang M, Shen J. Blood compatibility of chitosan/heparin complex surface modified ePTFE vascular grafy. Appl Surf Sci, 2005, 241(3/4): 485-492.
24. 吴人杰. 高聚物的表面与界面. 北京: 科学出版社, 1998: 173.
25. 刘贯一. 聚丙烯中空纤维膜表面亲水性改进试验. 河北理工学院学报, 2000, 11: 80-85.
26. Iwata H, Matsuda T. Preparation and properties of novel environment sensitive membranes prepared by graft polymerization onto a porous membrane. J Membr Sci, 1988, 38(2): 185-188.
27. 武衡, 王翔. 介入导管的表面改性研究进展. Sci Technol Inf, 2010, 10: 12-13.
28. 王传栋, 刘庆, 赵成如, 等. 介入导管的研究进展. 医学影像学杂志, 2003, (13): 682-686.
29. Kai Dan, Prabhakaran M P, Stahl B, et al. Mechanical properties and in vitro behavior of nanofiber-hydrogel composites for tissue engineering applications. Nanotechnology, 2012, 23(9): 095705.
30. Schlichting K E, Copeland-Johnson T M, Goodman M, et al. Synthesis of a novel photopolymerized nanocomposite hydrogel for treatment of acute mechanical damage to cartilage. Acta Biomater, 2011, 7(8): 3094-3100.