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醛基化透明质酸—聚天冬酰肼可注射原位交联型水凝胶的改性及应用

Detailed Characterization of an Injectable Hyluronic Acid-Polyaspartyl Hydrazide Hydrogel and Its Application

【作者】 刘敏

【导师】 谭天伟;

【作者基本信息】 北京化工大学 , 生物工程(专业学位), 2014, 硕士

【摘要】 生物医用材料(Biomedical materials)是指具有诊断治疗生物体中疾病或修复替代机体中组织器官的功能生物材料。透明质酸(Hyaluronic acid)是一种广泛存在于人体组织中的高分子聚合物,具有优良的粘弹性和生物相容性;聚氨基酸材料(Polyamino Acid)作为人工合成生物高分子的一种,在其的降解过程中,会随着主链的断裂释放出无毒无害的天然氨基酸组分。本文主要选用戊二醛和京尼平对醛基化透明质酸-聚天冬酰肼水凝胶(HAALD-PAHy hydrogel)进行改性。制备得到戊二醛改性后的水凝胶(HAALD-PAHy-GA)和京尼平改性后的水凝胶(HAALD-PAHy-GN),本文从成胶量、平衡溶胀比、流变性能及热性能等方面对两种水凝胶进行了综合考察。实验结果表明,通过调节加入戊二醛的量,能将水凝胶的弹性模量由2537Pa提高到3752Pa,而调节加入京尼平的量则能将弹性模量进一步提高到4859Pa。改性后水凝胶的三维网状结构也更加致密,通过改性成功提高了水凝胶的力学性能。本文利用水凝胶的三维网状结构,考察了水凝胶对大分子模型药物牛血清白蛋白(BSA)的控释情况,实验结果表明和HAALD-PAHy水凝胶类似,改性后的HAALD-PAHy-GA和HAALD-PAHy-GN两种水凝胶均具有对pH值和盐离子浓度的双重敏感性,能对BSA稳定持续的释放。最后本文还对HAALD-PAHy水凝胶进行了动物实验,验证其在泪点栓子上的应用,拓宽了水凝胶的应用领域。

【Abstract】 Biomedical Materials are a kind of biomaterials with the functions of disease diagnosis and treatment or tissues and organs replacement and repair. Hyaluronic acid (HA) is a polymer which is widely present in humanbody. HA has excellent viscoelasticity and biocompatibility. Poly-aspartic acid (PASP) is a synthetic biopolymer, whose main chain will be broke down into non-toxic and harmless natural amino acids during the degradation process.To improve the mechanical property of the hyaluronic acid-polyaspartic acid hydrazide hydrogel (HAALD-PAHy hydrogel), we added glutaraldehyde (GN) and Genipin (GN) into the HAALD-PAHy gel system. Then we got the hydrogels modified by glutaraldehyde (HAALD-PAHy-GA) and hydrogels modified by genipin (HAALD-PAHy-GN). Thereafter, crosslinked hydrogels were characterized by gel content, swelling ratio,rheological and thermal properties. Furthermore, the crosslinking degree of the hydrogels can be controlled by adjusting the concentration of GA or GN. Our results showed that the by adding GA or GN will increase the gel content. Scanning electronic microscopy (SEM) showed that the hydrogel exhibited smaller porous. The rheological analysis revealed that the storage modulus (G’) of the hydrogel was3752Pa and4859Pa, respectively.Subsequently, stimulation and sensitization experiments were done and the results proved the good biocompatibility of the hydrogel. Finally, this hydrogel system was injected into rabbit’s lacrimal ductules to investigate its effect of embolization. It took sodium fluorescein about20min to get from rabbit’s eyes to its nasal cavity at14days after the injection. These results suggest that our hydrogels can become promising material for lacrimal plugs.

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