丁二酸淫羊藿苷单酯的制备及其在骨和软骨组织工程中的应用

发布时间：2018-05-25 04:40

本文选题：丁二酸淫羊藿苷单酯壳聚糖羟基磷灰石透明质酸组织工程支架 + 　；参考：《成都理工大学》2017年硕士论文

【摘要】：目前,作为组织生长的促进剂,生长因子存在价格昂贵,易于失活及潜在的免疫原性等缺点,选用性质更为稳定的细胞生长调节因子来替代生长因子成为当下研究的热点。淫羊藿苷是一种具有良好的促进成骨和成软骨效用的小分子化合物,本文将淫羊藿苷(Ica)共价引入壳聚糖(CHS),再分别与羟基磷灰石(HAp)和透明质酸(HA)复合构建组织工程支架,期望构建长效的骨和软骨组织工程支架。主要研究内容及结果有:(1)通过丁二酸酐(SA)和Ica的酯化反应,得到活性羧基取代度约为2.5的丁二酸淫羊藿苷单酯(Ica-SA)。(2)通过CHS和Ica-SA酰胺化反应,制备Ica-SA共价修饰壳聚糖(Ica-CHS),考察Ica-CHS的载药量和药物释放,并进一步考察了酰胺化缩合剂1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDCI)和N-羟基琥珀酰亚胺(NHS)对CHS成胶性能的影响。结果表明:Ica-CHS载药量为3.6%,通过酰胺键和酯键断裂持续缓慢地释放药物;缩合剂的引入使得壳聚糖交联形成抗酸溶解的水凝胶。(3)通过CHS在EDCI和NHS作用下的凝胶化反应,将Ica-CHS与羟基磷灰石(HAp)复合制备Ica-CHS/HAp支架,该支架可持续稳定地释放药物,并促进BMSCs增殖和成骨分化。(4)将Ica-CHS与酸性粘多糖透明质酸(HA)复合制备Ica-CHS/HA支架,该复合支架能以较稳定的浓度水平缓慢释放药物,细胞实验显示Ica-CHS/HA支架有利于软骨细胞的增殖和软骨细胞表型的维持。结果证明,Ica-CHS/HAp支架和Ica-CHS/HA支架有望成为较理想的骨和软骨组织工程支架。
[Abstract]:At present, as a promoter of tissue growth, growth factors have the disadvantages of high price, easy inactivation and potential immunogenicity. Icariin is a small molecular compound with good osteogenic and chondrogenic effects. In this paper, Ica-icariin was covalently introduced into chitosan (CHS) and then combined with hydroxyapatite (HApa) and hyaluronic acid (HA) to construct tissue engineering scaffolds. A long-term scaffold for bone and cartilage tissue engineering is expected to be constructed. The main contents and results were as follows: (1) by the esterification of succinic anhydride (SA) with Ica, the active carboxyl monoester Ica-SAG with about 2.5 degree of substitution was obtained by CHS and Ica-SA amidation. Ica-SA covalent modified chitosan (Ica-CHS) was prepared to investigate the drug loading and drug release of Ica-CHS, and the effects of amidation reagents 1-N- (3-dimethylamino-propyl) -3-ethylcarbodiimide hydrochloride (EDCI) and N-hydroxysuccinimide (N-hydroxysuccinimide) on the gelation properties of CHS were further investigated. The results showed that the drug was loaded at 3.6% Ica-CHS and released slowly through the breaking of amide bond and ester bond, and the introduction of condensation agent made chitosan crosslinked to form an acid-resistant hydrogel, which was gelatinized by CHS under the action of EDCI and NHS. Ica-CHS was combined with hydroxyapatite apatite (HAP) to prepare Ica-CHS/HAp scaffold. The stents released drugs steadily and promoted BMSCs proliferation and osteogenic differentiation. 4) Ica-CHS was combined with acid mucopolysaccharide hyaluronic acid to prepare Ica-CHS/HA scaffold. The composite scaffold could release drugs slowly at a stable concentration level. Cell experiments showed that Ica-CHS/HA scaffolds were beneficial to the proliferation of chondrocytes and the maintenance of chondrocyte phenotypes. The results show that Ica-CHS / HAP and Ica-CHS/HA stents are expected to be ideal scaffolds for bone and cartilage tissue engineering.
【学位授予单位】：成都理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TQ460.6;R318.08

【参考文献】