丁二酸淫羊藿苷單酯的制備及其在骨和軟骨組織工程中的應(yīng)用
發(fā)布時間:2018-05-25 04:40
本文選題:丁二酸淫羊藿苷單酯殼聚糖羥基磷灰石透明質(zhì)酸組織工程支架 + ; 參考:《成都理工大學(xué)》2017年碩士論文
【摘要】:目前,作為組織生長的促進(jìn)劑,生長因子存在價格昂貴,易于失活及潛在的免疫原性等缺點,選用性質(zhì)更為穩(wěn)定的細(xì)胞生長調(diào)節(jié)因子來替代生長因子成為當(dāng)下研究的熱點。淫羊藿苷是一種具有良好的促進(jìn)成骨和成軟骨效用的小分子化合物,本文將淫羊藿苷(Ica)共價引入殼聚糖(CHS),再分別與羥基磷灰石(HAp)和透明質(zhì)酸(HA)復(fù)合構(gòu)建組織工程支架,期望構(gòu)建長效的骨和軟骨組織工程支架。主要研究內(nèi)容及結(jié)果有:(1)通過丁二酸酐(SA)和Ica的酯化反應(yīng),得到活性羧基取代度約為2.5的丁二酸淫羊藿苷單酯(Ica-SA)。(2)通過CHS和Ica-SA酰胺化反應(yīng),制備Ica-SA共價修飾殼聚糖(Ica-CHS),考察Ica-CHS的載藥量和藥物釋放,并進(jìn)一步考察了酰胺化縮合劑1-(3-二甲氨基丙基)-3-乙基碳二亞胺鹽酸鹽(EDCI)和N-羥基琥珀酰亞胺(NHS)對CHS成膠性能的影響。結(jié)果表明:Ica-CHS載藥量為3.6%,通過酰胺鍵和酯鍵斷裂持續(xù)緩慢地釋放藥物;縮合劑的引入使得殼聚糖交聯(lián)形成抗酸溶解的水凝膠。(3)通過CHS在EDCI和NHS作用下的凝膠化反應(yīng),將Ica-CHS與羥基磷灰石(HAp)復(fù)合制備Ica-CHS/HAp支架,該支架可持續(xù)穩(wěn)定地釋放藥物,并促進(jìn)BMSCs增殖和成骨分化。(4)將Ica-CHS與酸性粘多糖透明質(zhì)酸(HA)復(fù)合制備Ica-CHS/HA支架,該復(fù)合支架能以較穩(wěn)定的濃度水平緩慢釋放藥物,細(xì)胞實驗顯示Ica-CHS/HA支架有利于軟骨細(xì)胞的增殖和軟骨細(xì)胞表型的維持。結(jié)果證明,Ica-CHS/HAp支架和Ica-CHS/HA支架有望成為較理想的骨和軟骨組織工程支架。
[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.
【學(xué)位授予單位】:成都理工大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:TQ460.6;R318.08
【參考文獻(xiàn)】
相關(guān)期刊論文 前10條
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