本文關(guān)鍵詞：雙緩釋藥物支架的制備及其生物學(xué)評價　出處：《西南交通大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 陶瓷 多孔材料 殼聚糖微球 聚(乳酸 羥基乙酸)微球 雙緩釋藥物支架

【摘要】：在骨組織工程中,支架材料扮演著重要的角色,它不僅為細(xì)胞的增殖、黏附和細(xì)胞外基質(zhì)的沉積提供生長模板,還可以引導(dǎo)組織的再生和血管化。但是單純利用生物材料自身組分來調(diào)控細(xì)胞的行為和促進組織再生,其效果是有限的。目前,將促進骨生長的藥物與多孔支架結(jié)合是加速骨組織生長的理想方法。但是簡單地將支架浸泡在藥物中,會導(dǎo)致藥物釋放過快、釋放時間短、局部藥物濃度過高等后果,不能有效地加速骨愈合。研究表明將藥物緩釋體系和支架結(jié)合構(gòu)建藥物緩釋支架能在局部保持長效而穩(wěn)定的藥物釋放,促進成骨細(xì)胞的生長,加速骨修復(fù)。然而目前的研究主要集中在多孔支架與單一藥物緩釋體系的結(jié)合,在骨修復(fù)過程只能提供一種藥效,不能滿足臨床上復(fù)雜的要求。因此,多孔支架與多級藥物緩釋體系提供多種藥效協(xié)同促進骨組織生長被認(rèn)為是一個新方向。本文采用模板浸出法制備了具有優(yōu)良貫通性的羥基磷灰石(HA)支架;分別采用化學(xué)交聯(lián)法和雙乳液/溶劑揮發(fā)法制備載丹酚酸B(Sal-B)的殼聚糖微球(Sal B-CS微球)和載地塞米松(dex)的聚(乳酸,羥基乙酸)微球(dex-PLGA微球)。通過靜電相互作用將Sal B-CS和dex-PLGA微球依次固定在預(yù)先涂覆海藻酸鹽的多孔HA支架上,干燥后獲得雙緩釋藥物支架(al-HAs/Sal B-CS/dex-PLGA支架)。本文研究了 al-HAs/SalB-CS/dex-PLGA支架的機械性能和對細(xì)胞生長的影響,主要結(jié)果如下:(1)Sal B-CS和dex-PLGA微球均為球形,且具有光滑的表面。Sal B-CS和dex-PLGA微球的平均粒徑分別為27μm、7μm。(2)Sal B-CS和dex-PLGA微球成功地固定在表面涂覆海藻酸鈉的多孔HA支架上,且載Sal B-CS微球均勻并穩(wěn)定地分布在支架表面,dex-PLGA微球圍繞在Sal B-CS微球周圍。(3)制備長徑比為3:2的長支架用于力學(xué)實驗,測定幾組不同支架的抗壓強度和孔隙率結(jié)果發(fā)現(xiàn):隨著海藻酸鹽進入支架表面微孔,HA支架的抗壓強度從1.06 MPa增強至1.55 MPa。此外,隨著微球與HA支架的結(jié)合,支架的孔隙率降低,但都高于70%,滿足臨床上對于骨修復(fù)支架的要求。(4)體外動力學(xué)實驗結(jié)果表明:與Sal B-CS和dex-PLGA微球相比,al-HAs/SalB-CS/dex-PLGA支架的初期藥物突釋量較低。在30天內(nèi),al-HAs/Sal B-CS/dex-PLGA支架培養(yǎng)液的pH值基本保持7.4不變。(5)用支架浸提液培養(yǎng)成骨細(xì)胞,結(jié)果表明幾組支架均無細(xì)胞毒性,具有良好的生物相容性。在幾種多孔支架表面培養(yǎng)成骨細(xì)胞發(fā)現(xiàn)大量成骨細(xì)胞粘附在支架表面。成骨細(xì)胞增殖實驗顯示:al-HAs/Sal B-CS/dex-PLGA支架比HA裸支架更利于成骨細(xì)胞的生長。炎性因子表達實驗表明,雙緩釋藥物支架下調(diào)IL-6的表達量;ALP表達實驗顯示,al-HAs/Sal B-CS/dex-PLGA支架能夠促進BMSCs向成骨細(xì)胞分化。
[Abstract]:Scaffolds play an important role in bone tissue engineering. They not only provide growth templates for cell proliferation, adhesion and deposition of extracellular matrix. It can also lead to tissue regeneration and vascularization. However, the effects of regulating cell behavior and promoting tissue regeneration by using biomaterial components alone are limited. The combination of bone growth-promoting drugs with porous scaffolds is an ideal way to accelerate bone tissue growth. But simply immersing the scaffolds in drugs can lead to drug release too fast and the release time is short. Local drug concentration too high can not effectively accelerate bone healing. Studies have shown that the combination of drug delivery system and stent can maintain long-term and stable drug release. Promote the growth of osteoblasts, accelerate bone repair. However, the current research focuses on the combination of porous scaffolds with a single drug delivery system, which can only provide one drug effect in the bone repair process. Can't meet complex clinical requirements. It is considered a new direction that porous scaffolds and multistage drug delivery systems provide synergistic effects to promote bone tissue growth. In this paper, hydroxyapatite (HA) scaffolds with excellent transfixibility were prepared by template leaching. Poly (lactic acid) was prepared by chemical crosslinking method and double emulsion / solvent volatilization method for preparation of chitosan microspheres carrying Salvianolic acid (Bal Sal-B) and dexamethasone (dexamethasone). Sal B-CS and dex-PLGA microspheres were sequentially immobilized on porous HA scaffolds coated with alginate by electrostatic interaction. Double sustained-release drug stents were obtained after drying. (alHAs-Sal B-CS-dex-PLGA stents). The mechanical properties of al-HAs/SalB-CS/dex-PLGA scaffold and its effect on cell growth were studied. The main results are as follows: Sal B-CS and dex-PLGA microspheres are spherical. The average particle size of Sal B-CS and dex-PLGA microspheres with smooth surface is 27 渭 m, respectively. Sal B-CS and dex-PLGA microspheres were successfully immobilized on porous HA scaffolds coated with sodium alginate. The Sal B-CS microspheres are uniformly and stably distributed on the surface of the scaffold. Dex-PLGA microspheres were surrounded by Sal B-CS microspheres. (3: 2) long scaffolds with aspect ratio of 3: 2 were prepared for mechanical experiments. The results showed that the compressive strength of HA scaffold increased from 1.06 MPa to 1.55 MPA with alginate entering the surface of the scaffold. With the combination of microspheres and HA scaffolds, the porosity of the scaffolds decreased, but were higher than 70%. To meet the clinical requirements for bone repair scaffolds. 4) the results of in vitro kinetic experiments showed that: compared with Sal B-CS and dex-PLGA microspheres. The initial drug release of al-HAs/SalB-CS/dex-PLGA stent was relatively low and within 30 days. The pH value of al-HAs/Sal B-CSR / dex-PLGA scaffold culture medium remained basically unchanged at 7.4.) Osteoblasts were cultured with scaffold extract. The results showed that the scaffolds had no cytotoxicity. Osteoblasts cultured on several porous scaffolds were found to adhere to the scaffold surface. B-CSR dex-PLGA scaffolds were more conducive to osteoblast growth than HA bare scaffolds. The expression of IL-6 was down-regulated by double sustained-release drug stents. ALP expression assay showed that Sal B-CSP-PLGA scaffold could promote the differentiation of BMSCs into osteoblasts.
【學(xué)位授予單位】：西南交通大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R318.08

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