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股骨頭壞死修復(fù)研究中可控釋淫羊藿苷-β-磷酸三鈣復(fù)合支架的制備

發(fā)布時(shí)間:2018-04-20 08:04

  本文選題:β-磷酸三鈣 + 淫羊藿苷; 參考:《南京中醫(yī)藥大學(xué)》2017年碩士論文


【摘要】:目的:評(píng)價(jià)淫羊藿苷-β-磷酸三鈣多孔復(fù)合支架的成型工藝,了解其力學(xué)及生物學(xué)性能,以驗(yàn)證淫羊藿苷-β-磷酸三鈣復(fù)合支架材料作為股骨頭壞死植入材料的可行性。方法:利用Solidworks建模軟件設(shè)計(jì)三維多孔支架模型,應(yīng)用擠出式3D打印機(jī)制作多孔β-磷酸三鈣支架胚體,經(jīng)干燥、燒結(jié)過(guò)程得到多孔β-磷酸三鈣支架成品。應(yīng)用掃描電子顯微鏡觀察其微觀結(jié)構(gòu),用阿基米德法測(cè)定孔隙率、吸水率,電子萬(wàn)能材料試驗(yàn)機(jī)測(cè)試其抗壓強(qiáng)度,并用X線衍射儀進(jìn)行物相分析;通過(guò)超聲乳化溶劑透析法制備含10-5M淫羊藿苷的聚乳酸-羥基乙酸共聚物/淫羊藿苷(PLGA/ICA)緩釋微球,將淫羊藿苷/N,N-二甲基甲酰胺(ICA/DMF)和N,N-二甲基甲酰胺/聚乳酸-羥基乙酸共聚物(DMF/PLGA)在冰浴中超聲條件下混合,然后將1%的聚乙烯醇溶液加入混合溶液中形成(O/W)復(fù)乳,將其置入透析袋中過(guò)夜以除去DMF,經(jīng)過(guò)離心、清洗、冷凍干燥可得ICA/PLGA緩釋微球;采用震蕩+離心灌注的方法將緩釋微球復(fù)合入多孔支架中,加入10%明膠后再次離心,經(jīng)冷凍干燥后即得到淫羊藿苷-β-磷酸三鈣復(fù)合支架;測(cè)定載藥微球的微觀結(jié)構(gòu)、載藥率、包封率,并進(jìn)行體外藥物緩釋實(shí)驗(yàn)。結(jié)果:用3D打印機(jī)制得的β-磷酸三鈣多孔支架外觀尺寸約為11mm× 11mm×6mm,孔隙間距為600μm,支架宏觀孔隙結(jié)構(gòu)規(guī)則,孔隙連通性良好。經(jīng)檢測(cè),多孔支架的孔隙率為(66.93±2.84)%。SEM觀察支架表面有較多微觀孔隙結(jié)構(gòu),微孔分布均勻,孔隙連通性較好。燒結(jié)前后β-TCP支架粉末的X線衍射分析結(jié)果顯示燒結(jié)前后無(wú)相轉(zhuǎn)變。對(duì)燒結(jié)后的β-TCP進(jìn)行抗壓性能測(cè)試,支架最大壓縮強(qiáng)度為(2.98±0.78)MPa,且加入納米ZnO,支架強(qiáng)度達(dá)到了(8.95±0.29)MPa,力學(xué)性能達(dá)到了松質(zhì)骨的抗壓強(qiáng)度。制得的ICA/PLGA緩釋微球,大體外觀結(jié)構(gòu)為淡黃色的粉末狀物質(zhì),掃描電鏡下觀察可見(jiàn)微球呈球形,粒徑約在1~4μm之間,在支架表面分布均勻,且多分布于支架微孔間隙。結(jié)論:制得的β-TCP支架為互聯(lián)多孔的結(jié)構(gòu)體,微觀孔隙結(jié)構(gòu)分布均勻,孔隙連通性好。力學(xué)性能能夠達(dá)到松質(zhì)骨的強(qiáng)度,可提供較好的力學(xué)支撐性能。支架可促進(jìn)細(xì)胞滿(mǎn)足細(xì)胞黏附、增殖及血管生成能力,以提高骨長(zhǎng)入。ICA/PLGA緩釋微球30天藥物累積釋放量達(dá)到60%,具有藥物緩釋的能力。制備的淫羊藿苷-β-磷酸三鈣復(fù)合支架可用于修復(fù)兔股骨頭壞死的研究。
[Abstract]:Aim: to evaluate the molding process of icariin-尾-tricalcium phosphate composite scaffold, to investigate its mechanical and biological properties, and to verify the feasibility of icariin-尾-tricalcium phosphate composite scaffold as implant material for osteonecrosis of the femoral head. Methods: the three-dimensional porous scaffold model was designed with Solidworks software, and the porous 尾 -tricalcium phosphate scaffold embryo was made by extrusion 3D printer. The finished product of porous 尾 -tricalcium phosphate scaffold was obtained by drying and sintering. The microstructure was observed by scanning electron microscope (SEM), the porosity and water absorption were measured by Archimedes method, the compressive strength was measured by electronic universal material testing machine, and the phase was analyzed by X-ray diffractometer. The sustained release microspheres containing 10-5 M icariin were prepared by phacoemulsification solvent dialysis method. Icariin / NN- dimethylformamide (ICA / DMF) and NN- dimethylformamide / poly (lactic acid-glycolic acid) copolymer (DMF / PLGA) were mixed in ice bath under ultrasonic conditions, then 1% polyvinyl alcohol solution was added to the mixed solution to form an O / W) composite emulsion. ICA/PLGA sustained release microspheres can be obtained by centrifugation, washing and freeze-drying. The sustained release microspheres are mixed into porous scaffolds by concussion centrifugation, 10% gelatin is added and centrifuged again. Icariin-尾-tricalcium phosphate composite scaffold was obtained after freeze-drying, and the microstructure, drug loading rate and encapsulation efficiency of the microspheres were determined, and drug release experiments in vitro were carried out. Results: the size of the porous 尾 -tricalcium phosphate scaffold was about 11mm 脳 11mm 脳 6 mm, the pore spacing was 600 渭 m. The macroporous structure of the scaffold was regular, and the pore connectivity was good. The porosity of the porous scaffold was 66.93 鹵2.84)%.SEM. The pore structure on the surface of the scaffold was observed. The micropore distribution was uniform and the pore connectivity was good. X-ray diffraction analysis of 尾 -TCP scaffold powder before and after sintering showed that there was no phase transition before and after sintering. The compressive properties of the sintered 尾 -TCP were tested. The maximum compressive strength of the scaffold was 2.98 鹵0.78 mpa, and the tensile strength of the scaffold reached 8.95 鹵0.29 mpa, and the mechanical properties reached the compressive strength of cancellous bone. The prepared ICA/PLGA sustained-release microspheres, with a broad appearance of yellowish powder substance, were observed to be spherical by scanning electron microscopy, with a particle size of about 1 渭 m, uniform distribution on the surface of the scaffold, and most of them distributed in the pore space of the scaffold. Conclusion: the 尾 -TCP scaffold is an interconnected porous structure with uniform distribution of micropore structure and good pore connectivity. Mechanical properties can reach the strength of cancellous bone and can provide better mechanical support properties. The scaffold could promote cell adhesion, proliferation and angiogenesis to increase the cumulative drug release of ICA / PLGA sustained-release microspheres for 30 days, which had the ability of drug sustained release. Icariin-尾-tricalcium phosphate composite scaffold can be used to repair femoral head necrosis in rabbits.
【學(xué)位授予單位】:南京中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類(lèi)號(hào)】:R318.08

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