【摘要】：在藥物釋放領(lǐng)域，高分子有著重要的應(yīng)用。將高分子作為藥物載體，一方面能夠?qū)崿F(xiàn)對(duì)藥物的控制釋放；另一方面，許多高分子材料具有可降解的特性，不會(huì)在人體內(nèi)長(zhǎng)期存在。在組織工程領(lǐng)域，高分子組織工程支架能夠?yàn)榧?xì)胞的粘附生長(zhǎng)以及新陳代謝提供類似于細(xì)胞外基質(zhì)的生長(zhǎng)空間，且隨著細(xì)胞的生長(zhǎng)而降解。無機(jī)鈣磷酸鹽既能提供骨組織修復(fù)中所需的鈣、磷等，同時(shí)能夠?qū)Ω叻肿咏到馑a(chǎn)生的酸性物質(zhì)進(jìn)行中和，避免局部過酸而對(duì)機(jī)體產(chǎn)生傷害。本論文針對(duì)藥物釋放以及組織工程進(jìn)行了兩部分的研究工作：第一部分為“抗結(jié)核藥物緩釋支架材料的制備與表征”，第二部分為“以聚乳酸/明膠復(fù)合纖維膜為模板制備羥基磷灰石”。 在本論文第一部分中，以聚乳酸（PLLA）作為基體材料，β-磷酸三鈣（β-TCP）作為添加物，載入抗結(jié)核藥物異煙肼（INH），制備成具有高達(dá)96%的孔隙率的均勻組織工程復(fù)合支架。對(duì)支架的藥物釋放行為進(jìn)行評(píng)價(jià)，PLLA/β-TCP/INH復(fù)合支架能夠持續(xù)80天以上的藥物釋放。同時(shí)對(duì)聚乳酸的降解行為以及藥物釋放過程中支架的性能變化進(jìn)行表征，聚乳酸在80天的藥物釋放期間降解不明顯，對(duì)緩沖液的酸度影響不大，支架的性能變化小。最后研究了PLLA/β-TCP/INH復(fù)合支架對(duì)成骨細(xì)胞生長(zhǎng)的影響以及其骨組織修復(fù)能力，結(jié)果顯示，細(xì)胞能夠很好的在支架上貼附生長(zhǎng)，并且動(dòng)物實(shí)驗(yàn)顯示骨組織缺損修復(fù)良好�？梢源_定PLLA/β-TCP/INH復(fù)合支架能夠在進(jìn)行藥物釋放治療骨結(jié)核病的同時(shí)引導(dǎo)缺損的骨組織進(jìn)行再生修復(fù)。 本論文第二部分對(duì)羥基磷灰石的仿生制備進(jìn)行了研究。將聚乳酸和明膠通過靜電紡絲法制備出均勻的復(fù)合纖維膜，采用模擬人體體液進(jìn)行生物礦化后，高溫煅燒處理得到羥基磷灰石�？刂频V化時(shí)間、煅燒溫度以及時(shí)間，，可獲得形貌和結(jié)晶性與鹿茸或人小腿脛骨煅燒產(chǎn)物相似的六棱柱形羥基磷灰石。最佳制備條件為：聚乳酸/明膠復(fù)合纖維在5倍模擬人體體液中礦化24小時(shí)，于1000℃下煅燒1小時(shí)。
[Abstract]:In the field of drug release, polymers have important applications. On the one hand, polymer as drug carrier can realize the controlled release of drugs; on the other hand, many polymer materials have degradable properties and will not exist in human body for a long time. In the field of tissue engineering, polymer tissue engineering scaffolds can provide a growth space similar to extracellular matrix for cell adhesion, growth and metabolism, and degrade with the growth of cells. Inorganic calcium phosphate can not only provide calcium, phosphorus and so on in bone tissue repair, but also neutralize the acid produced by polymer degradation, so as to avoid local excessive acid and harm to the body. In this paper, drug release and tissue engineering are studied in two parts: the first part is "preparation and characterization of antituberculosis drug sustained release stents". In the second part, hydroxyapatite was prepared by using polylactic acid / gelatin composite fiber membrane as template. In the first part of this paper, polylactic acid (PLLA) was used as matrix material and 尾-tricalcium phosphate (尾-TCP) as additive to load isoniazid (INH), an antituberculosis drug. Uniform tissue engineering composite scaffolds with porosity of up to 96% were prepared. The drug release behavior of stents was evaluated. PLLA/ 尾-TCP/INH composite stents could release drugs for more than 80 days. At the same time, the degradation behavior of polylactic acid and the performance changes of scaffolds during drug release were characterized. The degradation of polylactic acid during 80 days of drug release was not obvious, but had little effect on the acidity of buffer, and the performance of stents changed little. Finally, the effect of PLLA/ 尾-TCP/INH composite scaffold on the growth of osteoblasts and the ability of bone tissue repair were studied. the results showed that the cells could adhere to the scaffold very well, and the animal experiments showed that the bone tissue defect was repaired well. It can be confirmed that PLLA/ 尾-TCP/INH composite stent can guide the regeneration and repair of defective bone tissue while drug release treatment of bone tuberculosis. In the second part of this paper, the biomimetic preparation of hydroxyapatite was studied. Polylactic acid and gelatin were prepared by electrospinning to prepare uniform composite fiber membrane. Hydroxyapatite was obtained by biomineralization of simulated human body fluid and calcination at high temperature. By controlling the mineralization time, calcination temperature and time, hexagonal hydroxyapatite with morphology and crystallization similar to the calcined products of velvet antler or human calf tibia can be obtained. The optimum preparation conditions were as follows: Polylactic acid / gelatin composite fiber was mineralized in 5 times simulated human body fluid for 24 hours and calcined at 1000 鈩

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