【摘要】：骨修復(fù)過(guò)程是一個(gè)受多種生長(zhǎng)因子影響的過(guò)程,這個(gè)過(guò)程中,多種因子的時(shí)空分布,對(duì)骨修復(fù)的成功率和速率起關(guān)鍵作用。利用組織工程的方法修復(fù)骨缺損是研究的熱點(diǎn),也取得了很多的進(jìn)展,然而當(dāng)前的骨支架材料只結(jié)合了單一的活性因子,或者多個(gè)因子的簡(jiǎn)單混合,未能模擬骨自然修復(fù)過(guò)程中多因子的時(shí)空分布,從而影響了治療方法的效率。因此,兩種或多種因子的延時(shí)控制釋放體系的研究是很有意義的。靜電噴霧技術(shù)是一種利用強(qiáng)靜電場(chǎng)作用來(lái)克服液體表面張力,從而獲得微球的一種技術(shù)。利用同軸靜電噴霧法可以制備殼-核結(jié)構(gòu)的高分子微球,這種高分子微球能依時(shí)間順序先后釋放兩種化學(xué)藥物,如前1-2周釋放一種藥物,之后開始釋放第二種藥物。通過(guò)變化殼-核結(jié)構(gòu)中核的相對(duì)大小,能精確控制兩種藥物的釋放節(jié)奏。因此,可以利用同軸靜電噴霧技術(shù)制備殼-核分別包含F(xiàn)GF-2和BMP-2這兩種生長(zhǎng)因子的微球,從而實(shí)現(xiàn)因子的延時(shí)控制釋放,達(dá)到促進(jìn)骨再生的目的。殼-核結(jié)構(gòu)高分子微球,雖然有一定機(jī)械性能,但不能滿足骨缺損部位,特別是受力部位的支撐作用,從而影響骨再生。ZK60鎂合金具有與自然骨接近的機(jī)械性能,而其降解產(chǎn)物鎂離子又是人體必需元素。所以,可以利用鎂合金作為殼-核微球的外部支撐材料,從而滿足骨再生的要求。但鎂合金過(guò)快的降解速度影響了其應(yīng)用,所以必需對(duì)其進(jìn)行表面改性,延緩其降解速率。Ca和P都是骨基質(zhì)的主要組成成分,研究結(jié)果顯示Ca-P涂層具有良好的生物相容性,并有很好的骨傳導(dǎo)性和誘骨活性。所以可以在ZK60鎂合金表面進(jìn)行Ca-P涂層,這樣既可以延緩降解速率,又可以促進(jìn)骨再生。本實(shí)驗(yàn)通過(guò)制備搭載包含兩種生長(zhǎng)因子的可控釋放微球的Ca-P改性ZK60鎂合金支架,即可以發(fā)揮殼-核結(jié)構(gòu)微球的蛋白質(zhì)緩釋方面的優(yōu)勢(shì),又可以在骨缺損處的應(yīng)用提供機(jī)械支撐,從而提高修復(fù)大面積骨缺損的效率。
[Abstract]:The process of bone repair is a process influenced by many growth factors. In this process, the spatial and temporal distribution of multiple factors plays a key role in the success rate and rate of bone repair. The application of tissue engineering in repairing bone defects is a hot topic and has made a lot of progress. However, the current bone scaffold materials only combine a single active factor or a simple mixture of multiple factors. The failure to simulate the temporal and spatial distribution of multiple factors in the process of natural bone repair affects the efficiency of the treatment. Therefore, the study of delay controlled release systems with two or more factors is of great significance. Electrostatic spray technology is a kind of technology which uses the strong electrostatic field to overcome the surface tension of liquid and obtain microspheres. Coaxial electrostatic spray method can be used to prepare shell-core polymer microspheres which can release two kinds of chemical drugs in order of time such as the release of one drug in the first 1-2 weeks and then the release of the second drug. By changing the relative size of the nuclei in the shell-nucleus structure, the release rhythm of the two drugs can be precisely controlled. Therefore, the coaxial electrostatic spray technique can be used to prepare the microspheres containing FGF-2 and BMP-2, respectively, so that the delayed release of the factors can be achieved and the bone regeneration can be promoted. Although the shell core structure polymer microspheres have some mechanical properties, they can not meet the support function of bone defect, especially the bearing parts, thus affecting the mechanical properties of bone regeneration. ZK60 magnesium alloy has the mechanical properties close to that of natural bone. Mg ~ (2 +), the degradation product of magnesium ion, is an essential element in human body. Therefore, magnesium alloy can be used as an external support material for shell-nuclear microspheres to meet the requirements of bone regeneration. However, the rapid degradation rate of magnesium alloy affects its application, so it is necessary to modify its surface and delay its degradation rate. Ca and P are the main components of bone matrix. The results show that Ca-P coating has good biocompatibility. It also has good bone conduction and osteoinductive activity. Therefore, Ca-P coating can be applied on ZK60 magnesium alloy surface, which can delay degradation rate and promote bone regeneration. In this experiment, Ca-P modified ZK60 magnesium alloy scaffolds with controllable release microspheres containing two growth factors were prepared, which can play the advantage of protein sustained release of shell core microspheres and provide mechanical support for bone defects. So as to improve the efficiency of repairing large-area bone defects.
【學(xué)位授予單位】：湖南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R318.08;R68

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