本文選題：聚乳酸 + 氧化石墨烯��； 參考：《上海大學(xué)》2016年博士論文

【摘要】：現(xiàn)代生物材料要求材料可以促進(jìn)細(xì)胞在其表面黏附、增殖等,從而可以使生物材料植入人體后快速與周圍組織整合,加速損傷組織或器官修復(fù),避免其它并發(fā)癥的出現(xiàn)。這就要求對(duì)傳統(tǒng)的生物材料進(jìn)行功能化改性,引入生物活性分子。本文以可生物降解的高分子材料聚乳酸(Poly(lactic acid),PLA)和新型碳材料氧化石墨烯(Graphene Oxide,GO)的功能化改性為研究對(duì)象,并系統(tǒng)地研究了改性后的材料與成骨細(xì)胞的相互作用,探索了其在生物醫(yī)學(xué)領(lǐng)域的應(yīng)用。聚乳酸(Poly(lactic acid),PLA)又稱聚丙交酯,因其性能良好,PLA已被美國(guó)食品和藥品管理局(FDA)批準(zhǔn)廣泛用作藥物控釋載體、醫(yī)用手術(shù)縫合線及骨折內(nèi)固定材料等生物醫(yī)用高分子材料。然而,聚乳酸,還存在一些不可忽視的缺點(diǎn),如親水性低,細(xì)胞親和性差,以及降解中會(huì)導(dǎo)致局部酸性積累而使植入體部位出現(xiàn)非感染性炎癥等。以上性能缺陷限制了聚乳酸在生物醫(yī)學(xué)領(lǐng)域中的應(yīng)用。為克服上述缺陷,人們對(duì)PLA做了大量的改性研究工作,以提高其親水性,改善其降解性能。本文創(chuàng)新性地設(shè)計(jì)合成了多聚賴氨酸改性聚乳酸的樹枝狀聚合物PLLA-d,該樹枝狀聚合物以疏水的PLLA為核心,賴氨酸分支在兩端提供了足量的表面正電荷。合成產(chǎn)物的化學(xué)結(jié)構(gòu)通過(guò)核磁共振氫譜(1H NMR)和凝膠滲透色譜(GPC)得到了證實(shí)。隨著賴氨酸的引入,PLLA的熔點(diǎn)降低,彈性模量降低,但親水性提高。得到的產(chǎn)物PLLA-d采用Breath-Figure方法制備了蜂窩狀多孔膜H-PLLA-d,用于研究小鼠成骨細(xì)胞MC3T3-E1與合成材料之間的相互作用。結(jié)果表明,相對(duì)于PLLA膜,MC3T3-E1細(xì)胞功能包括細(xì)胞黏附、增殖和分化在H-PLLA-d膜上有顯著地提高。氧化石墨烯(GO),石墨烯的重要衍生物,是從氧化石墨剝離而得到的。和石墨烯相比,GO在水中分散性好,表面含氧基團(tuán)豐富使其更容易被功能化改性,而且制備成本低,因此,氧化石墨烯已經(jīng)被廣泛應(yīng)用于生物傳感器、生物成像、藥物遞送,以及組織工程支架材料等生物醫(yī)學(xué)領(lǐng)域。GO在生物醫(yī)學(xué)領(lǐng)域的應(yīng)用已經(jīng)顯示出很大的潛力,但其生物相容性仍然沒(méi)有定論,為了開拓其在生物醫(yī)學(xué)領(lǐng)域的應(yīng)用,提高其生物相容性非常必要。為此,我們采用精氨酸-甘氨酸-天冬氨酸(Arg-Gly-Asp,RGD)三肽序列改性GO得到GO-RGD,通過(guò)對(duì)GO上的羧基進(jìn)行活化后,一步合成了GO-RGD。得到的產(chǎn)物通過(guò)元素分析和傅氏轉(zhuǎn)換紅外線光譜分析(FTIR)證實(shí)了新的化學(xué)結(jié)構(gòu)的出現(xiàn),采用掃描電子顯微鏡(SEM)和透射電子顯微鏡(TEM)對(duì)GO-RGD的表面形貌進(jìn)行了研究,通過(guò)TEM觀察改性前后GO形貌的變化進(jìn)一步確定了RGD的綁定。細(xì)胞實(shí)驗(yàn)結(jié)果表明,相對(duì)于GO膜,MC3T3-E1細(xì)胞功能包括細(xì)胞黏附、增殖和分化在GO-RGD膜上有顯著地提高,而且這種促進(jìn)作用和RGD含量相關(guān)。該GO-RGD的促進(jìn)成骨作用,使得其有望應(yīng)用于骨修復(fù)等生物醫(yī)學(xué)領(lǐng)域。同時(shí),我們通過(guò)一步反應(yīng),制備了明膠(gelatin)功能化改性的GO。通過(guò)FTIR、X射線光電子能譜分析(XPS)、SEM等表征手段確認(rèn)了功能化的完成。并在生物醫(yī)用鎳鈦合金表面制備了GO涂層GO@NiTi,以及gelatin功能化改性GO的涂層GOGel@NiTi。通過(guò)系統(tǒng)地研究涂層樣品對(duì)MC3T3-E1成骨細(xì)胞的影響,結(jié)果表明,相對(duì)于NiTi合金,涂層后樣品明顯提高了細(xì)胞黏附、增值和分化,特別是GOGel@NiTi在三者中具有最好的成骨細(xì)胞相容性。此外,我們采用菌落計(jì)數(shù)法、死活細(xì)胞染色法,以及SEM研究了涂層樣品對(duì)大腸桿菌E.coli的影響。通過(guò)對(duì)涂層樣品的抗菌性能研究,發(fā)現(xiàn)涂層對(duì)大腸桿菌E.coli具有一定的抗菌能力,細(xì)菌的細(xì)胞膜結(jié)構(gòu)被涂層樣品破壞。總體來(lái)說(shuō),GO基涂層顯示出良好的成骨細(xì)胞相容性,同時(shí)具有抑制細(xì)菌的作用。這一發(fā)現(xiàn),使得GO有潛力應(yīng)用于植入材料表面改性和涂層方面�？傊�,通過(guò)對(duì)PLA和GO的功能化改性,明顯提高了它們的生物相容性,為開拓它們?cè)谏镝t(yī)學(xué)領(lǐng)域的應(yīng)用提供了基礎(chǔ)。本研究也為設(shè)計(jì)、合成新型的具有生物功能的PLA和GO基生物材料提供了理論和數(shù)據(jù)支持。
[Abstract]:Modern biomaterials require materials to promote the adhesion and proliferation of cells on its surface, which can make biomaterials integrated quickly with surrounding tissues, accelerate damaged tissue or organ repair, and avoid other complications. This requires the functional modification of traditional biological materials and the introduction of bioactive molecules. The functional modification of biodegradable polymer material polylactic acid (Poly (lactic acid), PLA) and new carbon material Graphene Oxide (GO) was studied. The interaction between the modified material and osteoblast was studied systematically, and its application in the field of biomedicine (Poly (lactic acid), P was explored. LA) also known as polylactide. Because of its good performance, PLA has been approved by the US Food and Drug Administration (FDA) to be widely used as a drug controlled-release carrier, surgical suture and fracture internal fixation materials. However, polylactic acid has some inattention shortcomings, such as low hydrophilicity, poor cell affinity, and degradation. In order to overcome these defects, people have done a lot of research on the modification of PLA to improve its hydrophilicity and improve its degradation performance. The dendritic polymer PLLA-d of polylactic acid modified polylactic acid, the dendrimer with hydrophobic PLLA as the core, the lysine branch provides full surface positive charge at both ends. The chemical structure of the synthetic product is confirmed by nuclear magnetic resonance (1H NMR) and gel permeation chromatography (GPC). With the introduction of lysine, the melting point of PLLA Decreasing the modulus of elasticity, but increasing the hydrophilicity, the product PLLA-d obtained the honeycomb porous membrane H-PLLA-d using the Breath-Figure method to study the interaction between the MC3T3-E1 and the synthetic materials in the mouse osteoblasts. The results show that the MC3T3-E1 cell function includes cell adhesion, proliferation and differentiation in H-PLLA-d relative to the PLLA membrane. Graphene oxide (GO), an important derivative of graphene, is obtained from graphite oxide. Compared with graphene, GO has good dispersibility in water and rich surface oxygen group, which makes it easier to be functionalized and has low preparation cost. Therefore, graphene oxide has been widely used in biosensors. The application of.GO in biomedical fields, such as physical imaging, drug delivery, and tissue engineering scaffold, has shown great potential in biomedical field, but its biocompatibility is still unsettled. In order to develop its application in the field of biomedicine, it is necessary to improve its biocompatibility. Therefore, we use arginine glycine. Arg-Gly-Asp (RGD) three peptide sequence modified GO obtained GO-RGD. After activation of the carboxyl group on GO, the products obtained by GO-RGD. were synthesized by elemental analysis and Fourier transform infrared spectroscopy (FTIR), which confirmed the appearance of new chemical structure, used scanning electron microscope (SEM) and transmission electron microscope (TEM). The surface morphology of GO-RGD was studied. The binding of RGD was further determined by the changes of GO morphology before and after the modification of TEM. The results of cell experiments showed that the function of MC3T3-E1 cells, including cell adhesion, proliferation and differentiation on the GO-RGD membrane, was significantly higher than that of the GO membrane, and this promotion was related to the RGD content. The GO-RGD To promote osteogenesis, it is expected to be applied to biomedical fields such as bone repair. At the same time, we have prepared the functional modified GO. of gelatin (gelatin) through FTIR, X ray photoelectron spectroscopy (XPS), SEM and other characterization methods to confirm the completion of the functionalization, and the preparation of GO coating GO@N on the surface of the biomedical NiTi alloy. ITi, and the gelatin functional modified GO coating GOGel@NiTi. systematically studied the effects of coated samples on MC3T3-E1 osteoblasts. The results showed that compared to NiTi alloy, the coated samples significantly improved cell adhesion, increment and differentiation, especially the best osteoblast compatibility of GOGel@NiTi in the three. In addition, we used the coating. Colony counting, dead cell staining, and SEM studied the effect of coating samples on Escherichia coli E.coli. Through the study of the antibacterial properties of the coated samples, it was found that the coating had certain antibacterial ability to the Escherichia coli E.coli, and the membrane structure of the bacteria was damaged by the coated samples. Generally, the GO based coating showed good osteogenesis. Cell compatibility and inhibition of bacteria. This discovery has the potential to apply GO to the surface modification and coating of implant materials. In a word, the biocompatibility of PLA and GO has been significantly improved by functional modification, which provides a basis for developing their applications in the biomedical domain. The new biological and functional PLA and GO based biomaterials provide theoretical and data support.
【學(xué)位授予單位】：上海大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R318.08

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