【作者】 李春燕；

【导师】 杨万泰；

【作者基本信息】 北京化工大学 ， 化学， 2012， 博士

【摘要】 聚合物膜的改性和功能化作为一种有效提高分离膜优良性能的方法目前已受到人们广泛关注,而聚合物基材的表面生物功能化也因其在生物医学方面的应用成为另一个研究热点。表面可控/活性自由基接枝聚合可以在不改变聚合物膜固有性能的前提下,通过表面修饰对分离膜和聚合物基材进行有效的功能化。由于聚合物基材的表面惰性,对其表面实施可控/活性自由基接枝聚合,表面引发基团的固定是最难,也是最重要的环节。本论文则详细研究了几种可控/活性自由基聚合表面引发方法及其功能化应用,提出了三种在聚合物膜材料表面固定引发剂的新方法,并制备出了pH敏感性、蛋白吸附性、细胞粘附性以及基因转染性等不同功能聚合物复合膜。主要工作及结果如下：1.在聚碳酸酯径迹蚀刻膜表面通过等离子处理进行表面氧化,然后引发丙烯酸的表面自由基接枝聚合,制备出了具有pH敏感的聚合物复合膜；引发效率高,聚合速度快,2wt%丙烯酸单体经过3h就成功得到了具有明显pH敏感特征的功能复合膜。2.首次提出通过聚多巴胺在尼龙微滤膜表面的沉积,进而固定ATRP引发剂的方法；聚多巴胺在膜表面沉积均匀；固定引发剂效率高；接枝聚合具有明显的活性可控特征,接枝率随聚合时间线性增长,由此可对接枝厚度进行控制；表面引发丙烯酸的接枝聚合,制备出了具有pH敏感尼龙功能膜；此研究对于无机、有机膜材料表面引发ATRP实现其功能化的改性有着重要的意义。3.提出通过胺化法在聚己内酯(PCL)膜表面固定ATRP引发剂的新方法；DMAEMA单体接枝聚合过程具有可控/活性特征；通过PDMAEMA与负性蛋白质的电荷吸引作用,在膜表面固定了明胶蛋白；通过HEK293细胞的培养,对空白PCL膜在表面接枝及沉积蛋白质后表面细胞粘附力的变化进行了研究,并对所吸附细胞进行了初步基因转染实验；此研究对聚酯类材料的功能化改性提供了新的思路,并对细胞培养及基因转染提供了相容性好,粘附力强的医用支架。4.在PCL支架上用胺化法固定ATRP引发剂,引发了GMA的表面接枝；PGMA通过环氧开环反应固定明胶蛋白；对明胶功能化的PCL膜进行了表面培养贴壁HEK293细胞和悬浮K562细胞试验；随后,对具有转染功能的复合物PEI/DNA的三种载入方式(前载式、后载式及前后载式)进行了研究,发现前后载式为最佳载入方式,基因转染效率最高；此研究丰富了对基因转染方式的医学研究。5.首次提出通过紫外光在含C-H基聚合物膜表面直接固定ATRP引发剂的方法；以BOPP为基材模型,在UV光照下将溴-4-对羟基苯乙酮(BHAP)直接固定在表面；通过金属掩膜的使用,可使引发剂二维图案化固定；对GMA和DMAEMA分别实施了ATRP接枝聚合,体系具有可控／活性特征；利用接枝的PGMA和PDMAEMA可直接固定免疫球蛋白(IgG),抗体免疫球蛋白(anti-IgG)与膜表面固定IgG的反应结果表明IgG不仅有效固定于BOPP膜表面,还具有生物活性；此研究为含C-H键聚合物膜的直接功能化改性提供了有效的实施方法,还为生物医学反应器件的制备提供了可参考方案。6. ATRP体系最大的缺点为过渡金属铜的使用,当涉及生物用途时更为突出,针对这个问题提出并探索了一个紫外光／半频那醇自由基协同无铜ATRP方法；初步结果显示,较低紫外光强(2mW/cm2)即可激发ATRP引发剂及半频那醇自由基实现表面引发接枝聚合,使聚合具有活性／可控特征；采用三组对比实验,对烷基溴及BXIAN的引发剂及催化剂作用分别进行了研究,并通过溶液中均聚实验对反应可控／活性特征进行了证实；另外,通过在光照中使用金属掩膜制备出了图形和高度均可控的功能性接枝聚合物表面层。7.通过UV/硫杂蒽酮(ITX)可将硫杂蒽酮半频那醇固定到聚合物基材上,然后在可见光下可实施接枝聚合,发现接枝的PEGMA表面具有非常好的抗细胞吸附性能,进而GMA与GMA-Polylysine在其表面进行二次活性共聚接枝,可在PEGMA表面形成PGMA-co-PGMA-Poly lysine的二次图案；通过对MA63细胞的培养,发现接枝PEGMA后表面有优良的抗细胞吸附性,而GMA与GMA-Polylysine接枝共聚后,细胞粘附性恢复并显著提高,形成较好的细胞粘附和生长图案；这些研究为聚合物膜表面生物功能改性,以及生物医学微型装置的制备提供了重要的新方法。更多还原

【Abstract】 The ability to modify and functionlize filter membrane has got a lot ofattention, and the bio-functionlization of polymer substract has been anotherhotspot. Covalent tethering of functional brushes by surface incitedcontrolled/living radical polymerization (SI-CRP) on polymer film surfacewithout any destruction of bulk properties is of crucial importance to impartnew surface performances. In SI-CRP, well defined dense and structurepolymer brush grows from the initiator immobilized on polymer surface toprepare the functional polymer film, and most polymer film surface is inert.Therefore, the initiator immobilization is quite important. In this thesis, theinitiator immobilization strategies and the applications of functional polymercomposite film was studied in detail, which enriched the SI-CRP techniques,and developed three new initiator immobilization methods to fabricatefunctional polymer composite film. The main contents were listed as followed:1. A simple and highly efficient method to initiate surface incited radicalpolymerization by plasma treatment on polycarbonate track-etched (PCTE)membrane was studied. The PCTE membranes was pretreated via plasma andoxidized by air to induce peroxy bond, and subseguently thermal-graftcopolymerization of acrylic acid (AAc) was carried out. Under the highefficient initiating, AAc monomer solution (2wt%) could be polymerized toprepare pH sensitive PCTE membrane after3h.2. A facile two-step method was first developed for the covalentimmobilization of ATRP initiators on the surface of Nylon membrane and itsinside pores. The Nylon membrane was firstly functionalized bypolydopamine, the bromoalkyl initiator was then immobilized on thepolydopamine functionalized Nylon membrane surface in a two-stepsolid-phase reaction, followed by ATRP of acrylic acid (AA) in a aqueoussolution. The resulting Nylon membranes with grafted PAA side chains werecharacterized and studied by XPS and SEM. The results showed that thegrafted PAA polymers were formed uniformly inside the pores throughout theentire membrane thickness. With increase in the pore-filling ratio, the porediameters of PAA-grafted membranes became smaller. An approximatelylinear increase in graft yield (GY) of the grafted PAA chains withpolymerization time was observed, indicating that the chain growth from thePCL-Br surface was consistent with a “controlled” and well-defined process. The Nylon-g-PAAc membranes exhibit rapid and reversible response of theflux to the environmental pH as pH is switched between3and9.3. An alternative aminolysis-based method was developed for thecovalent immobilization of ATRP initiators on the polycaprolactone (PCL)film surfaces. It is possible to introduce free amino and hydroxyl groups onPCL film surfaces through the aminolysis reaction, and is followed with thereaction of2-bromoisobutyryl bromide (BIBB) to produce the ATRP initiatorspecies. Well-defined PDMAEMA brushes were subsequently prepared viasurface-initiated ATRP from the initiator functionalized PCL surfaces. Thecell-adhesion property on the functionalized PCL surface could be controlledby adjusting the ratio of PDMAEMA/gelatin and the gene transfectionproperty on the immobilized cells was dependent on the density of theimmobilized cells. With the good cell-adhesive nature of gelatin and theefficient gene transfection on the dense immobilized cells, the incorporatingthe suitable of PDMAEMA/gelatin complexes onto PCL surfaces could endowthe PCL substrates new and interesting properties for potential tissue enginering applications.4. The gelatin-functionalized PCL film surfaces are prepared viaSI-ATRP of GMA. The gelatin-functionalized PCL film surfaces exhibitexcellent cell-adhesion ability to both adherent and suspension cells. Theattached adherent cells demonstrate the characteristic elongated morphologieswith good spreading capability, while the attached suspension cells can maintain the original status of the round morphologies without spreading. Thegelatin coupled on the PCL surface could be used to absorb the cationicvector/plasmid deoxyribonucleic acid (pDNA) complexes via electrostaticinteraction. The local gene transfection property on the immobilized cells isdependent on both the density of the immobilized cells and the loading typesof pDNA complexes. The transfection efficiency of different assemblemethods of pDNA complex was compared. With the pre-and post-loadingsandwitch-like gene transfection, the gelatin-functionalized PCL film surfacecan substantially enhance the transfection properties to different cell lines. Thepresent study is very useful to spatially control local gene delivery and directcellular functions within PCL-based tissue scaffolds.5. The photo-induced one-step method was first developed for thecovalent immobilization of ATRP initiators on the C-H group-containingsubstrates such as biaxially oriented polypropylene (BOPP). The ATRPinitiators could be patterned immobilized by using of metal mask. The C-Hbonds of precise location of inert polymer surfaces were readily transferred tobromoalkyl initiator with the present of metal mask, followed by ATRP of2-(dimethylamino) ethyl methacrylate (DMAEMA) and glycidyl methacrylate(GMA) respectively to produce the resultant patterned BOPP-g-PDMAEMAand BOPP-g-PGMA films. The epoxy groups of the PGMA microdomainscould be aminated for covalently coupling IgG, while the PDMAEMAmicrodomains were used for immobilizing IgG via electronic interactions. The resultant IgG-coupled microdomains could interact with the correspondingtarget proteins, anti-IgG.6. The biggest drawback of ATRP is the use of copper, and it is moreserious when it applied in the biomedicine. A novel none-copper ATRPsystem collaborated by UV and BIXAN semipinacol radicals is exploed tosolve this problem. Preliminary results shows that under the low lightintensity of2mW/cm2, an approximately linear increase in GY of the graftedPDMAEMA chains with polymerization time was observed, indicating thatthe chain growth from the BOPP-BHAP surface was consistent with a“controlled” process. Through some comparison experiments, the role ofBHAP and BXIAN was studied. The controlled/living character wasconfirmed by the homopolymerization in solution under similar condition.7. The Low density polyethylene (LDPE) film surface was conjugatedwith PEGMA from the “dormant” ITXSP groups for forming antifoulingbackground, and subsequently block polymerized the copolymer of PGMAand (PGMA-Polylysine) from the ITXSP sits at the end of PEGMA chains.The epoxy groups of the GMA prior were aminated with cell-adhesive proteinPoly lysine to protect epoxy groups from ring-opening reaction. Thefunctionalized LDPE film surfaces both exhibit excellent antifouling andcell-adhesion property at different location. The attached adherent cellsdemonstrate the characteristic elongated morphologies with good spreadingcapability. The present study is very useful to spatially control local cell attachment and direct cellular functions within LDPE-based tissue scaffolds.The design and microfabrication of the active patterning on polymer substratesvia surface-initiated photochemical modification is of crucial importance indeveloping novel functional materials.更多还原