新型季铵盐和无定型磷酸钙材料对牙本质粘接系统改性的研究

发布时间：2018-07-15 10:46

【摘要】：复合树脂及其粘接系统因为具有优良的美学效果，以及简便的临床操作过程等优势，近年来广泛应用于修复牙体缺损和改善牙齿外观。但相较其他口腔修复材料，复合树脂更容易在表面堆积菌斑生物膜，同时复合树脂的聚合收缩和粘接不良易导致边缘微渗漏，成为唾液和细菌进出的通道，即菌斑生物膜的入侵途径。菌斑生物膜是引起继发龋和修复失败的主要原因，一方面会直接引起某些口腔软硬组织感染性疾病，，如继发龋、义齿性口炎，另一方面则能造成材料的老化粗糙，导致材料性能下降，从而更易吸引细菌黏附。这样的恶性循环最终将会造成修复失败，甚至对全身产生不良影响。修复失败的再修复所花费的时间占到牙医操作时间的50-70%，而全美每年再修复的花费更是超过200亿美金。正因为复合树脂缺乏抗菌作用，赋予复合树脂本身，及将复合树脂与牙体粘接起来的粘接系统抗菌作用，就显得尤为必要。具有抗菌性能的复合树脂和粘接系统能减小对口腔微生态环境的影响，改善修复体的长期临床效果，维护口腔微生态环境的健康。各国研究人员在研制开发具有抗菌作用的复合树脂和粘接系统等材料方面进行了大量的研究，以期达到抑制细菌生长，防止菌斑生物膜的附着，预防继发龋的发生，防治修复失败和因修复体引发的感染和炎症的目的。本课题主要从以下四个部分进行研究：第一部分抗菌粘接系统的研发和检测:季铵盐和纳米银颗粒改性牙本质粘接剂对粘接强度和牙菌斑生物膜的影响; 第二部分添加无定型磷酸钙纳米颗粒，赋予粘接剂再矿化性能：新型含纳米银和无定形磷酸钙的牙本质粘接剂；第三部分烷基链长度的影响：含有新型抗菌季铵盐单体甲基丙烯酸十二烷基二甲铵的牙本质粘接系统；第四部分长期效果：水老化对抗菌粘接系统的机械性能及抗菌性能影响。第一部分季铵盐和纳米银颗粒改性牙本质粘接剂对粘接强度和牙菌斑生物膜的影响目的：抗菌牙本质粘接剂在抑制残留细菌和阻止细菌入侵方面有很重要的作用。本研究的目的是开发一种含有新型季铵盐单体二甲基丙烯酸季铵（quaternary ammonium dimethacrylate， QADM）和纳米银颗粒（nanoparticles of silver, NAg）的抗菌牙本质粘接剂，并对含有QADM-NAg的粘接剂及底胶对牙本质粘接强度和牙菌斑生物膜的影响进行研究。方法：商品化的牙本质粘接剂及底胶Scotchbond Multi-Purpose作为本实验的对照组。实验组粘接剂和底胶是在对照组中加入QADM和NAg。测试了10组人牙本质剪切粘接强度（n=10）。使用人唾液培养所得到牙菌斑全菌生物膜模型来研究生物膜的代谢活性，菌落形成单位（colony forming unit, CFU）计数，产乳酸量，死/活细菌染色（n=6）。结果：添加了QADM和NAg的牙本质粘接剂和底胶，其牙本质剪切粘接强度没有下降，仍介于30至35兆帕间（P0.1）。扫描电子显微镜（scanningelectron microscope, SEM）照片显示有大量树脂突形成，这在对照组和添加了QADM和NAg的实验组中是相同的。与对照组相比，添加QADM和NAg的对照组菌斑生物膜的代谢活性显著降低。在粘接剂里同时添加QADM和NAg比添加单一的抗菌成分具有更强的抗菌作用（P0.05）。与对照组相比，同时在粘接剂和底胶中添加QADM和NAg具有最强的抗菌活性，最大程度降低了菌斑生物膜代谢活性，减少了CFU计数和一个数量级的产乳酸量。意义：在不影响牙本质粘接强度和树脂突形态的前提下，本研究第一次证实了含有QADM和NAg的牙本质粘接剂和底胶，对牙菌斑生物膜具有较强的抗菌作用。含有QADM和NAg的牙本质粘接剂和底胶在抑制窝洞中残留细菌和阻止细菌入侵方面有很重要的作用，因此可以预防继发龋的的发生。QADM和NAg添加到其他牙本质粘接系统可能同样具有广泛的应用前景。第二部分新型含纳米银和无定形磷酸钙的牙本质粘接剂目的：抗菌牙本质粘接剂在抑制窝洞中残留细菌和在修复体边缘阻止细菌入侵方面发挥重要的作用。钙（Ca）和磷酸根离子（PO4）的释放曾被证明能够促进病变牙的再矿化。本研究的目标是将纳米银颗粒NAg和无定形磷酸钙纳米颗粒（Ca3[PO4]2, nanoparticles of amorphous calcium phosphate, NACP）添加到牙本质粘接剂中，以研究其对牙本质粘接强度和牙菌斑生物膜的影响。方法：SBMP粘接系统作为本实验的对照组。NAg按质量分数0.1%被添加到对照粘接剂和底胶中。NACP则按质量分数10％，20％，30％和40％与对照粘接剂混合。使用人唾液培养所得到牙菌斑全菌生物膜模型来研究生物膜，让其附着在由复合树脂，粘接剂和底胶构成的试件上进行生长。测定了牙菌斑生物膜的代谢活性，CFU计数和产乳酸量。结果：人牙本质剪切粘接强度介于26至34兆帕间，说明添加了NAg和NACP后粘接强度没有显著下降（P0.1）。与对照组相比，添加了NAg和NACP牙本质粘接剂和底胶大大减少了生物膜活力和代谢活性。添加了NAg和NACP的实验组全菌，总链球菌，变形链球菌CFU计数较对照组降低了近一个数量级。添加了NAg和NACP的实验组产乳酸量减少到对照组的1/4。 SEM观察发现牙本质小管内充填有大量树脂突，并且牙本质小管和粘接剂层内都渗透了大量的NACP。意义：本研究第一次证实了含有NAg和NACP的粘接剂可以显著降低菌斑生物膜活力和产乳酸量，并且不损害牙本质粘接强度。这种添加NAg和NACP的方法可能在其他牙本质粘接系统中同样具有广泛的应用前景。第三部分含有新型抗菌季铵盐单体甲基丙烯酸十二烷基二甲铵（dimethylaminododecyl methacrylate, DMADDM）的牙本质粘接系统目的：树脂修复失败的主要原因是菌斑生物膜产酸引起的继发龋。修复失败的再修复花费的时间占到牙医操作时间的50-70%。本研究的目标是把新的季铵盐单体DMADDM和纳米银颗粒NAg添加到牙本质粘接剂和底胶中，探讨其对粘接系统抗菌性能和粘接强度的影响。方法：SBMP粘接系统作为本实验的对照组。合成DMADDM并将其与NAg添加到粘接剂和底胶中。使用人唾液培养所得到牙菌斑全菌生物膜模型来研究生物膜，检测生物膜代谢活力，CFU计数，产乳酸量，并测量人牙本质剪切粘接强度。结果：DMADDM的最低抑菌浓度（minimal inhibitory concentration, MIC）和最低杀菌浓度（minimal bactericidal concentration, MBC）较原先的QADM降低了多个数量级。未固化的加入DMADDM的底胶，其琼脂平板抑菌环的直径远大于加入QADM的底胶所形成的抑菌环直径（P0.05）。而固化的加入了DMADDM-NAg的粘接剂和底胶大大降低了菌斑生物膜代谢活性（P 0.05）。同时加入DMADDM和NAg的实验组，CFU计数的结果少于单独加入DMADDM的实验组（P0.05）。与对照组相比，加入了DMADDM-NAg的实验组，菌斑生物膜产乳酸量减少了20倍。在粘接系统中加入DMADDM和NAg对牙本质粘接强度没有不利影响。意义：本研究合成了一种新的抗菌单体DMADDM，并第一次将其添加到牙本质粘接剂和底胶中。抗菌牙本质粘接剂在抑制残留细菌和阻止细菌入侵方面有很重要的作用。DMADDM和NAg在牙本质粘接系统和复合树脂修复方面，有良好的应用前景。第四部分水老化对含有新型单体dimethylaminododecyl methacrylate的牙本质粘接剂粘接强度和抗生物膜活性的影响目的：本研究的目的是将新的抗菌单体DMADDM以及纳米银颗粒NAg和无定形磷酸钙纳米颗粒NACP添加到牙本质粘接系统中，开发出新的具有抗菌性能的牙本质粘接系统，并第一次通过6个月的水老化方法，检测其牙本质粘接强度和抗菌性能的长期效果。方法：检测了以下四组粘接系统：SBMP对照组；SBMP+5％DMADDM；SBMP+5％DMADDM+0.1％NAg和SBMP+5％DMADDM+0.1％NAg，粘接剂另加入20％NACP。试件在37℃下水老化1天和6个月，然后测量牙本质的剪切粘接强度。使用人唾液培养所得到牙菌斑全菌生物膜模型来研究生物膜，并测量生物膜代谢活性，CFU计数，和产乳酸量。结果：SBMP对照组经过6个月的水老化后，牙本质粘接强度降低了35％（n=10），相比之下，加入抗菌粘接剂的实验组没有出现粘接强度下降。含有DMADDM-NAg-NACP的实验组表现出了强的DMADDM抗菌效果，菌斑生物膜活力大大降低，代谢活动和产酸均显著减少。与对照组相比，CFU计数减少超过两个数量级。此外，含有DMADDM-NAg-NACP的粘接系统具有长期的抗菌性能，1天和6个月的抗菌效果没有显着差异（P0.1）。结论：添加DMADDM-NAg-NACP的牙本质粘接系统具有强效和持久的抗菌性能，经过6个月水老化后的粘接强度远大于商品化对照组。这种新型抗菌粘接系统能有效抑制菌斑生物膜的生长和修复体边缘的继发龋。本方法在其他牙本质粘接系统，正畸粘接剂和复合树脂的改性方面具有广泛的适用性。
[Abstract]:Composite resin and its bonding system have been widely used in repairing tooth defects and improving tooth appearance because of their excellent aesthetic effects and simple clinical operation. But compared with other dental restorative materials, composite resins are more likely to accumulate the biofilm on the surface of the dental plaque, and the polymerization shrinkage and bonding of the composite resin. It is easy to lead to marginal microleakage, which is the channel of saliva and bacteria entering and out, that is, the invasion pathway of plaque biofilm. The plaque biofilm is the main cause of secondary caries and failure to repair. On the one hand, it will directly cause some oral and soft tissue infectious diseases, such as secondary caries, denture stomatitis, and on the other hand it can cause material aging. Such a vicious cycle will eventually cause failure to repair and even have a bad effect on the whole body. The time taken to repair the failed repair takes up to 50-70% of the dentist's operation time, and the cost of repairment in the United States is more than 20 billion dollars a year. There is no antibacterial effect of resin. It is particularly necessary to give the composite resin itself, and the antibacterial effect of the adhesive system which adhesive to the tooth body. The composite resin and adhesive system with antibacterial properties can reduce the effect on the microecological environment of the mouth, improve the long-term clinical effect of the restorations and maintain the microecological environment of the oral cavity. Health. A great deal of research has been made in the development and development of composite resins and bonding systems with antibacterial effects, in order to inhibit the growth of bacteria, prevent the adhesion of plaque biofilms, prevent the occurrence of secondary caries, prevent the failure of repair and the infection and inflammation caused by the restorations.
This topic is mainly studied from the following four parts:
The first part is the development and detection of antibacterial adhesive system: the effect of quaternary ammonium salt and nano silver particles modified dentin adhesive on bonding strength and plaque biofilm.
The second part is to add amorphous calcium phosphate nanoparticles to give the adhesive remineralization ability: a new dentin adhesive containing nano silver and amorphous calcium phosphate.
The third part is the effect of alkyl chain length: a dentin bonding system containing a new antibacterial quaternary ammonium monomer, methacrylic acid, twelve alkyl, two methylamine.
The fourth part is the long-term effect: the effect of water aging on the mechanical properties and antibacterial properties of the antibacterial adhesive system.
Part one: effect of quaternary ammonium salt and nano silver particles modified dentin adhesive on bonding strength and plaque biofilm.
Objective: antibacterial dentine adhesives play an important role in inhibiting residual bacteria and preventing bacterial invasion. The purpose of this study is to develop an antiseptic dentin that contains a new quaternary ammonium salt monomer (quaternary ammonium dimethacrylate, QADM) and nano silver particles (nanoparticles of silver, NAg). The effects of adhesive and base glue containing QADM-NAg on dentin bonding strength and plaque biofilm were studied.
Methods: the commercial dentin adhesive and the bottom glue Scotchbond Multi-Purpose were used as the control group in this experiment. The adhesive and bottom glue in the experimental group were tested in the control group by adding QADM and NAg. to the 10 groups of human dentin shear adhesion strength (n=10). Xie activity, colony forming unit (CFU) count, lactoacid production, dead / live bacteria staining (n=6).
Results: the dentin adhesive and bottom glue added QADM and NAg, the dentin shear bond strength did not decrease, still between 30 and 35 MPa (P0.1). The scanning electron microscope (SCANNINGELECTRON microscope, SEM) photo showed a large number of resin process formation, which was the same in the control group and the experimental group adding QADM and NAg. Compared with the control group, the metabolic activity of the plaque biofilm with the addition of QADM and NAg was significantly reduced. The addition of QADM and NAg to the adhesive was stronger than the addition of a single antibacterial component (P0.05). Compared with the control group, adding QADM and NAg to the adhesive and the bottom glue had the strongest antibacterial activity, and the maximum decreased. The metabolic activity of plaque biofilms decreased the CFU count and the milk yield of an order of magnitude.
Significance: on the premise of not affecting dentin adhesion strength and resin process, this study first confirmed the dentin adhesives and sealant containing QADM and NAg, and has strong antibacterial effect on dental plaque biofilms. Dentine adhesives and sealant containing QADM and NAg are used to inhibit residual bacteria in pit holes and prevent bacterial invasion. It plays an important role in preventing secondary caries..QADM and NAg can also be widely applied to other dentin bonding systems.
The second part is a new dentin adhesive containing nano silver and amorphous calcium phosphate.
Objective: antiseptic dentine adhesives play an important role in inhibiting residual bacteria in pit holes and preventing bacterial invasion at the edge of the prosthesis. The release of calcium (Ca) and phosphate radical ions (PO4) has been proved to be able to promote remineralization of diseased teeth. The aim of this study is to make nano silver particles NAg and amorphous calcium phosphate nanoparticles (Ca3[PO4]). 2, nanoparticles of amorphous calcium phosphate, NACP) was added to dentin adhesive to study its effect on dentin adhesion strength and dental plaque biofilm.
Methods: the SBMP adhesive system was used as a control group in the control group, and the.NAg was added to the control binder and the bottom glue according to the mass fraction of 0.1%. The.NACP was mixed with the mass fraction of 10%, 20%, 30% and 40% with the control adhesive. The growth of dental plaque and biofilm was tested. The metabolic activity, CFU count and lactone content of dental plaque biofilm were determined.
Results: the bonding strength of human dentin shear bond was between 26 and 34 MPa, indicating that the adhesion strength of NAg and NACP was not significantly decreased (P0.1). Compared with the control group, the addition of NAg and NACP dentin adhesives and bottom adhesives greatly reduced the bioactivity and metabolic activity of the biofilm. The experimental group, total Streptococcus, and deformable chain with NAg and NACP were added. The CFU count was nearly one order of magnitude lower than that of the control group. The amount of lactic acid produced in the experimental group with NAg and NACP decreased to the 1/4. SEM of the control group and found a large number of resin processes filled in the dentinal tubules, and a large amount of NACP. was permeated in the dentinal tubules and the adhesive layer.
Significance: This study confirms for the first time that the adhesives containing NAg and NACP can significantly reduce plaque organisms.
Membrane activity and milky acid content, and do not damage dentin adhesion strength. This method of adding NAg and NACP may also have extensive application prospects in other dentin bonding systems.
The third part contains the dentin bonding system of a new antibacterial quaternary ammonium salt monomer, dimethylaminododecyl methacrylate (DMADDM), twelve methacrylic acid (DMADDM).
Objective: the main reason for the failure of resin repair is secondary caries caused by acid production of plaque biofilm. The cost of repairing failed repair is the 50-70%. of dental operation time. The aim of the study is to add the new quaternary ammonium salt DMADDM and nano silver particle NAg to dentin adhesive and bottom glue, and to discuss the resistance to the adhesive system. The effect of bacterial performance and adhesion strength.
Methods: the SBMP adhesive system was used as the control group in this experiment. DMADDM was synthesized and added with NAg to the adhesive and bottom glue. The whole bacterial biofilm model of dental plaque was used to study the biofilm by human saliva culture. The metabolic activity of biofilm, the count of CFU, the milk yield and the shear bond strength of human dentin were measured.
Results: the minimum inhibitory concentration (minimal inhibitory concentration, MIC) and the lowest bactericidal concentration (minimal bactericidal concentration, MBC) of DMADDM decreased more than one order of magnitude compared with the original QADM. The diameter of the agar plate bacteriostasis ring was far greater than the inhibitory ring formed by the bottom glue adding QADM. Diameter (P0.05). However, the metabolic activity of plaque biofilm (P 0.05) was greatly reduced by the addition of DMADDM-NAg adhesive and bottom glue. At the same time, the result of CFU count was less than that of the experimental group adding DMADDM alone (P0.05) with the addition of DMADDM and NAg. Compared with the control group, the experimental group was added to the DMADDM-NAg experimental group and the production of Lactobacillus in the plaque biofilm decreased. 20 times. The addition of DMADDM and NAg to the adhesive system did not adversely affect the bonding strength of dentin.
Significance: a new antibacterial monomer, DMADDM, was synthesized and added to dentin adhesives and adhesives for the first time. Antibacterial dentine adhesives have an important role in inhibiting residual bacteria and preventing bacterial invasion..DMADDM and NAg have good application prospects in dentin bonding system and restoration of complex resin.
The fourth part is the effect of water aging on bonding strength and anti biofilm activity of dentin adhesive containing new monomer dimethylaminododecyl methacrylate.
Objective: the aim of this study was to add new antibacterial monomer DMADDM, nano silver particles NAg and amorphous calcium phosphate nanoparticles NACP into dentin bonding system and develop new antibacterial dentin bonding system. The dentin bonding strength and antibacterial properties were detected for the first time through 6 months of water aging method. The long-term effect.
Methods: the following four groups of adhesive systems were detected: SBMP control group, SBMP+5%DMADDM, SBMP+5%DMADDM+0.1%NAg and SBMP+5%DMADDM+0.1%NAg, and the adhesive was added to the 20%NACP. specimen for 1 days and 6 months at 37, and then the shear bond strength of dentin was measured. The whole bacterial biofilm of dental plaque was obtained by using human Tuo Yepei. Models were used to study biofilms, and to measure biofilm metabolic activity, CFU counts, and lactol production.
Results: after 6 months of water aging in the SBMP control group, the dentin bonding strength decreased by 35% (n=10). In contrast, the experimental group adding antibacterial adhesive did not decrease the adhesion strength. The experimental group containing DMADDM-NAg-NACP showed a strong DMADDM antibacterial effect, the activity of the plaque biofilm was greatly reduced, the metabolic activity and the acid production were all Significantly less. Compared with the control group, the CFU count decreased by more than two orders of magnitude. In addition, the adhesive system containing DMADDM-NAg-NACP had long-term antibacterial properties, and there was no significant difference between 1 days and 6 months of antibacterial effect (P0.1).
Conclusion: the dentin bonding system with DMADDM-NAg-NACP has strong and lasting antibacterial properties. The adhesion strength after 6 months of water aging is much greater than that of the commercialized control group. This new antibacterial adhesive system can effectively inhibit the growth of plaque biofilm and repair the caries on the edge of the prosthesis. This method is used in other dentin bonding systems, The modification of orthodontic adhesive and composite resin has wide applicability.
【学位授予单位】：首都医科大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R783.1

【共引文献】