Reasons for poor durability of resin-dentin bonds

树脂-牙本质粘接耐久性差的原因

基本信息

  • 批准号:
    8294440
  • 负责人:
  • 金额:
    $ 64.44万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2004
  • 资助国家:
    美国
  • 起止时间:
    2004-03-01 至 2014-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): A major reason for the poor durability of tooth-colored resin restorations is that collagenolytic MMPs in the dentin matrix are uncovered and activated during resin bonding procedures (Pashley et al., 2004; Tay et al., 2006b; Nishitani et al., 2006; Mazzoni et al., 2006). This results in gradual but continuous degradation of collagen fibrils that anchor these fillings to underlying mineralized dentin. The recent discovery that chlorhexidine (CHX), a potent antimicrobial agent, also has potent anti-MMP -2, -8 and -9 activity (Gendron et al., 1999), led us to determine if CHX can stabilize resin-bonded collagen and increase the durability of resin- dentin bonds thereby saving the cost of frequent replacement of bonded restorations. Our in vitro success (Pashley et al., 2004; Nishitani et al., 2006, Carrilho et al., 2007a, Breschi et al., 2009a) using CHX to increase the durability of resin-dentin bonds led us to demonstrate CHX's success in increasing the stability of bonds in vivo (Hebling et al., 2005; Carrilho et al., 2007b; Brackett et al., 2007). These results have stimulated this grant application to delve more deeply into the mechanisms responsible for CHX inhibition of MMPs. We noted that CHX contains biguanide groups that form acidic addition salts with a cationic charge delocated over the five neighboring secondary amine nitrogen atoms of the biguanides. These function similarly to quaternary ammonium compounds that also form polycations that are also antibacterial. We have recently discovered several quaternary ammonium-containing monomers that can inhibit Clostridium collagenase. This result may cause a paradigm shift in adhesive formulations. By incorporating "therapeutic monomers" capable of inhibiting MMPs in adhesive blends, we may be able to extend the service of all adhesive resin restorations. Before this goal can be realized, we need to evaluate this new class of adhesive monomers. Although they inhibit bacterial collagenase, will they inhibit true MMPs? We will test the ability of a number of anticollagenolytic ("AC") monomers for their ability to inhibit soluble dentin MMP activity using soluble fluorescein-labeled collagen. Then we will test their ability to inhibit matrix-bound MMPs using the same soluble collagen substrate. Finally, we will determine if the "AC" monitors can inhibit bound-MMPs activity on the dentin matrix itself, as a substrate. We will also determine if "AC" monomers prevent the decrease in mechanical properties of dentin matrices that normally occur over time. Finally, we will learn how to blend these "AC" monomers with adhesive comonomers without reducing their degree of conversion, ability to wet dentin, or lowering their initial (24 hr) bond strength. Once we have proven that we can produce high bond strengths, we will test the durability of resin-dentin bonds made with control comonomers versus comonomers mixed with "AC" monomers using fatigue lifetime studies and initial versus 1 yr interfacial fracture toughness studies. If the results of this work are successful, we will then seek additional support for clinical trials of the best of these "AC" monomers, in our goal to provide more durable resin-dentin bonds. PUBLIC HEALTH RELEVANCE: Our successful use of topical chlorhexidine (CHX) application to acid-etched dentin to inhibit dentin MMPs and maintain the integrity of resin-dentin bonds in vitro and in vivo has been very gratifying. Chlorhexidine contains strongly basic biguanide groups that impart cationic charges to the molecules. Quaternary ammonium compounds (QAC) contain similar cationic charges that are responsible for their antibacterial properties that are responsible both for its antimicrobial activity and for its anti-MMP activity. We have discovered a number of QAC-containing monomers that inhibit collagenases. If we can incorporate them into adhesive resins, we may be able to permanently inhibit dentin MMPs that are thought to degrade resin-dentin bonds, while we are bonding. This new class of MMP-inhibitors is an exciting new discovery with profound clinical potential. Their successful use in adhesive resins could potentially save billions of dollars currently spent on the replacement of tooth-colored resin composites.
描述(由申请人提供):牙齿着色树脂固化的耐久性差的主要原因是牙本质基质中的胶原溶解性MMP在树脂粘合过程中未被覆盖并被激活(Pashley等人,2004; Tay等人,2006 b; Nishitani等人,2006; Mazzoni等人,2006年)。这导致将这些填充物锚到下面的矿化牙本质的胶原纤维逐渐但连续地降解。最近发现氯己定(CHX),一种有效的抗微生物剂,也具有有效的抗MMP-2、-8和-9活性(Gendron等人,1999),使我们确定CHX是否可以稳定树脂结合的胶原蛋白并增加树脂-牙本质结合的耐久性,从而节省频繁更换结合的牙本质的成本。我们的体外成功(Pashley等人,2004; Nishitani等人,2006年,Carrilho等人,2007 a,Breschi等人,2009 a)使用CHX增加树脂-牙本质键的耐久性使我们证明了CHX在增加体内键的稳定性方面的成功(Hebling等人,2005; Carrilho等人,2007 b; Brackett等人,2007年)。这些结果刺激了本基金申请更深入地研究负责CHX抑制MMP的机制。我们注意到,CHX含有双胍基团,其形成具有在双胍的五个相邻仲胺氮原子上离位的阳离子电荷的酸性加成盐。这些功能类似于季铵化合物,季铵化合物也形成聚阳离子,聚阳离子也是抗菌的。我们最近发现了几种含季铵的单体,可以抑制梭菌胶原酶。这一结果可能会导致粘合剂配方的范式转变。通过在粘合剂共混物中加入能够抑制MMP的“治疗性单体”,我们可能能够扩展所有粘合剂树脂混合物的服务。在实现这一目标之前,我们需要评估这类新的粘合剂单体。虽然它们抑制细菌胶原酶,但它们会抑制真正的MMPs吗?我们将使用可溶性荧光素标记的胶原来测试许多抗胶原溶解(“AC”)单体抑制可溶性牙本质MMP活性的能力。然后,我们将使用相同的可溶性胶原底物测试它们抑制基质结合的MMPs的能力。最后,我们将确定“AC”监测器是否可以抑制结合基质金属蛋白酶的活动对牙本质基质本身,作为一个基板。我们还将确定“AC”单体是否能防止牙本质基质的机械性能随时间推移而降低。最后,我们将学习如何将这些“AC”单体与粘合剂共聚单体混合,而不降低其转化程度,润湿牙本质的能力,或降低其初始(24小时)粘合强度。一旦我们证明我们可以产生高粘结强度,我们将使用疲劳寿命研究和初始与1年界面断裂韧性研究,测试用对照共聚单体与共聚单体与“AC”单体混合制成的树脂-牙本质粘结的耐久性。如果这项工作的结果是成功的,我们将寻求更多的支持,为临床试验的最佳这些“AC”单体,在我们的目标,以提供更持久的树脂牙本质债券。 公共卫生关系:我们成功地使用局部洗必泰(CHX)应用于酸蚀牙本质,以抑制牙本质MMPs,并保持树脂-牙本质键的完整性,在体外和体内已经非常令人满意。氯己定含有强碱性双胍基团,可赋予分子阳离子电荷。季铵化合物(QAC)含有类似的阳离子电荷,这是其抗菌特性的原因,而抗菌特性是其抗微生物活性和抗MMP活性的原因。我们已经发现了许多抑制胶原酶的含QAC的单体。如果我们能将它们加入到粘合树脂中,我们可能能够永久地抑制牙本质MMPs,这些MMPs被认为会在我们粘合时降解树脂-牙本质粘合。这类新的MMP抑制剂是一个令人兴奋的新发现,具有深远的临床潜力。它们在粘合剂树脂中的成功使用可能会节省目前用于更换牙齿颜色树脂复合材料的数十亿美元。

项目成果

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DAVID H PASHLEY其他文献

DAVID H PASHLEY的其他文献

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{{ truncateString('DAVID H PASHLEY', 18)}}的其他基金

Reasons for poor durability of resin-dentin bonds
树脂-牙本质粘接耐久性差的原因
  • 批准号:
    8509659
  • 财政年份:
    2004
  • 资助金额:
    $ 64.44万
  • 项目类别:
Reasons for poor durability of resin-dentin bonds
树脂-牙本质粘接耐久性差的原因
  • 批准号:
    7938919
  • 财政年份:
    2004
  • 资助金额:
    $ 64.44万
  • 项目类别:
Reasons for poor durability of resin-dentin bonds
树脂-牙本质粘接耐久性差的原因
  • 批准号:
    7015622
  • 财政年份:
    2004
  • 资助金额:
    $ 64.44万
  • 项目类别:
Reasons for poor durability of resin-dentin bonds
树脂-牙本质粘接耐久性差的原因
  • 批准号:
    7420927
  • 财政年份:
    2004
  • 资助金额:
    $ 64.44万
  • 项目类别:
Reasons for poor durability of resin-dentin bonds
树脂-牙本质粘接耐久性差的原因
  • 批准号:
    8105097
  • 财政年份:
    2004
  • 资助金额:
    $ 64.44万
  • 项目类别:
Reasons for poor durability of resin-dentin bonds
树脂-牙本质粘接耐久性差的原因
  • 批准号:
    7781442
  • 财政年份:
    2004
  • 资助金额:
    $ 64.44万
  • 项目类别:
Reasons for poor durability of resin-dentin bonds
树脂-牙本质粘接耐久性差的原因
  • 批准号:
    6861770
  • 财政年份:
    2004
  • 资助金额:
    $ 64.44万
  • 项目类别:
Reasons for poor durability of resin-dentin bonds
树脂-牙本质粘接耐久性差的原因
  • 批准号:
    6770682
  • 财政年份:
    2004
  • 资助金额:
    $ 64.44万
  • 项目类别:
Reasons for poor durability of resin-dentin bonds
树脂-牙本质粘接耐久性差的原因
  • 批准号:
    7215711
  • 财政年份:
    2004
  • 资助金额:
    $ 64.44万
  • 项目类别:
Determinants of the Durability of Resin-Dentin Bonds
树脂-牙本质粘结耐久性的决定因素
  • 批准号:
    6687957
  • 财政年份:
    2003
  • 资助金额:
    $ 64.44万
  • 项目类别:

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