Nitric Oxide Releasing Biomimetic Nanomatrix Gel for Root Revitalization

项目总结 暴露在机械创伤或龋齿过程中的牙髓组织可导致根管 和/或根尖周感染，可通过根管治疗。一种再生性牙髓治疗 程序(REP)试图从先前坏死或发炎的牙髓中恢复牙髓-牙本质组织，因此， 允许牙髓-牙本质结构的持续发展，特别是对于年轻的未成熟的根。 然而，目前的REP已经导致了不利的结果，包括牙齿变色，颈根 骨折，牙髓-牙本质组织结构形成不充分，以及多次就诊。 为了应对当前代表的挑战，高度跨学科和创新的战略是 建议使用抗生素和硝酸盐进行有效的根管消毒和牙髓-牙本质组织振兴 氧化物(NO)释放仿生纳米基质凝胶。我们假设抗生素和一氧化氮的释放 纳米基质凝胶将显示出有效的抗菌作用，并招募内源干细胞诱导 牙髓-牙本质活化，同时提供良好的牙髓-牙本质组织模仿细胞外基质 环境。建议的策略比目前的方法有几个优点：1)预防牙齿 去除米诺环素引起的变色，2)避免钙离子以防止颈根骨折 氢氧化物，3)NO的抗菌作用，4)通过酶抑制NO从纳米基质凝胶中释放出来 中介降解，5)通过避免重新开放根管和减少炎症反应 刺激出血，6)纳米基质凝胶作为功能性细胞外的生物相容性和生物降解性 基质，以及7)较少的广泛的牙髓通路开放、临床访问和使用具有成本效益的材料的修复 如复合树脂。 因此，我们提出了三个具体的目标来评估这一假说。具体目标1是评估 抗菌药物和NO释放仿生纳米基质凝胶的抗生物被膜作用 牙髓感染。具体目标2是评估抗生素和NO释放的细胞效应。 牙髓干细胞上的仿生纳米基质凝胶。具体目标3是开发一颗感染了比格犬的牙齿 模拟和评价抗生素和NO释放的仿生纳米基质凝胶的活化能力。 这项建议的结果将展示抗生物被膜的效果和振兴潜力 抗生素和NO释放型纳米基质凝胶治疗牙髓感染。此外，结果是 也将导致未来对年轻的未成熟的根管以及成熟的根管感染的临床研究 创伤性暴露和细菌相关病例。

PROJECT SUMMARY Dental pulp tissue exposed to a mechanical trauma or cariogenic process can result in root canal and/or periapical infections, which can be treated via an endodontic procedure. A regenerative endodontic procedure (REP) attempts to revitalize pulp-dentin tissue from a previously necrotic or inflamed pulp, thus, allowing for continued development of the pulp-dentin structure, particularly for a young immature root. However, the current REP has resulted in unfavorable outcomes, including tooth discoloration, cervical root fractures, inadequate pulp-dentin tissue structure formation, and multiple clinic visits. In order to tackle the challenges of the current REP, a highly interdisciplinary and innovative strategy is proposed for efficient root canal disinfection and pulp-dentin tissue revitalization using an antibiotics and nitric oxide (NO) releasing biomimetic nanomatrix gel. We hypothesize that the antibiotics and NO releasing nanomatrix gel will demonstrate an efficient antibacterial effect and recruit endogenous stem cells to induce pulp-dentin revitalization, while providing a favorable pulp-dentin tissue mimicking extracellular matrix environment. The proposed strategy has several advantages over the current REP: 1) preventing tooth discolorations by removal of minocycline, 2) preventing cervical root fractures by avoidance of calcium hydroxide, 3) antibacterial effect of the NO, 4) sustained NO release from the nanomatrix gel by enzyme mediated degradation, 5) reducing inflammatory responses by avoidance of reopening root canals and stimulated bleeding, 6) biocompatibility and biodegradability of the nanomatrix gel as a functional extracellular matrix, and 7) less extensive pulp access opening, clinical visits, and restorations with cost-effective materials such as composites resin. Therefore, three specific aims are proposed to evaluate the hypothesis. Specific Aim 1 is to evaluate the anti-biofilm effects of the antibiotics and NO releasing biomimetic nanomatrix gel in clinical samples from the endodontic infection. Specific Aim 2 is to evaluate the cellular effects of the antibiotics and NO releasing biomimetic nanomatrix gel on dental pulp stem cells. Specific Aim 3 is to develop a beagle infected tooth model and evaluate the revitalization capacity of the antibiotics and NO releasing biomimetic nanomatrix gel. The outcomes from this proposal will demonstrate the anti-biofilm effect and revitalization potential of the antibiotics and NO releasing nanomatrix gel for the treatment of endodontic infections. Further, the outcomes will also lead to future clinical studies for a young immature root as well as a mature root canal infection with traumatic exposure and bacterial associated cases.