NITRIC OXIDE RELEASING BIOMIMETRIC NANOMATRIX GELF OR ROOT REVITALIZATION

项目摘要 暴露于机械创伤或致龋过程的牙髓组织可导致根管和/或牙髓炎。 根尖周感染，可以通过牙髓手术治疗。再生牙髓手术 (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， 牙髓-牙本质结构的持续发育，特别是对于年轻的未成熟牙根。但目前 REP导致了不利的结果，包括牙齿变色，颈根骨折， 牙髓-牙本质组织结构的形成，以及多次就诊。为了应对当前REP的挑战， 高度跨学科和创新的策略，提出了有效的根管消毒和牙髓牙本质 使用抗生素和释放一氧化氮（NO）的仿生纳米基质凝胶进行组织再生。我们 假设抗生素和NO释放纳米基质凝胶将显示有效的抗菌效果 并募集内源性干细胞以诱导牙髓-牙本质再生，同时提供有利的牙髓-牙本质 模拟细胞外基质环境的组织。所提出的策略与 目前的REP：1）通过去除米诺环素预防牙齿变色，2）预防颈根骨折 通过避免氢氧化钙，3）NO的抗菌作用，4）从纳米基质持续释放NO 凝胶通过酶介导的降解，5）通过避免重新打开根管来减少炎症反应 和刺激出血，6）纳米基质凝胶的生物相容性和生物可降解性作为功能性 细胞外基质，和7）不太广泛的牙髓进入开放，临床访问，并具有成本效益的净化 复合材料树脂等材料。因此，提出了三个具体目标来评估假设。 具体目的1是评价抗生素和NO释放仿生纳米基质的抗生物被膜效果 凝胶在牙髓感染的临床样本中。具体目标2是评估细胞的影响， 抗生素和NO释放仿生纳米基质凝胶对牙髓干细胞的影响。具体目标3：发展 建立大鼠感染牙模型，评价抗生素和NO释放仿生剂的修复能力 纳米基质凝胶该提案的结果将证明抗生物膜效应和振兴 抗生素和释放NO的纳米基质凝胶治疗牙髓感染的潜力。此外，本发明还 结果也将导致未来的临床研究，为年轻的未成熟的根以及成熟的根管 与创伤暴露和细菌相关的感染病例。

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. 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 rat 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.