Nitric Oxide Releasing Biomimetic Nanomatrix Gel for Root Revitalization

释放一氧化氮的仿生纳米基质凝胶用于根部再生

• 批准号: 10219231
• 负责人: Kyounga Cheon
• 金额: $ 13.29万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-20 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10219231
• 关键词: Alkaline Phosphatase; Anatomy; Animals; Anti-Bacterial Agents; Antibiotics; Biocompatible Materials; Biological; Biological Assay; Biomimetics; Blood Vessels; Catheters; Cells; Cervical; Clinic Visits; Clinical; Clinical Research; Collagen; Complex; Composite Resins; Dental Pulp; Dental crowns; Dentin; Development; Disinfection; Encapsulated; Endodontics; Enterococcus faecalis; Environment; Enzymes; Excision; Exposure to; Extracellular Matrix; Financial Hardship; Fracture; Future; Gel; General Population; Goals; Hemorrhage; Human; Immunohistochemistry; Implant; In Vitro; Infection; Inflammatory Response; Injectable; Laser Scanning Confocal Microscopy; Lead; Mechanics; Mediating; Methods; Microbial Biofilms; Microfluidics; Minocycline; Modeling; Natural regeneration; Necrosis; Neurons; Nitric Oxide; Odontoblasts; Oral cavity; Outcome; Patients; Plant Roots; Procedures; Process; Public Health; Publishing; Pulp Canals; Regulation; Reporting; Role; Sampling; Stains; Structure; System; Testing; Therapeutic; Time; Tissues; Tooth Discoloration; Tooth Socket; Tooth structure; Trauma; Treatment Protocols; Treatment outcome; Treponema denticola; Visit; biomaterial compatibility; calcium hydroxide; cost effective; design; dosage; in vivo; innovation; instrumentation; microCT; microbiota; migration; mineralization; periapical; polymicrobial biofilm; prevent; recruit; regenerative; restoration; stem cell differentiation; stem cell proliferation; stem cells; subcutaneous; success; tissue regeneration; tissue repair

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.

项目摘要 牙髓组织暴露于机械创伤或致龋过程可导致根管 和/或根尖周感染，其可以通过牙髓手术治疗。一种再生牙髓， 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， 允许牙髓-牙本质结构的继续发育，特别是对于年轻的未成熟牙根。 然而，目前的REP导致了不利的结果，包括牙齿变色，颈根， 骨折、牙髓-牙本质组织结构形成不充分以及多次就诊。 为了应对当前REP的挑战， 建议使用抗生素和硝酸进行有效的根管消毒和牙髓牙本质组织再生 一氧化氮（NO）释放仿生纳米基质凝胶。我们假设抗生素和NO的释放 纳米基质凝胶将显示出有效的抗菌效果，并招募内源性干细胞以诱导 牙髓-牙本质再生，同时提供模拟细胞外基质的有利牙髓-牙本质组织 环境与目前的REP相比，所提出的策略具有以下几个优点：1）防止牙齿脱落 通过去除米诺环素，2）通过避免钙来预防颈根骨折 氢氧化物，3）NO的抗菌作用，4）通过酶从纳米基质凝胶中持续释放NO 介导的降解，5）通过避免重新打开根管来减少炎症反应， 刺激出血，6）纳米基质凝胶作为功能性细胞外基质的生物相容性和生物降解性， 基质，和7）较少的广泛的牙髓进入开口，临床访问，和具有成本效益的材料的漂白 例如复合树脂。 因此，提出了三个具体目标来评估假设。具体目标1是评估 抗生素和释放NO的仿生纳米基质凝胶在临床样品中的抗生物被膜效果， 牙髓感染具体目的2是评价抗生素和NO释放的细胞效应 仿生纳米基质凝胶对牙髓干细胞的影响具体目标3是开发比格犬感染牙齿 模型，并评价抗生素和NO释放仿生纳米基质凝胶的再生能力。 该提案的结果将证明抗生物膜效果和再生潜力， 抗生素和释放NO的纳米基质凝胶用于治疗牙髓感染。此外，结果 还将导致未来对年轻未成熟根以及成熟根管感染的临床研究 创伤暴露和细菌相关病例。