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

基本信息

批准号：
9429388
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
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-20 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9429388
关键词：
Alkaline Phosphatase Anatomy Animals Anti-Bacterial Agents Antibiotics Biocompatible Materials Biological Biological Assay Biomimetics Blood Vessels Catheters Cell Proliferation 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 Extracellular Matrix 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 Plasticizers Procedures Process Public Health Publishing Pulp Canals Recruitment Activity Regulation Reporting Role Sampling Staining method Stains Stem cells Structure System Testing Therapeutic Time Tissues Tooth Discoloration Tooth Socket Tooth structure Trauma Treatment Protocols Treatment outcome Treponema denticola Visit X-Ray Computed Tomography biomaterial compatibility calcium hydroxide cost effective dosage in vivo innovation instrumentation microbiota microorganism migration mineralization periapical prevent regenerative restoration subcutaneous success tissue repair

项目摘要

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.

项目概要牙髓组织暴露于机械创伤或致龋过程可能会导致根管和/或根尖周感染，可以通过牙髓手术治疗。再生牙髓手术 (REP) 试图使先前坏死或发炎的牙髓恢复活力，因此，允许牙髓-牙本质结构的持续发育，特别是对于年轻的未成熟的牙根。然而，目前的REP却导致了一些不良后果，包括牙齿变色、颈椎病等。骨折、牙髓-牙本质组织结构形成不足以及多次就诊。为了应对当前 REP 的挑战，需要采取高度跨学科和创新的战略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释放氧化物（NO）的仿生纳米基质凝胶。我们假设抗生素和 NO 释放纳米基质凝胶将表现出有效的抗菌作用，并招募内源性干细胞诱导牙髓-牙本质再生，同时提供模仿细胞外基质的有利牙髓-牙本质组织环境。与当前的 REP 相比，所提出的策略有几个优点：1）防止牙齿脱落通过去除米诺环素来变色，2) 通过避免钙来预防颈椎根部骨折氢氧化物，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和刺激出血，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，7) 不太广泛的牙髓通路开口、临床就诊以及使用具有成本效益的材料进行修复如复合树脂。因此，提出了三个具体目标来评估该假设。具体目标 1 是评估抗生素和 NO 释放仿生纳米基质凝胶在临床样本中的抗生物膜作用牙髓感染。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 是培育一颗比格犬感染的牙齿模型并评估抗生素和释放 NO 的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振兴潜力抗生素和释放 NO 的纳米基质凝胶用于治疗牙髓感染。此外，结果还将导致未来针对年轻未成熟牙根以及成熟根管感染的临床研究外伤暴露和细菌相关病例。