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: 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
• 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

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 暴露于机械外伤或致癌过程的牙纸浆组织可能导致根管 和/或根尖感染，可以通过牙髓手术治疗。再生牙髓 程序（REP）试图从先前坏死或发炎的纸浆中振兴牙髓丁丁组织 允许继续开发纸浆丁丁结构，特别是对于年轻的未成熟根。 但是，当前的代表导致不利的结果，包括牙齿变色，颈根 骨折，牙髓丁丁组织结构不足和多次临床就诊。 为了应对当前代表的挑战，高度跨学科和创新的策略是 提议使用抗生素和硝酸 氧化物（NO）释放仿生纳米疗法凝胶。我们假设抗生素和没有释放 Nanomatrix凝胶将表现出有效的抗菌作用，并募集内源性干细胞以诱导 牙髓丁丁振兴，同时提供了模仿细胞外基质的有利的纸浆丁丁组织 环境。提出的策略比当前代表具有多个优点：1）防止牙齿 通过去除米诺环素的变色，2）通过避免钙防止颈根骨折 氢氧化物，3）NO，4）酶从纳米质凝胶中持续不释放的抗菌作用。 介导的降解，5）通过避免重新打开根管和 刺激的出血，6）纳米瘤凝胶的生物相容性和生物降解性作为功能细胞外 矩阵和7）较少广泛的纸浆接入开放，临床访问和具有成本效益材料的修复 例如复合材料树脂。 因此，提出了三个特定目标来评估该假设。特定目标1是评估 抗生素的抗生物膜作用和临床样品中均未释放的仿生纳米质凝胶 牙髓感染。特定目的2是评估抗生素的细胞效应，而无释放 牙髓干细胞上的仿生纳米质凝胶。特定目标3是开发猎犬感染的牙齿 模型并评估抗生素的振兴能力，没有释放仿生纳米疗法凝胶。 该提案的结果将证明抗生物膜的效应和振兴潜力 抗生素，无释放纳米疗法凝胶治疗牙髓感染。此外，结果 还将导致未来的未来未成熟根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。