Low Temperature Plasma as an Approach for the Treatment of Peri-Implantitis

低温血浆治疗种植体周围炎的方法

• 批准号: 9804697
• 负责人: Paulo G Coelho
• 金额: $ 21.17万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9804697
• 关键词: Actinomyces naeslundii; Address; Adjuvant; Affect; Amoxicillin; Animal Model; Antimicrobial Resistance; Argon; Biological Assay; Biomechanics; Bone Resorption; Bone Tissue; Candida albicans; Cell Survival; Cell membrane; Cells; Characteristics; Chlorhexidine; Chronic; Complex; Coupled; Data; Debridement; Dental Implants; Dose; Environment; Epidemiology; Epithelium; Etiology; Event; Family suidae; Foundations; Future; Gases; Gingiva; Goals; Histology; Human; Implant; Implantation procedure; In Vitro; Individual; Inflammation; Jaw; Lead; Ligature; Maintenance; Mediating; Metronidazole; Microbial Biofilms; Miniature Swine; Modeling; Morphology; Mucous Membrane; Natural regeneration; Operative Surgical Procedures; Oral; Osseointegration; Osteoclasts; Osteogenesis; Patients; Plasma; Play; Porphyromonas gingivalis; Prevalence; Procedures; Process; Protocols documentation; Public Health; Publishing; Regimen; Role; Rupture; Sampling; Scanning Electron Microscopy; Site; Staphylococcus aureus; Streptococcus; Streptococcus oralis; Structure; Surface; Testing; Therapeutic Effect; Three-Dimensional Image; Time; Tissues; Titanium; Toxic effect; Translating; Translations; antimicrobial; bactericide; base; bone; bone healing; bone loss; clinical practice; cold temperature; cytotoxicity; dosage; effective therapy; experimental study; healing; image reconstruction; implantable device; in vitro testing; in vivo; in vivo Model; microbial; microorganism; oral care; oral cavity epithelium; peri-implantitis; polymicrobial biofilm; pre-clinical; reconstitution; response; sample fixation; side effect; treatment strategy

Biofilm formed around dental implants trigger inflammation, which plays a leading role into promoting osteoclast mediated bone resorption and inhibiting bone formation, resulting in net bone loss around implants referred to as peri-implantitis. Once established, peri-implantitis progresses and leads to implant loss. The use of low temperature plasma (LTP) as a co-adjuvant to treat peri-implantitis is promising, as unlike current peri-implantitis treatment strategies and demonstrated by our preliminary data, has the unique potential to simultaneously (i) decontaminate infected surfaces while (ii) allowing for the creation of a suitable environment for bone regrowth around the implant (iii) without damaging peri-implant related tissues. Advantages of LTP over traditional antimicrobial applications are that LTP can be used for site-specific treatment, provides an almost instantaneous bactericidal response, antimicrobial resistance is less likely to occur, and there are minimal side effects. Our hypothesis is that LTP, coupled with surgical debridement, is a unique efficacious approach for treatment of peri-implantitis. To address our hypothesis, the following specific aims are proposed: Aim 1) To determine the LTP protocol most disruptive to in vitro multispecies peri-implantitis related biofilms, while maintaining low cytotoxicity. Biofilms in several levels of maturation comprising of Streptococcus oralis, Actinomyces naeslundii, Veillonela dispar, and Porphyromonas gingivalis will be treated with LTP in different conditions and compared to controls, which includes gas flow, 0.12% Chlorhexidine, 14 µg/mL of amoxycillin and 140 µg/mL metronidazole, individually or in combination. Efficacy, in the absence of toxicity, will be confirmed using in vitro reconstituted oral (ROE) and gingival epithelium (RGE) infected or not with P. gingivalis; Aim 2) To evaluate the effect of LTP treatment on peri-implantitis using a Gottingen minipig model. Ligature induced peri-implantitis will be developed in the jaws of miniature swine. These will be surgically treated coupled with two LTP regimens or with appropriate controls, allowed to heal, and the level of both soft and hard tissue reattachment evaluated by histology assays and three-dimensional image reconstruction. Anabolic and catabolic events will also be assessed. The proposed project will expand on our preliminary experiments and refine a unique approach for the treatment of emerging problem of peri-implantitis, using LTP’s synergistic effects to decontaminate and/or detoxify the infected peri- implantitis site, and create a suitable environment for bone regrowth around the implant, all of this in a single and short time application (minutes) and low-toxicity to the mucosa. Furthermore, our proposed experiments will test LTP in a large preclinical animal model that is remarkably similar to humans allowing direct translation of findings toward clinical practice.

牙齿围绕牙科触发注入的生物膜，在促进破骨细胞中起着领先的作用 介导的骨骼分辨率和抑制骨形成，导致净骨质流失周围 作为植入物炎。建立后，植入体炎会进展并导致植入物丢失。使用低 温度血浆（LTP）作为治疗植入周围炎的共辅助症是有希望的，因为与当前的种植体植入炎 治疗策略并通过我们的初步数据证明，具有简单的独特潜力（i） 净化感染的表面，而（ii）允许创建合适的骨改革环境 在植入物周围（III）周围，而不会损坏植入物与植入物相关的组织。 LTP比传统的优势 抗微生物应用是LTP可用于特定于现场的治疗，几乎可以瞬时 杀菌反应，抗菌耐药性不太可能发生，并且副作用最少。我们的 假设是LTP加上外科调试，是一种用于治疗的独特有效方法 种植体炎。为了解决我们的假设，提出了以下具体目标：目标1）确定 LTP方案对体外多种植物周围性炎的生物膜最具破坏性，同时保持低 细胞毒性。在几个级别的成熟链球菌口腔，静脉肌动菌，naeslundii， Veillonela dispar和Porphyromonas牙龈将在不同条件下用LTP处理，并与 对照，包括气流，0.12％的洗涤甲啶，14 µg/ml的阿莫西林和140 µg/ml甲硝唑， 单独或组合。在没有毒性的情况下，功效将使用体外重组确认 口服（ROE）和牙龈上或不感染牙龈疟原虫的牙龈上皮（RGE）；目标2）评估LTP的效果 使用Gottingen Minipig模型对种植体炎症炎进行治疗。结扎诱导的植入周围炎将开发 在微型猪的颚中。这些将与两个LTP方案相结合或适当的 对照，允许愈合，以及通过组织学分析评估的软组织保留的水平 和三维图像重建。合成代谢和分解代谢事件也将进行评估。提议 项目将扩大我们的初步实验，并完善一种独特的方法来治疗新兴的方法 使用LTP的协同作用去抗污染和/或排毒的植入植物炎的问题 植入炎部位，并为植入物周围的骨改革创造一个合适的环境，所有这些都单一 以及短时间施用（分钟）和对粘膜的低毒性。此外，我们提出的实验将 在大型临床前动物模型中测试LTP，与人类非常相似，允许直接翻译 临床实践的发现。