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.

牙种植体周围形成的生物膜会引发炎症，这对促进破骨细胞发挥主导作用 介导骨吸收并抑制骨形成，导致种植体周围的净骨损失 如种植体周围炎。一旦形成，种植体周围炎就会进展并导致种植体脱落。使用低 与目前的种植体周围炎不同，温度等离子体（LTP）作为治疗种植体周围炎的辅助佐剂是有前景的 我们的初步数据表明，治疗策略具有独特的潜力，可以同时 (i) 净化受感染的表面，同时 (ii) 为骨骼再生创造合适的环境 围绕种植体 (iii) 不损伤种植体周围相关组织。 LTP相对于传统的优势 抗菌应用的特点是 LTP 可用于特定部位的治疗，提供几乎瞬时的 杀菌反应小，不易发生抗菌药物耐药性，且副作用极小。我们的 假设 LTP 与手术清创相结合是一种独特且有效的治疗方法 种植体周围炎。为了解决我们的假设，提出了以下具体目标： 目标 1) 确定 LTP 方案对体外多物种种植体周围炎相关生物膜最具破坏性，同时保持较低水平 细胞毒性。多种成熟水平的生物膜，包括口腔链球菌、内氏放线菌、 Veillonela dispar 和 Porphyromonas gingivalis 将在不同条件下用 LTP 处理，并与 对照品，包括气流、0.12% 氯己定、14 µg/mL 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，将使用体外重构来确认功效 口腔（ROE）和牙龈上皮（RGE）是否感染牙龈卟啉单胞菌；目标 2) 评估 LTP 的效果 使用哥廷根小型猪模型治疗种植体周围炎。将发生结扎引起的种植体周围炎 在小型猪的嘴里。这些将通过手术治疗结合两种 LTP 方案或适当的 控制，允许愈合，并通过组织学测定评估软组织和硬组织重新附着的水平 以及三维图像重建。还将评估合成代谢和分解代谢事件。拟议的 项目将扩展我们的初步实验，并完善治疗新兴疾病的独特方法 种植体周围炎的问题，利用 LTP 的协同效应来净化和/或解毒受感染的周围 种植体炎部位，并为种植体周围的骨再生创造一个合适的环境，所有这一切都在一个单一的过程中 使用时间短（分钟），对粘膜毒性低。此外，我们提出的实验将 在大型临床前动物模型中测试 LTP，该模型与人类非常相似，可以直接翻译 研究结果用于临床实践。