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

牙种植体周围形成的生物膜会引发炎症，炎症在促进破骨细胞方面起主导作用。 介导骨吸收和抑制骨形成，导致种植体周围骨丢失 作为种植体周围炎。一旦确定，种植体周围炎就会进展并导致种植体丢失。LOW的使用 与目前的种植体周围炎不同，温度等离子体(LTP)作为辅助辅助治疗种植体周围炎是很有前途的。 治疗策略和我们的初步数据表明，具有同时(I)的独特潜力 净化受感染的表面，同时(Ii)允许为骨骼再生创造合适的环境 种植体周围(III)，不损伤种植体周围相关组织。LTP相对于传统协议的优势 抗菌应用是，LTP可用于部位特异性治疗，提供几乎瞬间的 杀菌反应、抗菌素耐药性发生的可能性较小，且副作用极小。我们的 假说认为，LTP结合外科清创是治疗慢性前列腺癌的唯一有效方法。 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周炎相关生物膜的破坏性最大，同时保持较低的 细胞毒性。不同成熟度的生物膜包括口腔链球菌、奈氏放线菌、 不同条件下LTP对Veillonela dispar和Pporromonas gigivalis的治疗效果 对照组，包括气体流量、0.12%洗必泰、14微克/毫升阿莫西林和140微克/毫升甲硝唑， 单独的或组合的。在没有毒性的情况下，将使用体外重组的方法来确认疗效。 口腔(ROE)和牙龈上皮(RGE)感染或未感染Pggivalis；目的2)评价LTP的疗效 哥廷根小型猪模型治疗种植体周围炎。结扎性种植体周围炎的发生 在小型猪的下巴里。这些将结合两种LTP方案或适当的手术治疗。 对照组，允许愈合，通过组织学分析评估软组织和硬组织再附着的水平 和三维图像重建。合成代谢和分解代谢项目也将被评估。建议数 该项目将扩大我们的初步实验，并改进一种独特的方法来治疗新出现的 种植周炎问题，利用LTP的协同效应来净化和/或解毒感染的周围炎。 种植体炎症部位，并为种植体周围的骨再生创造合适的环境，所有这些都在一个单一的 给药时间短(分钟)，对粘膜毒性低。此外，我们提议的实验将 在大型临床前动物模型中测试LTP，该模型与人类非常相似，允许直接翻译 临床实践中的发现。

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.