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

牙种植体周围形成的生物膜引发炎症反应，在促进破骨细胞形成中起主导作用 介导的骨吸收和抑制骨形成，导致种植体周围的净骨丢失， 种植体周围炎一旦建立，种植体周围炎进展并导致种植体丢失。使用低 与目前的种植体周围炎不同，低温等离子体（LTP）作为治疗种植体周围炎的辅助剂是有希望的 治疗策略，并证明了我们的初步数据，具有独特的潜力，同时（i） 净化受感染的表面，同时（ii）允许为骨再生创造合适的环境 （iii）植入物周围，而不损伤植入物周围相关组织。LTP相对于传统 LTP可用于特定部位的治疗，提供了几乎瞬时的抗微生物应用， 杀菌反应，抗菌素耐药性不太可能发生，并且副作用很小。我们 假设LTP结合外科清创术是治疗 种植体周围炎为了解决我们的假设，提出了以下具体目标： LTP方案对体外多种属种植体周围炎相关生物膜的破坏性最大，同时维持低水平 细胞毒几种成熟水平的生物膜，包括口腔链球菌，内氏放线菌， 将在不同条件下用LTP处理Veillonela dispar和牙龈卟啉单胞菌，并与 对照，包括气流、0.12%氯己定、14 µg/mL阿莫西林和140 µg/mL甲硝唑， 单独地或组合地。在无毒性的情况下，将使用体外复溶的 目的2）评价LTP治疗牙龈卟啉单胞菌感染的效果 使用哥廷根小型猪模型治疗种植体周围炎。结扎引起的种植体周围炎将发生 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 对照，允许愈合，并通过组织学测定评价软组织和硬组织再附着的水平 和三维图像重建。还将评估合成代谢和分解代谢事件。拟议 该项目将扩大我们的初步实验，并完善一个独特的方法来治疗新兴的 种植体周围炎的问题，使用LTP的协同效应来净化和/或解毒受感染的牙周组织， 种植体炎部位，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 并且施用时间短（分钟），对粘膜的毒性低。此外，我们提出的实验将 在与人类非常相似的大型临床前动物模型中测试LTP， 临床实践的发现。

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.