3D-Printed Superhydrophobic-Tipped Optical Fiber for Targeted Periodontal Photodynamic Therapy

用于靶向牙周光动力治疗的 3D 打印超疏水尖端光纤

• 批准号: 10018842
• 负责人: QianFeng Xu
• 金额: $ 75.44万
• 依托单位: SINGLETO2 THERAPEUTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10018842
• 关键词: 3D Print; Actinomyces naeslundii; Address; Adoption; Affect; Air; Antibiotics; Area; Bacteria; Businesses; Caliber; Chlorhexidine; Clinical Trials; Dental; Dentistry; Dentists; Development; Devices; Diffuse; Disease; Disinfection; Dyes; Effectiveness; Ensure; Environment; Evaluation; Exhibits; Fiber Optics; Future; Generations; Gram-Negative Bacteria; Gram-Positive Bacteria; Histology; Human; Hydroxyapatites; Hypoxia; In Vitro; Lead; Ligature; Local Anti-Infective Agents; Methods; Microbial Biofilms; Modeling; Molds; Molecular; Oral cavity; Oxygen; PUVA Photochemotherapy; Pain; Painless; Penetration; Performance; Periodontal Diseases; Periodontal Pocket; Periodontitis; Phase; Photobiology; Photochemistry; Photosensitization; Photosensitizing Agents; Pilot Projects; Porphyromonas gingivalis; Productivity; Property; Rattus; Singlet Oxygen; Site; Small Business Technology Transfer Research; Stains; Sterilization; Streptococcus mutans; Study models; Surface; System; Technology; Therapeutic; Time; Tissue Stains; Tissues; Tooth structure; Translations; Update; Visit; Wistar Rats; Work; appropriate dose; bacterial resistance; bactericide; commercialization; cost; cytotoxic; design; efficacy study; implantation; improved; in vivo; innovation; materials science; miniaturize; novel; optical fiber; oral bacteria; oral care; polymicrobial biofilm; prevent; restorative material; scaling and root planing; standard care; treatment strategy

Eradication of bacteria located in periodontal pockets presents a daunting challenge to dentists and oral care professionals. The problem is significant; severe periodontitis is the 6th most prevalent disease worldwide with over 743 million people affected. The global cost of lost productivity from severe periodontitis is estimated to be $54 billion USD/year. Antibiotics with scaling and root planing (SRP) have been the mainstays of current treatments but may lead to the development of antibioticresistant bacteria. Photodynamic therapy (PDT) is a beneficial alternative, however, there are several challenges to its implantation including staining of tissue and a short penetration depth because the dye is introduced directly into the periodontal pocket as well as long treatment times due lack of oxygen in hypoxic pockets. Thus, there is an urgent need for further advances in periodontal bacteria eradication. The superhydrophobic fiber optic PDT (SH-PDT) device tip developed by SingletO2 Therapeutics LLC delivers bactericidal singlet oxygen (1O2, a cytotoxic excited state of molecular oxygen) in a direct, controllable fashion. This device is a major breakthrough for the precise delivery of reactive singlet oxygen to kill hypoxic bacteria for treatment of periodontal diseases. Using precision molding and 3D printing technologies, the device integrates a sensitizer onto the tip of an optical fiber that can painlessly be inserted between the tooth and gum killing bacteria which are the cause of periodontitis. Our superhydrophobic design prevents contact between biofluids and the sensitizer, eliminating staining. Moreover, disinfection of the periodontal pocket will be achieved in a single visit due to the efficiency of the superhydrophobic system to trap air, which will provide oxygen to otherwise hypoxic environments. The approach will also not induce bacterial resistance, and it will be equally effective on gram-negative and gram-positive bacteria. In this Phase II STTR project, we propose to study the efficacy of the SH-PDT device in two ways. First we will quantify the ability of the device to kill a bacterial biofilm in vitro that is comprised of three different bacteria strains associated with periodontitis. Secondly, we will quantify the ability of the device to kill periodontitis in vivo using a Wistar rat ligature model. A pilot study will be conducted to determine the appropriate dose, followed by a full study to acquire statistically significant results. Successful results from these studies will be used to design human clinical trials in the future.

根除牙周口袋中的细菌对牙医和 口腔护理专业人员。问题很重要；严重的牙周炎是第六最普遍的 全球疾病，有超过7.43亿人受到影响。全球生产力失去生产力的成本 严重的牙周炎估计为540亿美元/年。抗生素具有缩放和根平面的抗生素 （SRP）一直是当前治疗的主要阶段，但可能导致抗生素抗药性的发展 细菌。光动力疗法（PDT）是一种有益的选择，但是有 其植入的几个挑战，包括组织染色和短深度 因为将染料直接引入牙周口袋以及长时间的治疗时间 由于缺氧口袋缺乏氧气。因此，迫切需要进一步发展 消除牙周细菌。 Singleto2 Therapeutics开发的超疏水光纤PDT（SH-PDT）设备尖端 有限责任公司在A中提供杀菌单重氧（1O2，一种分子氧的细胞毒性激发态） 直接，可控制的时尚。该设备是精确输送反应性的重大突破 单线氧杀死缺氧细菌以治疗牙周疾病。使用精确成型 和3D打印技术，该设备将灵敏度集成到光纤的尖端上 可以在牙齿和牙龈杀死细菌之间无痛地插入 牙周炎。我们的超疏水设计可防止生物流体与敏化剂之间的接触， 消除染色。此外，一次访问将实现牙周口袋的消毒 由于超疏水系统诱捕空气的效率，这将为氧气提供氧气 否则低氧环境。该方法也不会引起细菌抗性，它将 对革兰氏阴性和革兰氏阳性细菌同样有效。 在此II阶段的STTR项目中，我们建议通过两种方式研究SH-PDT设备的功效。 首先，我们将量化设备在体外杀死细菌生物膜的能力，该生物膜由 与牙周炎有关的三种不同细菌菌株。其次，我们将量化 使用Wistar大鼠结扎模型杀死体内牙周炎的装置。试点研究将是 进行确定适当剂量的进行，然后进行全面研究以统计获取 重大结果。这些研究的成功结果将用于设计人类的临床试验 将来。

项目成果

Antimicrobial Photodynamic Inactivation Using Topical and Superhydrophobic Sensitizer Techniques: A Perspective from Diffusion in Biofilms.

• DOI: 10.1111/php.13461
• 发表时间: 2021-11
• 期刊: PHOTOCHEMISTRY AND PHOTOBIOLOGY
• 影响因子: 3.3
• 作者: Tonon, Caroline Coradi;Ashraf, Shoaib;Alburquerque, Jose Quilez;de Souza Rastelli, Alessandra Nara;Hasan, Tayyaba;Lyons, Alan M.;Greer, Alexander
• 通讯作者: Greer, Alexander

Evaluation of photosensitizer-containing superhydrophobic surfaces for the antibacterial treatment of periodontal biofilms.

含光敏剂的超疏水表面对牙周生物膜抗菌治疗的评价。

• DOI: 10.1016/j.jphotobiol.2022.112458
• 发表时间: 2022
• 期刊: Journal of photochemistry and photobiology. B, Biology
• 作者: Tonon,CarolineCoradi;Ashraf,Shoaib;deSouzaRastelli,AlessandraNara;Ghosh,Goutam;Hasan,Tayyaba;Xu,QianFeng;Greer,Alexander;Lyons,AlanM
• 通讯作者: Lyons,AlanM