Rechargeable Infection-responsive Anticandidal Denture Materials

可充电感染反应型抗念珠菌义齿材料

• 批准号: 9886070
• 负责人: CHIH-KO YEH
• 金额: --
• 依托单位: SOUTH TEXAS VETERANS HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-10-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9886070
• 关键词: 3-Dimensional; Affect; Aging; Animal Testing; Antibiotics; Antifungal Agents; Antifungal Therapy; Appearance; Attention; Behavior; Binding; Candida; Catheters; Cell Culture Techniques; Chemicals; Chlorhexidine; Clinical; Clinical Trials; Coculture Techniques; Complete Denture; Dental Implants; Dental caries; Dentistry; Denture Bases; Denture Stomatitis; Denture Wear; Dentures; Development; Devices; Diabetes Mellitus; Dimensions; Disease; Disinfection; Dissociation; Elderly; Energy-Generating Resources; Environment; Epithelial; Epithelial Cells; Epithelium; Financial Hardship; Funding; Goals; Habits; Healthcare; Human; Hygiene; Immunologics; Infection; Kinetics; Lead; Life; Maxilla; Medical; Medical Device; Methacrylates; Miconazole; Microbial Biofilms; Modeling; Nosocomial Infections; Oral health; Outcome; Patient Care; Patients; Performance; Periodontal Diseases; Personal Satisfaction; Pharmaceutical Preparations; Plant Resins; Plasma; Polymers; Prevention; Procedures; Property; Prosthesis; Psyche structure; Pyrrolidinones; Quality of life; Rattus; Research; Resistance; Risk Factors; Saliva; Smoking; Speech; Steroid therapy; Surface; System; Systemic infection; Technology; Testing; Therapeutic; Thinness; Tissues; Tooth Diseases; Tooth Loss; Treatment Efficacy; Tube; Veterans; antimicrobial; base; biomaterial compatibility; candida biofilm; clinical application; effective therapy; endotracheal; experimental study; fighting; functional group; gastrointestinal; implantable device; improved; in vivo; individualized medicine; mechanical properties; medical complication; microbial; microbial colonization; new technology; next generation; novel; nutrition; oral care; oral infection; personalized medicine; polymethacrylic acid; premature; prevent; research clinical testing; risk minimization; treatment choice; treatment strategy

Candida-associated denture stomatitis (CADS) is a common, recurring disease among denture wearers and can lead to other oral health problems, systemic infections, compromised quality of life, and even life threating conditions. Our elderly veteran denture wearers are more prone to develop CADS since many of them are medically and immunologically compromised due to systemic, physical, and mental diseases and their associated therapies (e.g., antibiotics, steroid therapies, and xerostomic drugs). Currently, there are no effective treatment strategies for controlling CADS and the reinfection rate is high, affecting up to 67% of denture wearers. This renewal application builds upon the results of our previous funding period in which we used a rechargeable “click-on/click-off” anticandidal technology to develop long-term, infection-responsive denture base materials. The functional polymer grafts, including poly-N-vinyl-2-pyrrolidinone (PNVP), polymethacrylic acid (PMAA), and poly-2-hydroxyethyl methacrylate (PHEMA), were covalently bound onto denture discs using plasma as an energy source. These novel functionalized denture materials were capable of binding sufficient quantities of antifungal drugs, such as miconazole and chlorhexidine digluconate, and provide potent longlasting antifungal effects by release of the drugs into PBS or human saliva over the course of weeks to months. At the end of the experiment (or therapy for a patient), any remaining drug bound to the surface could be “washed off’ with a quenching solution. For clinical applications, the “quenched” denture could be returned to the patient for regular use or, if the infection recurred or persisted, be recharged with the same or different class of antifungal agent. Our long-term goal is to develop this rechargeable, “click-on/click-off” anticandidal technology to control CADS in clinical applications. Previous studies of denture discs have not addressed problems associated with the topology, bulk properties, physical/mechanical properties, dimensional stability, and drug loading/releasing properties from 3D complete dentures. The objective of this renewal is to further demonstrate proof of principle in this pre-translational stage regarding clinical utility of the new strategy. The specific aims of the proposed research are to: (1) fabricate 3D dentures, using the “click on/click off” anticandidal technology, for use in a rat model and evaluate their physical/mechanical properties and drug binding/releasing behaviors; (2) evaluate the new anticandidal rat 3D dentures for their biocompatibility and anticandidal activity under clinically simulated conditions; and (3) evaluate the new anticandidal 3D dentures in a rat denture stomatitis model. Further development of this new technology has the potential to significantly improve the quality of oral care delivered to our veterans by effectively managing CADS and its accompanying complications. If successful, this new denture material will be the first therapeutic denture, capable of delivering personalized treatment for long-term management of CADS, and benefit our aging veterans.

念珠菌相关假牙口腔炎 (CADS) 是假牙佩戴者中常见的、复发性疾病， 可能导致其他口腔健康问题、全身感染、生活质量下降，甚至危及生命 状况。我们的老年退伍假牙佩戴者更容易患上 CADS，因为他们中的许多人 由于全身、身体和精神疾病及其造成的医学和免疫学受损 相关疗法（例如抗生素、类固醇疗法和口腔干燥药物）。目前，没有 控制CADS的有效治疗策略和再感染率很高，影响高达67% 假牙佩戴者。 该续签申请建立在我们之前资助期间的结果之上，其中我们使用了 可充电“卡扣式/卡扣式”抗念珠菌技术，用于开发长期、感染反应性义齿 基础材料。功能性聚合物接枝物，包括聚-N-乙烯基-2-吡咯烷酮（PNVP）、聚甲基丙烯酸 使用聚甲基丙烯酸 (PMAA) 和聚甲基丙烯酸 2-羟乙酯 (PHEMA) 共价结合到义齿盘上 等离子体作为能源。这些新型功能化义齿材料能够结合足够的 大量的抗真菌药物，例如咪康唑和二葡萄糖酸氯己定，并提供有效的 通过在数周内将药物释放到 PBS 或人类唾液中，以达到持久的抗真菌作用 几个月。在实验（或对患者的治疗）结束时，任何残留在表面上的药物都可能 用淬火溶液“洗掉”。对于临床应用，“淬火”的义齿可以返回 供患者定期使用，或者如果感染复发或持续存在，则使用相同或不同的产品进行充电 一类抗真菌剂。 我们的长期目标是开发这种可充电的“点击/点击关闭”抗念珠菌技术来控制 CADS 在临床应用中。先前对义齿盘的研究尚未解决与义齿盘相关的问题 拓扑结构、体积特性、物理/机械特性、尺寸稳定性和药物负载/释放 3D 全口义齿的属性。此次更新的目的是进一步证明原理证明 在这个关于新策略的临床实用性的预翻译阶段。拟议的具体目标 研究目的是：(1) 使用“点击/点击关闭”抗念珠菌技术制造 3D 假牙，用于大鼠 建模并评估其物理/机械特性和药物结合/释放行为； (2)评价 新型抗念珠菌大鼠 3D 假牙在临床上的生物相容性和抗念珠菌活性 模拟条件； (3) 在大鼠假牙口腔炎模型中评估新型抗念珠菌 3D 假牙。 这项新技术的进一步发展有可能显着提高口腔护理质量 通过有效管理 CADS 及其伴随的并发症，为我们的退伍军人提供服务。如果成功的话， 这种新的义齿材料将是第一个治疗性义齿，能够为患者提供个性化治疗 长期管理CADS，造福我们的老年退伍军人。