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: 10907403
• 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 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10907403
• 关键词: 3-Dimensional; Affect; Aging; Animal Testing; Antibiotics; Antifungal Agents; Antifungal Therapy; Appearance; Attention; Behavior; Binding; Candida; Catheters; Cell Culture Techniques; Cessation of life; Charge; 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 Cells; Epithelium; Financial Hardship; Funding; Goals; Habits; Healthcare; Human; Hygiene; Immunologics; Infection; Kinetics; 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; Recurrent disease; 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; biomaterial compatibility; candida biofilm; clinical application; effective therapy; endotracheal; experimental study; fighting; functional group; gastrointestinal; implantable device; improved; in vivo; individualized medicine; infection rate; manufacture; mechanical properties; medical complication; microbial; microbial colonization; new technology; next generation; novel; nutrition; oral care; oral infection; personalized medicine; polymethacrylic acid; premature; prevent; recurrent infection; 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.

与念珠菌相关的义齿口腔炎（CADS）是牙医佩戴者和 可能导致其他健康问题，系统性感染，造成的生活质量，甚至威胁生命 状况。我们古老的老将牙医穿着者更容易开发CAD，因为其中许多是 由于系统性，身体和精神疾病及其 相关疗法（例如抗生素，类固醇疗法和静态药物）。目前，没有 控制CAD和再感染率的有效治疗策略很高，影响多达67％ 义齿佩戴者。 此续订应用程序建立在我们以前的资金期结果的基础上，我们在其中使用了 可充电的“点击/点击”抗偶氮技术，以发展长期，感染响应密度 基本材料。功能性聚合物移植物，包括聚-N-乙烯基-2-吡咯烷酮（PNVP），聚合物晶 使用酸（PMAA）和聚-2-羟基乙基甲基丙烯酸酯（Phema）共价结合到牙科盘上 等离子体作为能源。这些新型的功能化密度材料能够结合足够 数量的抗真菌药物，例如红唑和氯己胺二甲酸，并提供有效的 通过将药物释放到PBS或人类唾液的过程中，几周内通过将药物释放到PBS或人类唾液中的长期抗真菌作用 月份。在实验结束时（或患者的治疗），与表面结合的任何剩余药物都可以 用淬火解决方案“被洗净”。对于临床应用，可以退还“淬火”牙医 给患者定期使用，或者，如果感染重复或持续，则以相同或不同的方式充电 抗真菌剂类。 我们的长期目标是开发这种可充电的“点击/点击”抗偶氮技术来控制CADS 在临床应用中。先前对牙科椎间盘的研究尚未解决与 拓扑，散装特性，物理/机械性能，尺寸稳定性和药物加载/释放 来自3D完整牙医的属性。这种续签的目的是进一步证明原则的证明 在这个关于新战略临床实用性的翻译前阶段。提议的具体目的 研究是：（1）使用“单击/单击”的抗偶氮技术来制造3D凹槽，用于老鼠 建模并评估其物理/机械性能和药物结合/释放行为； （2）评估 新型的抗偶氮大鼠3D牙医在临床上的生物相容性和抗粉状活性 模拟条件； （3）评估大鼠牙科口腔炎模型中新的抗粉状3D牙医。 这项新技术的进一步发展有可能显着提高口腔护理的质量 通过有效管理CAD及其参与的并发症来交付给我们的退伍军人。如果成功， 这种新的牙医材料将是第一个治疗牙科，能够提供个性化治疗 CAD的长期管理，并使我们的老年退伍军人受益。

项目成果

N-trimethylchitosan/alginate layer-by-layer self assembly coatings act as "fungal repellents" to prevent biofilm formation on healthcare materials.

• DOI: 10.1002/adhm.201400428
• 发表时间: 2015-02-18
• 期刊: ADVANCED HEALTHCARE MATERIALS
• 影响因子: 10
• 作者: Jiang, Fuguang;Yeh, Chih-Ko;Wen, Jianchuan;Sun, Yuyu
• 通讯作者: Sun, Yuyu

Quaternized chitosans bind onto preexisting biofilms and eradicate pre-attached microorganisms.

• DOI: 10.1039/c4tb01131g
• 发表时间: 2014-12-28
• 期刊: Journal of materials chemistry. B
• 作者: Jiang F;Deng Y;Yeh CK;Sun Y
• 通讯作者: Sun Y

Controlling fungal biofilms with functional drug delivery denture biomaterials.

• DOI: 10.1016/j.colsurfb.2015.12.028
• 发表时间: 2016-04-01
• 期刊: Colloids and surfaces. B, Biointerfaces
• 作者: Wen J;Jiang F;Yeh CK;Sun Y
• 通讯作者: Sun Y

Antifungal activity, biofilm-controlling effect, and biocompatibility of poly(N-vinyl-2-pyrrolidinone)-grafted denture materials.

• DOI: 10.1016/j.colsurfb.2013.04.043
• 发表时间: 2013-10-01
• 期刊: COLLOIDS AND SURFACES B-BIOINTERFACES
• 影响因子: 5.8
• 作者: Sun, Xinbo;Cao, Zhengbing;Yeh, Chih-Ko;Sun, Yuyu
• 通讯作者: Sun, Yuyu

Silk fibroin scaffolds promote formation of the ex vivo niche for salivary gland epithelial cell growth, matrix formation, and retention of differentiated function.

丝素蛋白支架促进唾液腺上皮细胞生长、基质形成和分化功能保留的离体生态位的形成。

• DOI: 10.1089/ten.tea.2014.0411
• 发表时间: 2015
• 期刊: Tissue engineering. Part A
• 作者: Zhang,Bin-Xian;Zhang,Zhi-Liang;Lin,AlanL;Wang,Hanzhou;Pilia,Marcello;Ong,JooL;Dean,DavidD;Chen,Xiao-Dong;Yeh,Chih-Ko
• 通讯作者: Yeh,Chih-Ko