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.

义齿相关性口炎（CADS）是义齿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、生活质量受损，甚至危及生命 条件我们的老年退伍军人假牙佩戴者更容易发展CADS，因为他们中的许多人是 由于全身性、身体和精神疾病及其 相关疗法（例如，抗生素、类固醇疗法和口干症药物）。目前没有 有效的治疗策略，控制CADS和再感染率高，影响高达67%的 戴假牙的人 这一更新申请建立在我们上一个资助期的结果基础上， 可充电“点击/点击关闭”抗牙床技术，以开发长期，感染响应义齿 基础材料功能高分子接枝物，包括聚N-乙烯基-2-吡咯烷酮（PNVP）、聚甲基丙烯酸 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充分结合 大量的抗真菌药物，如咪康唑和氯己定二葡萄糖酸盐，并提供有效的 通过在数周内将药物释放到PBS或人唾液中， 个月在实验（或对患者的治疗）结束时，结合到表面的任何剩余药物都可能被释放。 用淬火溶液“洗掉”。对于临床应用，可以返回“淬火”义齿 给患者定期使用，或者，如果感染复发或持续， 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”的anticandidal技术来控制CADS 在临床应用中。以前的研究义齿盘没有解决的问题， 拓扑结构、本体性质、物理/机械性质、尺寸稳定性和药物装载/释放 3D全口义齿的性能。此次更新的目的是进一步证明原则性 在这个翻译前阶段，关于新策略的临床实用性。建议的具体目标 研究的目的是：（1）制作三维义齿，使用“点击/点击关闭”anticandidal技术，用于大鼠 模拟并评价其物理/机械性能和药物结合/释放行为;（2）评价 新型大鼠抗龋三维义齿的生物相容性和临床抗龋活性 模拟条件;（3）在大鼠义齿性口炎模型中评价新的前牙3D义齿。 这项新技术的进一步发展有可能显著提高口腔护理的质量 通过有效地管理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， 这种新的义齿材料将是第一个治疗义齿，能够提供个性化的治疗， CADS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.

Quaternized壳聚糖结合了先前存在的生物膜，并消除了预先附着的微生物。

• 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