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: 10158399
• 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/10158399
• 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; 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.

念珠菌相关性假牙口炎（CADS）是假牙佩戴者中常见的复发性疾病