Phase II year
2019
(last award dollars: 2020)
Phase II Amount
$1,475,659
This project responds to the need identified by NIDCR to develop improved methods to detect and predict progression of dental caries (tooth decay) to improve human health. Worldwide, caries is the most common chronic disease affecting almost everyone. Dental disease is a major cause of economic and social loss and leads to complications including pain, tooth loss and even death. Generally inactive lesions require no treatment while active lesions do. Early active lesions permit conservative treatment, whereas cavitated lesions require more costly and invasive restoration. Since the early 40s, caries diagnosis has been performed visually and using a dental explorer, but early cavities are missed and the explorer can cause cavitation. Alternatively, X- Rays identify more fully developed cavities but are unable to identify early forming lesions. Newer methods for caries diagnosis show little benefit and incur greater cost to dentist and patient. Current methods diagnose a surface defect in the enamel but cannot distinguish activity, a critical need in modern dentistry. Our goal is to develop a new clinically valid test to diagnose early and active carious lesions that also enables effective monitoring of conservative treatment. We have invented a nanoparticle technology which specifically targets active carious lesions. The nanoparticles are made from food grade corn starch and have been functionalized to specifically target the subsurface of carious lesions. They are tagged with a safe fluorescent dye so the caries will illuminate and be easily seen using a standard dental curing lamp, allowing dentists to quickly differentiate whether a carious lesion is active or inactive and to monitor treatment results. The product is a mouth rinse or oral gel containing a low concentration of the nanoparticles in water, enabling visual detection of early active carious lesions otherwise invisible on the tooth surface, because the extremely small nanoparticles can penetrate through surface microchannels into the early active sub-surface lesion. The starch-based nature of the nanoparticles facilitates rapid degradation by amylase enzyme present in human saliva, so teeth will no longer fluoresce upon leaving the dentists office. With earlier detection of caries and treatment of the disease before cavitation occurs, invasive treatments will be prevented, resulting in the enablement of Minimally Invasive Dentistry and improved oral health. Our Phase I research has demonstrated the potential of this technology, and the functionalities on the nanoparticles were successfully optimized to provide a viable product with sufficient targeting and fluorescence contrast to be macroscopically visible by the dental professional on various tooth surfaces when using a standard dental curing light available in a dental practice. Phase II involves in vitro assessment of the tests diagnostic capabilities including in vitro sensitivity and specificity, in vivo biocompatibility and studies required for FDA submission, clinical feasibility, and scaling of production. Successful completion of the Phase II Aims will facilitate commercialization in Phase III, and meet clinical development, regulatory and manufacturing milestones to support clinical validation and longitudinal clinical outcome studies.
Public Health Relevance Statement: PUBLIC HEALTH RELEVANCE STATEMENT In this SBIR, GreenMark Biomedical Inc. will develop a diagnostic test which will be used by dental professionals as part of the routine dental exam to better detect and predict progression of dental caries, a need identified by NIDCR. The product will be a mouth rinse or oral gel product containing small fluorescent particles made from corn starch, which are targeted into active carious lesions and illuminate when using a standard dental curing lamp found in every dental practice. It will result in improved long term oral health outcomes for patients through greater conservative treatment and less overtreatment of dental caries.
Project Terms: Address; Adopted; Affect; Amylases; aqueous; base; biomaterial compatibility; Blinded; Carbohydrates; Cessation of life; Characteristics; Charge; Chronic Disease; Clinical; Clinical assessments; clinical development; commercialization; cost; Cyclic GMP; Data; Defect; demineralization; Dental; Dental caries; Dental Enamel; Dental General Practice; Dental Implants; Dentistry; Dentists; design; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Disease; Early Diagnosis; Economics; Ensure; Enzymes; Evaluation; Failure; FDA approved; Feedback; Fluorescence; Fluorescent Dyes; Food; Formulation; Gel; Goals; Health; Healthcare; Hour; Human; Image; improved; In Vitro; in vivo; Infection; Legal patent; Lesion; Light; Methods; micropore; minimally invasive; Mission; Modernization; Monitor; nanoparticle; National Institute of Dental and Craniofacial Research; Nature; novel diagnostics; off-patent; Operative Surgical Procedures; Oral; Oral cavity; Oral health; Outcome; Outcome Study; overtreatment; Pain; particle; Particle Size; patient population; Patient-Focused Outcomes; Patients; Penetration; Performance; Phase; point of care; pre-clinical; Preclinical Testing; prevent; Process; Production; programs; prototype; public health relevance; Quality of life; remineralization; Reproducibility; Research; restoration; restorative treatment; Risk Assessment; Roentgen Rays; Safety; Saliva; Sensitivity and Specificity; Small Business Innovation Research Grant; social; Starch; success; Surface; Tactile; Technology; Testing; Tooth Diseases; Tooth Loss; Tooth structure; tooth surface; Toxicology; Transillumination; United States National Institutes of Health; usability; Validation; validation studies; Visual; Water
