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Introduction
Dental caries, the most prevalent non-communicable disease globally, stems from oral microbiome dysbiosis and the rise of acidogenic bacteria. Early-stage caries is reversible with topical fluoride, but traditional methods lack real-time monitoring capabilities. Current diagnostic tools, such as the caries activity test, are time-consuming and don't offer real-time data. The need for a sensitive, point-of-care system integrating sensing and therapy is critical for early prevention and treatment. Caries lesions are formed by the accumulation of acidogenic and aciduric bacteria that metabolize carbohydrates, producing acids that demineralize tooth enamel. Existing intraoral sensing attempts using mouthguards are hampered by bulky batteries and data transmission modules, limiting miniaturization and comfort. Near-field communication (NFC) technology offers a solution for wireless energy harvesting and data transmission in miniaturized devices. This research aims to develop a conformal wearable electronic system incorporating NFC and a low-power electrochemical sensor for in situ monitoring of the oral microenvironment. Timely treatment is crucial, as caries is not self-limiting. Fluoride is highly effective in preventing caries by promoting remineralization and inhibiting bacterial growth. However, traditional delivery methods (toothpaste, mouthwash) offer poor control and local retention. Electrically controlled drug release using intrinsically conducting polymers provides a solution for on-demand, controlled fluoride delivery. This study introduces a fully integrated, battery-free dental patch for wireless monitoring of the oral microenvironment and on-demand drug delivery. The patch consists of a miniaturized control circuit and a functional electrode array, enabling electrochemical detection of acidic environments and electrically controlled fluoride release. The NFC module facilitates wireless energy and data transmission with mobile terminals.
Literature Review
The authors reviewed existing literature on the connection between oral microbiome dysbiosis and dental caries. They discussed the limitations of current diagnostic methods, highlighting the need for real-time monitoring of the oral microenvironment. The review also covered existing attempts at intraoral sensing using mouthguards, pointing out the limitations of these devices in terms of size, battery life, and user comfort. The authors also covered existing methods for fluoride delivery, noting the challenges of topical drug delivery in the oral cavity due to saliva interference and poor local retention. The literature review extensively discussed the advantages of using NFC technology for power and data transmission in miniaturized and flexible wearable sensors. The use of intrinsically conducting polymers for electrically controlled drug delivery was also reviewed, emphasizing their potential for precise and controlled release of therapeutic agents in the oral cavity.
Methodology
The researchers designed a double-layered dental patch system. The first layer contained the control circuit, including the NFC chip, microcontroller unit (MCU), resistors, and capacitors, along with a copper NFC antenna. The second layer comprised the electrode array, with a pH-sensitive sensor and a drug delivery electrode. The electrochemical sensor employed a carbon working electrode and an Ag/AgCl reference electrode. For the sensor, gold nanoparticles were deposited on the carbon electrode to enhance conductivity, followed by in situ synthesis of polyaniline (PANi) as the pH-sensing layer. The reference electrode was coated with a polyvinyl butyral (PVB) mixture containing carbon nanotubes and saturated sodium chloride. The drug delivery module used polypyrrole (PPy) as the electrically responsive drug carrier. Fluorides were loaded onto the electrode by electrochemical chronopotentiometry in a sodium fluoride solution containing pyrrole. A polyanion, polystyrene sulfonate (PSS), was added as a dopant to reduce spontaneous fluoride release. The flexible electrode array was fabricated using screen-printed conductive inks, copper wires, and copper spots, encapsulated with polyimide (PI) and polydimethylsiloxane (PDMS) films. The in vitro characterization of the pH sensor involved open-circuit potentiometry using McIlvaine's buffers. The sensor's sensitivity, linearity, repeatability, and selectivity were evaluated. The sensor was validated using Streptococcus mutans (S. mutans) dental plaque growth experiments, monitoring pH changes over 10 hours and comparing results with a standard pH meter. In situ oral microenvironment monitoring was performed on volunteers using the dental patch attached to their teeth with a transparent dental strip. The impact of consuming liquids with varying pH and the long-term pH fluctuations during a day were recorded. A commercial caries activity test was conducted for validation. The drug delivery module's performance was assessed by determining the amount of fluoride released based on synthesis time, spontaneous release, and applied voltage. The antibacterial activity of the electrically controlled fluoride delivery was evaluated using S. mutans cultures stained with a bacterial viability kit and observed via confocal laser scanning microscopy (CLSM).
Key Findings
The developed wearable dental patch system successfully achieved wireless energy harvesting and data transmission via NFC. The miniaturized design ensured user comfort and easy integration into the oral cavity. The pH sensor demonstrated high sensitivity (62.97 mV per decade of H+ concentration), excellent selectivity to H+ ions, and reliable real-time monitoring of oral pH changes. The in vitro experiments with S. mutans showed consistent pH decreases over time, correlating with plaque formation stages. In vivo studies confirmed the patch's ability to monitor real-time oral pH changes following the consumption of different beverages and throughout the day, with fluctuations influenced by meals and saliva buffering. The caries activity test results corroborated the patch's pH measurements. The electrically controlled fluoride delivery module showed that the amount of fluoride released could be precisely controlled by adjusting the applied voltage and synthesis time, minimizing spontaneous release. The released fluorides exhibited significant antibacterial activity against S. mutans, as evidenced by CLSM imaging showing reduced bacterial viability in the treated group.
Discussion
The findings demonstrate the feasibility and effectiveness of a wearable, battery-free dental patch for the real-time monitoring and on-demand treatment of dental caries. This innovative system addresses the limitations of current caries management approaches by providing continuous monitoring of the oral microenvironment and enabling targeted, controlled drug delivery. The high sensitivity and selectivity of the pH sensor allow for early detection of caries lesions before they become clinically apparent. The controlled fluoride release mechanism offers a personalized approach to treatment, avoiding the overuse of fluorides and minimizing potential side effects. The wireless functionality and user-friendly design make the system suitable for long-term monitoring and home-based management of dental health. The system's capabilities have implications for personalized preventive dentistry, allowing for early intervention and tailored treatment strategies based on an individual's specific oral microenvironment. The success of the study underscores the potential of wearable technology in improving oral healthcare.
Conclusion
This study successfully developed and validated a wearable, battery-free, theranostic dental patch for in situ monitoring and on-demand treatment of dental caries. The system combines a highly sensitive and selective pH sensor with an electrically controlled fluoride delivery module, offering a new approach to caries prevention and management. Future research could explore the integration of other biomarkers into the system to provide a more comprehensive assessment of oral health. Investigating the efficacy of other therapeutic agents beyond fluoride would broaden the system's applicability. Further research should also focus on improving the long-term stability of the patch and exploring different attachment methods for enhanced user comfort and convenience.
Limitations
The study's sample size for in vivo testing was relatively small. Long-term stability and durability of the patch in the oral environment need further investigation. The current NFC communication range might be limited, necessitating potential modifications for broader applications. The study focused primarily on S. mutans; evaluating the system's effectiveness against other oral pathogens is needed. While the study demonstrated the antibacterial effect of released fluorides, more comprehensive in vivo studies are needed to demonstrate its clinical efficacy in caries prevention and treatment.
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