Introduction
Effective wound management is crucial, especially for prolonged healing or high infection risk. Traditional methods rely on visual inspection or lab tests, which are subjective and time-consuming. This research addresses the need for smart bandages that offer quantitative wound monitoring and on-demand treatment. Wounds exhibit dynamic changes in physiological parameters like pH and uric acid (UA) levels. pH changes significantly during healing, shifting from mildly acidic to alkaline in prolonged healing or infection. UA, a biomarker associated with inflammation, fluctuates with wound severity and infection. Existing UA biosensors often neglect fluctuating wound pH, leading to inaccurate readings. Therefore, a system capable of simultaneous pH and UA detection with on-demand drug delivery is highly desirable. This innovative approach promotes personalized therapy, minimizing frequent dressing changes and medical visits. This paper details the development of a smart bandage incorporating multiple sensors and a drug delivery system based on conducting polymers (CPs). CPs are chosen due to their biocompatibility, ease of functionalization, and diverse properties suitable for sensing and drug delivery.
Literature Review
Numerous studies highlight the potential of smart bandages for wound care. These systems utilize various sensing modalities to monitor wound parameters such as oxygen levels, pH, UA, and immune proteins. Continuous real-time monitoring improves wound assessment and facilitates timely interventions. Previous research explored the use of individual sensors for pH or UA, but integrating these with drug delivery capabilities remains a challenge. The existing literature also demonstrates the use of conducting polymers for biosensing and drug delivery applications. However, the simultaneous integration of multiple sensors and a drug delivery system in a single platform is less well explored, especially within a smart bandage for wound management. The development of flexible electronics and microfluidic systems is another key area, critical for creating versatile and biocompatible smart bandages.
Methodology
The study developed a three-dimensional (3D) multiplex sensor and drug delivery array based on conducting polymers (CPs) integrated into a flexible patch and a smart bandage. Laser-induced graphene (LIG) electrodes provided a cost-effective platform. Polyaniline (PANi) was used for pH sensing due to its reversible protonation/deprotonation. Functionalized PEDOT was employed for UA biosensing through its electrocatalytic capabilities. Polypyrrole (PPy) served as the drug delivery vehicle due to its volume expansion upon electrical stimulation. A facile one-pot electrochemical deposition method was developed to prepare PEDOT:PB (Prussian Blue) composites for the UA biosensor. Ciprofloxacin (Cipro) was incorporated into PPy for electrically triggered release. The sensor array and drug carrier were integrated into a 3D patch with a flexible printed circuit board (FPCB) containing a microcontroller and Bluetooth for wireless communication. The pH sensor's performance was evaluated by measuring the electromotive force (EMF) in solutions with varied pH (4-10). The UA biosensor's response was assessed by amperometry with varying UA concentrations (up to 0.9 mM) at different pH levels. pH compensation was applied to improve UA measurement accuracy. Electrically triggered drug release was evaluated by applying various potentials to the PPy:Cipro patch and quantifying the released Cipro via UV-Vis spectroscopy. In vitro evaluation was performed using artificial wound exudate on porcine skin. The sensor array's performance was assessed by comparing the measured pH and UA values with standard methods. Antimicrobial efficacy of the released Cipro was evaluated using a disc diffusion assay against E. coli. The FPCB's design and functionality were described and the integration of the entire system into a functional smart bandage was demonstrated.
Key Findings
The PANi-based pH sensor exhibited a linear response across a pH range of 4–10, with a sensitivity of -59.5 mV pH⁻¹, close to the theoretical Nernstian slope. The PEDOT-based UA biosensor showed a linear response up to 0.9 mM UA, with a sensitivity of 1.20 μA mM⁻¹ at pH 7.5. Simultaneous pH and UA detection, combined with a pH-dependent sensitivity correction factor, significantly improved UA measurement accuracy. Electrically triggered release of Cipro from the PPy:Cipro patch was achieved at 0.6 V, showing a significantly higher release rate compared to passive release (at least 19 times higher). In vitro testing demonstrated good correlation between the measured pH and UA values from the smart bandage and the reference methods. The electrically triggered release of Cipro showed potent antimicrobial activity against E. coli. The integrated system, including the 3D patch and FPCB, was successfully embedded into a wound bandage, demonstrating the feasibility of wireless wound monitoring and on-demand drug delivery. The system demonstrated a high cumulative release ratio (around 80.8% after 210 min) at 0.6 V active stimulation.
Discussion
The study successfully addressed the need for a smart bandage capable of simultaneous multi-parameter wound monitoring and on-demand drug delivery. The findings highlight the effectiveness of using conducting polymers for creating such a system. The ability to accurately measure UA concentration by compensating for pH variations is a significant advance over existing technologies. The electrically triggered drug release mechanism offers targeted therapy, potentially reducing the risk of systemic side effects and improving treatment efficacy. The integration of the sensors and drug delivery system into a user-friendly smart bandage further enhances the practical applicability of this technology. The results suggest the potential of this smart bandage to revolutionize wound care by providing real-time wound status assessment and personalized treatment.
Conclusion
This research successfully demonstrated a novel smart bandage platform for wound theranostics, integrating multiplexed sensing and electrically triggered drug delivery. The use of conducting polymers enabled the creation of a flexible, biocompatible, and effective system. Future work could focus on in vivo studies, exploring the long-term stability and efficacy of the bandage in various wound types. Further refinement of the drug release mechanism to achieve precise control over drug release could enhance the system's capabilities. Developing closed-loop control algorithms that automatically adjust drug release based on sensor data could also improve treatment outcomes. The integration of advanced machine learning algorithms for interpreting sensor array responses holds promise for enhanced diagnostics.
Limitations
The current study is limited to in vitro evaluations. Further in vivo studies are necessary to confirm the efficacy and safety of the smart bandage in a clinical setting. The artificial wound exudate used in the in vitro studies may not fully represent the complexity of real wound fluids. Long-term stability of the sensors and drug delivery system under in vivo conditions needs to be investigated. The current prototype relies on user-initiated drug release. Developing a closed-loop system that automatically adjusts drug delivery based on sensor readings would be beneficial, especially for chronic wound management. The study only tested against E. Coli, and testing against other pathogens is needed.
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