Biology subjects

Asefifeyzabadi, N.

Publications and source records attributed to Asefifeyzabadi, N..

6 recordsLinked to original sources

bioRxiv2025

Fluoxetine Delivery for Wound Treatment Through an Integrated Bioelectronic Device - Pharmacokinetic Parameters and Safety Profile in Swine

Wound infections are a significant medical challenge, often leading to chronicity or systemic infection. Selective serotonin reuptake inhibitors (SSRIs) have emerged as potential non-antibiotic candidates with demonstrated ability to limit growth and biofilm formation in Gram-negative bacteria, in addition to their pro-healing activity. Here, we compared direct delivery of the SSRI fluoxetine by topical bolus dosing to delivery from an iontophoresis bandage device with an actuator for temporally controlled drug delivery, in a porcine excisional wound model. Device delivery of fluoxetine resulted in a maximum concentration of 12.25 ng fluoxetine per mg tissue, compared to 2.926 ng/mg following bolus dosing, and tissue fluoxetine levels were higher after application using the device than after bolus dosing across the range of doses tested (p=0.0041). The half-life of fluoxetine in the wound tissue was 0.988 {+/-} 0.256 days. Fluoxetine was not detected in the pig plasma, and plasma serotonin levels were not affected by the topical application. Fluoxetine delivery using the device, but not bolus delivery, produced tissue concentrations above the minimum inhibitory concentration (MIC) for some clinically important species of bacteria. The experimental device can effectively deliver topical fluoxetine to the wound, producing higher tissue concentrations of fluoxetine at lower cumulative doses compared to bolus dosing, and with minimal risk of off-target effects. The device may simplify wound treatment by reducing the burden for daily drug application, possibly increasing adherence to a prescribed treatment regimen.

bioengineering↗

bioRxiv2024

Design and Validation of a Wearable Imaging System for Automated Wound Monitoring in Porcine Model

Effective wound monitoring has the potential to guide treatment regiments and improve healing outcomes, yet current clinical assessment methods remain largely subjective and labor-intensive. To address this challenge, we present a high-resolution wearable imaging system designed for continuous wound monitoring. The system integrates a 64 MP camera with a plano-convex lens housed in an enclosure measuring 73 mm in diameter and 36.1 mm in height, and features a custom printed circuit board (PCB) for programmable LED illumination. The 3D-printed device enclosure is designed to accommodate a silicone bioelectronic device and can be securely attached using a commercially available ostomy skin barrier. In porcine model validation studies, the system successfully captured daily wound progression over periods up to 7 days. The captured images were wirelessly transmitted to a processing unit where DeepMapper, a machine learning algorithm, processed z-stacked images and performed multi-level feature extraction to predict wound healing stages and indicate potential complications such as infection. This imaging system enables automated analysis of wound progression and supports the development of smart wound care platforms for personalized treatment strategies. The integrated design approach demonstrates the feasibility of creating compact, high-resolution imaging systems suitable for clinical wound monitoring applications.

bioengineering↗

bioRxiv2024

Accelerating Wound Healing Through Deep Reinforcement Learning: A Data-Driven Approach to Optimal Treatment

Advancements in bioelectronic sensors and actuators have paved the way for real-time monitoring and control of wound healing progression. Real-time monitoring allows for precise adjustment in treatment strategies that align with an individuals unique biological response. However, due to the complexities of human-drug interactions and a lack of predictive models it is challenging to determine just how one should adjust drug dosage to achieve the desired biological response. This work proposes an adaptive closed-loop control framework that integrates deep learning, optimal control, and reinforcement learning to update treatment strategies in real-time with the goal of accelerating wound closure. The proposed approach eliminates the need for mathematical modeling of complex nonlinear wound healing dynamics. We demonstrate the convergence of the controller via an in silico experimental setup, where the proposed approach successfully accelerates the wound healing process by 17.71%. Finally, we share the experimental setup and results of an in vivo implementation to highlight the translational potential of our work. Our data-driven model estimates a 40% acceleration in wound closure.

systems biology↗

bioRxiv2024

Remote-Controlled Wireless Bioelectronics for Fluoxetine Therapy to Promote Wound Healing in a Porcine Model

Wound healing presents a significant challenge in biomedical science, requiring precise therapeutic delivery and real-time monitoring. Bioelectronic systems offer a promising solution but remain largely unexplored for wound care, particularly in large animal models that reflect human healing dynamics. This study introduces a remote controlled wireless bioelectronic platform equipped with an iontophoretic pump to deliver fluoxetine, a selective serotonin reuptake inhibitor that promotes wound repair. In vitro and ex-vivo testing validated efficient on demand fluoxetine delivery. In vivo experiments in a porcine wound model demonstrated clear therapeutic efficacy over 3-day and 7-day periods. The system enhanced healing outcomes, increasing re-epithelialization by 37% (H&E staining), reducing the M1/M2 macrophage ratio by 33%, and stimulating neuronal growth at the wound site. This bioelectronic platform delivers fluoxetine in a controlled, remotely-controlled manner while allowing for wound direct wound imaging that can be used to monitor wound healing progress. Additionally, it allows precise dose and temporal delivery of treatment to enhance the outcome of future large animal wound healing studies.

bioengineering↗

bioRxiv2024

Wireless bioelectronic device for wound healing

Wireless bioelectronic actuators have been developed to deliver targeted treatments over multiple days while continuously monitoring delivery, thereby improving wound healing. Specifically, these devices can deliver charged biomolecules such as fluoxetine cations (Flx+) and electric field (EF) in freely moving pigs. Treatments can be controlled and monitored in real time via WiFi, with options for both user-specified delivery rates and durations, as well as automated closed-loop (CL) control. The devices are engineered to handle various failure scenarios that may arise in dynamic, real-world experiments--such as communication or power interruptions--ensuring that valuable experimental data is collected with minimal disruption. The ion pump features eight drug reservoirs and channels arranged around a 20 mm diameter-wound, with a central ground electrode (0 V). When voltages above 0 V are applied to the outer channels, currents flow from the reservoirs and channels into the wound, delivering Flx+ and/or EF depending on the reservoir solution. The device records applied voltages and currents locally to a microSD card at a high sampling rate, while simultaneously transmitting real-time measurements via a local WiFi network to a wound healing algorithm running on a nearby laptop. CL control of current/delivery rate is performed by an onboard microcontroller unit (MCU) and current-source microchips, based on instructions received from the wound healing algorithm. A graphical user interface (GUI) provides intuitive user control and real-time data visualization, with support for multiple devices. In vivo studies over seven days showed that Flx+-treated wounds had a 20% lower M1/M2 macrophage ratio and 41.67% greater re-epithelialization compared to controls (standard-of-care), demonstrating the actuators potential to enhance wound healing.

biochemistry↗

bioRxiv2023

Programmable delivery of fluoxetine via wearable bioelectronics for wound healing in vivo

The ability to deliver drugs with precise dosages at specific time points can significantly improve disease treatment while reducing side effects. Drug encapsulation for gradual delivery has opened up the doors for superior treatment regimen. To expand on this ability, programming bioelectronic devices to deliver small molecules enables ad-hoc personalized therapeutic profiles that are more complex than simple gradual release. Here, we introduce a wearable bioelectronic bandage with an integrated electrophoretic ion pump that affords on-demand drug delivery with precise dose control. Delivery of fluoxetine to wounds in mice resulted in a 27.2% decrease in the macrophage ratio (M1/M2) and a 39.9% increase in re-epithelialization, indicating a shorter inflammatory phase and faster overall healing. Programmable drug delivery using wearable bioelectronics in wounds introduces a broadly applicable strategy for the long-term delivery of a prescribed treatment regimen with minimal external intervention.

bioengineering↗