Biodegradable triboelectric nanogenerator as a implantable power source for embedded medicine devices

Implantable medical devices significantly improve healthcare, but limitations like battery replacement and the need for surgical removal exist. This necessitates the development of biodegradable, self-powered implants that integrate seamlessly with the body. Triboelectric nanogenerators (TENGs) show promise as energy sources for such devices, offering applications in antimicrobial therapies, wound healing, and ultrasound energy harvesting. Chemotherapy, using drugs like doxorubicin (DOX), is a common cancer treatment, but side effects and drug resistance are significant concerns. Targeted drug delivery systems (DDSs) aim to mitigate these issues, and red blood cells (RBCs), with their biocompatibility and long half-life, are promising carriers. Electric field (EF) stimulation offers a precise and minimally invasive method for controlled drug release. This study aims to design a biodegradable TENG (BI-TENG) for cancer treatment by generating an electric field to control DOX release from RBCs within a DDS.

The literature review extensively covers existing implantable electronic devices and their limitations. It highlights the growing interest in biodegradable implants and the potential of TENGs as power sources for in vivo applications, citing numerous research efforts in biomedicine and energy harvesting. The use of targeted DDSs to address the challenges of chemotherapy is also discussed. Various drug carriers like micelles, nanoparticles, microcapsules, and nanogels are examined, highlighting their limitations in terms of biotoxicity and imprecise drug delivery. The unique advantages of red blood cells (RBCs) as drug carriers due to their biocompatibility, long half-life, and ability to penetrate tumor tissue via the enhanced permeability and retention (EPR) effect are emphasized. Finally, the potential of electric field (EF) stimulation for controlled drug release is explored, referencing existing research on EF's efficacy and minimal invasiveness.

The BI-TENG was fabricated using biodegradable materials: polylactic acid (PLA) and reed film as triboelectric layers, and magnesium (Mg) as electrodes. The selection of these materials was based on their biocompatibility, biodegradability, and ability to generate sufficient electrical output. The fabrication process involved layering these materials on an acrylic substrate to create a vertical contact/separation-mode TENG. The electrical performance of the BI-TENG was characterized by measuring the open-circuit voltage (Voc) and short-circuit current (Isc) under pulsed mechanical force. The biocompatibility of the materials was assessed using cell viability assays on mouse colon cancer cells (MC38). The in vivo performance of a miniaturized BI-TENG was evaluated after subcutaneous implantation in mice. The generated voltage and current were measured, and blood tests were conducted to assess biocompatibility and potential adverse effects. Finally, the BI-TENG was used to control DOX release from DOX-loaded RBCs in a simulated tumor environment, assessing the impact of the electric field on drug release and its effect on cancer cell viability.

The BI-TENG, using PLA and reed film, exhibited high electrical output, reaching 368 V Voc and 5.37 µA Isc at 5 Hz. Cell viability assays showed excellent biocompatibility of the materials. *In vivo*, the implanted BI-TENG generated 0.176 V Voc and 192 nA Isc from mouse movement. Blood tests revealed no significant adverse effects. The BI-TENG-generated electric field significantly accelerated DOX release from RBCs, suggesting potential for targeted cancer therapy. Material selection was optimized based on a triboelectric series, demonstrating that PLA and reed film offered superior performance compared to rice paper and ginkgo biloba. The BI-TENG showed significant degradation in a simulated in vivo environment (PBS). In vivo experiments demonstrated that the BI-TENG was well tolerated by the mice, with the device being situated between the muscular and dermal tissue, exhibiting minimal inflammatory response.

The results demonstrate the successful development of a fully biodegradable and self-powered TENG for potential applications in implantable medical devices. The high voltage output, coupled with excellent biocompatibility and *in vivo* performance, addresses the key limitations of traditional implantable devices. The ability to control drug release using the BI-TENG-generated electric field opens new avenues for targeted cancer therapy, potentially reducing side effects and improving treatment efficacy. The choice of biodegradable materials ensures the device's safe degradation within the body, eliminating the need for surgical removal. Further research could focus on optimizing device design and exploring additional therapeutic applications.

This study successfully developed a biodegradable triboelectric nanogenerator (BI-TENG) capable of generating electricity in vivo and stimulating controlled drug release. The device showed excellent biocompatibility and promising results in accelerating doxorubicin release from red blood cells, suggesting its potential as a self-powered platform for targeted cancer therapy and other implantable medical applications. Future work should investigate the long-term stability and efficacy of the BI-TENG in larger animal models and explore its adaptability for other therapeutic agents and diseases.

The study primarily focused on the proof of concept using a mouse model, and further studies in larger animal models are needed to confirm the long-term biocompatibility and efficacy of the BI-TENG. The study investigated the effect of the BI-TENG on DOX release in vitro and in vivo, and additional studies examining the direct anticancer effect and overall therapeutic efficacy are necessary. The mechanism of accelerated DOX release through the electric field, while demonstrated, could warrant further investigations at a molecular level.