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

The study addresses limitations of current implantable medical devices that rely on batteries and often require secondary surgeries for removal, causing patient burden. It proposes biodegradable, biocompatible, self-powered implants that can operate in vivo and safely degrade. The research explores triboelectric nanogenerators (TENGs) as implantable energy harvesters to power biomedical functions, notably to drive electric fields for therapeutic purposes. The specific research question is whether a fully biodegradable TENG can be engineered to harvest in vivo mechanical energy reliably and biocompatibly, and whether its output can control and enhance targeted drug delivery (DDS) for cancer therapy, specifically modulating doxorubicin release from red blood cells to improve tumor targeting and minimize systemic side effects.

The paper situates the work within growing interest in implantable electronics for diagnostics and therapy, noting advances in in vivo sensors and therapeutics using TENGs for antimicrobial action, wound healing, and energy harvesting. It reviews challenges in chemotherapy such as side effects and drug resistance, motivating targeted drug delivery systems (DDS) leveraging the enhanced permeability and retention (EPR) effect. Conventional carriers (micelles, nanoparticles, microcapsules, nanogels) can have toxicity and limited accuracy. Red blood cells (RBCs) are highlighted as attractive DDS carriers due to biocompatibility, long half-life (~120 days), suitable size within the EPR range (300 nm–4.7 µm), membrane flexibility, and potential for ligand and magnetic nanoparticle functionalization to improve targeting. Electric field (EF) stimulation is noted as a simple, low-cost, minimally harmful modality to influence drug release and therapy, suggesting synergy with implantable TENGs that could generate EF in situ.

Device materials and selection: Biodegradable friction layers were screened, focusing on differences in electron affinity. Polylactic acid (PLA, synthetic, biodegradable, biocompatible) was selected as the positive triboelectric layer and reed film (natural, cellulose-based, biodegradable) as the negative layer. Magnesium (Mg) films served as electrodes. PLA’s origin, biodegradability, and biomedical use are noted. Reed film structure was characterized (elongated cell wall, ~43.4 µm width).

Prototype TENG fabrication and operation: A vertical contact–separation mode TENG (active area 5 cm × 5 cm) was built on an acrylic substrate with PLA and reed films as friction layers and Mg electrodes. Pulsed forces from a linear motor (5 Hz) were applied. Electrical characterization included open-circuit voltage (Voc), short-circuit current (Isc), load-dependent behavior, power density, capacitor charging, LED lighting, and cycling stability. Measurements: Voc up to 368 V; Isc up to 5.37 µA at 5 Hz. Load tests showed increasing voltage and decreasing current with resistance; maximum power density 0.256 W m^-2 at 10 MΩ. The device charged a capacitor to 0.727 V within 140 s and powered 60 red LEDs. Stability persisted over 10,000 cycles at constant frequency.

Mechanism: Contact–separation of dissimilar triboelectric layers generates opposite surface charges. Upon separation and re-contact, electrons flow through the external circuit to balance electrostatic potential, producing alternating current signals.

Material comparison and triboelectric series: Additional biodegradable materials (rice paper, Ginkgo biloba leaf powder) were characterized by SEM, FTIR, XRD, and water contact angle. Using Kapton as a reference counter layer, relative electron gain/loss ability was ranked as PLA > reed film > ginkgo leaf > rice paper. Combinations among these materials were tested (5 × 5 cm^2 devices), with PLA + reed film showing the best Voc/Isc performance.

Biocompatibility testing (in vitro): MC38 mouse colon cancer cells were cultured on PLA, reed film, and Mg. Cell viability remained high at 24, 48, and 72 h; OD readings indicated good cell growth, suggesting cytocompatibility of materials.

Biodegradation assessment: Components (PLA, Mg, reed film) were incubated in PBS to simulate in vivo conditions. Degradation observed: Mg ~1 day, reed film ~3 days, PLA notable degradation by ~30 days.

Implantable BI-TENG fabrication and in vivo testing: A miniaturized BI-TENG used PLA for both substrate and encapsulation to ensure full biodegradability and environmental isolation. The device was sterilized (75% ethanol) and implanted subcutaneously in mice under standards GB 14925-2001. Histology before/after implantation showed placement between muscle and dermis without obvious inflammation, indicating good biocompatibility. Electrical output in vivo was measured by tapping the implant site under anesthesia to prevent wound interference: Voc ~0.176 V; Isc ~190 nA. Performance reduction relative to benchtop tests was attributed to tissue compression limiting TENG motion. Reliability in PBS remained good after 8000 operations. Hematology (RBC, WBC, platelets) before and 2 days post-implantation showed decreases but within normal ranges, indicating no anemia or inflammatory reaction.

Drug delivery system (DDS) preparation and EF control: Doxorubicin (DOX) was loaded into RBCs via hypoosmotic chromatography. A RBC suspension was mixed with DOX (200 µg mL^-1), with glutathione (GSH) and ATP added to prevent membrane oxidation and maintain integrity. Samples were kept at 4 °C to swell RBCs and facilitate DOX entry; cells were then washed and transferred to hypertonic buffer for incubation to reseal membranes. The BI-TENG was connected to an interdigital electrode to generate an electric field to modulate DOX release from RBCs. Under baseline conditions, DOX-loaded RBCs released drug; application of EF accelerated release; upon cessation of EF, release returned to baseline.

• Material pairing: PLA (positive) and reed film (negative) formed the optimal biodegradable triboelectric pair among tested materials (PLA, reed film, ginkgo leaf, rice paper), yielding the highest outputs.
• Prototype electrical performance (5 × 5 cm^2, 5 Hz): Voc up to 368 V; Isc up to 5.37 µA. Maximum power density 0.256 W m^-2 at 10 MΩ load. Capacitance charging to 0.727 V in 140 s; capable of lighting 60 red LEDs; stable over 10,000 cycles.
• Biocompatibility: In vitro MC38 cell viability remained high over 72 h on PLA, reed film, and Mg. Histology post-implantation showed no obvious inflammation.
• Biodegradability: In PBS, Mg degraded ~1 day, reed film ~3 days, PLA showed clear degradation by ~30 days. The assembled BI-TENG visibly degraded over time in PBS.
• In vivo performance: Subcutaneous implantation in mice produced Voc ~0.176 V and Isc ~190 nA under external tapping; device maintained function after 8000 cycles in PBS reliability tests. Blood tests pre- and 2-days post-implantation showed RBC, WBC, and platelet counts decreased but remained within normal ranges.
• Drug delivery control: The BI-TENG-driven electric field accelerated DOX release from RBC carriers; after stopping EF, release normalized, enabling more precise on-demand drug delivery and effective cancer cell killing in the described model.

The study demonstrates that a fully biodegradable TENG based on PLA and reed film can harvest mechanical energy and generate usable electrical signals in vivo with good biocompatibility. By leveraging an interdigital electrode, the BI-TENG’s output electric field provides external control over drug release kinetics from RBC-based carriers, directly addressing the need for targeted, on-demand chemotherapy with minimized systemic exposure. The material comparison established a practical triboelectric pairing guide among biodegradable candidates, with PLA + reed film delivering superior output. In vivo results, including modest but stable voltage/current and normal-range hematology with no inflammatory histology, support feasibility for implantable power generation. The EF-induced acceleration and reversibility of DOX release show a viable method for spatiotemporal control of chemotherapy, suggesting potential to improve therapeutic indices in cancer treatment. While in vivo outputs are lower than benchtop values due to tissue constraints, they were sufficient to modulate release, indicating that design optimization could further enhance therapeutic utility.

This work introduces a biodegradable, biocompatible triboelectric nanogenerator using PLA and reed film that effectively converts mechanical energy into electricity and functions as an implantable power source. It provides on-demand control of doxorubicin release from RBC-based carriers via an electric field, enabling precise drug delivery and demonstrating potential in cancer therapy. Key contributions include: (1) identification of optimal biodegradable triboelectric materials (PLA + reed film) with strong output; (2) validation of device stability, biodegradability, and biocompatibility; (3) demonstration of in vivo power generation and electric field–controlled drug release. Future work should optimize device architecture to boost in vivo output, comprehensively characterize long-term biodegradation and tissue responses, and quantify therapeutic efficacy in relevant animal tumor models, including dosing schedules and EF parameters, toward eventual translation.

• The in vivo electrical output (Voc ~0.176 V; Isc ~190 nA) is substantially lower than benchtop values due to tissue-induced motion constraints, potentially limiting certain applications without further optimization.
• Detailed in vivo therapeutic efficacy metrics (e.g., tumor growth inhibition, survival) and quantitative DOX release kinetics under EF vs. baseline are not provided in the excerpt.
• Degradation timelines of components differ (Mg degrades rapidly; PLA more slowly), which may affect long-term device integrity and function; comprehensive in vivo degradation and byproduct profiling over extended periods were not detailed.
• The implant testing involved tapping under anesthesia to elicit output; performance during natural, unconstrained animal motion remains to be fully characterized.
• The full affiliation information for all authors and some experimental parameters (e.g., complete DDS incubation conditions) are not fully detailed in the provided text.