On-Demand Bioresorbable OptoElectronic System for In-Vivo and In-Situ Monitoring of Chemotherapeutic Drugs

Informazioni relative al progetto

RESORB

ID dell’accordo di sovvenzione: 101046946

DOI

10.3030/101046946

Progetto chiuso

Data della firma CE 25 Marzo 2022

Data di avvio 1 Aprile 2022

Data di completamento 30 Settembre 2025

Finanziato da

• The European Innovation Council (EIC)

Costo totale

€ 2 606 250,00

Contributo UE

€ 2 606 250,00

Coordinato da

UNIVERSITA DI PISA
Italy

Periodic Reporting for period 2 - RESORB (On-Demand Bioresorbable OptoElectronic System for In-Vivo and In-Situ Monitoring of Chemotherapeutic Drugs)

Periodo di rendicontazione: 2023-04-01 al 2025-09-30

Sintesi del contesto e degli obiettivi generali del progetto

Imagine your doctor could implant a miniaturized sensor beneath your skin to continuously monitor the concentration of virtually any molecule in your bloodstream in real time. Such technology would revolutionize diagnostics, providing individualized, continuous insights into disease progression and drug efficacy. Now imagine this sensor communicating wirelessly with your smartphone, transmitting clinically relevant data—such as biomarker or drug levels—directly to your doctor. This would transform healthcare from single-point testing to dynamic, personalized, and timely medical feedback. Finally, envision that once monitoring is no longer needed, the implanted sensor safely RESORBs within your body, eliminating the need for surgical removal and offering a “red-button” safety option for instant deactivation in case of inflammation, malfunction, or treatment completion.

The RESORB project aims to revolutionize clinical diagnostics by developing implantable, bioresorbable chemical sensing systems capable of real-time in vivo monitoring of therapeutic drugs and other clinically relevant biomarkers—shifting the paradigm from external analysis of withdrawn fluids to fully integrated, transient sensing inside the body.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

RESORB key results:

MIPs for doxorubicin and thermoreversible hydrogel
• Developed bioresorbable molecularly imprinted polymers (d-MIPs) as selective receptors for doxorubicin, detecting 0.1–10 µg mL⁻¹.
• Established two imprinting routes—photo-iniferter and solvent-free vapor-phase polymerization.
• Demonstrated >90 % selectivity and ≥12 weeks stability under physiological conditions.
• Designed thermoresponsive MC/PEG-based hydrogels with temperature-triggered degradability.
• Improved hydrogel durability identifying MC/PEG/PAA as optimal for protection and antifouling.
• Validated biocompatibility and controlled dissolution in vitro.

Bioresorbable sensor for doxorubicin
• Developed d-MIP/nPSiO2 fluorescence sensors enabling selective DOXO quantification (0.1–5 µg mL⁻¹; LoD = 2.7 ng mL⁻¹; RSD < 2 %).
• Implemented HSA-based nPSiO2 sensors (0.1–2 µg mL⁻¹; LoD = 3.4 ng mL⁻¹) with 125× fluorescence gain.
• Maintained linearity in drug cocktails and ISF, effectively measuring free pharmacologically active DOXO.
• Fabricated HSA–agarose optical fibers (Ø ≈ 1.8 mm) with LoD = 0.07 µg mL⁻¹ (PBS) and 0.14 µg mL⁻¹ (ISF), showing up to 4× sensitivity gain.
• Verified reversible DOXO binding, in-situ fiber extrusion, and through-tissue detection.
• Patent applications: EP25170221.3 (device) and EP24209472.2 (fiber).

Microbattery and LED
• Developed the first bioresorbable Na-ion microbattery (µNIB) from fully biocompatible materials, achieving >1 mAh cm⁻², high stability, and cycling performance.
• Demonstrated rechargeable µNIB (7 mAh cm⁻²).
• Designed the first biodegradable OLED (Alq₃-based) on chitosan substrate with blue–green emission for DOXO excitation.
• Integrated µNIB and OLED, demonstrating functional excitation module and control circuitry.
• EU patents: EP23170468.5 and EP24306269.2.

Sensing system
• Assembled multilayer “dummy” bioresorbable sensing stack (OLED, µNIB, sensor, hydrogel) for in-vivo testing.
• Integrated OLED and µNIB within PLGA layers (~50 µm) ensuring adhesion and transparency.
• Incorporated d-MIP sensors (nPSiO2/PLGA) in the OLED-µNIB stack with hydrogel encapsulation.
• Developed wearable reader patch with LED, photodiode, and Bluetooth for non-invasive fluorescence monitoring.
• Demonstrated in-vitro DOXO detection through synthetic skin (0.1–2 µg mL⁻¹; LoD = 5 ng mL⁻¹; R² > 0.99; CV < 2.2 % at >10 mm depth).

In-vivo validation
• Conducted in-vivo studies on PLGA, nPSiO2, MIPs, HSA sensors, MC/PEG/PAA hydrogels, µNIBs, OLEDs, and integrated systems.
• Demonstrated no local/systemic toxicity or inflammation, confirming ISO 10993 compliance.
• Verified full bioresorption within 8–12 weeks of materials/devices and on-demand hydrogel dissolution at 25–30 °C.
• Validated implanted HSA–nPSiO2 sensor for in-vivo DOXO mesurement and pharmacokinetic tracking.
• Provided key biological feedback on degradation, coatings, and integration for iterative optimization across WPs.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

RESORB major breakthroughs:

• Validated bioresorbable components
– Receptors: Molecularly imprinted polypyrrole (d-MIPs) and HSA coatings with >90 % selectivity for doxorubicin (DOXO) over other chemotherapeutics.
– Optical transducers: Nanoporous SiO2 (nPSiO2)/PLGA membranes providing ≈125× fluorescence gain and agarose-based optical fibers extrudable in vivo.
– Sensors: High-sensitivity DOXO detection using d-MIP/nPSiO2 (LoD = 2.7 ng mL⁻¹, ISF), HSA/nPSiO2 (LoD = 3.4 ng mL⁻¹), and HSA–agarose fibers (LoD = 0.7 ng mL⁻¹, PBS; 0.14 ng mL⁻¹, ISF).
– Light source & power: Optimized OLED (λ ≈ 521 nm, EQE ≈ 0.9 %, L ≈ 1246 cd m⁻² @ 5 V) and Na-ion microbattery (1–1.25 V, ≈ 7 mAh cm⁻², rechargeable).
– Encapsulation: MC/PEG/PAA hydrogel showing reversible gel–sol transition at ≈ 25 °C for on-demand dissolution.
• In-vivo demonstration
Accurate DOXO detection (0.1–2 µg mL⁻¹) in mice; full sensor resorption within 3 months; no systemic or local toxicity (ALT/AST normal).
• Contingency innovation
A wearable optical reader patch enabled transdermal interrogation and wireless data transfer, ensuring full functionality despite the unavailability of a biodegradable RF-switch.
• Scientific output
12 peer-reviewed papers (including Nat. Rev. Electr. Eng. 2025), > 5 under review, > 90 presentations, > 15 invited lectures, and > 70 open-access items (datasets, protocols, deliverables) on Zenodo.
• Technology readiness
Advanced TRL from 2 to 4, establishing Europe’s first validated bioresorbable optoelectronic sensing platform.

Impact

Economic Impact
• Intellectual Property: Four patents filed—optical fibers (EP 24209472.2) Na-ion microbattery (EP 24306269.2 EP 23170468.5) and drug-sensing device (P1215IT00); one additional patent (die-cast electrodes) in preparation.
• Industrial Collaboration: Partnership with ab medica S.p.A. for co-development of a wireless clinical reader, confirming early market interest.
• Follow-up Funding: Two EIC Transition and two Pathfinder Open proposals (one funded – ALERT ID 101257530). UNIPI also joined the MSCA Doctoral Industrial Network INTROS, reinforcing research and training capacity in transient bioelectronics.
• Market Outlook: Targets the > € 5 billion (by 2030) biodegradable implantable biosensor market.
• Economic Benefit: Hybrid wearable–implant design lowers healthcare costs by avoiding explant surgery and reducing recovery time.

Societal Impact
• Patient Acceptance: Survey of 104 oncology patients (Santa Chiara Hospital, Pisa) showed ≈ 70 % willingness to adopt implantable bioresorbable sensors for personalized chemotherapy.
• Public Engagement: > 10 press releases, 4 TV features (TG Leonardo, Sky TG 24), 1 radio feature, participation in EU Researchers’ Night 2022–23 (> 100 participants).
• Digital Reach: > 12 000 website impressions and > 800 social-media interactions.
• Environmental & Health Benefits: Fully resorbable devices eliminate removal surgeries and biomedical waste, aligning with the EU Green Deal.
• Scientific Leadership: Organization of MRS Spring Meeting 2025 Symposium “Degradable Materials and Devices” (≈ 70 participants, 40 speakers) confirmed Europe’s leadership in transient bioelectronics.

Visual identity of RESORB