A biodegradable, flexible photonic patch for in vivo phototherapy

Illuminating internal organs is crucial for optical diagnosis, laser surgery, and light-activated therapies, yet existing approaches struggle to meet diverse clinical requirements for depth, area, wavelength, and power, particularly for large-area, deep illumination on moving targets like the heart and lungs. External irradiation is limited by tissue absorption, scattering, and autofluorescence. Implantable strategies (e.g., NFC-powered LEDs, upconversion nanoparticles) are constrained by energy transfer and conversion efficiencies. Optical fibers provide precise, broadband, high-power delivery and can be placed minimally invasively, but conventional flat-end or side-emitting designs largely project light forward, often necessitating tissue puncture and yielding small illumination volumes. Modifications (tapering, etching, side polishing, planar waveguides) improve distribution but still struggle to deliver large-area, deep, non-destructive, controllable illumination. This work addresses these gaps by introducing iCarP, a biodegradable patch leveraging a tapered fiber and an engineered air gap to scatter and laterally guide light across broad areas and depths without tissue penetration.

Prior in vivo illumination strategies include: (1) External light sources (including NIR-I/II) limited by tissue absorption/scattering and autofluorescence; (2) Implantable wireless LEDs via NFC power transfer, subject to transfer efficiency limits; (3) Upconversion nanoparticles that convert long- to short-wavelength light in situ, constrained by penetration and quantum conversion efficiencies; (4) Optical fibers integrated with endoscopy or MRI guidance enabling minimally invasive placement for applications such as laser thermotherapy and optogenetics. Conventional flat-end fibers emphasize forward illumination; side-polished/etched fibers emit radially but locally; tapered fibers concentrate light into defined regions; planar waveguides attached to fiber tips spread light forward but typically require puncture. These approaches have not universally achieved simultaneous large-area, deep, non-destructive illumination with controllable power and wavelength on moving organs.

Device design and fabrication: A multimode tapered optical fiber (TOF) with a short taper length (~280 µm) and ~1 µm tip was fabricated using a Fujikura 80S+ fusion splicer (elongation 400 µm), plasma-cleaned, and fluorinated with trichloro(1H,1H,2H,2H-tridecafluoro-n-octyl)silane (12 h, <0.09 MPa) to reduce adhesion. The TOF tip was embedded parallel to tissue within a UV-crosslinked, transparent PMCL patch (n=1.49) synthesized by ring-opening polymerization of 4-methyl-ε-caprolactone followed by end acrylation and 365 nm photocuring (500 mW/cm², 10 min). An adjustable micrometer-scale air gap (5–25 µm targeted) between the TOF tip and PMCL was created by controlled pull-out to enhance scattering via TOF/air and air/PMCL refractions. Variants without an air gap and with flat-end fibers were also fabricated. Optical modeling and characterization: Light scattering was simulated using BPM (RSoft) with geometry reconstructed in MATLAB; refractive indices used were 1.4613 (core), 1.4562 (cladding), and 1.49 (PMCL); LP01 mode assumed. Fluorescent path visualization used Rhodamine B in 52% glycerol-water (n≈1.40). Divergence angles and illumination patterns were measured, and parameter d (distance from TOF tip to air-gap tip) was analyzed to quantify the fraction of power outside the forward propagation region. Ex vivo and in vivo illumination: iCarP was adhered to rat epicardium with a rapid biodegradable adhesive (CCS@gel) and evaluated for stability under >300 bpm and >10% strain. Illumination modes included continuous and pulsatile (1 Hz) and multiple wavelengths (405, 445, 473, 520, 660, 808 nm) with intensity control via diode driver current. Ex vivo porcine hearts were used to evaluate area and depth of penetration (tissue cuboids of 1.5 cm thickness; 660 nm, 75 mW). Functional assays: Photosynthesis was tested by immersing iCarP or TOF in Chlorella suspensions (2×10^7 mL^-1) while recording dissolved oxygen (660 nm, 55 mW). Tumor photothermal therapy: Female BALB/c nude mice with 4T1 tumors received AuNRs (0.1 mg/mL, 50 µL) prior to 808 nm laser (300 mW) delivered via iCarP or flat-end fiber; thermal imaging and histology (H&E, TUNEL) were performed 48 h post-treatment. Photodynamic therapy used FITC (473 nm) with repeated daily illuminations over 3 days in iCarP-indwelled mice. Myocardial infarction (MI) model and photosynthesis therapy: SD rats underwent LAD ligation; groups: Sham, MI, iCarP+/Light− (mechanical support only), iCarP+/Light+ (Chlorella injection into infarct, iCarP illumination 660 nm, 55 mW, 3 h). Outcomes included apoptosis (TUNEL, day 3), fibrosis (Masson’s trichrome, day 28), echocardiographic function (LVEF at days 7 and 28), and molecular markers (Bcl-2, Bax, cleaved Caspase-3; RNA-seq of pro-apoptosis/fibrosis genes). Safety assays included cardiomyocyte ROS and viability under prolonged illumination. Minimally invasive implantation: Thoracoscopic delivery was demonstrated ex vivo and in canine surgery using 1.2 cm Trocar ports; iCarP (2.5 cm diameter) was advanced while illuminated, unfolded on exit, adhered to epicardium, and monitored for stability and cardiac effects. TOF removal was tested in closed-chest rats post-illumination to leave only biodegradable PMCL in place. Statistical analyses used t-tests and one-way ANOVA with Tukey post-test; data reported as mean ± SD.

- Optical performance: Tapering increased divergence versus flat-end fibers; TOF in PMCL measured ~40° divergence; TOF in air simulated ~97°; iCarP achieved ~130° divergence due to dual refractions at TOF/air and air/PMCL interfaces and internal reflection within PMCL, producing a bulb-like lateral illumination with a dark forward region. Optimal air-gap distance d≈5–25 µm maximized lateral scattering, yielding ~80% of output power outside the forward propagation region. - Photosynthesis enhancement: In Chlorella suspension (660 nm, 55 mW), TOF alone produced 115.6 µmol/L O2 in the first hour and ~66.0 µmol/L over the next 2 h (total ~181.6 µmol/L); iCarP increased first-hour O2 by ~10% and sustained higher rates in hours 2–3, reaching a total of 284.2 µmol/L. - Ex vivo tissue illumination: On porcine myocardium (660 nm), all devices penetrated 0.5 cm; only iCarP showed detectable light on the opposite side of 1.5 cm tissue. iCarP produced broader, more uniform lateral illumination, covering and extending ~0.5 cm beyond patch edges, yielding ~3 cm diameter illuminated areas, stable under tissue deformation. - Tumor photothermal therapy (808 nm with AuNRs): iCarP produced higher peak temperature (56 °C) and larger >45 °C zone (~2 mm diameter) than flat-end fiber (49 °C peak; ~1 mm >45 °C zone). Histology showed larger necrotic volumes with iCarP (approximate 2 mm hemi-ellipsoid) versus smaller columnar necrosis (~1 mm diameter) with flat-end fiber. - Photodynamic therapy: With FITC (473 nm), repeated daily iCarP illuminations over 3 days significantly inhibited tumor growth versus flat-end fiber, increasing tumor necrosis and apoptosis and reducing vessel density. - MI photosynthesis therapy: In rats, iCarP adherence was stable for >100,000 heartbeats; TOF could be removed post-illumination leaving PMCL adhered. iCarP+/Light+ reduced cardiomyocyte apoptosis versus MI and iCarP+/Light−, lowered fibrosis at day 28 (MI: 25.6±2.8%; iCarP+/Light−: 22.1±2.0%; iCarP+/Light+: 20.1±2.5%), and significantly improved LVEF compared to MI and iCarP+/Light−. Molecular analyses showed increased Bcl-2 and reduced Bax and cleaved Caspase-3 in iCarP+/Light+; fibrosis-related genes (Tgfb1, Tgfb2, Col5a3) were downregulated versus MI. - Multi-wavelength, programmable operation: iCarP supported 405, 445, 473, 520, 660, and 808 nm; continuous and 1 Hz pulsatile modes; precise intensity modulation; sustained 3 h illumination in closed chest with potential for repeated sessions. - Minimally invasive compatibility and safety: A 2.5 cm device passed through a 1.2 cm Trocar, unfolded, adhered securely, and maintained illumination; thoracoscopic canine implantation showed stable illumination without arrhythmia or heart-rate changes. In vitro and in vivo tests indicated no ROS accumulation or cardiotoxicity with extended illumination.

The iCarP architecture integrates a tapered fiber, a micrometer-scale air gap, and a high-index, transparent biodegradable patch to convert forward-propagating light into wide-angle, laterally directed illumination parallel to tissue, enabling large-area, deep illumination without tissue puncture. The air gap is pivotal, exploiting large index contrast to amplify divergence and uniformly distribute optical energy across the patch-tissue interface while diminishing forward hotspots. Compared with conventional flat-end or side-emitting fibers, iCarP simultaneously achieves broad area and clinically relevant depth of penetration, maintaining function on moving organs and under deformation. Functionally, iCarP enhances light-driven processes: it boosts photosynthesis efficiency in vitro, improves thermal coverage and therapeutic outcomes in photothermal tumor ablation, enables repeated photodynamic therapy, and supports in situ myocardial photosynthesis that reduces apoptosis and fibrosis and improves cardiac function. The device operates across visible to NIR wavelengths, supports programmable intensity and temporal patterns, and is compatible with minimally invasive delivery and post-treatment fiber removal, minimizing long-term foreign materials. Collectively, iCarP broadens the utility of optical therapies and diagnostics by delivering controllable illumination microenvironments tailored to internal targets.

This work introduces iCarP, a biodegradable, flexible photonic patch that laterally scatters and guides light via a tapered optical fiber and engineered air gap within a high-index PMCL substrate, achieving wide-area, deep, noninvasive illumination on internal organs. iCarP supports broad-spectrum, continuous or pulsatile operation with stable performance on moving tissues and compatibility with minimally invasive implantation. Demonstrations include enhanced photosynthesis, superior tumor photothermal and photodynamic therapy coverage and efficacy, and improved outcomes in a rat MI model via in situ photosynthesis. The approach is broadly compatible with diverse photosensitizers and fiber types and can integrate with portable sources and sensing for closed-loop theranostics. Future work should optimize long-term biocompatibility/degradation profiles, enable extended continuous illumination, and incorporate directional coatings to prevent off-target illumination.

- Long-term foreign body responses to iCarP were not comprehensively assessed; PMCL degrades slowly, and adhesions to the thoracic wall were observed. - Illumination duration in rats was limited to 3 hours by anesthesia constraints; safety and efficacy of longer continuous illumination require evaluation. - Light scatters from both sides of the device, potentially illuminating non-target tissues; adding reflective coatings could confine light to the target side. - While ex vivo and small-animal in vivo results are promising, larger-scale, chronic studies and clinical translation pathways remain to be established.