Results of an interlaboratory study on the working curve in vat photopolymerization.

The working curve informs resin properties and print parameters for stereolithography, digital light processing, and other photopolymer additive manufacturing (PAM) technologies. First demonstrated in 1992, the working curve measurement of cure depth vs radiant exposure of light is now a foundational measurement in the field of PAM. Despite its widespread use in industry and academia, there is no formal method or procedure for performing the working curve measurement, raising questions about the utility of reported working curve parameters. Here, an interlaboratory study (ILS) is described in which 24 individual laboratories performed a working curve measurement on an aliquot from a single batch of PAM resin. The ILS reveals that there is enormous scatter in the working curve data and the key fit parameters derived from it. The measured depth of light penetration Dp varied by as much as 7x between participants, while the critical radiant exposure for gelation Ec varied by as much as 70x. This significant scatter is attributed to a lack of common procedure, variation in light engines, epistemic uncertainties from the Jacobs equation, and the use of measurement tools with insufficient precision. The ILS findings highlight an urgent need for procedural standardization and better hardware characterization in this rapidly growing field.

Stereolithographic (SLA) 3D Printing for Preprocedural Planning in Endovascular Aortic Repair of a Thoracic Aneurysm.

BACKGROUND: When treating aortic aneurysm patients with complex anatomical features, preprocedural planning aided by 3D-printed models offers valuable insights for endovascular intervention. This study highlights the use of stereolithographic (SLA) 3D printing to fabricate a phantom of a challenging aortic arch aneurysm with a complex neck anatomy. CLINICAL CASE: A 75-year-old female presented with a 58 mm descending thoracic aortic aneurysm (TAA) extending to the distal arch, involving the left subclavian artery (LSA) and the left common carotid artery (LCCA). The computed tomography (CT) scans underwent scrutiny by radiology and vascular teams. Nevertheless, the precise spatial relationships of the ostial origins proved to be challenging to ascertain. To address this, a patient-specific phantom of the aortic arch was fabricated utilizing an SLA printer and a biomedical resin. The thoracic endovascular aortic repair (TEVAR) procedure was simulated using fluoroscopy on the phantom to enhance procedural preparedness. Subsequently, the patient underwent a right carotid-left carotid bypass and a right carotid-left subclavian bypass. After a 24-hour interval, the patient underwent the TEVAR procedure, during which a 37 mm × 150 mm stent graft (CTAG, WL Gore and Associates, Flagstaff, AZ, USA) and a 40 mm × 200 mm stent graft (CTAG, WL Gore and Associates, Flagstaff, AZ, USA) were deployed, effectively covering the LSA and LCCA. Notably, the aneurysm exhibited complete sealing, with no indications of endoleaks or graft infoldings. At the 12-month follow-up, the patient remains in good health, with no evidence of endoleaks or any other surgery-related complication. CONCLUSION: This report showcases the successful use of a 3D-printed endovascular phantom in guiding the decision-making process during the preparation for a TEVAR procedure. The simulation played a pivotal role in selecting the appropriate stent graft, ensuring an intervention protocol optimized based on the patient-specific anatomy.

Fabrication of Soft Transparent Patient-Specific Vascular Models with Stereolithographic 3D printing and Thiol-Based Photopolymerizable Coatings.

An ideal vascular phantom should be anatomically accurate, have mechanical properties as close as possible to the tissue, and be sufficiently transparent for ease of visualization. However, materials that enable the convergence of these characteristics have remained elusive. The fabrication of patient-specific vascular phantoms with high anatomical fidelity, optical transparency, and mechanical properties close to those of vascular tissue is reported. These final properties are achieved by 3D printing patient-specific vascular models with commercial elastomeric acrylic-based resins before coating them with thiol-based photopolymerizable resins. Ternary thiol-ene-acrylate chemistry is found optimal. A PETMP/allyl glycerol ether (AGE)/polyethylene glycol diacrylate (PEGDA) coating with a 30/70% AGE/PEGDA ratio applied on a flexible resin yielded elastic modulus, UTS, and elongation of 3.41 MPa, 1.76 MPa, and 63.2%, respectively, in range with the human aortic wall. The PETMP/AGE/PEGDA coating doubled the optical transmission from 40% to 80%, approaching 88% of the benchmark silicone-based elastomer. Higher transparency correlates with a decrease in surface roughness from 2000 to 90 nm after coating. Coated 3D-printed anatomical replicas are showcased for pre-procedural planning and medical training with good radio-opacity and echogenicity. Thiol-click chemistry coatings, as a surface treatment for elastomeric stereolithographic 3D-printed objects, address inherent limitations of photopolymer-based additive manufacturing.

Two-photon isomerization properties of donor-acceptor Stenhouse adducts.

Donor-acceptor Stenhouse adducts (DASAs) are important photo-responsive molecules that undergo electrocyclic reactions after light absorption. From these properties, DASAs have received extensive attention as photo-switches with negative photochromism. Meanwhile, several photochemical applications require isomerization events to take place in highly localized volumes at variable depths. Such focused photoreactions can be achieved if the electronic excitation is induced through a non-linear optical process. In this contribution we describe DASAs substituted with extended donor groups which provide them with significant two-photon absorption properties. We characterized the photo-induced transformation of these DASAs from the open polymethinic form to their cyclopentenic isomer with the use of 800 nm femtosecond pulses. These studies verified that the biphotonic excitation produces equivalent photoreactions as linear absorbance. We also determined these DASAs' two-photon absorption cross sections from measurements of their photoconverted yield after biphotonic excitation. As we show, specific donor sections provide these systems with important biphotonic cross-sections as high as 615 GM units. Such properties make these DASAs among the most non-linearly active photo-switchable molecules. Calculations at the TDDFT level with the optimally tuned range-separated functional OT-CAM-B3LYP, together with quadratic response methods indicate that the non-linear photochemical properties in these molecules involve higher lying electronic states above the first excited singlet. This result is consistent with the observed relation between their two-photon chemistry and the onset of their short wavelength absorption features around 400 nm. This is the first report of the non-linear photochemistry of DASAs. The two-photon isomerization properties of DASAs extend their applications to 3D-photocontrol, non-linear lithography, variable depth birefringence, and localized drug delivery schemes.

Nanocaging Rose Bengal to Inhibit Aggregation and Enhance Photo-induced Oxygen Consumption†.

Photosensitized crosslinking of proteins in tissues has many medical applications including sealing wounds, strengthening tissues, and beneficially altering tissue properties. Rose Bengal (RB) is used most frequently as the photosensitizer but is not as efficient as would be desired for broad utilization in medicine. Aggregation of RB, at the high concentrations used for medical treatments, decreases the yield of singlet oxygen, which mediates protein crosslinking. We hypothesized that nanocages that sequester RB would inhibit self-association, increasing photosensitization efficiency. We tested cucurbituril and cyclodextrin nanocages, demonstrating that hydroxypropyl-functionalized cyclodextrins are most effective in inhibiting RB aggregation. For these RB/cyclodextrin solutions, we investigated the effect of nanocaging on the photobleaching and oxygen consumption kinetics under 530 nm LED light in aqueous phosphate-buffered solutions. At 100 µm RB, the initial oxygen consumption rates increased by 58% and 80% compared with uncaged RB for the ß and γ (2-hydroxypropyl) cyclodextrins, respectively. For 1 mm RB, the enhancement in these rates was much greater, about 200% and 300%, respectively. In addition, at 1 mm RB these two cyclodextrins increased the RB photobleaching rate by ~20% and ~75%. These results suggest that nanocages can minimize RB aggregation and may lead to higher-efficiency photo-medical therapies.

Exponential Amplification Using Photoredox Autocatalysis.

Exponential molecular amplification such as the polymerase chain reaction is a powerful tool that allows ultrasensitive biodetection. Here, we report a new exponential amplification strategy based on photoredox autocatalysis, where eosin Y, a photocatalyst, amplifies itself by activating a nonfluorescent eosin Y derivative (EYH3-) under green light. The deactivated photocatalyst is stable and rapidly activated under low-intensity light, making the eosin Y amplification suitable for resource-limited settings. Through steady-state kinetic studies and reaction modeling, we found that EYH3- is either oxidized to eosin Y via one-electron oxidation by triplet eosin Y and subsequent 1e-/H+ transfer, or activated by singlet oxygen with the risk of degradation. By reducing the rate of the EYH3- degradation, we successfully improved EYH3--to-eosin Y recovery, achieving efficient autocatalytic eosin Y amplification. Additionally, to demonstrate its flexibility in output signals, we coupled the eosin Y amplification with photoinduced chromogenic polymerization, enabling sensitive visual detection of analytes. Finally, we applied the exponential amplification methods in developing bioassays for detection of biomarkers including SARS-CoV-2 nucleocapsid protein, an antigen used in the diagnosis of COVID-19.

Influence of Rose Bengal Dimerization on Photosensitization.

Protein crosslinking photosensitized by rose Bengal (RB2- ) has multiple medical applications and understanding the photosensitization mechanism can improve treatment effectiveness. To this end, we investigated the photochemical efficiencies of monomeric RB2- (RBM 2- ) and dimeric RB2- (RBD 2- ) and the optimal pH for anaerobic RB2- photosensitization in cornea. Absorption spectra and dynamic light scattering (DLS) measurements were used to estimate the fractions of RBM 2- and RBD 2- . RB2- self-photosensitized bleaching was used to evaluate the photoactivity of RBM 2- and RBD 2- . The pH dependence of anaerobic RB2- photosensitization was evaluated in ex vivo rabbit corneas. The 549 nm/515 nm absorption ratio indicated that concentrations > 0.10 mm RB contained RBD 2- . Results from DLS gave estimated mean diameters for RBM 2- and RBD 2- of 0.70 ± 0.02 nm and 1.75 ± 0.13 nm, respectively, and indicated that 1 mm RB2- contained equal fractions of RBM 2- and RBD 2- . Quantum yields for RB2- bleaching were not influenced by RBD 2- in RB2- solutions although accounting for RB2- concentration effects on the reaction kinetics demonstrated that RBD 2- is not a photosensitizer. Optimal anaerobic photosensitization occurred at pH 8.5 for solutions containing 200 mm Arg. These results suggest potential approaches to optimizing RBM 2- -photosensitized protein crosslinking in tissues.

Functional Comparison of Bioactive Cellulose Materials Incorporating Engineered Binding Proteins.

Whatman No. 1 chromatography paper is widely used as a substrate for cellulose-based immunoassays. The immobilized proteins are used to capture target biomarkers for detection. However, alternative paper substrates may facilitate mass production of immunoassays as diagnostic tests. Here, we assessed the physical characteristics and protein immobilization capabilities of different commercial papers. Some substrates fulfilled our design criteria, including adequate flow rate and sufficient protein immobilization for efficient target capture. This study demonstrates that a variety of paper substrates can be bioactivated and used to capture target biomarkers, enabling development of affordable diagnostic tests from a range of starting materials.

UV-Vis/FT-NIR in situ monitoring of visible-light induced polymerization of PEGDA hydrogels initiated by eosin/triethanolamine/O2.

In conjunction with a tertiary amine coinitiator, eosin, a photoreducible dye, has been shown to successfully circumvent oxygen inhibition in radical photopolymerization reactions. However, the role of O2 in the initiation and polymerization processes remains inconclusive. Here, we employ a UV-Vis/FT-NIR analytical tool for real-time, simultaneous monitoring of chromophore and monomer reactive group concentrations to investigate the eosin-activated photopolymerization of PEGDA-based hydrogels under ambient conditions. First, we address the challenges associated with spectroscopic monitoring of the polymerization of hydrogels using UV-Vis and FT-NIR, proposing metrics for quantifying the extent of signal loss from reflection and scattering, and showing their relation to microgelation and network formation. Second, having established a method for extracting kinetic information by eliminating the effects of changing refractive index and scattering, the coupled UV-Vis/FT-NIR system is applied to the study of eosin-activated photopolymerization of PEGDA in the presence of O2. Analysis of the inhibition time, rate of polymerization, and rate of eosin consumption under ambient and purged conditions indicates that regeneration of eosin in the presence of oxygen and consumption of oxygen occur via a nonchain process. This suggests that the uniquely high O2 resilience is due to alternative processes such as energy transfer from photo-activated eosin to oxygen. Uncovering the intricacies of the role of O2 in eosin-mediated initiation aids the design of O2 resistant free radical polymerization systems relevant to photonics, optoelectronics, biomaterials, and biosensing.

Spatial and Temporal Control of Thiol-Michael Addition via Photocaged Superbase in Photopatterning and Two-Stage Polymer Networks Formation.

Photochemical processes enable spatial and temporal control of reactions, which can be implemented as an accurate external control approach in both polymer synthesis and materials applications. "Click" reactions have also been employed as efficient tools in the same field. Herein, we combined photochemical processes and thiol-Michael "click" reactions to achieve a "photo-click" reaction that can be used in surface patterning and controlled polymer network formation, owing to the ease of spatial and temporal control through use of photolabile amines as appropriate catalysts.

Photoinduced diffusion through polymer networks.

Photomediated addition-fragmentation chemistry is applied to demonstrate the precisely controlled diffusion of chemical species through polymer networks. Fluorescent groups connected to polymer networks by allyl sulfide moieties become mobile upon irradiation with UV light due to radical-mediated addition-fragmentation bond exchange. Photoinduced transport through the bulk, into solution, and across film interfaces is demonstrated.

Visible-light organic photocatalysis for latent radical-initiated polymerization via 2e⁻/1H⁺ transfers: initiation with parallels to photosynthesis.

We report the latent production of free radicals from energy stored in a redox potential through a 2e(-)/1H(+) transfer process, analogous to energy harvesting in photosynthesis, using visible-light organic photoredox catalysis (photocatalysis) of methylene blue chromophore with a sacrificial sterically hindered amine reductant and an onium salt oxidant. This enables light-initiated free-radical polymerization to continue over extended time intervals (hours) in the dark after brief (seconds) low-intensity illumination and beyond the spatial reach of light by diffusion of the metastable leuco-methylene blue photoproduct. The present organic photoredox catalysis system functions via a 2e(-)/1H(+) shuttle mechanism, as opposed to the 1e(-) transfer process typical of organometallic-based and conventional organic multicomponent photoinitiator formulations. This prevents immediate formation of open-shell (radical) intermediates from the amine upon light absorption and enables the "storage" of light-energy without spontaneous initiation of the polymerization. Latent energy release and radical production are then controlled by the subsequent light-independent reaction (analogous to the Calvin cycle) between leuco-methylene blue and the onium salt oxidant that is responsible for regeneration of the organic methylene blue photocatalyst. This robust approach for photocatalysis-based energy harvesting and extended release in the dark enables temporally controlled redox initiation of polymer syntheses under low-intensity short exposure conditions and permits visible-light-mediated synthesis of polymers at least 1 order of magnitude thicker than achievable with conventional photoinitiated formulations and irradiation regimes.