Light activation of 3D-printed structures: from millimeter to sub-micrometer scale

Three-dimensional (3D) printing enables the fabrication of complex, highly customizable structures, which are difficult to fabricate using conventional fabrication methods. Recently, the concept of four-dimensional (4D) printing has emerged, which adds active and responsive functions to 3D-printed structures. Deployable or adaptive structures with desired structural and functional changes can be fabricated using 4D printing; thus, 4D printing can be applied to actuators, soft robots, sensors, medical devices, and active and reconfigurable photonic devices. The shape of 3D-printed structures can be transformed in response to external stimuli, such as heat, light, electric and magnetic fields, and humidity. Light has unique advantages as a stimulus for active devices because it can remotely and selectively induce structural changes. There have been studies on the light activation of nanomaterial composites, but they were limited to rather simple planar structures. Recently, the light activation of 3D-printed complex structures has attracted increasing attention. However, there has been no comprehensive review of this emerging topic yet. In this paper, we present a comprehensive review of the light activation of 3D-printed structures. First, we introduce representative smart materials and general shape-changing mechanisms in 4D printing. Then, we focus on the design and recent demonstration of remote light activation, particularly detailing photothermal activations based on nanomaterial composites. We explain the light activation of 3D-printed structures from the millimeter to sub-micrometer scale.

Characterization and Modification of Light-Sensitive Phosphodiesterases from Choanoflagellates

Enzyme rhodopsins, including cyclase opsins (Cyclops) and rhodopsin phosphodiesterases (RhoPDEs), were recently discovered in fungi, algae and protists. In contrast to the well-developed light-gated guanylyl/adenylyl cyclases as optogenetic tools, ideal light-regulated phosphodiesterases are still in demand. Here, we investigated and engineered the RhoPDEs from Salpingoeca rosetta, Choanoeca flexa and three other protists. All the RhoPDEs (fused with a cytosolic N-terminal YFP tag) can be expressed in Xenopus oocytes, except the AsRhoPDE that lacks the retinal-binding lysine residue in the last (8th) transmembrane helix. An N296K mutation of YFP::AsRhoPDE enabled its expression in oocytes, but this mutant still has no cGMP hydrolysis activity. Among the RhoPDEs tested, SrRhoPDE, CfRhoPDE1, 4 and MrRhoPDE exhibited light-enhanced cGMP hydrolysis activity. Engineering SrRhoPDE, we obtained two single point mutants, L623F and E657Q, in the C-terminal catalytic domain, which showed ~40 times decreased cGMP hydrolysis activity without affecting the light activation ratio. The molecular characterization and modification will aid in developing ideal light-regulated phosphodiesterase tools in the future.

Light-Assisted Enhancement of Gas Sensing Property for Micro-Nanostructure Electronic Device: A Mini Review

In recent years, gas sensing electronic devices have always attracted wide attention in the field of environment, industry, aviation and others. In order to improve the gas sensing properties, many micro- and nano-fabrication technologies have been proposed and investigated to develop high-performance gas sensing devices. It is worth noting that light irradiation is an effective strategy to enhance gas sensitivity, shorten the response and recovery time, reduce operating temperature. In this review, firstly, the latest research advances of gas sensors based on different micro-nanostructure materials under UV light and visible light activation is introduced. Then, the gas sensing mechanism of light-assisted gas sensor is discussed in detail. Finally, this review describes the present application of gas sensors with improved properties under light activation assisted conditions and the perspective of their applications.

Dental-Plaque Decontamination around Dental Brackets Using Antimicrobial Photodynamic Therapy: An In Vitro Study

Background: In orthodontic therapy, the enamel around brackets is very susceptible to bacterial-plaque retention, which represents a risk factor for dental tissues. The aim of this study was to evaluate the effect of methylene blue and a chlorophyllin–phycocyanin mixture, used with and without light activation, in contrast with a 2% chlorhexidine solution, on Streptococcus mutans colonies. Methods: Twenty caries-free human extracted teeth were randomized into five groups. A Streptococcus mutans suspension was inoculated on teeth in groups B, C, D, and E (A was the positive-control group). Bacterial colonies from groups C, D, and E (B was the negative-control group) were subjected to photosensitizers and 2% chlorhexidine solution. For groups C and D, a combined therapy consisting of photosensitizer and light activation was performed. The Streptococcus mutans colonies were counted, and smears were examined with an optical microscope. Two methods of statistical analysis, unidirectional analysis of variance and the Tukey–Kramer test, were used to evaluate the results. Results: A statistically significant reduction in bacterial colonies was detected after the combined therapy was applied for groups C and D, but the most marked bacterial reduction was observed for group D, where a laser-activated chlorophyll–phycocyanin mixture was used. Conclusions: Photodynamic therapy in combination with methylene blue or chlorophyllin–phycocyanin mixture sensitizers induces a statistically significant decrease in the number of bacterial colonies.

Systematic optimization of visible light-induced crosslinking conditions of gelatin methacryloyl (GelMA)

Gelatin methacryloyl (GelMA) is one of the most widely used photo-crosslinkable biopolymers in tissue engineering. In in presence of an appropriate photoinitiator, the light activation triggers the crosslinking process, which provides shape fidelity and stability at physiological temperature. Although ultraviolet (UV) has been extensively explored for photo-crosslinking, its application has been linked to numerous biosafety concerns, originated from UV phototoxicity. Eosin Y, in combination with TEOA and VC, is a biosafe photoinitiation system that can be activated via visible light instead of UV and bypasses those biosafety concerns; however, the crosslinking system needs fine-tuning and optimization. In order to systematically optimize the crosslinking conditions, we herein independently varied the concentrations of Eosin Y [(EY)], triethanolamine (TEOA), vinyl caprolactam (VC), GelMA precursor, and crosslinking times and assessed the effect of those parameters on the properties the hydrogel. Our data showed that except EY, which exhibited an optimal concentration (~ 0.05 mM), increasing [TEOA], [VA], [GelMA], or crosslinking time improved mechanical (tensile strength/modulus and compressive modulus), adhesion (lap shear strength), swelling, biodegradation properties of the hydrogel. However, increasing the concentrations of crosslinking reagents ([TEOA], [VA], [GelMA]) reduced cell viability in 3-dimensional (3D) cell culture. This study enabled us to optimize the crosslinking conditions to improve the properties of the GelMA hydrogel and to generate a library of hydrogels with defined properties essential for different biomedical applications.

Dramatic Reduction of Distant Pancreatic Metastases Using Local Light Activation of Verteporfin with Nab-Paclitaxel

Despite substantial drug development efforts, pancreatic adenocarcinoma (PDAC) remains a difficult disease to treat, and surgical resection is the only potentially curative option. Unfortunately, 80% of patients are ineligible for surgery due to the presence of invasive disease and/or distant metastases at the time of diagnosis. Treatment strategies geared towards reclassifying these patients as surgical candidates by reducing metastatic burden represents the most promising approach to improve long-term survival. We describe a photodynamic therapy (PDT) based approach that, in combination with the first-line chemotherapeutic nab-paclitaxel, effectively addresses distant metastases in three separate orthotopic PDAC models in immunodeficient mice. In addition to effectively controlling local tumor growth, PDT plus nab-paclitaxel primes the tumor to elicit systemic effects and reduce or abrogate metastases. This combination dramatically inhibits (up to 100%) the eventual development of metastases in models of early stage PDAC, and completely eliminates metastasis in 55% of animals with already established distant disease in late-stage models. Our findings suggest that this light activation process initiates local biological and/or physiological changes within the tumor microenvironment that can be leveraged to treat both localized and distant disease, and potentially reclassify patients with previously inoperable disease as surgical candidates.

Photodynamic Priming Improves the Anti-Migratory Activity of Prostaglandin E Receptor 4 Antagonist in Cancer Cells In Vitro

The combination of photodynamic agents and biological inhibitors is rapidly gaining attention for its promise and approval in treating advanced cancer. The activity of photodynamic treatment is mainly governed by the formation of reactive oxygen species upon light activation of photosensitizers. Exposure to reactive oxygen species above a threshold dose can induce cellular damage and cancer cell death, while the surviving cancer cells are “photodynamically primed”, or sensitized, to respond better to other drugs and biological treatments. Here, we report a new combination regimen of photodynamic priming (PDP) and prostaglandin E2 receptor 4 (EP4) inhibition that reduces the migration and invasion of two human ovarian cancer cell lines (OVCAR-5 and CAOV3) in vitro. PDP is achieved by red light activation of the FDA-approved photosensitizer, benzoporphyrin derivative (BPD), or a chemical conjugate composed of the BPD linked to cetuximab, an anti-epithelial growth factor receptor (EGFR) antibody. Immunoblotting data identify co-inhibition of EGFR, cAMP-response element binding protein (CREB), and extracellular signal-regulated kinase 1/2 (ERK1/2) as key in the signaling cascades modulated by the combination of EGFR-targeted PDP and EP4 inhibition. This study provides valuable insights into the development of a molecular-targeted photochemical strategy to improve the anti-metastatic effects of EP4 receptor antagonists.