Temporal Release Research Articles

Nanofibrous 3D scaffolds capable of individually controlled BMP and FGF release for the regulation of bone regeneration

The current clinical applications of bone morphogenetic proteins (BMPs) are limited to only a few specific indications. Locally controlled delivery of combinations of growth factors can be a promising strategy to improve BMP-based bone repair. However, the success of this approach requires the development of an effective release system and the correct choice of growth factors capable of enhancing BMP activity. Basic fibroblast growth factor (bFGF, also known as FGF-2) has shown promise in promoting bone repair, although conflicting results have been reported. Considering the complex biological activities of FGF-2, we hypothesized that FGF-2 can promote BMP-induced bone regeneration only if the dosage and kinetic parameters of the two factors are individually tailored. In this study, we conducted systematic in vitro studies on cell proliferation, differentiation, and mineralization in response to factor dose, delivery mode (sequential or simultaneous), and release rate. Subsequently, we designed individually controlled BMP-7 and FGF-2 release poly(lactide-co-glycolide) (PLGA) nanospheres attached to the poly(l-lactic acid) (PLLA) nanofibrous scaffolds. The data showed that BMP-7-induced bone formation was accelerated by a relatively higher FGF-2 dose (100 ng/scaffold) delivered at a faster release rate, or by a relatively lower FGF-2 dose (10 ng/scaffold) at a slower release rate in an in vivo bone regeneration model. In contrast, a very high dose of FGF-2 (1000 ng/scaffold) inhibited bone regeneration under all conditions. In vitro and in vivo data suggest that FGF-2 improved BMP-7-induced bone regeneration by coordinating FGF-2 dosage and release kinetics to enhance stem cell migration, proliferation, and angiogenesis. Statement of significanceBone morphogenetic proteins (BMPs) are the most potent growth/differentiation factors in bone development and regeneration. However, the clinical applications of BMPs have been limited to only a few specific indications due to the required supraphysiological dosages with the current BMP products and their side effects. Locally controlled delivery of BMPs and additional growth factors that can enhance their osteogenic potency are highly desired. However, different growth factors act with different mechanisms. Here we report a nanofibrous scaffold that mimics collagen in size and geometry and is immobilized with biodegradable nanospheres to achieve local and distinct release profiles of BMP7 and FGF2. Systematic studies demonstrated low dose BMP7 and FGF2 with different temporal release profiles can optimally enhance bone regeneration.

Immunomodulatory hydrogel orchestrates pro-regenerative response of macrophages and angiogenesis for chronic wound healing

Chronic wound healing often encounters challenges characterized by prolonged inflammation and impaired angiogenesis. While the immune response plays a pivotal role in orchestrating the intricate process of wound healing, excessive inflammation can hinder tissue repair. In this study, a bilayer alginate hydrogel system encapsulating polyelectrolyte complex nanoparticles (PCNs) loaded with anti-inflammatory cytokines and angiogenic growth factors is developed to address the challenges of chronic wound healing. The alginate hydrogel is designed using two distinct crosslinking methods to achieve differential degradation, thereby enabling precise spatial and temporal controlled release of PCNs. Initially, interleukin-10 (IL-10) is released to mitigate inflammation, while unsaturated PCNs bind and remove accumulated pro-inflammatory cytokines at the wound site. Subsequently, angiogenic growth factors, including vascular endothelial growth factor and platelet-derived growth factor, are released to promote vascularization and vessel maturation. Our results demonstrate that the bilayer hydrogel exhibits distinct degradation kinetics between the two layers, facilitating the staged release of multiple signaling molecules. In vitro experiments reveal that IL-10 can activate the Jak1/STAT3 pathway, thereby suppressing pro-inflammatory cytokines and chemokines while down-regulating inflammation-related genes. In vivo studies demonstrate that application of the hydrogel in chronic wounds using diabetic murine model promotes healing by positively modulating multiple integral reparative mechanisms. These include reducing inflammation, promoting macrophage polarization towards a pro-regenerative phenotype, enhancing keratinocyte migration, stimulating angiogenesis, and expediting wound closure. In conclusion, our hydrogel system effectively mitigates inflammatory responses and provides essential physiological cues by inducing a synergistic angiogenic effect, thus offering a promising approach for the treatment of chronic wounds.

How dependent are quantitative volcanic ash concentration and along‐flight dosage forecasts to model structural choices?

AbstractProducing quantitative volcanic ash forecasts is challenging due to multiple sources of uncertainty. Careful consideration of this uncertainty is required to produce timely and robust hazard warnings. Structural uncertainty occurs when a model fails to produce accurate forecasts, despite good knowledge of the eruption source parameters, meteorological conditions and suitable parameterizations of transport and deposition processes. This uncertainty is frequently overlooked in forecasting practices. Using a Lagrangian particle dispersion model, simulations with varied output spatial resolution, temporal averaging period and particle release rate are performed to quantify the impact of these structural choices. This experiment reveals that, for the 2019 Raikoke eruption, structural choices give measurements of peak ash concentration spanning an order of magnitude, significantly impacting decision‐relevant thresholds used in aviation flight planning. Conversely, along‐flight dosage estimates exhibit less sensitivity to structural choices, suggesting it is a more robust metric to use in flight planning. Uncertainty can be reduced by eliminating structural choices that do not result in a favourable level of agreement with a high‐resolution reference simulation. Reliable forecasts require output spatial resolution 80 km, temporal averaging periods 3 h and particle release rates 5000 particles/h. This suggests that simulations with relatively small numbers of particles could be used to produce a large ensemble of simulations without significant loss of accuracy. Comparison with previous Raikoke simulations indicates that the uncertainty associated with these constrained structural choices is smaller than those associated with satellite constrained eruption source parameter and internal model parameter uncertainties. Thus, given suitable structural choices, other epistemic sources of uncertainty are likely to dominate. This insight is useful for the design of ensemble methodologies which are required to enable a shift from deterministic to probabilistic forecasting. The results are applicable to other long‐range dispersion problems and to Eulerian dispersion models.

Inverse identification of a pollutant source in an apartment with multiple rooms by joint multi-zone model and CFD

In case a hazardous agent is accidentally released inside a building, both the pollutant source location and the temporal release rates must be determined in order to guide emergency actions. Inverse modeling based on either a multi-zone model or computational fluid dynamics (CFD) may help to find the pollutant source. This investigation proposed the inverse identification of both the release location and dynamic release rate profile of a pollutant source in an apartment with multiple rooms. In the first stage of the solution, the room containing the pollutant source was identified by the inverse multi-zone model; then, in the second stage, the occupant who released the pollutant was determined by the inverse CFD model. Both models solved for the possible pollutant release rate profiles with a regularized, inverted matrix at all candidate zones/positions based on information from a sensor. Next, the occurrence probability at each candidate zone/position was interpreted by the Bayesian probability model with input from another sensor. The results revealed that the two types of models could be used in conjunction to efficiently identify both the room in which the pollutant was released and the exact occupant who released it, as well as the dynamic release rate profile.

Physiological and molecular responses of the copepods Acartia clausi and Acartia tonsa to nickel nanoparticles and nickel chloride

Nickel compounds in dissolved form or as nanoparticles may affect planktonic invertebrates in marine ecosystems. Here, we assessed the physiological (naupliar mortality, egg production, egg hatching success) and molecular (quantitative gene expression) responses of the crustacean copepods Acartia clausi (indigenous Mediterranean species) and Acartia tonsa (model organism in ecotoxicology), to nickel nanoparticles (NiNPs) and nickel chloride (NiCl2), over time. We also measured NPs size and the temporal release of Ni ions in aqueous solution, through dynamic light scattering (DLS) and inductively coupled plasma-mass spectrometry (ICP-MS), respectively.Nauplii of A. clausi were highly vulnerable to NiCl2 in the 48 h acute test, with an EC50 in the range of Ni concentrations measured in polluted waters. Females of both species exhibited a decreased egg production and hatching success after the 4-day exposure to NiNPs. Molecular responses in A. clausi incubated in NiNPs and NiCl2 showed a stronger up- or down-regulation, compared to A. tonsa, of genes associated with detoxification (phospholipid-hydroperoxide glutathione peroxidase, glutathione-S-transferase sigma), oxidative stress (superoxide dismutase), nervous system functioning (acetylcholinesterase), and oogenesis (vitellogenin).In conclusion, new information was here obtained on the effects of different forms of nickel on physiological and molecular responses of A. clausi, that could help to identify biomarker genes of exposure to be used as early-warning indicators. Our results also highlighted the need of employing indigenous copepod species to better evaluate the ecotoxicological impact of pollutants in different geographical area.

VR23 and Bisdemethoxycurcumin Enhanced Nanofiber Niche with Durable Bidirectional Functions for Promoting Wound Repair and Inhibiting Scar Formation.

Chronic wounds pose a significant clinical challenge worldwide, which is characterized by impaired tissue regeneration and excessive scar formation due to over-repair. Most studies have focused on developing wound repair materials that either facilitate the healing process or control hyperplastic scars caused by over-repair, respectively. However, there are limited reports on wound materials that can both promote wound healing and prevent scar hyperplasia at the same time. In this study, VR23-loaded dendritic mesoporous bioglass nanoparticles (dMBG) are synthesized and electrospun in poly(ester-curcumin-urethane)urea (PECUU) random composite nanofibers (PCVM) through the synergistic effects of physical adsorption, hydrogen bond, and electrospinning. The physicochemical characterization reveals that PCVM presented matched mechanical properties, suitable porosity, and wettability, and enabled sustained and temporal release of VR23 and BDC with the degradation of PCVM. In vitro experiments demonstrated that PCVM can modulate the functions and polarization of macrophages under an inflammatory environment, and possess effective anti-scarring potential and reliable cytocompatibility. Animal studies further confirmed that PCVM can efficiently promote re-epithelialization and angiogenesis and reduce excessive inflammation, thereby remarkably accelerating wound healing while preventing potential scarring. These findings suggest that the prepared PCVM holds promise as a bidirectional regulatory dressing for effectively promoting scar-free healing of chronic wounds.

Mesenchymal stem cells in PRP and PRF containing poly(3-caprolactone)/gelatin Scaffold: a comparative in-vitro study.

Scaffold design is one of the three most essential parts of tissue engineering. Platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) have been used in clinics and regenerative medicine for years. However, the temporal release of their growth factors limits their efficacy in tissue engineering. In the present study, we planned to synthesize nanofibrous scaffolds with the incorporation of PRP and PRF by electrospinning method to evaluate the effect of the release of PRP and PRF growth factors on osteogenic gene expression, calcification, proliferation, and cell adhesion of human bone marrow mesenchymal stem cell (h-BMSC) as they are part of scaffold structures. Therefore, we combined PRP/PRF, derived from the centrifugation of whole blood, with gelatin and Polycaprolactone (PCL) and produced nanofibrous electrospun PCL/Gel/PRP and PCL/Gel/PRF scaffolds. Three groups of scaffolds were fabricated, and h-BMSCs were seeded on them: (1) PCL/Gel; (2) PCL/Gel/PRP; (3) PCL/Gel/PRF. MTS assay was performed to assess cell proliferation and adhesion, and alizarin red staining confirmed the formation of bone minerals during the experiment. The result indicated that PCL/Gel did not have any better outcomes than the PRP and PRF group in any study variants after the first day of the experiment. PCL/gelatin/PRF was more successful regarding cell proliferation and adhesion. Although PCL/gelatin/PRP showed more promising results on the last day of the experiment in mineralization and osteogenic gene expression, except RUNX2, in which the difference with PCL/gelatin/PRF group was not significant.

Free-Standing Hierarchically Porous Silica Nanoparticle Superstructures: Bridging the Nano- to Microscale for Tailorable Delivery of Small and Large Therapeutics.

Nanoscale colloidal self-assembly is an exciting approach to yield superstructures with properties distinct from those of individual nanoparticles. However, the bottom-up self-assembly of 3D nanoparticle superstructures typically requires extensive chemical functionalization, harsh conditions, and a long preparation time, which are undesirable for biomedical applications. Here, we report the directional freezing of porous silica nanoparticles (PSiNPs) as a simple and versatile technique to create anisotropic 3D superstructures with hierarchical porosity afforded by microporous PSiNPs and newly generated meso- and macropores between the PSiNPs. By varying the PSiNP building block size, the interparticle pore sizes can be readily tuned. The newly created hierarchical pores greatly augment the loading of a small molecule-anticancer drug, doxorubicin (Dox), and a large macromolecule, lysozyme (Lyz). Importantly, Dox loading into both the micro- and meso/macropores of the nanoparticle assemblies not only gave a pore size-dependent drug release but also significantly extended the drug release to 25 days compared to a much shorter 7 or 11 day drug release from Dox loaded into either the micro- or meso/macropores only. Moreover, a unique temporal drug release profile, with a higher and faster release of Lyz from the larger interparticle macropores than Dox from the smaller PSiNP micropores, was observed. Finally, the formulation of the Dox-loaded superstructures within a composite hydrogel induces prolonged growth inhibition in a 3D spheroid model of pancreatic ductal adenocarcinoma. This study presents a facile modular approach for the rapid assembly of drug-loaded superstructures in fully aqueous environments and demonstrates their potential as highly tailorable and sustained delivery systems for diverse therapeutics.

Experimental exploration of potassium compounds in the vicinity of a burning biomass pellet: From near-surface to downstream

The concentrations of gas-phase potassium hydroxide (KOH), potassium chloride (KCl) and atomic potassium (K(g)) were quantitatively measured from the near-surface to downstream area of burning pinewood pellets by a newly developed photofragmentation tunable diode laser absorption spectroscopy (PF-TDLAS) technique to reveal the original form of the released potassium. The novel arrangement of the PF-TDLAS system enabled a spatial resolution of ∼1 mm3, which made it possible to obtain temporal release profiles of K(g)/KOH/KCl at different heights above the burning pellet surface. Surface temperature and mass loss of the wood pellet as well as the gas temperature at measurement points were measured simultaneously. During the devolatilization stage, the release of all three potassium species was observed, with each of them accounting for ∼1/3; while in char oxidation stage, the release of KOH was dominant, but the release intensity was strongly influenced by the local oxygen content. The results from different measurement heights showed there was a notable difference in potassium release profiles of different potassium species over the near-surface area, where the detected potassium forms were the best representative of the originally released forms of potassium. For a period of time during the devolatilization stage, only K(g) was detected in the near-surface area, and the concentration was significantly lower than the downstream area where KOH and KCl coexisted. This suggested that a large amount of potassium might leave the pellet as organic-K, which cannot be detected by the PF-TDLAS method. During char oxidation stage, the total potassium concentration at the near-surface area was also lower than the downstream area, but it was due to the lack of oxygen at the measurement position. A potassium release mechanism during the devolatilization stage of biomass combustion was proposed based on the experimental measurements, and the results also indicated the importance of spatially resolved measurement.

Differential temporal release and lipoprotein loading in B. thetaiotaomicron bacterial extracellular vesicles.

Bacterial extracellular vesicles (BEVs) contribute to stress responses, quorum sensing, biofilm formation and interspecies and interkingdom communication. However, the factors that regulate their release and heterogeneity are not well understood. We set out to investigate these factors in the common gut commensal Bacteroides thetaiotaomicron by studying BEV release throughout their growth cycle. Utilising a range of methods, we demonstrate that vesicles released at different stages of growth have significantly different composition, with early vesicles enriched in specifically released outer membrane vesicles (OMVs) containing a larger proportion of lipoproteins, while late phase BEVs primarily contain lytic vesicles with enrichment of cytoplasmic proteins. Furthermore, we demonstrate that lipoproteins containing a negatively charged signal peptide are preferentially incorporated in OMVs. We use this observation to predict all Bacteroides thetaiotaomicron OMV enriched lipoproteins and analyse their function. Overall, our findings highlight the need to understand media composition and BEV release dynamics prior to functional characterisation and define the theoretical functional capacity of Bacteroides thetaiotaomicron OMVs.

Heterogeneous presynaptic receptive fields contribute to directional tuning in starburst amacrine cells.

The processing of visual information by retinal starburst amacrine cells (SACs) involves transforming excitatory input from bipolar cells (BCs) into directional calcium output. While previous studies have suggested that an asymmetry in the kinetic properties of BCs along the soma-dendritic axes of the postsynaptic cell could enhance directional tuning at the level of individual branches, it remains unclear whether biologically relevant presynaptic kinetics contribute to direction selectivity (DS) when visual stimulation engages the entire dendritic tree. To address this question, we built multicompartmental models of the bipolar-SAC circuit and trained them to boost directional tuning. We report that despite significant dendritic crosstalk and dissimilar directional preferences along the dendrites that occur during whole-cell stimulation, the rules that guide BC kinetics leading to optimal DS are similar to the single-dendrite condition. To correlate model predictions to empirical findings, we utilized two-photon glutamate imaging to study the dynamics of bipolar release onto ON- and OFF-starburst dendrites in the murine retina. We reveal diverse presynaptic dynamics in response to motion in both BC populations; algorithms trained on the experimental data suggested that the differences in the temporal release kinetics are likely to correspond to heterogeneous receptive field properties among the different BC types, including the spatial extent of the center and surround components. In addition, we demonstrate that circuit architecture composed of presynaptic units with experimentally recorded dynamics could enhance directional drive but not to levels that replicate empirical findings, suggesting other DS mechanisms are required to explain SAC function. Our study provides new insights into the complex mechanisms underlying DS in retinal processing and highlights the potential contribution of presynaptic kinetics to the computation of visual information by SACs.

Heterogeneous presynaptic receptive fields contribute to directional tuning in starburst amacrine cells

The processing of visual information by retinal starburst amacrine cells (SACs) involves transforming excitatory input from bipolar cells (BCs) into directional calcium output. While previous studies have suggested that an asymmetry in the kinetic properties of BCs along the soma-dendritic axes of the postsynaptic cell could enhance directional tuning at the level of individual branches, it remains unclear whether biologically relevant presynaptic kinetics contribute to direction selectivity (DS) when visual stimulation engages the entire dendritic tree. To address this question, we built multicompartmental models of the bipolar–SAC circuit and trained them to boost directional tuning. We report that despite significant dendritic crosstalk and dissimilar directional preferences along the dendrites that occur during whole-cell stimulation, the rules that guide BC kinetics leading to optimal DS are similar to the single-dendrite condition. To correlate model predictions to empirical findings, we utilized two-photon glutamate imaging to study the dynamics of bipolar release onto ON- and OFF-starburst dendrites in the murine retina. We reveal diverse presynaptic dynamics in response to motion in both BC populations; algorithms trained on the experimental data suggested that the differences in the temporal release kinetics are likely to correspond to heterogeneous receptive field properties among the different BC types, including the spatial extent of the center and surround components. In addition, we demonstrate that circuit architecture composed of presynaptic units with experimentally recorded dynamics could enhance directional drive but not to levels that replicate empirical findings, suggesting other DS mechanisms are required to explain SAC function. Our study provides new insights into the complex mechanisms underlying DS in retinal processing and highlights the potential contribution of presynaptic kinetics to the computation of visual information by SACs.

TRPC3 signalling contributes to the biogenesis of extracellular vesicles

AbstractExtracellular vesicles (EVs) contribute to a wide range of pathological processes including cancer progression, yet the molecular mechanisms underlying their biogenesis remain incompletely characterized. The development of tetraspanin‐based pHluorin reporters has enabled the real‐time analysis of EV release at the plasma membrane. Here, we employed CD81‐pHluorin to investigate mechanisms of EV release in ovarian cancer (OC) cells and report a novel role for the Ca2+‐permeable transient receptor potential (TRP) channel TRPC3 in EV‐mediated communication. We found that specific activation of TRPC3 increased Ca2+ signalling in SKOV3 cells and stimulated an immediate increase in EV release. Ca2+‐stimulants histamine and ionomycin likewise induced EV release, and imaging analysis revealed distinct stimulation‐dependent temporal and spatial release dynamics. Interestingly, inhibition of TRPC3 attenuated histamine‐stimulated Ca2+‐entry and EV release, indicating that TRPC3 is likely to act downstream of histamine signalling in EV biogenesis. Furthermore, we found that direct activation of TRPC3 as well as the application of EVs derived from TRPC3‐activated cells increased SKOV3 proliferation. Our data provides insights into the molecular mechanisms and dynamics underlying EV release in OC cells, proposing a key role for TRPC3 in EV biogenesis.

Study on the Temporal and Spatial Release Behavior of Alkali Metals during the Combustion of Different Solid Fuels

Study on the Temporal and Spatial Release Behavior of Alkali Metals during the Combustion of Different Solid Fuels

Implications of transient methane flux on associated biological communities in high-arctic seep habitats, Storbanken, Norwegian Barents Sea

The continental margins of the Arctic Ocean basin contain methane seeps, where transient fluxes of seafloor methane are released due to the thermal dissociation of gas hydrates. An increase in shallow methane seeps identified over the past decade, potentially due to enhanced warming of the Arctic Ocean bottom water and associated destabilization of hydrate structure. Biological communities associated with methane release east of Svalbard in the Barents Sea (Storbanken Crater site, 76° 46.7′N, 35° 43.5′E, depths between 120 m–300 m depths) were investigated using towed camera imagery and ship-based platforms during a 2017 CAGE17-2 cruise on the RV Helmer Hanssen. We analyzed relationships among methane flux data, seafloor habitat characteristics, and biological community structure (i.e., presence and distribution of megafauna and expression of microbial mats) from a total of 14 surveys (6827 images and 40 multicore sediment cores) within the Storbanken Crater area and compared it to 2015 data. Unlike seep expressions at deeper sites (∼1200 m) in the Norwegian margin region, no seep-endemic, chemosynthetic-associated megafaunal species were observed at the shallow surveyed sites and all sites hosted similarly diverse communities of non-seep species, including commercially important fish and crustaceans. Methane concentrations did not markedly differ between the crater and non-crater sites. Rates of methane gas advection through sediments (in the form of flares) were relatively low and concentration of methane was even lower in porewater samples at the crater site. We present the first evidence of methane flare flux and intermittent microbial mat distribution with associated folliculinid ciliates, which suggests a long history of methane emissions and a transient seep environment in spatial and temporal flux. Together, this study presents a critical baseline on the temporal release of arctic methane and benthic biological communities to initiate temporal studies that identify future changes and predict the impact of climate change.

Hyaluronic acid hydrogel for controlled release of heterobifunctional photocleavable linker-modified epidermal growth factor in wound healing

Peptide and protein drugs, such as epidermal growth factor (EGF), face challenges related to stability and bioavailability. Recently, hydrogels have emerged as promising carriers for these drugs. This study focuses on a light-responsive hydrogel-based drug delivery system for the controlled release of EGF in wound healing. A photocleavable (PC) linker was designed to bind EGF to the hydrogel matrix, enabling UV light-triggered release of EGF. Hydrogels have evolved from drug reservoirs to controlled release systems, and the o-nitrobenzyl-based PC linkers offer selective cleavage under UV irradiation. We used a thiol-ene crosslinked hyaluronic acid (HA) hydrogel matrix modified with the PC-linked EGF. The release of EGF from the HA hydrogel under UV irradiation was evaluated, along with in vitro and in vivo experiments to assess the controlled effect of EGF on wound healing. Our results indicate that the successful development of a light-responsive hydrogel-based system for precise temporal release of EGF enhances the therapeutic potential in wound healing. This study highlights the importance of incorporating stimulus-responsive functionalities into hydrogel-based drug delivery systems to optimize protein drugs in clinical applications.

Accelerated -Rule-Out of acute Myocardial Infarction using prehospital copeptin and in-hospital troponin: The AROMI study.

The present acute myocardial infarction (AMI) rule-out strategies are challenged by the late temporal release of cardiac troponin. Copeptin is a non-specific biomarker of endogenous stress and rises early in AMI, covering the early period where troponin is still normal. An accelerated dual-marker rule-out strategy combining prehospital copeptin and in-hospital high-sensitivity troponin T could reduce length of hospital stay and thus the burden on the health care systems worldwide. The AROMI trial aimed to evaluate if the accelerated dual-marker rule-out strategy could safely reduce length of stay in patients discharged after early rule-out of AMI. Patients with suspected AMI transported to hospital by ambulance were randomized 1:1 to either accelerated rule-out using copeptin measured in a prehospital blood sample and high-sensitivity troponin T measured at arrival to hospital or to standard rule-out using a 0 h/3 h rule-out strategy. The AROMI study included 4351 patients with suspected AMI. The accelerated dual-marker rule-out strategy reduced mean length of stay by 0.9 h (95% confidence interval 0.7-1.1 h) in patients discharged after rule-out of AMI and was non-inferior regarding 30-day major adverse cardiac events when compared to standard rule-out (absolute risk difference -0.4%, 95% confidence interval -2.5 to 1.7; P-value for non-inferiority = 0.013). Accelerated dual marker rule-out of AMI, using a combination of prehospital copeptin and first in-hospital high-sensitivity troponin T, reduces length of hospital stay without increasing the rate of 30-day major adverse cardiac events as compared to using a 0 h/3 h rule-out strategy.

Sorafenib-Loaded PLGA Carriers for Enhanced Drug Delivery and Cellular Uptake in Liver Cancer Cells.

Currently, conventional treatments of hepatocellular carcinoma (HCC) are not selective enough for tumor tissue and lead to multidrug resistance and drug toxicity. Although sorafenib (SOR) is the standard first-line systemic therapy approved for the clinical treatment of HCC, its poor aqueous solubility and rapid clearance result in low absorption efficiency and severely limit its use for local treatment. Herein, we present the synthesis of biodegradable polymeric Poly (D, L-Lactide-co-glycolide) (PLGA) particles loaded with SOR (PS) by emulsion-solvent evaporation process. The particles are carefully characterized focusing on particle size, surface charge, morphology, drug loading content, encapsulation efficiency, in vitro stability, drug release behaviour and tested on HepG2 cells. Additionally, PLGA particles have been coupled on side emitting optical fibers (seOF) integrated in a microfluidic device for light-triggered local release. PS have a size of 248 nm, tunable surface charge and a uniform and spherical shape without aggregation. PS shows encapsulation efficiency of 89.7% and the highest drug loading (8.9%) between the SOR-loaded PLGA formulations. Treating HepG2 cells with PS containing SOR at 7.5 µM their viability is dampened to 40%, 30% and 17% after 48, 129 and 168 hours of incubation, respectively. The high PS stability, their sustained release profile and the rapid cellular uptake corroborate the enhanced cytotoxicity effect on HepG2. With the prospect of developing biomedical tools to control the spatial and temporal release of drugs, we successfully demonstrated the potentiality of seOF for light-triggered local release of the carriers. Our prototypical system paves the way to new devices integrating microfluidics, optical fibers, and advanced carriers capable to deliver minimally invasive locoregional cancer treatments.

Temporal Release of Cell Cycle Regulator α-Lipoic Acid: An NIR-Light (Two-Photon) Activatable Quinoxaline-Based Nano-Prodrug Delivery System.

The regulation of the cell cycle has recently opened up a new research perspective for cancer treatment. So far, no effort has been made for temporal control of cell cycles using a photocleavable linker. Presented herein is the first report of regulation of disrupted cell cycles through the temporal release of a well-known cell cycle regulator α-lipoic acid (ALA), enabled by a newly designed NIR-active quinoxaline-based photoremovable protecting group (PRPG). The suitable quinoxaline-based photocage of ALA (tetraphenylethelene conjugated) has been formulated as fluorescent organic nanoparticles (FONs) and used effectively as a nano-DDS (drug delivery system) for better solubility and cellular internalization. Fascinatingly, the enhanced TP (two-photon) absorption cross section of the nano-DDS (503 GM) signifies its utility for biological applications. Using green light, we have successfully controlled the time span of cell cycles and cell growth of skin melanoma cell lines (B16F10) by the temporal release of ALA. Further, in silico studies and PDH activity assay supported the observed regulatory behavior of our nano-DDS with respect to photoirradiation. Overall, this approach expands the research path toward a futuristic photocontrolled toolbox for cell cycle regulation.

Controlled Cascade‐Release and High Selective Sterilization by Core–Shell Nanogels for Microenvironment Regulation of Aerobic Vaginitis (Adv. Healthcare Mater. 15/2023)

Aerobic Vaginitis Aerobic vaginitis is closely related to the imbalance of the vaginal microenvironment. In article 2202432 by Tong-Yi Sun, Yuanyuan Gao, Li-Li Li, and co-workers, a dynamically responsive core–shell nanogel (CSNG) is designed. CSNG can achieve a controlled temporal release of the antimicrobial peptide and prebiotic, which can achieve high selective sterilization of pathogenic bacteria and promote the growth of beneficial bacteria simultaneously.