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Achieving precise spatiotemporal control over the release of proangiogenic factors is crucial for vasculogenesis, the process of de novo blood vessel formation. Although various strategies have been explored, there is still a need to develop cell-laden biomaterials with finely controlled release of proangiogenic factors at specific locations and time points. We report on the developed of a near-infrared (NIR) light-responsive collagen hydrogel comprised of gold nanorods (GNRs)-conjugated liposomes containing proangiogenic growth factors (GFs). We demonstrated that this system enables on-demand dual delivery of GFs at specific sites and over selected time intervals. Liposomes were strategically formulated to encapsulate either platelet-derived growth factor (PDGF) or vascular endothelial growth factor (VEGF), each conjugated to gold nanorods (GNRs) with distinct geometries and surface plasmon resonances at 710 nm (GNR710) and 1064 nm (GNR1064), respectively. Using near infrared (NIR) irradiation and two-photon (2P) luminescence imaging, we successfully demonstrated the independent release of PDGF from GNR710 conjugated liposomes and VEGF from GNR1064-conjugated liposomes. Our imaging data revealed rapid release kinetics, with localized PDGF released in approximately 4 min and VEGF in just 1 and a half minutes following NIR laser irradiation. Importantly, we demonstrated that the release of each GF could be independently triggered using NIR irradiation with the other GF formulation remaining retained within the liposomes. This light-responsive collagen hydrogels holds promise for various applications in regenerative medicine where the establishment of a guided vascular network is essential for the survival and integration of engineered tissues. STATEMENT OF SIGNIFICANCE: In this study, we have developed a light-responsive system with gold nanorods (GNRs)-conjugated liposomes in a collagen hydrogel, enabling precise dual delivery of proangiogenic growth factors (GFs) at specific locations and timepoints. Liposomes, containing platelet-derived growth factor (PDGF) or vascular endothelial growth factor (VEGF), release independently under near- infrared irradiation. This approach allows external activation of desired GF release, ensuring high cell viability. Each GF can be triggered independently, retaining the other within the liposomes. Beyond its application in establishing functional vascular networks, this dual delivery system holds promise as a universal platform for delivering various combinations of two or more GFs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The recovery of patients after severe burns is a long and complex process. Recently, genomic analysis of white blood cells from burn and trauma patients revealed excessive and prolonged innate immune activation in patients with complicated outcomes. However, translating this knowledge into practical biomarkers has not been possible yet. Although several biomarkers for monitoring burn patients have been proposed, their ability to accurately distinguish between inflammation stemming from initial tissue destruction, infections, and organ failure complications is limited. Here, we focused on monocytes, critical innate immune cells in the response to burn injured tissues. We measured the monocyte anisocytosis (quantified as monocyte distribution width, MDW, a recently emerged marker of sepsis) throughout the recovery of patients from the time of burn injury until the end of the hospital stay. We observed that MDW increases in patients during the first week after major burns. Among the patients with major burns who survive, MDW starts decreasing in the second week and normalizes by the end of the hospital stay. The duration of hospital stay appears to be proportional to how fast MDW decreases during the second week after the injury. We also found that MDW decreases significantly in most patients after excision and debridement surgeries but not after allo- and auto-graft surgeries. Moreover, high MDW values correlated with a higher rate of positive microbiology blood culture samples and respiratory infections. These findings underscore the importance of monitoring MDW as a potential biomarker for the risk of complications during burn patient recovery., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Understanding the principles that guide the uptake of engineered nanomaterials (ENMs) by cells is of interest in biomedical and occupational health research. While evidence has started to accumulate on the role of membrane proteins in ENM uptake, the role of membrane lipid chemistry in regulating ENM endocytosis has remained largely unexplored. Here, we have addressed this issue by altering the plasma membrane lipid composition directly in live cells using a methyl-α-cyclodextrin (MαCD)-catalyzed lipid exchange method. Our observations, in an alveolar epithelial cell line and using silica nanoparticles, reveal that the lipid composition of the plasma membrane outer leaflet plays a significant role in ENM endocytosis and the intracellular fate of ENMs, by affecting nonspecific ENM diffusion into the cell, changing membrane fluidity, and altering the activity of scavenger receptors (SRs) involved in active endocytosis. These results have implications for understanding ENM uptake in different subsets of cells, depending on cell membrane lipid composition.

The role of interferon-gamma (IFN-γ) in Chronic Myelogenous/Myeloid Leukemia (CML) and in the treatment of CML remains unclear; specifically, the effect of IFN-γ on apoptosis. There is reported interplay between IFN-γ and glycogen synthase kinase-3 (GSK-3), a kinase which has been implicated in both cell death and, conversely, cell survival. Thus, we utilized the CML-derived HAP1 cell line and a mutant HAP1 GSK-3β knocked-down cell line (GSK-3β 31bp) to investigate whether GSK-3 modulates IFN-γ's action on CML cells. Significantly less GSK-3β 31bp cells, relative to HAP1 cells, were present after 48 h treatment with IFN-γ. IFN-γ treatment significantly decreased GSK-3β 31bp substrate adhesiveness (relative to HAP1 cells); an observation often correlated with cell death. Fluorescence microscopy revealed that IFN-γ induces a modest level of apoptosis in the HAP1 cells and that IFN-γ induced apoptosis is significantly enhanced in GSK-3β 31bp cells. Utilizing a complementary GSK-3β knocked-down cell line (8bp) we found, via flow cytometric analysis, that IFN-γ induced apoptosis is significantly enhanced in GSK-3β 8bp cells relative to HAP1 cells. Combined, our findings suggest that IFN-γ induces apoptosis of CML cells and that loss of GSK-3β significantly augments IFN-γ-induced apoptosis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Understanding the mechanisms by which engineered nanomaterials disrupt the cell plasma membrane is crucial in advancing the industrial and biomedical applications of nanotechnology. While the role of nanoparticle properties in inducing membrane damage has received significant attention, the role of the lipid chemical structure in regulating such interactions is less explored. Here, we investigated the role of the lipid chemical structure in the disruption of lipid vesicles by unmodified silica, carboxyl-modified silica, and unmodified polystyrene nanoparticles (50 nm). The role of the lipid headgroup was examined by comparing nanoparticle effects on vesicles composed of 1,2-dioleoyl- sn -glycero-3-phosphocholine (DOPC) vs an inverse phosphocholine (PC) with the same acyl chain structure. The role of acyl chain saturation was examined by comparing nanoparticle effects on saturated vs unsaturated PCs and sphingomyelins. Nanoparticle effects on PCs (glycerol backbone) vs sphingomyelins (sphingosine backbone) were also examined. Results showed that the lipid headgroup, backbone, and acyl chain saturation affect nanoparticle binding to and disruption of the membranes. A low headgroup tilt angle and the presence of a trimethylammonium moiety at the vesicle surface are required for unmodified nanoparticles to induce membrane disruption. Lipid backbone structure significantly affects nanoparticle-membrane interactions, with carboxyl-modified particles only disrupting lipids containing cis unsaturation and a sphingosine backbone. Acyl chain saturation makes vesicles more resistant to particles by increasing lipid packing in vesicles, impeding molecular interactions. Finally, nanoparticles were capable of changing the lipid packing, resulting in pore formation in the process. These observations are important in interpreting nanoparticle toxicity to biological membranes.

Background: Despite their growing popularity, the potential respiratory toxicity of electronic cigarettes (e-cigarettes) remains largely unknown. One potential aspect of e-cigarette toxicity is the effect of e-cigarette vapor on lung surfactant function. Lung surfactant is a mixture of lipids and proteins that lines the alveolar region. The surfactant layer reduces the surface tension of the alveolar fluid, thereby playing a crucial role in lung stability. Due to their small size, particulates in e-cigarette vapor can penetrate the deep lungs and come into contact with the lung surfactant. The current study sought to examine the potential adverse effects of e-cigarette vapor and conventional cigarette smoke on lung surfactant interfacial properties., Methods: Infasurf ® , a clinically used and commercially available calf lung surfactant extract, was used as lung surfactant model. Infasurf ® films were spread on top of an aqueous subphase in a Langmuir trough with smoke particulates from conventional cigarettes or vapor from different flavors of e-cigarettes dispersed in the subphase. Surfactant interfacial properties were measured in real-time upon surface compression while surfactant lateral structure after exposure to smoke or vapor was examined using atomic force microscopy (AFM)., Results: E-cigarette vapor regardless of the dose and flavoring of the e-liquid did not affect surfactant interfacial properties. In contrast, smoke from conventional cigarettes had a drastic, dose-dependent effect on Infasurf ® interfacial properties reducing the maximum surface pressure from 65.1 ± 0.2 mN/m to 46.1 ± 1.3 mN/m at the highest dose. Cigarette smoke and e-cigarette vapor both altered surfactant microstructure resulting in an increase in the area of lipid multilayers. Studies with individual smoke components revealed that tar was the smoke component most disruptive to surfactant function., Conclusions: While both e-cigarette vapor and conventional cigarette smoke affect surfactant lateral structure, only cigarette smoke disrupts surfactant interfacial properties. The surfactant inhibitory compound in conventional cigarettes is tar, which is a product of burning and is thus absent in e-cigarette vapor.

Fungal glucosylceramide (GlcCer) is a plasma membrane sphingolipid in which the sphingosine backbone is unsaturated in carbon position 8 (C8) and methylated in carbon position 9 (C9). Studies in the fungal pathogen, Cryptococcus neoformans, have shown that loss of GlcCer synthase activity results in complete loss of virulence in the mouse model. However, whether the loss of virulence is due to the lack of the enzyme or to the loss of the sphingolipid is not known. In this study, we used genetic engineering to alter the chemical structure of fungal GlcCer and studied its effect on fungal growth and pathogenicity. Here we show that unsaturation in C8 and methylation in C9 is required for virulence in the mouse model without affecting fungal growth in vitro or common virulence factors. However, changes in GlcCer structure led to a dramatic susceptibility to membrane stressors resulting in increased cell membrane permeability and rendering the fungal mutant unable to grow within host macrophages. Biophysical studies using synthetic vesicles containing GlcCer revealed that the saturated and unmethylated sphingolipid formed vesicles with higher lipid order that were more likely to phase separate into ordered domains. Taken together, these studies show for the first time that a specific structure of GlcCer is a major regulator of membrane permeability required for fungal pathogenicity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Blood vessels, especially large vessels have a greater thermal effect on freezing tissue during cryosurgery. Vascular networks act as heat sources in tissue, and cause failure in cryosurgery and reappearance of cancer. The aim of this study is to numerically simulate the effect of probe location and multiprobe on heat transfer distribution. Furthermore, the effect of nanoparticles injection is studied. It is shown that the small probes location near large blood vessels could help to reduce the necessary time for tissue freezing. Nanoparticles injection shows that the thermal effect of blood vessel in tissue is improved. Using Au, Ag and diamond nanoparticles have the most growth of ice ball during cryosurgery. However, polytetrafluoroethylene (PTFE) nanoparticle can be used to protect normal tissue around tumor cell due to its influence on reducing heat transfer in tissue. Introduction of Au, Ag and diamond nanoparticles combined with multicryoprobe in this model causes reduction of tissue average temperature about 50% compared to the one probe., (Copyright © 2015 Elsevier Ltd. All rights reserved.)