| 1. |
- Bruder, Lukas, et al.
(författare)
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Coherent multidimensional spectroscopy in the gas phase
- 2019
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Ingår i: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 52:18
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Tidskriftsartikel (refereegranskat)abstract
- Recent work applying multidimentional coherent electronic spectroscopy at dilute samples in the gas phase is reviewed. The development of refined phase cycling approaches with improved sensitivity has opened up new opportunities to probe even dilute gas-phase samples. In this context, first results of two-dimensional spectroscopy performed at doped helium droplets reveal the femtosecond dynamics upon the electronic excitation of cold, weakly-bound molecules, and even the induced dynamics from the interaction with the helium environment. Such experiments, offering well-defined conditions at low temperatures, are potentially enabling the isolation of fundamental processes in the excitation and charge transfer dynamics of molecular structures which so far have been masked in complex bulk environments.
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| 2. |
- Gasek, Nathan, et al.
(författare)
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Development of alginate and gelatin-based pleural and tracheal sealants
- 2021
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061. ; 131, s. 222-235
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Tidskriftsartikel (refereegranskat)abstract
- Pleural and tracheal injuries remain significant problems, and an easy to use, effective pleural or tracheal sealant would be a significant advance. The major challenges are requirements for adherence, high strength and elasticity, dynamic durability, appropriate biodegradability, and lack of cell or systemic toxicity. We designed and evaluated two sealant materials comprised respectively of alginate methacrylate and of gelatin methacryloyl, each functionalized by conjugation with dopamine HCl. Both compounds are cross-linked into easily applied as pre-formed hydrogel patches or as in situ hydrogels formed at the wound site utilizing FDA-approved photo-initiators and oxidants. Material testing demonstrates appropriate adhesiveness, tensile strength, burst pressure, and elasticity with no significant cell toxicity in vitro assessments. Air-leak was absent after sealant application to experimentally-induced injuries in ex-vivo rat lung and tracheal models and in ex vivo pig lungs. Sustained repair of experimentally-induced pleural injury was observed for up to one month in vivo rat models and for up to 2 weeks in vivo rat tracheal injury models without obvious air leak or obvious toxicities. The alginate-based sealant worked best in a pre-formed hydrogel patch whereas the gelatin-based sealant worked best in an in situ formed hydrogel at the wound site thus providing two potential approaches. These studies provide a platform for further pre-clinical and potential clinical investigations. Statement of significance: Pneumothorax and pleural effusions resulting from trauma and a range of lung diseases and critical illnesses can result in lung collapse that can be immediately life-threatening or result in chronic leaking (bronchopleural fistula) that is currently difficult to manage. This leads to significantly increased morbidity, mortality, hospital stays, health care costs, and other complications. We have developed sealants originating from alginate and gelatin biomaterials, each functionalized by methacryloylation and by dopamine conjugation to have desired mechanical characteristics for use in pleural and tracheal injuries. The sealants are easily applied, non-cytotoxic, and perform well in vitro and in vivo model systems of lung and tracheal injuries. These initial proof of concept investigations provide a platform for further studies.
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| 3. |
- Hoffman, Evan T., et al.
(författare)
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Human alveolar hydrogels promote morphological and transcriptional differentiation in iPSC-derived alveolar type 2 epithelial cells
- 2023
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Ingår i: Scientific Reports. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Alveolar type 2 epithelial cells (AT2s) derived from human induced pluripotent stem cells (iAT2s) have rapidly contributed to our understanding of AT2 function and disease. However, while iAT2s are primarily cultured in three-dimensional (3D) Matrigel, a matrix derived from cancerous mouse tissue, it is unclear how a physiologically relevant matrix will impact iAT2s phenotype. As extracellular matrix (ECM) is recognized as a vital component in directing cellular function and differentiation, we sought to derive hydrogels from decellularized human lung alveolar-enriched ECM (aECM) to provide an ex vivo model to characterize the role of physiologically relevant ECM on iAT2 phenotype. We demonstrate aECM hydrogels retain critical in situ ECM components, including structural and basement membrane proteins. While aECM hydrogels facilitate iAT2 proliferation and alveolosphere formation, a subset of iAT2s rapidly change morphology to thin and elongated ring-like cells. This morphological change correlates with upregulation of recently described iAT2-derived transitional cell state genetic markers. As such, we demonstrate a potentially underappreciated role of physiologically relevant aECM in iAT2 differentiation.
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| 4. |
- Hoffman, Evan T., et al.
(författare)
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Regional and disease specific human lung extracellular matrix composition
- 2023
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612. ; 293
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), are characterized by regional extracellular matrix (ECM) remodeling which contributes to disease progression. Previous proteomic studies on whole decellularized lungs have provided detailed characterization on the impact of COPD and IPF on total lung ECM composition. However, such studies are unable to determine the differences in ECM composition between individual anatomical regions of the lung. Here, we employ a post-decellularization dissection method to compare the ECM composition of whole decellularized lungs (wECM) and specific anatomical lung regions, including alveolar-enriched ECM (aECM), airway ECM (airECM), and vasculature ECM (vECM), between non-diseased (ND), COPD, and IPF human lungs. We demonstrate, using mass spectrometry, that individual regions possess a unique ECM signature characterized primarily by differences in collagen composition and basement-membrane associated proteins, including ECM glycoproteins. We further demonstrate that both COPD and IPF lead to alterations in lung ECM composition in a region-specific manner, including enrichment of type-III collagen and fibulin in IPF aECM. Taken together, this study provides methodology for future studies, including isolation of region-specific lung biomaterials, as well as a dataset that may be applied for the identification of novel ECM targets for therapeutics.
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| 5. |
- Ryan, Amy L, et al.
(författare)
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Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases 2017 : An Official American Thoracic Society Workshop Report
- 2019. - 4
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The University of Vermont Larner College of Medicine, in collaboration with the National Heart, Lung, and Blood Institute (NHLBI), the Alpha-1 Foundation, the American Thoracic Society, the Cystic Fibrosis Foundation, the European Respiratory Society, the International Society for Cell & Gene Therapy, and the Pulmonary Fibrosis Foundation, convened a workshop titled "Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases" from July 24 through 27, 2017, at the University of Vermont, Burlington, Vermont. The conference objectives were to review and discuss current understanding of the following topics: 1) stem and progenitor cell biology and the role that they play in endogenous repair or as cell therapies after lung injury, 2) the emerging role of extracellular vesicles as potential therapies, 3) ex vivo bioengineering of lung and airway tissue, and 4) progress in induced pluripotent stem cell protocols for deriving lung cell types and applications in disease modeling. All of these topics are research areas in which significant and exciting progress has been made over the past few years. In addition, issues surrounding the ethics and regulation of cell therapies worldwide were discussed, with a special emphasis on combating the growing problem of unproven cell interventions being administered to patients with lung diseases. Finally, future research directions were discussed, and opportunities for both basic and translational research were identified.
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| 6. |
- Thiebes, Anja Lena, et al.
(författare)
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Endoscopic atomization of mesenchymal stromal cells : in vitro study for local cell therapy of the lungs
- 2021
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Ingår i: Cytotherapy. - : Elsevier BV. - 1465-3249. ; 23:4, s. 293-300
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Tidskriftsartikel (refereegranskat)abstract
- Background aims: Cell-based therapies of pulmonary diseases with mesenchymal stromal cells (MSCs) are increasingly under experimental investigation. In most of these, MSCs are administered intravenously or by direct intratracheal instillation. A parallel approach is to administer the cells into the lung by endoscopic atomization (spraying). In a previous study, the authors developed a flexible endoscopic atomization device that allows administration of respiratory epithelial cells in the lungs with high survival. Methods: In this study, the authors evaluated the feasibility of spraying MSCs with two different endoscopic atomization devices (air and pressure atomization). Following atomization, cell viability was evaluated with live/dead staining. Subsequent effects on cytotoxicity, trilineage differentiation and expression of MSC-specific markers as well as on MSC metabolic activity and morphology were analyzed for up to 7 days. Results: MSC viability immediately after spraying and subsequent metabolic activity for 7 days was not influenced by either of the devices. Slightly higher cytotoxicity rates could be observed for pressure-atomized compared with control and air-atomized MSCs over 7 days. Flow cytometry revealed no changes in characteristic MSC cell surface marker expression, and morphology remained unchanged. Standard differentiation into osteocytes, chondrocytes and adipocytes was inducible after atomization. Conclusions: In the literature, a minimal survival of 50% was previously defined as the cutoff value for successful cell atomization. This is easily met with both of the authors’ devices, with more than 90% survival. Thus, there is a potential role for atomization in intrapulmonary MSC-based cell therapies, as it is a feasible and easily utilizable approach based on clinically available equipment.
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| 7. |
- Uhl, Franziska, et al.
(författare)
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Functional Role of Glycosaminoglycans in Decellularized Lung Extracellular Matrix
- 2020
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1878-7568 .- 1742-7061. ; 102, s. 231-246
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Tidskriftsartikel (refereegranskat)abstract
- Despite progress in use of decellularized lung scaffolds in ex vivo lung bioengineering schemes, including use of gels and other materials derived from the scaffolds, the detailed composition and functional role of extracellular matrix (ECM) proteoglycans (PGs) and their glycosaminoglycan (GAG) chains remaining in decellularized lungs, is poorly understood. Using a commonly utilized detergent-based decellularization approach in human autopsy lungs resulted in disproportionate losses of GAGs with depletion of chondroitin sulfate/dermatan sulfate (CS/DS) > heparan sulfate (HS) > hyaluronic acid (HA). Specific changes in disaccharide composition of remaining GAGs were observed with disproportionate loss of NS and NS2S for HS groups and of 4S for CS/DS groups. No significant influence of smoking history, sex, time to autopsy, or age was observed in native vs. decellularized lungs. Notably, surface plasmon resonance demonstrated that GAGs remaining in decellularized lungs were unable to bind key matrix-associated growth factors FGF2, HGF, and TGFβ1. Growth of lung epithelial, pulmonary vascular, and stromal cells cultured on the surface of or embedded within gels derived from decellularized human lungs was differentially and combinatorially enhanced by replenishing specific GAGs and FGF2, HGF, and TGFβ1. In summary, lung decellularization results in loss and/or dysfunction of specific GAGs or side chains significantly affecting matrix-associated growth factor binding and lung cell metabolism. GAG and matrix-associated growth factor replenishment thus needs to be incorporated into schemes for investigations utilizing gels and other materials produced from decellularized human lungs.
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| 8. |
- Uriarte, Juan J., et al.
(författare)
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Lung bioengineering : advances and challenges in lung decellularization and recellularization
- 2018
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Ingår i: Current opinion in organ transplantation. - 1087-2418. ; 23:6, s. 673-678
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: Bioengineering the lung based on its natural extracellular matrix (ECM) offers novel opportunities to overcome the shortage of donors, to reduce chronic allograft rejections, and to improve the median survival rate of transplanted patients. During the last decade, lung tissue engineering has advanced rapidly to combine scaffolds, cells, and biologically active molecules into functional tissues to restore or improve the lung's main function, gas exchange. This review will inspect the current progress in lung bioengineering using decellularized and recellularized lung scaffolds and highlight future challenges in the field.RECENT FINDINGS: Lung decellularization and recellularization protocols have provided researchers with tools to progress toward functional lung tissue engineering. However, there is continuous evolution and refinement particularly for optimization of lung recellularization. These further the possibility of developing a transplantable bioartificial lung.SUMMARY: Bioengineering the lung using recellularized scaffolds could offer a curative option for patients with end-stage organ failure but its accomplishment remains unclear in the short-term. However, the state-of-the-art of techniques described in this review will increase our knowledge of the lung ECM and of chemical and mechanical cues which drive cell repopulation to improve the advances in lung regeneration and lung tissue engineering.
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| 9. |
- Wituschek, Andreas, et al.
(författare)
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High-gain harmonic generation with temporally overlapping seed pulses and application to ultrafast spectroscopy
- 2020
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Ingår i: Optics Express. - 1094-4087. ; 28, s. 29976-90
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Tidskriftsartikel (refereegranskat)abstract
- Collinear double-pulse seeding of the High-Gain Harmonic Generation (HGHG) process in a free-electron laser (FEL) is a promising approach to facilitate various coherent nonlinear spectroscopy schemes in the extreme ultraviolet (XUV) spectral range. However, in collinear arrangements using a single nonlinear medium, temporally overlapping seed pulses may introduce nonlinear mixing signals that compromise the experiment at short time delays. Here, we investigate these effects in detail by extending the analysis described in a recent publication (Wituschek et al., Nat. Commun., 11, 883, 2020). High-order fringe-resolved autocorrelation and wave packet interferometry experiments at photon energies > 23 eV are performed, accompanied by numerical simulations. It turns out that both the autocorrelation and the wave-packet interferometry data are very sensitive to saturation effects and can thus be used to characterize saturation in the HGHG process. Our results further imply that time-resolved spectroscopy experiments are feasible even for time delays smaller than the seed pulse duration.
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| 10. |
- Wituschek, Andreas, et al.
(författare)
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Tracking attosecond electronic coherences using phase-manipulated extreme ultraviolet pulses
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The recent development of ultrafast extreme ultraviolet (XUV) coherent light sources bears great potential for a better understanding of the structure and dynamics of matter. Promising routes are advanced coherent control and nonlinear spectroscopy schemes in the XUV energy range, yielding unprecedented spatial and temporal resolution. However, their implementation has been hampered by the experimental challenge of generating XUV pulse sequences with precisely controlled timing and phase properties. In particular, direct control and manipulation of the phase of individual pulses within an XUV pulse sequence opens exciting possibilities for coherent control and multidimensional spectroscopy, but has not been accomplished. Here, we overcome these constraints in a highly time-stabilized and phase-modulated XUV-pump, XUV-probe experiment, which directly probes the evolution and dephasing of an inner subshell electronic coherence. This approach, avoiding any XUV optics for direct pulse manipulation, opens up extensive applications of advanced nonlinear optics and spectroscopy at XUV wavelengths.
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| 11. |
- Wrenn, Sean M, et al.
(författare)
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Avian lungs : A novel scaffold for lung bioengineering
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:6, s. 0198956-0198956
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic lung transplant is limited both by the shortage of available donor lungs and by the lack of suitable long-term lung assist devices to bridge patients to lung transplantation. Avian lungs have different structure and mechanics resulting in more efficient gas exchange than mammalian lungs. Decellularized avian lungs, recellularized with human lung cells, could therefore provide a powerful novel gas exchange unit for potential use in pulmonary therapeutics. To initially assess this in both small and large avian lung models, chicken (Gallus gallus domesticus) and emu (Dromaius novaehollandiae) lungs were decellularized using modifications of a detergent-based protocol, previously utilized with mammalian lungs. Light and electron microscopy, vascular and airway resistance, quantitation and gel analyses of residual DNA, and immunohistochemical and mass spectrometric analyses of remaining extracellular matrix (ECM) proteins demonstrated maintenance of lung structure, minimal residual DNA, and retention of major ECM proteins in the decellularized scaffolds. Seeding with human bronchial epithelial cells, human pulmonary vascular endothelial cells, human mesenchymal stromal cells, and human lung fibroblasts demonstrated initial cell attachment on decellularized avian lungs and growth over a 7-day period. These initial studies demonstrate that decellularized avian lungs may be a feasible approach for generating functional lung tissue for clinical therapeutics.
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| 12. |
- Zechner, Olivia, et al.
(författare)
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NextGen training for medical first responders : advancing mass-casualty incident preparedness through mixed reality technology
- 2023
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Ingår i: Multimodal Technologies and Interaction. - Basel : MDPI. - 2414-4088. ; 7:12
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Tidskriftsartikel (refereegranskat)abstract
- Mixed reality (MR) technology has the potential to enhance the disaster preparedness of medical first responders in mass-casualty incidents through new training methods. In this manuscript, we present an MR training solution based on requirements collected from experienced medical first responders and technical experts, regular end-user feedback received through the iterative design process used to develop a prototype and feedback from two initial field trials. We discuss key features essential for an effective MR training system, including flexible scenario design, added realism through patient simulator manikins and objective performance assessment. Current technological challenges such as the responsiveness of avatars and the complexity of smart scenario control are also addressed, along with the future potential for integrating artificial intelligence. Furthermore, an advanced analytics and statistics tool that incorporates complex data integration, machine learning for data analysis and visualization techniques for performance evaluation is presented.
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