| 1. |
- De Santis, Martina M, et al.
(författare)
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Extracellular-Matrix-Reinforced Bioinks for 3D Bioprinting Human Tissue
- 2021
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Ingår i: Advanced Materials. - : Wiley. - 1521-4095 .- 0935-9648. ; 33:3
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Tidskriftsartikel (refereegranskat)abstract
- Recent advances in 3D bioprinting allow for generating intricate structures with dimensions relevant for human tissue, but suitable bioinks for producing translationally relevant tissue with complex geometries remain unidentified. Here, a tissue-specific hybrid bioink is described, composed of a natural polymer, alginate, reinforced with extracellular matrix derived from decellularized tissue (rECM). rECM has rheological and gelation properties beneficial for 3D bioprinting while retaining biologically inductive properties supporting tissue maturation ex vivo and in vivo. These bioinks are shear thinning, resist cell sedimentation, improve viability of multiple cell types, and enhance mechanical stability in hydrogels derived from them. 3D printed constructs generated from rECM bioinks suppress the foreign body response, are pro-angiogenic and support recipient-derived de novo blood vessel formation across the entire graft thickness in a murine model of transplant immunosuppression. Their proof-of-principle for generating human tissue is demonstrated by 3D bioprinting human airways composed of regionally specified primary human airway epithelial progenitor and smooth muscle cells. Airway lumens remained patent with viable cells for one month in vitro with evidence of differentiation into mature epithelial cell types found in native human airways. rECM bioinks are a promising new approach for generating functional human tissue using 3D bioprinting.
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| 2. |
- Lovén, Karin, et al.
(författare)
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Toxicological effects of zinc oxide nanoparticle exposure : an in vitro comparison between dry aerosol air-liquid interface and submerged exposure systems
- 2021
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Ingår i: Nanotoxicology. - : Taylor and Francis Ltd.. - 1743-5390 .- 1743-5404. ; 15:4, s. 494-510
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Tidskriftsartikel (refereegranskat)abstract
- Engineered nanomaterials (ENMs) are increasingly produced and used today, but health risks due to their occupational airborne exposure are incompletely understood. Traditionally, nanoparticle (NP) toxicity is tested by introducing NPs to cells through suspension in the growth media, but this does not mimic respiratory exposures. Different methods to introduce aerosolized NPs to cells cultured at the air-liquid-interface (ALI) have been developed, but require specialized equipment and are associated with higher cost and time. Therefore, it is important to determine whether aerosolized setups induce different cellular responses to NPs than traditional ones, which could provide new insights into toxicological responses of NP exposure. This study evaluates the response of human alveolar epithelial cells (A549) to zinc oxide (ZnO) NPs after dry aerosol exposure in the Nano Aerosol Chamber for In Vitro Toxicity (NACIVT) system as compared to conventional, suspension-based exposure: cells at ALI or submerged. Similar to other studies using nebulization of ZnO NPs, we found that dry aerosol exposure of ZnO NPs via the NACIVT system induced different cellular responses as compared to conventional methods. ZnO NPs delivered at 1.0 µg/cm2 in the NACIVT system, mimicking occupational exposure, induced significant increases in metabolic activity and release of the cytokines IL-8 and MCP-1, but no differences were observed using traditional exposures. While factors associated with the method of exposure, such as differing NP aggregation, may contribute toward the different cellular responses observed, our results further encourage the use of more physiologically realistic exposure systems for evaluating airborne ENM toxicity. © 2021 The Author(s).
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| 3. |
- Stenlo, Martin, et al.
(författare)
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Monitoring lung injury with particle flow rate in LPS- and COVID-19-induced ARDS
- 2021
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 9:13
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Tidskriftsartikel (refereegranskat)abstract
- In severe acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO) is a life-prolonging treatment, especially among COVID-19 patients. Evaluation of lung injury progression is challenging with current techniques. Diagnostic imaging or invasive diagnostics are risky given the difficulties of intra-hospital transportation, contraindication of biopsies, and the potential for the spread of infections, such as in COVID-19 patients. We have recently shown that particle flow rate (PFR) from exhaled breath could be a noninvasive, early detection method for ARDS during mechanical ventilation. We hypothesized that PFR could also measure the progress of lung injury during ECMO treatment. Lipopolysaccharide (LPS) was thus used to induce ARDS in pigs under mechanical ventilation. Eight were connected to ECMO, whereas seven animals were not. In addition, six animals received sham treatment with saline. Four human patients with ECMO and ARDS were also monitored. In the pigs, as lung injury ensued, the PFR dramatically increased and a particular spike followed the establishment of ECMO in the LPS-treated animals. PFR remained elevated in all animals with no signs of lung recovery. In the human patients, in the two that recovered, PFR decreased. In the two whose lung function deteriorated while on ECMO, there was increased PFR with no sign of recovery in lung function. The present results indicate that real-time monitoring of PFR may be a new, complementary approach in the clinic for measurement of the extent of lung injury and recovery over time in ECMO patients with ARDS.
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