This study describes a complex human in vitro model for evaluating anti-inflammatory drug response in the alveoli that may contribute to the reduction of animal testing in the pre-clinical stage of drug development. The model is based on the human alveolar epithelial cell line Arlo co-cultured with macrophages differentiated from the THP-1 cell line, creating a physiological biological microenvironment. To mimic the three-dimensional architecture and dynamic expansion and relaxation of the air-blood-barrier, they are grown on a stretchable microphysiological lung-on-chip.
View Article and Find Full Text PDFJ Heart Lung Transplant
February 2025
Background: The lung Composite Allocation Score (CAS) accounts separately for biological disadvantages stemming from candidate blood type and height using consensus-derived heuristics, which do not reflect the true supply of compatible organs available to candidates with specific combinations of blood type and height. Here, we develop an alternative CAS biological disadvantages subscore using a novel measure of donor supply.
Methods: Using Scientific Registry of Transplant Recipients data from February 19, 2015 to September 1, 2021, we modeled daily distance-adjusted supply of compatible donors, as a function of candidate blood type, height, and diagnosis group, using Poisson rate regression and applied the model to create a 10-point supply-based subscore.
Mucus layers, viscoelastic gels abundant in anionic mucin glycoproteins, obstruct therapeutic delivery across all mucosal surfaces. We found that strongly positively charged nanoparticles (NPs) rapidly adsorb a mucin protein corona in mucus, impeding cell binding and uptake. To overcome this, we developed mucus-evading, cell-adhesive (MECS) NPs with variable surface charge using Flash NanoPrecipitation, by blending a neutral poly(ethylene glycol) (PEG) corona for mucus transport with a small amount, 5 wt%, of polycationic dimethylaminoethyl methacrylate (PDMAEMA) for increased cell targeting.
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