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  1. Objective

    Significant morbidity and mortality are associated with clinical use of synthetic tissue‐engineered tracheal grafts (TETG). Our previous work focused on an electrospun polyethylene terephthalate and polyurethane (PET/PU) TETG that was tested in sheep using a long‐segment tracheal defect model. We reported that graft stenosis and limited epithelialization contributed to graft failure. The present study determined if the epithelialization defect could be attributed to: 1) postsurgical depletion of native airway basal stem/progenitor cells; 2) an inability of the PET/PU‐TETG to support epithelial migration; or 3) compromised basal stem/progenitor cell proliferation within the PET/PU environment.

    Study Design



    Basal stem/progenitor cell frequency in sheep that underwent TETG implantation was determined using the clone‐forming cell frequency (CFCF) method. A novel migration model that mimics epithelial migration toward an acellular scaffold was developed and used to compare epithelial migration toward a control polyester scaffold and the PET/PU scaffold. Basal stem/progenitor cell proliferation within the PET/PU scaffold was evaluated using the CFCF assay, doubling‐time analysis, and mitotic cell quantification.


    We report that TETG implantation did not decrease basal stem/progenitor cell frequency. In contrast, we find that epithelial migration toward the PET/PU scaffold was significantly less extensive than migration toward a polyester scaffold and that the PET/PU scaffold did not support basal stem/progenitor cell proliferation.


    We conclude that epithelialization of a PET/PU scaffold is compromised by poor migration of native tissue‐derived epithelial cells and by a lack of basal stem/progenitor cell proliferation within the scaffold.

    Level of Evidence


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  2. Abstract

    Projected changes in air temperature, precipitation, and vapor pressure for the Willamette River Basin (Oregon, USA) over the next century will have significant impacts on the river basin water balance, notably on the amount of evapotranspiration (ET). Mechanisms of impact on ET will be both direct and indirect, but there is limited understanding of their absolute and relative magnitudes. Here, we developed a spatially explicit, daily time‐step, modeling infrastructure to simulate the basin‐wide water balance that accounts for meteorological influences, as well as effects mediated by changing vegetation cover type, leaf area, and ecophysiology. Three CMIP5 climate scenarios (Lowclim, Reference, and HighClim) were run for the 2010–2100 period. Besides warmer temperatures, the climate scenarios were characterized by wetter winters and increasing vapor pressure deficits. In the mid‐range Reference scenario, our landscape simulation model (Envision) projected a continuation of forest cover on the uplands but a threefold increase in area burned per year. A decline (12–30%) in basin‐wide mean leaf area index (LAI) in forests was projected in all scenarios. The lower LAIs drove a corresponding decline in ET. In a sensitivity test, the effect of increasing CO2on stomatal conductance induced a further substantial decrease (11–18%) in basin‐wide mean ET. The net effect of decreases in ET and increases in winter precipitation was an increase in annual streamflow. These results support the inclusion of changes in land cover, land use, LAI, and ecophysiology in efforts to anticipate impacts of climate change on basin‐scale water balances.

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