One of the largest challenges facing the field of tissue engineering is the incorporation of a functional vasculature, allowing effective nourishment of graft tissue beyond diffusion length scales. Here, we demonstrate a methodology for inducing the robust self-assembly of endothelial cells into stable three-dimensional perfusable networks on millimeter and centimeter length scales. Utilizing broadly accessible cell strains and reagents, we have rigorously tested a state space of cell densities (0.5-2.0×106 cell/mL) and collagen gel densities (2-6 mg/mL) that result in robust vascular network formation. Further, over the range of culture conditions with which we observed robust network formation, we advanced image processing algorithms and quantitative metrics to assess network connectivity, coverage, tortuosity, lumenization, and vessel diameter. These data demonstrate that decreasing collagen density produced more connected networks with higher coverage. Finally, we demonstrated that this methodology results in the formation of perfusable networks, is extensible to arbitrary geometries and centimeter scales, and results in networks that remain stable for 21 days without the need for the co-culture of supporting cells. Given the robustness and accessibility, this system is ideal for studies of tissue-scale biology, as well as future studies on the formation and remodeling of larger engineered graft tissues.

No abstract

Ultraviolet germicidal irradiation (UVGI) systems can be used to decontaminate filtering facepiece respirators that are in short supply during the current COVID-19 pandemic, but are costly and scarce. n Custom-built UVGI systems can be easily and affordably created using common items found in hardware stores and within research institutions. n Health care workers and administrators should consider this setup as a cost-effective option to combat personal protective equipment (PPE) shortages during the current pandemic. n Academic institutions should consider fostering collaborations with local health care institutions to provide idle resources to front line health care workers facing PPE shortages.

Abnormal pulmonary vascular development is a critical factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Despite the well-established sex-specific differences in the incidence of BPD, the molecular mechanism(s) behind these are not completely understood. Exposure to high concentration of oxygen (hyperoxia) contributes to BPD and creates a pro-fibrotic environment in the lung. Our objective was to elucidate the sex-specific differences in neonatal human pulmonary microvascular endothelial cells (HPMECs) in normoxic and hyperoxic conditions including propensity for endothelial to mesenchymal transition. HPMECs (18-24 weeks gestation donors; 6 male and 5 female) were subjected to hyperoxia (95% O and 5% CO) or normoxia (air and 5% CO2) up to 72 h. We assessed cell migration and angiogenesis at baseline. Cell proliferation, viability, and expression of endothelial (CD31) and fibroblast markers (α-SMA) were measured upon exposure to hyperoxia. Female HPMECs had significantly higher cell migration when assessed by the wound healing assay (40.99 ± 4.4 %) compared to male (14.76 ± 3.7 %) and showed greater sprouting (1710 ± 962 μm in female vs 789 ± 324 in male) compared to male endothelial cells in normoxia. Hyperoxia exposure decreased cell viability (by 9.8% at 48h and 11.7% at 72h) and proliferation (by 26.7% at 72 h) markedly in male HPMECs, while viability was sustained in female endothelial cells. There was greater expression of α-SMA (2.5-fold) and decreased expression (5-fold) of CD31 in male HPMECs, upon exposure to hyperoxia. The results indicate that cellular sex affects response in HPMECs in normoxia and hyperoxia.

Drug abuse alone has been shown to cause epigenetic changes in brain tissue that have been shown to play roles in addictive behaviors. In conjunction with HIV-1 infection, it can cause epigenetic changes at the viral promoter that can result in altered gene expression, and exacerbate disease progression overall. This review entails an in-depth look at research conducted on the epigenetic effects of three of the most widely abused drugs (cannabinoids, opioids, and cocaine), with a particular focus on the mechanisms through which these drugs interact with HIV-1 infection at the viral promoter. Here we discuss the impact of this interplay on disease progression from the point of view of the nature of gene regulation at the level of chromatin accessibility, chromatin remodeling, and nucleosome repositioning. Given the importance of chromatin remodeling and DNA methylation in controlling the retroviral promoter, and the high susceptibility of the drug abusing population of individuals to HIV infection, it would be beneficial to understand the way in which the host genome is modified and regulated by drugs of abuse.