Immune cells and inflammatory mediators cause endothelial dysfunction in a vascular microphysiological system.

Functional assessment of endothelium serves as an important indicator of vascular health and is compromised in vascular disorders including hypertension, atherosclerosis, and preeclampsia. Endothelial dysfunction in these cases is linked to dysregulation of the immune system involving both changes to immune cells and increased secretion of inflammatory cytokines. Herein, we utilize a well-established microfluidic device to generate a 3-dimensional vascular microphysiological system (MPS) consisting of a tubular blood vessel lined with human umbilical vein endothelial cells (HUVECs) to evaluate endothelial function measured via endothelial permeability and Ca2+ signaling. We evaluated the effect of a mixture of factors associated with inflammation and cardiovascular disease (TNFα, VEGF-A, IL-6 at 10 ng ml-1 each) on vascular MPS and inferred that inflammatory mediators contribute to endothelial dysfunction by disrupting the endothelial barrier over a 48 hour treatment and by diminishing coordinated Ca2+ activity over a 1 hour treatment. We also evaluated the effect of peripheral blood mononuclear cells (PBMCs) on endothelial permeability and Ca2+ signaling in the HUVEC MPS. HUVECs were co-cultured with PBMCs either directly wherein PBMCs passed through the lumen or indirectly with PBMCs embedded in the supporting collagen hydrogel. We revealed that phytohemagglutinin (PHA)-M activated PBMCs cause endothelial dysfunction in MPS both through increased permeability and decreased coordinated Ca2+ activity compared to non-activated PBMCs. Our MPS has potential applications in modeling cardiovascular disorders and screening for potential treatments using measures of endothelial function.

Long-term outcome of absorbable synthetic mesh in clean ventral hernia repairs.

BACKGROUND: There are many materials available for the reinforcement of complex abdominal wall reconstruction, including permanent synthetic, biologic, and absorbable synthetic meshes. The recurrence rate of complex hernia repairs beyond 5 years has not been reported. We hypothesized that the use of absorbable synthetic mesh in clean wounds would yield favorable long-term outcomes. STUDY DESIGN: Patients who underwent open complex ventral hernia repair with clean wounds (CDC class 1) using absorbable synthetic mesh (Bio-A, Gore, Flagstaff, AZ) in the retrorectus position were retrospectively reviewed. Chart review and a validated telephone questionnaire to screen for recurrence were utilized to evaluate and document hernia recurrence. RESULTS: A total of 49 patients were included in this study. Patients were followed for recurrences for up to 105 months, with a mean follow-up time of 62.4 months (5.2 years). The total number of midline hernia recurrence was 7 out of the original 49 patients (14%). The mean and median recurrence time are 37.4 and 38.8 months, respectively. Kaplan-Meier survival analysis estimated hernia recurrence rate as 2%, 4.6%, 7.1%, 12%, 15%, and 18% at 12, 24, 36, 48, 60, and 72 months, respectively. CONCLUSION: The use of absorbable synthetic mesh in clean wound ventral hernia repair resulted in favorable long-term recurrence rates. The recurrence rate of absorbable synthetic mesh is similar to that of permanent synthetic mesh, which gives a viable option for patients in whom permanent synthetic mesh is not an option.