Vascular 3D Printing with a Novel Biological Tissue Mimicking Resin for Patient-Specific Procedure Simulations in Interventional Radiology: a Feasibility Study.

Three-dimensional (3D) printing of vascular structures is of special interest for procedure simulations in Interventional Radiology, but remains due to the complexity of the vascular system and the lack of biological tissue mimicking 3D printing materials a technical challenge. In this study, the technical feasibility, accuracy, and usability of a recently introduced silicone-like resin were evaluated for endovascular procedure simulations and technically compared to a commonly used standard clear resin. Fifty-four vascular models based on twenty-seven consecutive embolization cases were fabricated from preinterventional CT scans and each model was checked for printing success and accuracy by CT-scanning and digital comparison to its original CT data. Median deltas (Δ) of luminal diameters were 0.35 mm for clear and 0.32 mm for flexible resin (216 measurements in total) with no significant differences (p > 0.05). Printing success was 85.2% for standard clear and 81.5% for the novel flexible resin. In conclusion, vascular 3D printing with silicone-like flexible resin was technically feasible and highly accurate. This is the first and largest consecutive case series of 3D-printed embolizations with a novel biological tissue mimicking material and is a promising next step in patient-specific procedure simulations in Interventional Radiology.

Long-QT syndrome-associated caveolin-3 mutations differentially regulate the hyperpolarization-activated cyclic nucleotide gated channel 4.

Background Caveolin-3 (cav-3) mutations are linked to the long-QT syndrome (LQTS) causing distinct clinical symptoms. Hyperpolarization-activated cyclic nucleotide channel 4 (HCN4) underlies the pacemaker current If. It associates with cav-3 and both form a macromolecular complex. Methods To examine the effects of human LQTS-associated cav-3 mutations on HCN4-channel function, HEK293-cells were cotransfected with HCN4 and wild-type (WT) cav-3 or a LQTS-associated cav-3 mutant (T78M, A85T, S141R, or F97C). HCN4 currents were recorded using the whole-cell patch-clamp technique. Results WT cav-3 significantly decreased HCN4 current density and shifted midpoint of activation into negative direction. HCN4 current properties were differentially modulated by LQTS-associated cav-3 mutations. When compared with WT cav-3, A85T, F97C, and T78M did not alter the specific effect of cav-3, but S141R significantly increased HCN4 current density. Compared with WT cav-3, no significant modifications of voltage dependence of steady-state activation curves were observed. However, while WT cav-3 alone had no significant effect on HCN4 current activation, all LQTS-associated cav-3 mutations significantly accelerated HCN4 activation kinetics. Conclusions Our results indicate that HCN4 channel function is modulated by cav-3. LQTS-associated mutations of cav-3 differentially influence pacemaker current properties indicating a pathophysiological role in clinical manifestations.

Severe obesity increases adipose tissue expression of interleukin-33 and its receptor ST2, both predominantly detectable in endothelial cells of human adipose tissue.

OBJECTIVE: Obesity is associated with chronic inflammation of the adipose tissue, which contributes to obesity-associated complications such as insulin resistance and type 2 diabetes. Interleukin (IL)-33 acts via its receptor ST2 and is involved in the pathogenesis of inflammatory disorders including atherosclerosis and heart disease. IL-33 has been demonstrated to promote endothelial cell inflammatory response, but also anti-inflammatory and protective actions such as TH2 and M2 polarization of T cells and macrophages, respectively. IL-33 and ST2 have been shown to be expressed in human and murine adipose tissue. Our objective was to investigate alterations in obesity and a possible role of IL-33 in adipose tissue inflammation. SUBJECTS AND METHODS: We investigated severely obese patients (BMI>40 kg m(-2), n=20) and lean to overweight controls (BMI<30 kg m(-2); n=20) matched for age and sex, as well as diet-induced obese and db/db mice, in order to determine the impact of obesity on IL-33 and ST2 gene and protein expression levels in adipose tissue and blood, and their correlation with inflammatory and metabolic parameters. Furthermore, we examined the cellular source and location of IL-33 and ST2 in situ. RESULTS: IL-33 and ST2 expression levels were markedly elevated in omental and subcutaneous adipose tissue of severely obese humans and in diet-induced obese mice, but not in leptin receptor-deficient db/db mice. In addition, soluble ST2, but not IL-33 serum levels, were elevated in obesity. The main source for IL-33 in adipose tissue were endothelial cells, which, in humans, exclusively expressed ST2 on their surface. IL-33 expression strongly correlated with leptin expression in human adipose tissue. CONCLUSIONS: Expression of IL-33 and its receptor ST2 in human adipose tissue is predominantly detectable in endothelial cells and increased by severe obesity indicating an autocrine action. Thus, the adipose tissue microvasculature could participate in obesity-associated inflammation and related complications via IL-33/ST2.