Disturbed flow induces a sustained, stochastic NF-κB activation which may support intracranial aneurysm growth in vivo

Intracranial aneurysms are associated with disturbed velocity patterns, and chronic inflammation, but the relevance for these findings are currently unknown. Here, we show that (disturbed) shear stress induced by vortices is a sufficient condition to activate the endothelial NF-kB pathway, possibly through a mechanism of mechanosensor de-activation. We provide evidence for this statement through in-vitro live cell imaging of NF-kB in HUVECs exposed to different flow conditions, stochastic modelling of flow induced NF-kB activation and induction of disturbed flow in mouse carotid arteries. Finally, CFD and immunofluorescence on human intracranial aneurysms showed a correlation similar to the mouse vessels, suggesting that disturbed shear stress may lead to sustained NF-kB activation thereby offering an explanation for the close association between disturbed flow and intracranial aneurysms

Endothelial cells on pet vascular prostheses impregnated with polyester-based copolymers and coated with cell-adhesive protein assemblies

Arterial bypass surgery with synthetic vascular prostheses achieves poor patency rates compared to autogenous natural materials, and this is a challenge for tissue engineering research concerning small caliber vascular grafts. Modifications of the prosthetic surface followed by endothelial cell seeding may reduce thrombogenicity and intimal hyperplasia. Planar polyethylene terephthalate (PET) vascular prosthetic samples were impregnated with the copolymer poly(glycolide-L-lactide) (PGL) or with the terpolymer poly(glycolide-L-lactide-(e)caprolactone) (PGLCap) in order to lower the permeability of the knitted fabrics and ensure a less adhesive background. Subsequent modification with adhesive protein assemblies composed of collagen type I (Co) in conjunction with laminin (LM), fibronectin (FN) or fibrin (Fb) gel was performed to enhance cell adhesion. Bovine pulmonary artery endothelial cells (EC) of the CPAE line were seeded on to the coatings and subjected to static tissue culture conditions for 7 days. Impregnation of the PET prostheses decreased the initial adhesion and proliferation of the EC. After coating with the protein assemblies, the impregnated PET provided better substrates for cell culture than the protein-coated PET, on which the EC population started decreasing after 4 days of culture. The cells proliferated better on the CoFN, CoFb and CoFbFN coatings than on the Co and CoLM coatings. Impregnation type and adhesive matrix protein deposition may play an important role in successful endothelialization, healing and clinical performance of vascular grafts

Transabdominal two-cavity approach for radical nephrectomy combined with inferior vena cava thrombectomy for malignant thrombus caused by renal cell carcinoma: a case series

Abstract Background Advanced renal cell carcinoma in some cases causes malignant intravascular thrombus with the potential for growth into the inferior vena cava or even the right atrium. Renal cell carcinoma is accompanied by malignant intravascular thrombus in up to 10% of cases. We present an overview of three patients diagnosed as having renal cell carcinoma with malignant intravascular thrombus requiring radical nephrectomy combined with inferior vena cava thrombectomy. Case presentation Three patients diagnosed as having renal cell carcinoma were indicated for renal cell carcinoma combined with inferior vena cava thrombectomy between 2014 and 2017 at our department: a 69-year-old white Caucasian woman, a 74-year-old white Caucasian woman, and a 58-year-old white Caucasian woman. According to the Novick classification of inferior vena cava tumor thrombus, there was one infrahepatic (level II) and two supradiaphragmatic (level IV) malignant intravascular thrombi. The average age of these patients was 67 years (range 58–74 years). All patients underwent radical nephrectomy combined with inferior vena cava thrombectomy through transabdominal approach. In patients with level IV malignant intravascular thrombus, transesophageal echocardiogram was used to guide the placement of the inferior vena cava cross-clamp above the diaphragm. In one patient the pericardium was opened to place a cross-clamp above a tumor just below the right atrium. There were no postoperative mortalities to date with an average follow-up of 23 months (range 2–48 months). To date, no patient has demonstrated recurrent inferior vena cava malignant intravascular thrombus requiring secondary inferior vena cava thrombectomy or any other treatment. A comparison of estimated blood loss and transfusion rate was not significantly different in all three cases. Conclusion Despite the technical complexity of the procedure, caval thrombectomy combined with radical nephrectomy currently represents the only radical treatment for renal cell carcinoma accompanied by malignant intravascular thrombus with good mid-term oncological outcomes

Fibrous scaffolds for bone tissue engineering: static and dynamic in vitro studies with MG 63 cells

Resorbowalne włókna z kopolimeru L-laktydu z glikolidem (PLG) i PLG z hydroksyapatytem rozprowadzonym w ich objętości (PLG-HAP) zostały otrzymane metodą formowania z roztworu. Włókna zostały przetworzone w trójwymiarowe podłoża za pomocą metody łączenia włókien. Mikrostrukturę otrzymanych podłoży scharakteryzowano za pomocą mikroskopu stereoskopowego. Wykazano, że podłoża miały różną porowatość, wielkość i orientację pojedynczych włókien. Oddziaływanie włóknistych podłoży z komórkami kostnymi MG 63 było badane in vitro w warunkach statycznych i dynamicznych. Liczba komórek i ich morfologia były oceniane po 3 i 7 dniach od założenia hodowli. Badania wykazały że liczba komórek na materiałach włóknistych rosła wraz z czasem prowadzenia hodowli, chociaż była znacznie niższa niż na płaskiej powierzchni kontrolnej (polistyren do celów kultur komórkowych). W dynamicznych warunkach hodowli obserwowano różną proliferację komórek w zależności od rodzaju użytego podłoża: na PLG występował spadek, zaś na PLG-HAP istotny wzrost liczby komórek. Wyniki sugerują, że obecność cząstek hydroksyapatytu rozprowadzonych w objętości włókien polimerowych poprawia adhezje i proliferacje osteoblastów.Resorbable poly(L-lactide-co-glycolide) fibres (PLG) and poly(L-lactide-co-glycolide) fibres containing hydroxyapatite nanoparticles in volume of PLG fibres (PLG-HAP) were manufactured by solution spinning process. The resultant fibres were processed into three-dimensional scaffolds using fibre bounding method. The microstructure of resorbable scaffolds was characterized by stereomicroscope. The results show that the scaffolds have different fibrous architecture including porosity, size and arrangement of individual fibres. The interaction of fibrous scaffolds with osteoblast-like MG 63 cells was tested in vitro in static and dynamic cell culture conditions. The number of adhering cells and their morphology were evaluated on days 3 and 7 after seeding. It was found that cell number increased with the cultivation time, although it was significantly lower than on control polystyrene dish (TCPS). During dynamic cultivation the number of cells decreased on PLG scaffolds, whereas on PLG-HAP scaffolds it increased. These results suggest that presence of hydroxyapatite distributed within the whole volume of resorbable polymer fibres promoted adhesion and proliferation of osteoblasts