The gold standard material in bypass surgery of blood vessels remains the patient’s own artery or vein. However, this material may be unavailable, or may suffer vein graft disease. Currently available vascular prostheses, namely polyethylene terephthalate (PET, Dacron) and expanded polytetrafluoroethylene (ePTFE), perform well as large-caliber replacements, but their long-term patency is discouraging in small-caliber applications (<6 mm), such as in coronary, crural or microvessel surgery. This failure is mainly a result of an unfavorable healing process with surface thrombogenicity, due to lack of endothelial cells and anastomotic intimal hyperplasia caused by hemodynamic disturbances. An ideal small-diameter vascular graft has become a major focus of research. Novel biomaterials have been manufactured, and tissue-biomaterial interactions have been optimized. Tissue engineering technology has proven that the concept of partially or totally living blood vessels is feasible. The purpose of this review is to outline the vascular graft materials that are currently being implanted, taking into account cell-biomaterial physiology, tissue engineering approaches and the collective achievements of the authors.

Introduction: Uterus transplantation (UTx) is a rapidly evolving treatment of uterine-factor infertility. We report the results of the first 10 UTx procedures performed at our institution. Methods: The program started in April 2016 as a two-arm study comparing the efficacy of UTx from live donors (LD) and deceased donors (DD). Results: Between April 2016 and April 2018, we performed five DD UTx and five LD UTx. Two grafts had to be removed early due to thrombosis. One graft was removed due to chronic rejection and previous herpes simplex infection at month 7. Graft survival is 70% at one year. Recipient survival is 100% at two years. Live donor survival is 100% at three years. Three live-births have been achieved, two from a LD and one from a graft from a nulliparous DD. Vaginal anastomotic stenosis occurred in 63% (5/8) of grafts. Self-expanding stents have shown preliminary suitability for the treatment of vaginal stenosis. Three recipients developed severe acute rejection. Conclusion: The interim results of our study demonstrate mid-term viability in 70% of grafts. The LD UTx produced two live births and the DD UTx produced one live birth. Nulliparous donors should be considered for donation.

No abstract

ClinicalTrials.gov number 03277430. The Institutional Review Board approval number 2044/15(NM-15-01). J.F. designed the trial, performed the transplantation as the head of the team, was involved in the follow-up of the patient, and wrote most of the article. L.J. coperformed the transplantation, codrafted the article, and was involved in the interpretation of the data. J.K. codrafted the article and participated in the follow-up. J.C. coperformed the transplantation and codrafted the article. M.P. participated in the follow-up during pregnancy, performed the C-section, and coauthored the article. R.N. helped with the acquisition of data and codrafted the article. J.M. was involved in the acquisition of data by evaluating biopsy specimens and codrafted the article. M.O. helped with the preparation of the trial, helped with interpretation of the data, and codrafted and revised the article.

Currently used vascular prostheses are hydrophobic and do not allow endothelial cell (EC) adhesion and growth. The aim of this study was to prepare fibrin (Fb)-based two-dimensional (2D) and three-dimensional (3D) assemblies coated with extracellular matrix (ECM) proteins and to evaluate the EC adhesion, proliferation and differentiation on these assemblies in vitro. Coating of Fb with collagen, laminin (LM), and fibronectin (FN) was proved using the surface plasmon resonance technique. On all Fb assemblies, ECs reached higher cell densities than on polystyrene after 3 and 7 days of culture. Immunoflurescence staining showed better assembly of talin and vinculin into focal adhesion plaques, and also more apparent staining of vascular endothelial cadherin on surface-attached 3D Fb and protein-coated Fb assemblies. On these samples, ECs also contained a lower concentration of intercellular adhesion molecule-1, measured by enzyme-linked immunosorbent assay. Higher concentrations of CD31 (platelet-endothelial cell adhesion molecule-1) were found on 3D Fb coated with LM, and higher concentrations of von Willebrand factor were found on 3D Fb coated with type I collagen or LM in comparison to 2D Fb layers. The results indicate that ECM protein-coated 2D and 3D Fb assemblies can be used for versatile applications in various tissue replacements where endothelialization is desirable, for example, vascular prostheses and heart valves.

Various techniques for coating synthetic surfaces with fibrin structures were tested for seeding bovine pulmonary artery endothelial cells (EC). Two-dimensional fibrin (Fb) structures (2D Fb) were obtained by successively repeating adsorption of fibrinogen (Fbg), incubating the surface with thrombin (Thr) solution, and inhibiting surface-attached Thr. Three-dimensional fibrin networks immobilized at the surface (3D Fb) were formed by catalytic action of surface-attached thrombin on an ambient Fbg solution. Ultra-thin 3D Fbs were obtained if thrombin inhibitors antithrombin III and heparin were added into an Fbg solution. The formation of surface fibrin structures was observed in situ using surface plasmon resonance. The morphology of the structures was studied by transmission and scanning electron microscopy. A polylactide fibrous scaffold was modified with a surface fibrin film without filling the inner pores with a bulk gel. The growth of EC seeded on a polystyrene surface coated with the Fb films was evaluated by the number and morphology of the adhering ECs and the concentration of beta-actin, vinculin, alpha(v)-intergrin, and von Willebrand factor (vWF). The best initial cell spreading after 1 day was observed on 2D Fb and ultra-thin 3D Fb. The highest concentration of vWF, a marker of EC differentiation, was observed after 3 days on thick 3D Fbs. The highest EC population densities after 7 days were observed on 2D Fb and thick 3D Fb.

Background: Uterus transplantation is a complex, multi-step experimental procedure used for the treatment of uterus absence or uterus anomaly that prevents embryo implantation or pregnancy completion. Method: To date, only 51 uterus transplants worldwide had been performed. When simplified, it is vascularized composite allograft transplantation. While it is still an experimental procedure with encouraging results for the future, there are still many issues that have to be clarified. The most serious complications of uterus transplantation are graft rejection or grafts vascular failure. Results: So far, no reference to the atherosclerotic arterial infiltration of the uterus arteries was suggested and studied as one of the main causes of graft's failure. Conclusion: In this review we summarized current knowledge and possible role of uterus arterial damage, including atherosclerotic changes on the graft's survival.

Recombinant interferon-α (IFN-α) treatment functionally cures chronic hepatitis B virus (HBV) infection in some individuals and suppresses virus replication in hepatocytes infected in vitro. We studied the antiviral effect of conditioned media (CM) from peripheral blood mononuclear cells (PBMCs) stimulated with agonists of Toll-like receptors (TLRs) 2, 7, 8 and 9. We found that CM from PBMCs stimulated with dual-acting TLR7/8 (R848) and TLR2/7 (CL413) agonists were more potent drivers of inhibition of HBe and HBs antigen secretion from HBV-infected primary human hepatocytes (PHH) than CM from PBMCs stimulated with single-acting TLR7 (CL264) or TLR9 (CpG-B) agonists. Inhibition of HBV in PHH did not correlate with the quantity of PBMC-produced IFN-α, but it was a complex function of multiple secreted cytokines. More importantly, we found that the CM that efficiently inhibited HBV production in freshly isolated PHH via various cytokine repertoires and mechanisms did not reduce covalently closed circular (ccc)DNA levels. We confirmed our data with a cell culture model based on HepG2-NTCP cells and the plasmacytoid dendritic cell line GEN2.2. Collectively, our data show the importance of dual-acting TLR agonists inducing broad cytokine repertoires. The development of poly-specific TLR agonists provides novel opportunities towards functional HBV cure.