The implantation of bioprosthetic heart valves (BHVs) is increasingly becoming the treatment of choice in patients requiring heart valve replacement surgery. Unlike mechanical heart valves, BHVs are less thrombogenic and exhibit superior hemodynamic properties. However, BHVs are prone to structural valve degeneration (SVD), an unavoidable condition limiting graft durability. Mechanisms underlying SVD are incompletely understood, and early concepts suggesting the purely degenerative nature of this process are now considered oversimplified. Recent studies implicate the host immune response as a major modality of SVD pathogenesis, manifested by a combination of processes phenocopying the long‐term transplant rejection, atherosclerosis, and calcification of native aortic valves. In this review, we summarize and critically analyze relevant studies on (1) SVD triggers and pathogenesis, (2) current approaches to protect BHVs from calcification, (3) obtaining low immunogenic BHV tissue from genetically modified animals, and (4) potential strategies for SVD prevention in the clinical setting.

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Calcifying nanoparticles (CNPs) (nanobacteria, nanobacteria-like particles, nanobes) were discovered over 25 years ago; nevertheless, their nature is still obscure. To date, nobody has been successful in credibly determining whether they are the smallest self-replicating life form on Earth, or whether they represent mineralo-protein complexes without any relation to living organisms. Proponents of both theories have a number of arguments in favor of the validity of their hypotheses. However, after epistemological analysis carried out in this review, all arguments used by proponents of the theory about the physicochemical model of CNP formation may be refuted on the basis of the performed investigations, and therefore published data suggest a biological nature of CNPs. The only obstacle to establish CNPs as living organisms is the absence of a fairly accurately sequenced genome at the present time. Moreover, it is clear that CNPs play an important role in etiopathogenesis of many diseases, and this association is independent from their nature. Consequently, emergence of CNPs in an organism is a pathological, not a physiological, process. The classification and new directions of further investigations devoted to the role of CNPs in biology and medicine are proposed.

The combination of a natural polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and a synthetic hydrophobic polymer poly(ε-caprolactone) (PCL) is promising for the preparation of biodegradable and biocompatible small-diameter vascular grafts for bypass surgery. However, physico-mechanical properties and endothelialization rate of PHBV/PCL grafts are poor. We suggested that incorporation of vascular endothelial growth factor (VEGF) into PHBV/PCL grafts may improve their physico-mechanical properties and enhance endothelialization. Here we compared morphology, physico-mechanical properties, and in vivo performance of electrospun small-diameter vascular grafts prepared from PHBV/PCL with and without VEGF. Structure of the graft surface and physico-mechanical properties were examined by scanning electron microscopy and universal testing machine, respectively. Grafts were implanted into rat abdominal aorta for 1, 3, and 6 months with the further histological, immunohistochemical, and immunofluorescence examination. PHBV/PCL grafts with and without VEGF were highly porous and consisted mostly of nanoscale and microscale fibers, respectively. Mean pore diameter and mean pore area were significantly lower in PHBV/PCL/VEGF compared to PHBV/PCL grafts (1.47 μm and 10.05 μm2; 2.63 μm and 47.13 μm2, respectively). Durability, elasticity, and stiffness of PHBV/PCL grafts with VEGF were more similar to internal mammary artery compared to those without, particularly 6 months postimplantation. Both qualitative examination and quantitative image analysis showed that three-fourths of PHBV/PCL grafts with VEGF were patent and had many CD31-, CD34-, and vWF-positive cells at their inner surface. However, all PHBV/PCL grafts without VEGF were occluded and had no or a few CD31-positive cells at the inner surface. Therefore, VEGF enhanced endothelialization and improved graft patency at all the time points in a rat abdominal aorta replacement model. In conclusion, PHBV/PCL grafts with VEGF have better biocompatibility and physico-mechanical properties compared to those without. Incorporation of VEGF improves graft patency and accelerates formation of endothelial cell monolayer.

Calcium phosphate bions (CPBs) are formed under blood supersaturation with calcium and phosphate owing to the mineral chaperone fetuin-A and representing mineralo-organic particles consisting of bioapatite and multiple serum proteins. While protecting the arteries from a rapid medial calcification, CPBs cause endothelial injury and aggravate intimal hyperplasia in balloon-injured rat aortas. Here, we asked whether CPBs induce intimal hyperplasia in intact rat arteries in the absence of cardiovascular risk factors. Normolipidemic Wistar rats were subjected to regular (once/thrice per week over 5 weeks) tail vein injections of either spherical (CPB-S) or needle-shaped CPBs (CPB-N), magnesium phosphate bions (MPBs), or physiological saline (n = 5 per group). Neointima was revealed in 3/10 and 4/10 rats which received CPB-S or CPB-N, respectively, regardless of the injection regimen or blood flow pattern in the aortic segments. In contrast, none of the rats treated with MPBs or physiological saline had intimal hyperplasia. The animals also did not display signs of liver or spleen injury as well as extraskeletal calcium deposits. Serum alanine/aspartate transaminases, interleukin-1β, MCP-1/CCL2, C-reactive protein, and ceruloplasmin levels did not differ among the groups. Hence, CPBs may provoke intimal hyperplasia via direct endothelial injury regardless of their shape or type of blood flow.