Background: Bioprosthetic heart valves (BHV) are widely used to treat heart valve disease but are fundamentally limited by structural valve degeneration (SVD). Non-calcific mechanisms of SVD entirely account for approximately 30% of SVD cases and contribute to calcific SVD but remain understudied. Glycation mechanisms have not been previously associated with SVD, despite being established as degenerative in collagenous native tissues. Objectives:To determine whether blood component infiltration-based glycation and concomitant human serum albumin (HSA) deposition contribute mechanistically to SVD.Methods: Immunohistochemistry (IHC) was used to identify advanced glycation end-products (AGEs) and serum albumin accumulation in 45 aortic valve BHV explanted due to SVD, glutaraldehyde-treated bovine pericardium (BP) incubated in vitro in glyoxal and HSA, and rat subcutaneous BP implants. Structural impacts of glycation-related mechanisms were evaluated by second harmonic generation (SHG) collagen imaging. Hydrodynamic effects of valve glycation and concomitant HSA exposure were studied with an ISO-5840-compliant pulse duplicator system using surgical grade BHV.Results: All 45 clinical explants and in vitro-incubated BP demonstrated accumulated AGE and HSA compared to un-implanted, un-exposed BHV. SHG revealed instigation of collagen malalignment similar to that in SVD explants by glycation and HSA infiltration. Rat subdermal explants also showed AGE and serum albumin accumulation. Pulse duplication demonstrated significantly reduced orifice area and increased pressure gradient and peak fluid velocity following glyoxal and HSA incubations. Conclusions:Glycation and concomitant HSA infiltration occur in clinical BHV and contribute to structural and functional degeneration of leaflet tissue, thus representing novel, interacting mechanisms of BHV SVD.

Valvular heart disease is an important source of cardiovascular morbidity and mortality. Current prosthetic valve replacement options, such as bioprosthetic and mechanical heart valves are limited by structural valve degeneration requiring reoperation or the need for lifelong anticoagulation. Several new polymer technologies have been developed in recent years in the hope of creating an ideal polymeric heart valve substitute that overcomes these limitations. These compounds and valve devices are in various stages of research and development and have unique strengths and limitations inherent to their properties. This review summarizes the current literature available for the latest polymer heart valve technologies and compares important characteristics necessary for a successful valve replacement therapy, including hydrodynamic performance, thrombogenicity, hemocompatibility, long-term durability, calcification, and transcatheter application. The latter portion of this review summarizes the currently available clinical outcomes data regarding polymeric heart valves and discusses future directions of research.

Introduction: Bioprosthetic heart valves (BHV) fabricated from glutaraldehyde treated bovine pericardium (BP) are widely used to treat heart valve disease. BHV dysfunction from structural valve degeneration (SVD) develops over time, often necessitating device replacement. SVD is associated with both calcification and the accumulation of advanced glycation end products (AGE) and serum proteins within BHV leaflets. Here, we introduce a new strategy for mitigating AGE-associated SVD by modifying BP with a poly(2-methyl-2-oxazoline) (POZ). Hypothesis: Attached POZ will prevent BP deterioration by mitigating serum protein and pro-inflammatory AGE uptake. Methods: Covalently modified BP-POZ was studied for its effects on serum albumin and AGE entry in vitro via a mass-uptake assay and immunostaining. Resistance of BP-POZ to oxidation was assessed in comparison to poly(ethylene glycol) (PEG). Macrophage studies assessed the inflammatory properties of BP-POZ. A juvenile rat subdermal model was used to study serum protein and AGE uptake and calcification within BP-POZ, with or without ethanol pretreatment. A heart valve pulse duplicator was used to assess the protective effects of BP-POZ on BHV hydrodynamics following accelerated glycation. Results: POZ mitigated the accumulation of serum albumin and AGE in vitro . After exposure to AGE and macrophages, POZ preserved BP collagen structure while TNFα levels remained at baseline. Under oxidation conditions, POZ retained its protective function, unlike PEG. In the rat model, POZ reduced BP AGE (p<0.001) and albumin (p<0.001) uptake. Ethanol pretreatment of BP-POZ was effective at reducing both AGE and calcification. POZ mitigated the hydrodynamic dysfunction of BHV exposed to accelerated glycation conditions (p<0.001). Conclusions: SVD due to AGE and serum proteins can be effectively mitigated through POZ modification, that does not interfere with ethanol pretreatment mitigation of BP calcification.

The past decade has witnessed an exponential growth of novel biomaterial-based grafts, scaffolds, therapies, and diagnostic tools for cardiovascular systems. The advances in engineering biomaterials have resulted in biomedical implants with various functionalities tailored for the desired application. In the cardiovascular field, the application of biomaterials is often challenging but holds great promise. Heart and blood vessels are structurally complex tissues that are blood-contacting in nature and consistently under dynamic mechanical loading conditions. These biological and engineering challenges create unique opportunities for advanced biomaterial-based approaches to deepen our understanding of cell and tissue interaction and revolutionize novel therapeutics. To highlight the progress in the field, we launched this Research Topic to feature recent efforts in engineering novel biomaterials for cardiovascular repair and regeneration.This Research Topic includes two review articles summarizing the clinical use of bovine jugular vein conduits and drug-eluting stents, two common cardiovascular implants. Li et al. first reviewed the clinical outcomes of current bovine jugular vein conduits and their common causes of failure. More importantly, the authors proposed strategies to modify and design the next-generation of bovine jugular vein conduits which have the potential to overcome the complications of current implants. Meanwhile, Hu and Jiang focused on the restenosis of cardiovascular stents. The authors provided a comprehensive summary of clinical reports, diagnostic tools, and common mechanisms of in-stent restenosis. It is important to note that the failure mechanisms