Guest Speaker: Dr. Andrey Zakharchenko

Heart disease remains the leading cause of death worldwide. Heart valve disease is life-threatening in which heart valves do not function properly. Surgery is required to repair or replace the damaged valve for severe valve disease. Bioprosthetic heart valves are made from animal-derived materials, such as bovine pericardium (BP) or porcine heart valves, often work for many years in adults. However, when used in children, they tend to fail as early as one year from valve calcification and structural degeneration. Mechanical valves used as an alternative in pediatric patients necessitate taking blood-thinning medications for the rest of the patients life. New evidence from our group demonstrated that BHV failure is related to glycation, a non-enzymatic reaction of blood sugar with proteins accumulated within the valve. These processes result in an inflammatory response, collagen damage, and ultimately valve structural degeneration, reducing valves' functional lifespan.

We developed a novel valve modification strategy to prevent this process using biocompatible and non-immunogenic polymer polyoxazoline (POZ). POZ blocks the accumulation of serum proteins and stabilizes the inner collagen structure while the valve's fluid performance is unaffected. Additionally, POZ coating is highly stable under oxidative conditions, overperforming polyethylene glycol coating, often used in biomedical applications. POZ has the potential to mitigate protein-glycation SVD mechanisms, reduce inflammatory response, and markedly improve biocompatibility. As alternative to macromolecular approach, glycation inhibitor drugs [(Aminoguanidine (AG), Pyridoxamine (PYR), and N-Acetylcysteine (NAC))]  were studied to mitigate BP glycation in model studies, both in vitro and in vivo. In vitro studies demonstrated that these agents significantly inhibited  glycation in BP. However, after 28-day rat subdermal BP implantation in vivo, only PYR demonstrated significant inhibition of glycation, calcification, and serum albumin accumulation.

This study is the first to demonstrate the use of POZ or AGE inhibitors in mitigating BHV glycation. Thus, this work provides a rationale for investigating POZ and PYR as possible candidates for improving the durability and biocompatibility of clinically used BHV, providing the solution for this unmet clinical need.

Dr. Andrey Zakharchenko is an instructor at The University of Pennsylvania. He specializes in bioprosthetic heart valve research and investigates the failure mechanisms of biomaterials used in these devices. His research interests are development of new biomaterials in medicine, novel therapies for heart valve disease, and nanomedicine. 

His work involves experiments design, synthetic materials synthesis and functionalization, in vitro cell models and in vivo testing using small animal models. He is actively involved in research manuscripts and grants preparation, patents development and supervision and training of junior lab members. 

Dr. Zakharchenko received his PhD in materials science from the University of Georgia in 2018. His work was focused on development of novel nanoparticles-based biomaterials for controlled delivery of bioactive molecules and drugs. He is a member of American Chemical Society (ACS), American Heart Association (AHA), and Biomedical Engineering Society (BMES).