POLYPHENOLS FOR THE MITIGATION OF VASCULAR CALCIFICATION; IN VITRO AND IN VIVO STUDIES
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Date
2025
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Clemson University
Abstract
Cardiovascular diseases remain the leading cause of mortality worldwide, and one contributing factor is vascular calcification—the abnormal accumulation of calcium within blood vessels. This process stiffens the vessel walls, disrupts normal blood flow, and significantly increases the risk of heart attacks, strokes, and other life-threatening complications. In severe cases, organ transplantation may be the only viable treatment. However, this approach is limited by donor shortages and the risks associated with long-term immunosuppressive therapy, including infection and rejection.
To address these limitations, the field of tissue engineering is exploring alternatives such as tissue-engineered vascular grafts (TEVGs), which aim to replace or restore damaged blood vessels. Despite its promise, this approach presents several scientific challenges: identifying appropriate cell types that mimic natural vascular behavior, ensuring those cells receive the necessary biological signals, and developing a scaffold that can support the graft structurally while remaining biocompatible.
In this study, we propose using decellularized porcine arteries as scaffolds, owing to their mechanical similarity to human vessels. We exposed these acellular tissues to calcifying conditions both in laboratory settings (in vitro) and in live animal models (in vivo) to investigate how vascular calcification develops. We also evaluated the therapeutic potential of Plant-derived antioxidant (PDA-1), for its ability to inhibit or reduce calcification.
Our experiments included a dynamic in vitro bioreactor that mimicked physiological flow, as well as subdermal implantation in juvenile rats to assess immune response, biocompatibility, and calcium deposition. Across both models, PDA-1 treatment was associated with a noticeable reduction in calcification, suggesting its promise as a preventative or therapeutic agent.
These findings support the potential of PDA-1 to improve outcomes in vascular grafts—either by direct application to calcified vessels or as a pre-treatment for off-the-shelf grafts. Future studies will focus on refining drug delivery methods, scaling the model, and progressing toward clinical translation.
Description
Globally, cardiovascular diseases, in most cases associated with calcification, are the main cause of death. However, currently, the only effective cure is to undergo surgery to augment or receive a healthy donor heart, which could be very difficult due to the long waiting list and the associated risks. The possibility of body rejection of the foreign organs is attributed to immunoreaction or the risk of infection, since the donor must be on immunosuppressant drugs that lower the body's immunity and facilitate the body's acceptance of the new organ as one of its own. Taking that into consideration, using tissue-engineered vascular grafts to re-perfuse or replace damaged heart tissues might be an alternative. The research in this field is still progressing. However, the main areas of research are attributed to solving three main challenges. The first challenge is to find the right type of cells that could function exactly like the original cells. Secondly, biocompatibility: finding the right chemical cues that help these cells to function well by creating a similar environment to that which we have in our bodies. Finally, to create a suitable supporting structure to carry these cells and chemicals and maintain them in our body without being loosened or degraded over time. To address those dilemmas, we propose an animal-based scaffold approach that utilizes a decellularized porcine artery, which has mechanical properties that closely resemble those of the human arteries. To study vascular calcification, we exposed the acellular tissue to pro-calcification conditions in vitro and in vivo. In addition, we tested Plant-derived antioxidant (PDA-1) as an antioxidant agent, aiming at inhibiting calcification. This was tested on a dynamic bioreactor model (in vitro) that reflects the physiologic conditions. In addition, we implanted samples in vivo subdermally in juvenile rats to evaluate the biocompatibility, immune reactions and calcification potential. Our results showed that vascular calcification can be modeled in vitro and in vivo, and that PDA-1 has the potential to inhibit or mitigate calcification. PDA-1 could be implemented clinically as a localized treatment to calcifying diseased arteries or as a pre-treatment for off-the-shelf implantable artificial arteries. In future studies, we will bridge the gap to clinical trials, translating these theories into actual solutions.
Keywords
Cardiovascular, Antioxidant