Polyphenols for the Mitigation of Vascular Calcification; In Vitro and In Vivo Studies

Author

Abdullah Altuhami, Clemson UniversityFollow

Date of Award

8-2025

Document Type

Thesis

Degree Name

Master of Science in Engineering (MSE)

Department

Bioengineering

Committee Chair/Advisor

Dan Simionescu, Ph.D.

Committee Member

Agneta Simionescu, Ph.D.

Committee Member

Dr. Leslie Sierad

Abstract

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 Penta-Galloyl-Glucose (PGG) 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 PGG has the potential to inhibit or mitigate calcification. PGG 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.

Recommended Citation

Altuhami, Abdullah, "Polyphenols for the Mitigation of Vascular Calcification; In Vitro and In Vivo Studies" (2025). All Theses. 4578.
https://open.clemson.edu/all_theses/4578