Abstract: In solid organ transplantation, the host immune system acts to reject the transplanted graft. This process is facilitated at the graft endothelial surface, where inflamed endothelial cells (ECs) upregulate adhesion molecules and recruit effector cells of the host immune system. To combat this dysfunctional inflammation locally and with more impact than globally administered therapies, anti-inflammatory agents can be administered directly to the graft endothelium. We have designed a strategy for local and sustained delivery of these agents using molecularly-targeted polymer nanoparticles (NPs) during a period of ex vivo normothermic machine perfusion (EVNMP) of the organ. I will present several approaches for therapeutic delivery using polymeric NPs as well as strategies to direct NPs using molecular targets to the ECs of interest. We have discovered that rapid accumulation of NPs on ECs relies on both the density and accessibility of the potential ligands, and that these parameters can be measured directly in the relevant human vessel setting. The experiments we have conducted within these platforms are being used to develop a high throughput preclinical approach to optimize immune therapy for local and robust treatment in human organ transplant.

Bio: I joined the faculty at Villanova University in the fall of 2022 in the Department of Chemical and Biological Engineering. I am continuing my research into NP-based therapeutic delivery to human vasculature and integrating these strategies with tissue-engineering to create tools for long-term immune modulation. Specifically, materials that provide support for tissue regrowth while temporarily inhibiting inflammation-related injury, thus reducing the burden of chronic inflammation. My work presented here today was done as a Postdoctoral Fellow in Biomedical Engineering at Yale University as part of Dr. W. Mark Saltzman’s research group. In my graduate work, I developed vascular, tissue engineered constructs using a combination of biological and synthetic materials at the University of Maryland with Dr. John Fisher in Bioengineering.