Developing Nanofibrous Sheets to Scavenge Storage Lesion to Enhance the Quality and Shelf Life of Stored Red Blood Cells and Prevent Transfusion related Complications

Abstract

Transfusion of healthy RBCs is a lifesaving process. However, upon storing Non-Leukoreduced (NLR) and Leuko reduced (LR) RBCs, a wide range of Damage Associated Molecular Patterns (DAMPs), such as cell-free DNA, nucleosomes, free-haemoglobin, and poly-unsaturated-fatty-acids (PUFAs), are generated. These DAMPs can further damage RBCs. Thus, the quality of stored RBCs declines during storage and limits their shelf life. Transfusion of old stored whole blood consists of a pool of DAMPs are known to be primary mediators in the pathophysiology of fatal diseases like Transfusion-Related Acute Lung Injury (TRALI), deep-vein thrombosis, and organ dysfunction. Since these DAMPs contain either positive or negatively charged species. Since these DAMPs consist of either positive or negative charged species, we developed taurine and acridine-containing Electrospun-nanofibrous-sheets (Tau-AcrNFS), featuring anionic, cationic charges and a DNA intercalating group on their surfaces. We show that Tau-AcrNFS efficiently scavenges DAMPs from stored human and mouse RBCs ex vivo. We find that intermittent scavenging of DAMPs by Tau-AcrNFS during the storage reduces the loss of RBC membrane integrity and reduces discocytes-to-spheroechinocytes transformation in stored old RBCs. We perform RBC-transfusion studies in mice to reveal that intermittent removal of DAMPs enhances the quality of stored old RBCs equivalent to freshly collected RBCs and increases their shelf-life by ~22%. Additionally, we have demonstrated that treating stored old blood with nanofibrous sheets prior to transfusion can prevent TRALI, in vivo newline