062 | Enriched bioplastics with natural compounds as innovative hemocompatible biomaterials targeting red blood cells

Stefano Putaggio, Annamaria Russo, Giuseppe Tancredi Patanè, Claudia Gravagno, Antonella Calderaro, Davide Barreca, Silvana Ficarra, Ester Tellone | Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Italy.

The development of functionalized biomaterials is currently a cornerstone of regenerative medicine, aiming to bridge the gap between synthetic surfaces and biological tissues. An ideal biomaterial must be able to restore the function of damaged tissues without triggering unwanted immune responses, facilitating self-healing processes, and gradually degrading after implantation. In this context, enriching bioplastics with bioactive natural compounds represents a promising strategy for developing multifunctional medical materials capable of combining biodegradability with antimicrobial, anti-inflammatory, and regenerative properties. This innovation is particularly critical in blood-contacting environments, where red blood cells (RBCs) serve as the primary interface. As the predominant cellular component, erythrocytes play crucial biological roles. Furthermore, they act as true biochemical markers, reacting to contact with exogenous molecules through specific structural, morphological, and metabolic changes. Given the extremely delicate nature of these cells, interaction with foreign bodies can alter their functionality and trigger adverse reactions, including cell death. Therefore, prior to any clinical application, it is essential to conduct rigorous in vitro analyses to ensure full hemocompatibility, preserving the integrity of circulating RBCs. In this context, the present work aims to evaluate the hemocompatibility of bioplastics enriched with quercetin (0.5–1 mM), specifically analyzing its effects on the erythrocyte component. PVA-based bioplastics were prepared using the casting solution method and subsequently enriched with quercetin (0.5–1.0 mM). Hemocompatibility tests included the evaluation of membrane integrity (hemolysis and morphology), oxidative state (methemoglobin, determination of -SH groups, and TBARS levels), metabolic activity, and cell viability (caspase-3 activity). Our results show no evidence of erythrocyte damage in the presence of the biomaterial, but instead demonstrate a protective effect on RBCs. Specifically, a reduction in the percentage of hemolysis and improved cellular morphology were observed in RBCs in the presence of quercetin-enriched bioplastics after 2 days of incubation, compared to the control (RBCs alone or with non-enriched bioplastic). After 48 hours of incubation, analysis of the oxidative status of erythrocytes in the presence of the enriched bioplastics showed a reduction in methemoglobin, lipid peroxidation levels, and thiol group oxidation compared to the control. No changes were observed in intra/extracellular ATP levels, protein tyrosine phosphatase 1B (PTP-1B) activity, or caspase-3 activity. The results obtained pave the way for new applications for these materials, whose biocompatibility and antioxidant action are crucial in preserving the integrity and function of RBCs. However, further studies will be needed to better explore their interaction with erythrocyte metabolism and confirm their definitive clinical safety.