Background: Biological sex differences are well-recognized as non-negligible factors in implementing precision medicine practice. Sex chromosomes influence protein expression and signaling, and thus cellular pathways are often regulated differently. Additionally, the importance of sex as a biological variable has gained significant traction in biomedical research, including transfusion medicine. Regarding transfusion medicine, several studies reveal the role of gender in blood transfusion, blood donors’ behavior towards donation, blood products’ composition and storage, transfusion therapy, and possibly post-transfusion patient outcomes. Methods: In this review, the role of sex and gender in the whole transfusion chain (from the blood donor to the blood product and the patient) is assessed and summarized using data from observational studies, registry analyses, and randomized trials. Results: Female donors face higher deferral rates due to biological factors (iron deficiency, low hemoglobin, pregnancy) and sociocultural factors (caregiving responsibilities, misinformation). However, women are more likely to donate based on empathy, moral duty, or community responsibility and are more consistent in sustaining voluntary donation during crises. Men donate more frequently, typically driven by external motivators, and provide red blood cell (RBC) products with higher hemoglobin content, whereas RBCs from female donors exhibit greater metabolic stability and reduced hemolysis during storage. Plasma from multiparous women possibly contains alloantibodies associated with adverse transfusion reactions, namely transfusion-related acute lung injury (TRALI). Platelet function also varies by sex, though its possible clinical impact is still unknown. Although observational studies suggest sex-mismatched transfusions are associated with increased morbidity and mortality—particularly in transfusions from female donors to male recipients—large registries and randomized controlled trials show inconsistent or negligible effect on survival. Conclusions: Donor and recipient sex are emerging variables of possible clinical importance in transfusion practice. Incorporating sex-informed insights into donor recruitment, blood product handling and transfusion policies may improve safety while advancing precision medicine. Further large-scale trials are needed to elucidate the impact of sex in transfusion, identify and eliminate possible risks, and bridge the gap between biological insights and clinical practice.

In this work, an innovative hybrid eutectogel-chitosan nanoparticles system was developed, suitable for biomedical applications. Chitosan (CS) was used as a matrix for the encapsulation of the naturally occurring flavonoid chrysin (Chr), known for its significant biological activities but with limited applications due to its very low aqueous solubility resulting in poor oral bioavailability. A natural deep eutectic solvent (NADES), namely choline chloride/lactic acid at a 1:2 molar ratio, was used as a multifunctional component in the preparation of chitosan nanoparticles (CS-NPs) for chrysin encapsulation, facilitating nanoparticle formation under the investigated conditions. The hydrodynamic diameter of the CS-Chr NPs was 138.8 nm, as determined using nanoparticle tracking analysis, with a high positive ζ-potential of +46.53 mV. The encapsulation efficiency of the CS-Chr NPs was 45%. CS-Chr NPs and blank-CS NPs were evaluated for their hemolytic properties and demonstrated hemolytic activity, within the limits of allowed nanotoxicity (hemolysis < 5%). Additionally, the NADES acted as a matrix, with xanthan gum functioning as a gelator, for the preparation of eutectogels. The resulting eutectogel was developed to combine the advantages of the NADES-based environment and chitosan–chrysin nanoparticles (CS–Chr NPs) with the structural integrity and prolonged retention provided by a gel matrix, thereby offering a stable and versatile platform for the localized delivery of chrysin. The prepared xanthan gum eutectogels showed significant swelling ratio capacity (120%) even after the swollen sample was kept in the aqueous HCl solution (pH 1.2) for 3 h, indicating a good stability of the network. The release of chrysin from CS-Chr NPs reached 94% after 8 h, and exhibited predominantly Fickian diffusion (n = 0.4099). Incorporation of the CS-Chr NPs into the xanthan-gum-based eutectogel resulted in a more sustained chrysin release (76% after 8 h). The eutectogel release was predominantly diffusion-driven (Higuchi, R² = 0.9796), with anomalous transport (n = 0.7247) indicating an additional contribution of polymer relaxation and/or swelling. The proposed NADES-based platform provides a sustainable strategy for the development of multifunctional nanocomposite eutectogels, combining biocompatible components with the unique functional properties of natural deep eutectic solvents for advanced biomedical delivery applications.