How Dendrimers\nImpact Fibrin Clot Formation,\nStructure, and Properties

Polyamidoamine (PAMAM)\ndendrimers, with their unique structural\nversatility and tunable surface functionalities, have emerged as promising\nnanomaterials for a wide range of biomedical applications. However,\ntheir in vivo use raises concerns, as unintended interactions between\ndendrimers and blood components could disrupt the delicate hemostatic\nbalance and lead to serious complications like bleeding or thrombosis.\nIn this study, we explored the impact of low-generation PAMAM dendrimers\non the kinetics of fibrin clot formation, along with their influence\non the structure, properties, and resistance to lysis of the resulting\nclots. For this purpose, we employed a multilevel characterization\napproach using purified fibrinogen, human plasma, and whole blood\nto assess the effects of four dendrimer types: G2-NH<sub>2</sub>,\nG4-NH<sub>2</sub>, G3.5-COOH, and G4-OH. Among the main findings,\nboth G2-NH<sub>2</sub> and G4-NH<sub>2</sub> significantly impaired\nthrombin generation and delayed clot formation, with G4-NH<sub>2</sub> also promoting fibrin aggregation, increasing clot permeability,\nand accelerating clot lysis. When present at high concentrations,\nG4-OH also affected critical clotting parameters, delaying thrombin\ngeneration and prolonging clotting time. Notably, the prolongation\nof clotting time by G4-OH was evident in both human plasma and whole\nblood. Interestingly, G3.5-COOH showed potential as a safer option\nsince it induced minimal alterations across most tested metrics. These\nresults will be important for guiding the rational design of dendrimers\nand identifying safe concentrations for future clinical applications.