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Chitosan and collagen were able to promote non-cytotoxic PBMCs activation through cytosolic and mitochondrial ROS production. There was a noteworthy phenotyping of lymphocytes T CD8+ and CD4+ counting and an increase of [Ca2+] cyt and ΔΨm levels. These results suggest that chitosan/collagen-based biomaterials produce immunostimulatory effects on PBMC with potential to biomedical approaches.Lanthanide (Ln) cations exhibit unique properties that include the ability to interact with DNA to form metal-DNA complexes, which are of great inte