Safety and Feasibility of Magnetic Separation‐Based Blood Purification

Direct selective removal of disease‐etiologic factors from blood is a potentially lifesaving intervention in multiple medical conditions (including sepsis). Magnetic separation‐based blood purification represents a selective therapeutic strategy addressing limitations of conventional extracorporeal devices. However, GLP‐compliant biological safety data demonstrating its separation efficiency and biocompatibility remain lacking. Here, we introduce an extracorporeal blood purification system (HemoSystem) designed to remove target compounds using injectable, magnetic nanoparticles (HemoBeads) comprising a nonoxidic iron core encapsulated by a functionalized graphene/polymer shell. HemoBeads are surface‐modified with compound‐specific binding moieties and are administered continuously into the extracorporeal circuit to capture target molecules before being magnetically extracted from the blood. We present ISO 10993‐compliant biocompatibility evaluations alongside preclinical studies in pig and rat models to assess: (i) the operational safety of the extracorporeal system, (ii) the efficiency of HemoBead removal prior to blood reinfusion, and (iii) the systemic toxicity, biodistribution, and long‐term fate of nanoparticles under exaggerated exposure conditions simulating a worst‐case slip‐through scenario. The results show that the HemoSystem appears safe and is easily integrated into clinical procedures. No clinically significant alterations in hemodynamic, hematological, or biochemical parameters were observed. Nanoparticles are efficiently (≥99.9%) extracted from the blood at a blood flow rate of 6 L h −1 . The beads did not accumulate in organs such as brain or heart and are gradually eliminated without pathological alterations. Our findings support the preclinical biological safety and translational feasibility of the HemoSystem as a next‐generation hemoperfusion platform for targeted extracorporeal removal of disease‐etiologic molecules from the bloodstream.