Interface-Engineered Polystyrene-Divinylbenzene Microspheres with Polyethylenimine and Metal-Phenolic Networks for Multifunctional Sepsis Hemoperfusion

Sepsis, a life-threatening organ dysfunction from a dysregulated infection response, causes many deaths, especially in the elderly. Aging population exacerbates the sepsis burden, requiring cost-effective prevention, detection, and treatment strategies. Hemoperfusion has emerged as an effective clinical treatment for sepsis. Herein, polystyrene-divinylbenzene microspheres functionalized with metal-phenolic networks and polyethylenimine (P-PEI Cu/TA_n microspheres) with endotoxin and cell-free DNA (cfDNA) adsorption, oxidative stress relief and antibacterial activity were constructed as a multifunctional adsorbent for hemoperfusion therapy toward sepsis. The adsorbent exhibited good blood compatibility, high-efficiency adsorption of endotoxin (with an adsorption capacity of 1239.6 EU/g) and cfDNA (with a clearance ratio of 74.8%), robust scavenging of reactive oxygen/nitrogen species, and antibacterial activity against <i>Escherichia coli</i> (84.6%) and <i>Staphylococcus aureus</i> (68.1%) within 4 h. In simulated hemoperfusion, P-PEI Cu/TA_0.5 microspheres achieved rapid endotoxin removal (75.3% clearance in 15 min) and effectively mitigated oxidative stress induced by endotoxin, as evidenced by preserved blood oxidoreductase activity. This work introduced a novel therapeutic approach that combines toxin adsorption, antioxidative protection, and antibacterial effects, holding significant promise for enhancing clinical sepsis management through extracorporeal blood purification.