Superior performance of chitosan microspheres loaded with hyperbranched polylysine for endotoxin adsorption: From...

Sepsis triggered by lipopolysaccharide (LPS) is a life-threatening condition. Inspired by the specific capture mechanism of innate proteins like LBP and CD14, we develop oxidized chitosan microspheres functionalized with hyperbranched polylysine (OCS-HBPL) as a sepsis detoxification agent. Isothermal titration calorimetry (ITC) reveals that HBPL-LPS binding is an enthalpy-driven process, distinct from the entropy-driven interaction of linear polylysine (LPL)-LPS. Validated by surface plasmon resonance (SPR), HBPL demonstrates superior affinity with a dissociation constant (K_D) of 2.44 × 10^-6 M, being 3.8-fold lower than that of LPL. Although both polymers show similar saturation adsorption capacities by quartz crystal microbalance with dissipation (QCM-D), HBPL exhibits significantly superior erythrocyte compatibility compared to LPL. The OCS-HBPL microspheres achieved a remarkable 73.6% LPS clearance ratio in simulated whole-blood hemoperfusion. Simultaneously, their bovine serum albumin (BSA) adsorption was restricted to 34 μg/g, only 10% of the OCS-LPL control. Crucially, the OCS-HBPL microspheres exhibit a negligible hemolysis ratio, standing in sharp contrast to the unsafe levels (>2%) observed in OCS-LPL. These results demonstrate that HBPL endows chitosan microspheres with both high LPS clearance capacity and excellent hemocompatibility. Thus, OCS-HBPL microspheres show great potential applications in sepsis treatment and open new routes in the development of biocompatible polysaccharide materials.