Abstract

Extracorporeal blood purification requires adsorbents with high mechanical strength, selective adsorption, and stability under high-flow conditions. In this study, dual-crosslinked cellulose microspheres were fabricated using short-chain 1,4-butanediol diglycidyl ether (BDDE) and long-chain poly(ethylene glycol) diglycidyl ether (PEGDGE-1000), optionally combined with glycerol, to form a robust interpenetrating network. Mechanical tests demonstrated that the composite crosslinking strategy significantly enhanced fracture force, hardness, and deformability, surpassing commercial cellulose microspheres. Hydrophobic modification via stearoyl chloride grafting introduced C18 alkyl chains, enabling selective bilirubin adsorption. Dynamic perfusion experiments revealed that microspheres with 10% modification (CL-G10%) achieved the highest bilirubin removal efficiency, maintained spherical integrity, and minimized interference from bovine serum albumin. Kinetic analyses indicated that adsorption follows a pseudo-second-order model, while isotherm studies revealed multilayer adsorption for unmodified microspheres and monolayer adsorption on hydrophobically modified ones. This work presents a scalable approach to produce cellulose microspheres with tunable mechanical properties and surface chemistry, demonstrating their potential as high-performance hemoperfusion materials for efficient blood purification.