The chemical modification of the aginate/chitosan/aginate (ACA) hydrogel microcapsule with methoxy poly(ethylene glycol) (MPEG) was investigated to reduce nonspecific protein adsorption and improve biocompatibility in vivo. The graft copolymer chitosan-g-M PEG (CS-g-M PEG) was synthesized. and then alginate/chitosan/alginate/CS-g-MPEG (ACAC(PEG)) multilayer hydrogel microcapsules were fabricated by the layer-by-layer (LBL) polyelectrolyte self-assembly method. A quantitative study of the modification was carried out by the gel permeation chromatography (G PC) technique, and protein adsorption on the modified microcapsules was also investigated. The results showed that the apparent graft density of the M PEG side chain on the microcapsules decreased with increases in the degree of substitution (DS) and the M PEG chain length. During the binding process, the apparent graft density of CS-g-M PEG showed rapid growth plateau rapid growth behavior, CS-g-M PEG was not only bound to the surface but also penetrated a certain depth into the microcapsule membranes. The copolymers that penetrated the microcapsules made a smaller contribution to protein repulsion than did the copolymers on the surfaces of the microcapsules. The protein repulsion ability decreased with the increase in DS from 7 to 29% with the same chain length of M PEG 2K. CS-g-MPEG with MPEG 2K was more effective at protein repulsion than CS-g-M PEG with M PEG 550, having a similar DS below 20%. In this study, the microcapsules modified with CS-g-MPEG2K-DS7% had the lowest IgG adsorption of 3.0 +/- 0.6 mu g/cm(2), a reduction of 61% compared to that on the chitosan surface.