AbstractThe protein adsorption and immuno-compatibility of hydrogels largely influence the clinical outcome in biomedical application scenarios. In this study photo-crosslinked 2-isocyanate ethyl methacrylate–functionalized oligo(ethylene glycol)–oligo(propylene glycol)–oligo(ethylene glycol) (IEMA–OEG–OPG–OEG–IEMA)-based polymer hydrogel films were explored with respect to endotoxin contaminations, intrinsic immuno-modulatory features, and protein adsorption of human fibronectin as well as serum albumin. Therefore three different hydrogel films were prepared from aqueous solutions of dimethacrylated OEG–OPG–OEG triblock copolymers (Mn = 12,700 g mol−1, 70 mol% OEG content) with varying wt% of the macromonomer (10 to 30%) resulting in polymeric networks, which differ in their crosslinking density and accordingly their physical properties. It could be shown that all three hydrogel film compositions do not cause complement and immune cell activation. The films were protein repellent, but reversible protein diffusion in and out of the hydrogel network, depending on the mesh size of the network, could be observed. In conclusion, the hydrogels can be considered as immuno-compatible, which qualifies them for biomedical applications such as drug release systems.