Hypothesis: Polyzwitterions as a promising class of materials are often used to construct antifouling surfaces with optimized conformation and compositions for a wide variety of antifouling applications. While numerous zwitterionic polymers have been identified for their antifouling capacity, the exact relationship among molecular structure, surface hydration property, and antifouling performance of zwitterionic polymers at different scales still remains elusive. Experiments: we first designed and synthesized a new zwitterionic monomer of 3-(4-(methacryloyloxy)-1-methylpiperidin-1-ium-1-yl)-propane-1-suljonate (MAMPS), then used MAMPS monomers to fabricate into homogenous polymer brushes on Au substrate using SI-ATRP and heterogeneous double-network (DN) hydrogels combining with Agar network via one-pot, heating-cooling-photopolymerization method, and finally evaluated their antifouling ability to resist the adsorption of protein/cell/bacteria on the two different polymer forms at microscopic and macroscopic scales. Findings: For microscopic polyMAMPS brushes, they exhibited excellent resistance to nonspecific protein adsorption from both undiluted blood serum/plasma (0.3-5 ng/cm(2)), cell adhesion up to 3 days, and clinically relevant bacterial attachment for 72 hat the optimal film thicknesses of 20-40 nm. For macroscopic Agar/polyMAMPS DN hydrogels, they also exhibited approximately 96% less protein adhesion than tissue culture polystyrene (TCPS). Different structured materials consisting of polyMAMPS at both micro- and macro-scales demonstrate its excellent, intrinsic antifouling property, which could be related to their highly water binding character of zwitterionic groups. PoIyMAMPS materials, alternative to commonly used poly(sulfobetaine methacrylate) (polySBMA) and poly(carboxybetaine methacrylate) (polyCBMA) zwitterions, hold great promise for antifouling designs and applications. (C) 2020 Elsevier Inc. All rights reserved.