Fully Synthetic, Biomimicking Polysulfates With Tunable Anticoagulant and Endothelial Cell-Selective Bioactivity

We present a versatile method for fabricating glycosaminoglycan (GAG)-inspired polyelectrolyte brush coatings from fully synthetic sulfated PHEMA block copolymers. Using a bioinert backbone enables evaluation of sulfation effects independently of natural GAGs' carbohydrate backbone. A degree of sulfation above 70% imparted anticoagulant activity, extending plasma coagulation times beyond 500 s at 0.1 mg mL^{- 1}. Controlled self-assembly enabled fabrication and photoimmobilization of uniform, nanometer-thin brushes on polystyrene substrates. The polysulfate brushes exhibited molecular weight-dependent properties: under serum-free conditions, endothelial cells (HUVECs) selectively proliferated on longer P2-OSO₃-BP (65 kDa) compared to shorter P1-OSO₃-BP (15 kDa) brushes, while smooth muscle cells (SMCs) remained quiescent. Despite comparable VEGF and bFGF surface densities (0.5 ng cm^-2), P2-OSO₃-BP coatings better preserved VEGF bioactivity, likely due to higher chain flexibility. In co-culture under serum conditions (5%), HUVEC/SMC ratios remained near unity with persistent colocalization, indicating restrained SMC overgrowth and stabilized vascular co-culture relevant to preventing neointimal hyperplasia. These findings highlight synthetic polysulfate brush coatings as a platform for studying sulfation-driven growth factor interactions and vascular cell competition at biomaterial interfaces, promoting reendothelialization in vitro. The system therefore represents a functional mimetic of GAGs, reproducing key electrostatic features while avoiding the structural complexity of native polysaccharides.