One-pot synthesis of a heparin-mimetic coating for supporting early subcutaneous endothelial cell recruitment and organization

Abstract Heparin-mimetic coatings are well-established for antithrombotic applications, but their capacity for promoting endothelial cell recruitment and organization without exogenous bioactive motifs remains underexplored. The incorporation of such motifs typically complicates the material system (e.g. multi-step conjugation), raises costs due to their rapid degradation and poses potential immunogenicity risks Here, we developed a heparin-mimetic coating without introducing bioactive motifs and validate its ability in supporting endothelial cell recruitment and organization. The heparin-mimetic coating was fabricated via a one-pot copolymerization of acrylic acid (AA), 2-acrylamido-2-methylpropane sulfonic acid (AMPS), and 4-benzoylphenyl acrylate (ABP), followed by UV-induced hydrocarbon insertion to achieve immobilization onto silanized substrates. The successful synthesis of the copolymer was confirmed by proton nuclear magnetic resonance spectroscopy ( 1 H NMR) and Fourier-transform infrared spectroscopy (FTIR) Atomic force microscopy (AFM) and energy-dispersive x-ray spectroscopy (EDS) analyses demonstrated uniform coating deposition on the substrate. Activated partial thromboplastin time (APTT) assays, together with Raman spectroscopy characterization of the fibrinogen-to-fibrin conversion, revealed promising in vitro anticoagulant activity, supporting further investigation in animal models. Furthermore, subcutaneous implantation in mice showed that the coating supporting subcutaneous early endothelial cell recruitment and organization without inducing adverse inflammatory responses. Taken together, this study establishes a one-pot strategy for the facile synthesis of a heparin-mimetic coating that support early subcutaneous endothelialization without the need for additional bioactive motifs.