Spatiotemporal evaluation of antithrombotic performance for biomaterials through monitoring β-sheet conformation changes at the blood interface

Thrombosis remains a critical challenge for blood-contacting medical devices, often resulting in device failure and potentially fatal complications. While various antithrombotic surfaces have been developed, the role of material-induced protein conformational changes in initiating coagulation is not fully understood. Here, we presented a Raman spectroscopy-based approach to monitor protein conformational changes during blood coagulation. An increase in β-sheet content was observed in both whole blood and plasma, which was attributed to fibrin polymerization. This β-sheet analysis was applied to evaluate heparin-mimicking polymer coatings (HMPCs) containing carboxylic and sulfonic acid groups. HMPCs with adequate polymer loading and an optimal carboxylic-to-sulfonic acid ratio prevented β-sheet elevation during recalcification and correlated with prolonged thrombin time. Raman mapping revealed spatially heterogenous β-sheet distribution on HMPC, delineating zones of effective antithrombotic performance. Collectively, Raman-based β-sheet analysis provides a spatiotemporal, in situ assessment of surface thrombogenicity, offering a valuable tool for guiding the design of nonthrombogenic biomaterials.