Nanostructured Surfaces That Mimic the Vascular Endothelial Glycocalyx Reduce Blood Protein Adsorption and Prevent Fibrin Network Formation.

Blood-contacting materials are critical in many applications where long-term performance is desired. However, there are currently no engineered materials used in cardiovascular implants and devices that completely prevent clotting when in long-term contact with whole blood. The most common approach to developing next-generation blood-compatible materials is to design surface chemistries and structures that reduce or eliminate protein adsorption to prevent blood clotting. This work proposes a new paradigm for controlling protein-surface interactions by strategically mimicking key features of the glycocalyx lining the interior surfaces of blood vessels: negatively charged glycosaminoglycans organized into a polymer brush with nanoscale domains. The interactions of two important proteins from blood (albumin and fibrinogen) with these new glycocalyx mimics are revealed in detail using surface plasmon resonance and single-molecule microscopy. Surface plasmon resonance shows that these blood proteins interact reversibly with the glycocalyx mimics, but have no irreversible adsorption above the limit of detection. Single-molecule microscopy is used to compare albumin and fibrinogen interactions on surfaces with and without glycocalyx-mimetic nanostructures. Microscopy videos reveal a new mechanism whereby the glycocalyx-mimetic nanostructures eliminate the formation of fibrin networks on the surfaces. This approach shows for the first time that the nanoscale structure and organization of glycosaminoglycans in the glycocalyx are essential to (i) reduce protein adsorption, (ii) reversibly bind fibrin(ogen), and (iii) inhibit fibrin network formation on surfaces. The insights gained from this work suggest new design principles for blood-compatible surfaces. New surfaces developed using these design principles could reduce risk of catastrophic failures of blood-contacting medical devices.

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