Selective albumin-binding surfaces modified with a thrombin-inhibiting peptide

Area of Science:

• Biomaterials Science
• Biochemistry
• Medical Devices

Background:

• Blood-contacting medical devices can cause blood clots by activating coagulation.
• Improving biomaterial hemocompatibility is crucial for preventing device-related thrombosis.
• Albumin adsorption can reduce biomaterial-induced clotting by reversibly binding to surfaces.

Purpose of the Study:

• To investigate the effect of immobilizing a thrombin inhibitor (fPrt) on nanostructured surfaces.
• To assess if immobilized fPrt can induce selective albumin adsorption and improve hemocompatibility.
• To evaluate the impact of fPrt concentration and surface chemistry on its antithrombotic properties.

Main Methods:

• Synthesized and immobilized a modified thrombin inhibitor (GGfPrt) onto self-assembled monolayers (SAMs) with varying ethylene glycol chain lengths and carboxylate ratios.
• Assessed GGfPrt's ability to inhibit thrombin activity in solution and after surface immobilization.
• Evaluated plasma clotting time and albumin adsorption on functionalized surfaces using various assays.

Main Results:

• Immobilized GGfPrt induced selective and reversible albumin adsorption on nanostructured surfaces.
• While GGfPrt lost some thrombin inhibitory activity upon immobilization, surfaces with low GGfPrt concentrations delayed thrombin's fibrinogen cleavage.
• All GGfPrt-containing surfaces exhibited resistance to coagulation, comparable to controls, due to albumin adsorption.

Conclusions:

• Immobilization of GGfPrt on nanostructured surfaces enhances hemocompatibility by promoting albumin adsorption.
• This strategy offers a promising approach to reduce thrombus formation in blood-contacting medical devices.
• Surface-bound GGfPrt's ability to modulate protein adsorption is key to improving biomaterial performance.