Tissue plasminogen activator-containing polyurethane surfaces for fibrinolytic activity

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Thrombosis Research

Background:

• Thrombus formation on blood-contacting devices is a significant clinical challenge.
• Tissue plasminogen activator (t-PA) is a key therapeutic agent for dissolving blood clots.
• Developing materials that can locally deliver active t-PA is crucial for preventing device-related thrombosis.

Purpose of the Study:

• To create novel polyurethane (PU) materials capable of minimizing thrombus formation.
• To functionalize PU surfaces with cationic groups to enhance t-PA binding and retention.
• To evaluate the t-PA loading, activity, and release characteristics of these modified materials.

Main Methods:

• Cationic PU surfaces were prepared by grafting poly(dimethylaminoethyl methacrylate) and quaternization.
• Surfaces were characterized using water contact angle and X-ray photoelectron spectroscopy.
• t-PA loading was quantified using radiolabeled t-PA; activity was assessed via clotting-dissolution and chromogenic assays; release kinetics were studied in plasma.

Main Results:

• Cationic PU surfaces demonstrated significantly higher t-PA uptake compared to unmodified PU (10-14 fold increase).
• Bound t-PA retained high enzymatic activity, comparable to unbound t-PA.
• t-PA release kinetics varied, with rapid release observed from the PU-CH(3)I material in plasma.

Conclusions:

• Functionalized cationic PU materials can effectively immobilize active t-PA.
• These materials show promise for developing blood-contacting surfaces with intrinsic clot-lysing capabilities.
• The developed approach offers a potential strategy for reducing thrombosis in medical devices.