Abstract Number: PB0397
Meeting: ISTH 2021 Congress
Background: There are several blood contacting medical devices that are widely used in medicine to enhance the quality of care. These include, for example, coronary stents, vascular grafts, and mechanical heart valves. A major problem that arises from use of such devices is a lack of biocompatibility that results in activation of enzyme cascades in the blood, leading to excess clotting and inflammation. This may lead to restrictions in blood flow through the device, device failure, embolism, and an increase in the risk of local and widespread infection. One strategy that has been employed to prevent clotting and inflammation on medical devices is the development of specialized surface coatings, inspired by natural anticoagulant systems. Our lab has recently developed an antifouling surface coating made from polydopamine and poly(N,N-dimethylacrylamide) (PDA/PDMA), to which modified proteins/molecules, such as heparin, may be covalently bound in predetermined orientations for optimal function. We and others have also shown that the lectin-like domain of thrombomodulin (TM-LLD) has profound anti-inflammatory properties.
Aims: This project aims to utilize the PDA/PDMA surface coating to conjugate heparin and TM-LLD, thereby developing a new and more effective anti-thrombotic and anti-inflammatory coating that may be used for a wide range of medical devices.
Methods: We have modified unfractionated heparin and TM-LLD at their terminal end, allowing them to be conjugated to the PDA/PDMA coating. Prior to conjugation, activity of modified heparin in solution was evaluated by aPTT and activity of modified TM-LLD was evaluated by leukocyte adhesion and complement ELISA.
Results: We have confirmed that PDA/PDMA-conjugated modified heparin binds to antithrombin and thus likely retains its anticoagulant properties. Modified TM-LLD in solution dampens leukocyte adhesion and complement activation and is similarly being prepared for conjugation to the PDA/PDMA.
Conclusions: These constructs will be evaluated individually and in combination for their capacity to reduce thrombo-inflammation on the biomaterial surface.
To cite this abstract in AMA style:Gonzalez K, Yu K, Lei V, Conway EM, Kizhakkedathu JN. Development of an Anti-thrombotic and Anti-inflammatory Coating for Medical Devices [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/development-of-an-anti-thrombotic-and-anti-inflammatory-coating-for-medical-devices/. Accessed September 24, 2021.
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