PROJECT SUMMARY/ABSTRACT: Blood-contacting medical devices, such as stents and heart valves, are common treatments in modern healthcare. Every year, approximately 1 million and 90,000 stent and prosthetic heart valve procedures are performed in the US, respectively. However, the use of these devices is associated with substantial risk of thrombosis, and the rate of failure due to clot formation can be as high as 6%. When whole blood plasma comes in contact with a foreign body (e.g., an implant), it leads to four main events capable of inducing a thrombogenic response in vivo: protein adsorption, platelet adhesion/activation, leukocyte recruitment, and further activation of complement and coagulation. Within seconds to minutes, key blood plasma proteins are adsorbed and undergo conformational changes on the surface. This layer of adsorbed protein will allow subsequent adhesion and activation of platelets, which promotes the formation of the fibrin clot, as well as the recruitment of leukocytes. The platelets then initiate an inflammatory immune response and promote a complex cascade of events resulting in thrombosis and/or fibrous encapsulation of the implant. Due to this complex foreign body response, hemocompatibility has been a significant issue for blood-contacting medical devices. To address this challenge, the development of novel biomaterials that can appropriately interact with blood and prevent thrombosis is vital for the success of many implantable devices. In this work, we propose to prevent thrombosis on implants by combining the promising properties of two biopolymers with nanoscale features on titania to develop a novel blood-compatible surface. Biopolymers are good candidates for these applications, because of their compatibility with the human body, biodegradability, processability and, in some cases, inherent antifouling and antithrombogenic properties. Our preliminary results indicate that carboxymethylation of kappa-carrageenan with monochloroacetic acid to form carboxymethyl-kappa-carrageenan (CMKC) improves the antithrombogenic properties. CMKC is chemically similar to heparin and prevents thrombosis through multiple mechanisms. However, CMKC is derived from algae, a renewable and low-cost source, while heparin is obtained from animal tissues. Moreover, CMKC does not cause the side effects that heparin presents, such as bleeding effects. Our group also has recently used of tanfloc (TA), a condensed tannin polymer as a biomaterial, and we have demonstrated its promising cytocompatibility, antioxidant activity, antimicrobial, and antifouling properties. Previous studies done by our group showed that the modification of titanium surfaces with TA and heparin decreased the blood protein adsorption/activation, and platelet adhesion and activation. This work aims to combine these promising properties of both biopolymers (CMKC and TA) to develop novel surfaces on titanium that can prevent thrombosis.

PROJECT NARRATIVE: Every year approximately 1 million and 90,000 stent and prosthetic heart valve procedures are performed in the US, respectively. The development of novel biomaterials that can appropriately interact with blood and prevent thrombosis is vital for the success of many implantable devices. In the proposed research, this will be accomplished by combining the promising properties of two biopolymers (carboxymethyl-kappa-carrageenan and tanfloc) with nanoscale features on titania.