Thrombosis‐Responsive Thrombolytic Coating Based on Thrombin‐Degradable Tissue Plasminogen Activator (t‐PA) Nanocapsules

Abstract

Surface modification with bioactive agents capable of combating thrombosis is a widely used strategy for developing antithrombotic biomaterials. However, exposure of the blood to the antithrombotic agent on the material surface may cause hemostatic disorders under normal conditions. Ideally an implanted biomaterial should respond appropriately on demand to a specific change in the physiologic environment, as happens in the body itself. In the present study, a thrombosis-responsive surface coating with the ability to lyse fibrin as it forms is reported. The coating consists of nanocapsules (NCs) in which the fibrinolysis activator t-PA is encapsulated in a thrombin-degradable hydrogel shell. The t-PA NCs are attached to several materials covalently through a polydopamine adhesive layer. The resulting surfaces are treated with the antifouling agent glutathione (GSH) to prevent further interactions with blood/plasma components. The t-PA NCs/GSHcoated surface is stable and remain inert in normal plasma environment while releasing t-PA and promoting fibrinolysis when thrombin is present. The fibrinolytic activity increases with increasing thrombin concentration, and therefore presumably with the extent of thrombosis. This work constitutes the first report of an antithrombotic coating whose function is triggered and regulated, respectively, by the appearance of thrombin and the extent of coagulation.

Inhibition of Inflammation‐Associated Thrombosis with ROS‐Responsive Heparin‐DOCA/PVAX Nanoparticles

“…In addition, the tails of HDP‐treated mice exhibit the similar structure as the normal mice with purple and blue structure dominantly; confirming that pretreatment with HDP‐2 and HDP‐4 nanoparticles restrains the clot formation effectively (Figure e,f). In addition, there is nearly no histological evidence of accumulated toxicity in the different organs after administration of nanoparticles for 3 days (Figure S8, Supporting Information), demonstrating the excellent biocompatibility of HDP nanoparticles . Taken together, we confirmed that the prepared HDP nanoparticles can be employed to treat thrombus associated with inflammation without lethal side effects on hemostasis.…”

Recent Advances in Nanomaterials for Diagnosis, Treatments, and Neurorestoration in Ischemic Stroke

“…The specificity of thrombin release, a key event in thrombosis, means that thrombin release can act as a specific trigger for the thrombotic response delivery system (Gunawan et al, 2015 ). In the current study, Li et al ( 2017 ) reported a thrombus-responsive surface coating with the ability to lyse fibrin. The coating consisted of nanocapsules (NCs) in which the fibrinolytic activator t-PA was encapsulated in a thrombin-degradable hydrogel shell.…”

Heparin-network-mediated long-lasting coatings on intravascular catheters for adaptive antithrombosis and antibacterial infection

“…The formation of CRT is a multi-component pathology after catheter implantation into blood vessels, such as various coagulation factors, proteins, blood cells, and inflammatory cells, etc 37 , 38 . Therefore, the anticoagulant mechanism of the coating was firstly investigated by exploring the relationship between the surface and the coagulation cascade, protein, and inflammatory cells.…”