(516f) Award Submission: Synthetic Platelets for Biomedical Applications

Arterial and venous thrombi result in life threatening complications depending on the site of formation or lodgment of embolus. These include cardiovascular diseases such as myocardial infarction and stroke that form the leading cause of deaths in United States. Thrombus formation, initiated by circulating platelets, is an important and initial step in repairing injured vasculature, however, excess clot formation results in pathological conditions such as thrombosis. Platelets perform several important biological functions such as hemostasis, release of growth factors and modulation of inflammatory processes. The unique physical features of platelets play an important role in their biological function. Here, using novel fabrication techniques, we have created synthetic replicates of platelets (sPlats) which mimic the important physical, chemical and biological attributes of natural platelets. sPlats have a size of 2-4 μm, a discoidal shape and a highly flexible membrane similar to natural platelets. sPlats are fabricated by layer-by-layer deposition of positively and negatively charged polyelectrolytes including proteins such as actin, an inherent component of the platelet cell membrane and poly-allyl amine hydrochloride on polymeric particles followed by dissolution of the polymeric core. Similar to their natural counterparts, GP1b coated sPlats show excellent adhesion propensity to VWF coated substrate. GP1b is the receptor on platelets that binds strongly to VWF expressed at the site of vascular injury. The adhesion propensity of sPlats was significantly higher than spheres, discoids and albumin coated sPlats indicating the importance of size, shape, mechanical flexibility and surface chemistry of sPlats. sPlats hold outstanding potential in various biomedical applications. Since sPlats mimic the important properties of natural platelets, they can serve as ideal drug delivery vehicles in the treatment of conditions associated with either a low platelet count or high platelet activity. The highly selective adhesion propensity of sPlats to VWF domain coupled with the ability to release growth factors make them excellent substitutes to natural platelets. Mimicking the structural properties of natural platelets may enable sPlats to exhibit prolonged circulation and high targeting efficiency, the properties highly desired in a drug delivery vehicle. sPlats hold promise in treatment of thrombosis by selectively attaching to the clot site and releasing thrombolytic drugs in a controlled manner. sPlats can also be tracked in real time since they can be encapsulated with iron oxide nanoparticles which show high contrast in magnetic resonance imaging. The fabrication of these novel platelet mimetic particles has opened up new avenues in the fields of drug delivery, diagnostic imaging, treatment of cardiovascular diseases and other platelet associated disorders and artificial blood synthesis.