Fluorination of Polylactides as a Path to Enhanced Hemocompatibility

Thesis (Ph.D.)--University of Washington, 2018Polymers derived from lactic acid have been extensively used for various biomedical applications such as sutures and implants due to their biocompatibility and biodegradability. The ability to modify the physiochemical properties of these polymers is a key to expand their application spectrum. Poly(lactic acid) (PLA) has been the predominant polymer for making bioresorbable vascular scaffolds; the first generation of fully bioresorbable stents made from PLA was recently approved by FDA to treat coronary artery disease. Although these bioresorbable stents are claimed to have long-term advantages such as vasomotion restoration and potential recovery of the endothelial function, they have shown higher rates of early thrombosis when compared with permanent metallic stents. Surface-induced thrombosis by biomaterials still remains a significant clinical concern for many types of blood-contacting medical devices. In particular, protein adsorption and platelet adhesion are important events due to their ability to trigger the coagulation cascade and initiate thrombosis. To resolve this clinical challenge, we developed a novel method for fluorinating PLA with trifluoromethyl functional groups using either surface or bulk modification techniques. Fluoropolymer medical devices such as expanded polytetrafluoroethylene vascular grafts have been generally used as blood-contacting materials in clinics, due to their increased thromboresistance and reduced platelet adhesion and activation. Fluorocarbon modification has been shown to decrease platelet adhesion and activation despite the presence of fibrinogen on the biomaterials surfaces. This is the first report of PLA fluorination, which would allow a PLA-based cardiovascular stent with greater blood compatibility. Relevant parameters associated with hemocompatibility including protein adsorption, platelet adhesion, and morphology were evaluated. We found that fluorinated PLA adsorbs and retains a higher ratio of albumin/fibrinogen and, relative to other materials tested here, exhibits a lower number of adherent platelets and a reduced degree of activation. Such promising characteristics pave the way for fabrication of a new generation of fluorinated PLA stents with improved hemocompatibility, alongside tunable degradability and drug release capabilities