A nano-inspired multifunctional POSS-PCU covered stent : endothelial progenitor cell capture with stealth liposomal drug release

• Main Author: Tan, A. J. K.
• Published: University College London (University of London) 2014
• Subjects: 617
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.631919

The 2 main unresolved issues inherent in coronary stents are in-stent restenosis (ISR) and late stent thrombosis (ST). ISR is largely due to vascular smooth muscle cell (VSMC) proliferation, and ST is attributed to a lack of re-endothelialization. This thesis describes the conceptualization and development of a biofunctionalized polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU) platform, for the express purpose of circumventing ISR and ST. A bare-metal stent is embedded between 3 layers of POSS-PCU facilitating endothelial progenitor cell (EPC) capture using antibodies, in tandem with sustained drug release using stealth liposomes. The luminal area is impregnated with anti-CD34 antibodies, covalently bonded to a POSS-PCU base platform, for EPC capture to enhance re-endothelialization. Results indicated successful antibody immobilization, with an increased propensity for EPC capture compared to controls. The abluminal area is integrated with paclitaxel-encapsulated stealth liposomes, with an ultrathin layer of POSS-PCU sprayed on top using an ultrasonic atomization spray system, for sustained drug release to inhibit VSMC proliferation. Results in this aspect demonstrated sustained drug release with augmented cell kill in a 28-day in vitro cell culture. Mechanical engineering tests performed on the finished product demonstrated superior mechanical functionality as a covered stent. Various sterilization techniques and a biodegradation model were also employed to robustly assess product viability, with results indicating that EPC capture potential and stealth liposomal drug elution were preserved. Taken together, this novel POSS-PCU covered stent can enhance re-endothelialization and inhibit VSMC proliferation, thereby addressing the issues of ST and ISR respectively. Furthermore, the covering membrane could also serve as a physical barrier against atherosclerotic plaque dislodgement to prevent thromboembolism. It is therefore hoped that the proof-of-principle demonstrated here in this thesis would serve as an impetus for further translational research, with the eventual goal of taking it from bench to bedside.