Thermo-Induced Shape-Memory PEG-PCL Copolymer as a Dual-Drug-Eluting Biodegradable Stent

Abstract

In this work, a thermo-induced shape-memory drug-eluting stent (SMDES) has been developed by cross-linking PEG-PCL copolymer (cPEG-PCL). The stent is able to perform the shape-memory effect from a temporary linear form to a permanent spiral shape with the transition temperature close to body temperature. The stent incorporates a controlled dual drug-release system for the purpose of preventing in-stent restenosis of the vessel for short- and long-term therapeutic effects. From the results, (1)H NMR and GPC indicate that the compositions of PEG-PCL block copolymers are similar to the feed ratios of PEG/ε-CL. A Young's modulus of the cPEG-PCL stent can be achieved that ranges from tens to one hundred megapascals by modulation of the mixing ratio of PEG/PCL. The cPEG-PCL stent is demonstrated to recover to its permanent shape with a high fixing ratio (>99%), recovery ratio (>90%), and recovery time (<10 s). DSC data reveals that the transition temperature is around body temperature (40 °C). Cytotoxicity tests prove that the cPEG-PCL_6040 stent has good biocompatibility. In vitro degradation tests show that the cPEG-PCL_6040 stent undergoes a bulk degradation of 47% after 60 days of incubation under flow conditions. Platelet adhesion and smooth muscle cell proliferation were significantly inhibited by coculture with a mitomycin C/curcumin-eluting stent as a result of the release of curcumin for antiplatelet adhesion during the initial 2 weeks followed by long-term inhibition of smooth muscle cell hyperproliferation for 60 days via mitomycin C. After 60 days of incubation in a bioreactor, the appearance of the stent remains intact and shows no signs of recoiling or collapse.