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.

Shape-Memory Terpolymer Rods with 17-β-estradiol for the Treatment of Neurodegenerative Diseases: an In Vitro and In Vivo Study

“…They are used in the treatment of arterial stenosis and in the prevention of restenosis. For this purpose, acetylsalicylic acid, dexamethasone, and mitomycin C with curcumin were proposed (27,28). In stents, shape-memory polymers play a double role, i.e.…”

Covalent Polyisobutylene–Paclitaxel Conjugates for Controlled Release from Potential Vascular Stent Coatings

“…[20][21][22] Biodegradable polymers such as poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) have also been explored as completely degradable platforms and as stent coatings. 10,11,[23][24][25][26][27] The immobilization of heparin as an anti-coagulant on the surfaces of stent coatings has been employed with the aim of imparting non-thrombogenic properties, and has met with variable success. [28][29][30][31] The conjugation of antibodies aimed at capturing endothelial progenitor cells to promote re-endothelialization are also being explored.…”

Responsive Biomaterials: Advances in Materials Based on Shape‐Memory Polymers

“…Interestingly, temperature-responsive SMP-based stents that elute curcumin (an antiproliferative and anticoagulant) and mitomycin C (an inhibitor of smooth muscle cell proliferation and neointima formation) over 14 and 60 days, respectively, were shown to simultaneously inhibit early thrombosis and long term smooth muscle cell proliferation, which are promising for the prevention of restenosis. [14] A particularly interesting example of a body-temperatureresponsive SMP-based stent is intended for use in patients suffering from esophageal stricture (sometimes induced by cancer or trauma), based on a copolymer of poly(caprolactone-co-DLlactide). Such SMP-based stents have prospects for the replacement of metal alloy-based stents displaying shape-memory properties because their mechanical properties are closer to those of the tissue in which they are implanted, and preclinical experiments using dogs have successfully demonstrated their potential advantage over traditional metallic devices.…”