1Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
2Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran
3Department of Bioengineering, Beckman Institute of Advanced Science and Technology, Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, USA
چکیده
The development of stents has been a major advancement in the treatment of obstructive vascular disease since the introduction of balloon angioplasty. However, the occurrence of neointimal hyperplasia, resulting in in-stent restenosis, remains a major obstacle in the long-term success of the percutaneous coronary intervention. Many advancements have been made in developing new materials for drug-eluting stents. However, biodegradability, sensitivity to medical imaging, and preventing re-stenosis remain major concerns in developing an ideal polymeric stent material. Metal-Organic Frameworks (MOFs) as advanced nanomaterials are utilized for applications in numerous fields. As nanoscience revolutionizes many existing biomedical devices, the development of MOF-based 'theranostic' macro-scale devices is reported here which is not achieved before. In this work, stent visualization with magnetic resonance imaging (MRI), controlled release of immunosuppressive and anticoagulant drugs, and long-term biodegradation are obtained in a MOF-based 'theranostic' stent. For this purpose, PCL and MOF-based polymeric composite films are prepared by combining a solution of a polymer (matrix phase) and a dispersion of a MOF or MOF containing Rapamycin (Rap@MOF, filler phase just for MOF composites) in dichloromethane. Then, thin films of composites with a thickness of 120 µm are cut using a laser cutter (Universal Laser Systems X-600, USA, power 45%, and speed 25%) for the fabrication of the stents based on a stent AutoCAD design. Finally, two sides of the laser engraved films were partially heated to be adhered for making 3D Rap@MOF reinforced PCL stent. To investigate the interactions between MOFs and polymeric chains, extensive physicochemical characterizations such as ATR-FTIR, XRD, ssNMR, DSC, TGA, SEM, and DMA were used to characterize stents composed of pure polycaprolactone (PCL), MOF@PCL, and Hep-(Rap@MOF)@PCL. The results demonstrated a proper interface between MOFs and the polymeric matrix. Blood coagulation tests were also performed to study the effects of MOF incorporation and heparin coating on interactions with blood. The susceptibility effect caused by iron inside the MOF structure (1.11% Wt of the stent) leads to an additional signal loss which can be observed with the T2*-weighted GRE sequence, which makes in vivo MRI visualization of the reinforced stents possible. The stents by the instability of MOFs were revealed to be highly biodegradable following degradation tests under various conditions (28% weight loss in 32 weeks compared to 5% weight loss of neat PCL in vitro).
