In-stent restenosis is still an important issue and stent thrombosis is an unresolved risk after coronary intervention. Biodegradable stents would provide initial scaffolding of the stenosed segment and disappear subsequently. The additive manufacturing technology Selective Laser Melting (SLM) enables rapid, parallel, and raw material saving generation of complex 3- dimensional structures with extensive geometric freedom and is currently in use in orthopedic or dental applications. Here, SLM process parameters were adapted for poly-L-lactid acid (PLLA) and PLLA-co-poly-ε-caprolactone (PCL) powders to generate degradable coronary stent prototypes. Biocompatibility of both polymers was evidenced by assessment of cell morphology and of metabolic and adhesive activity at direct and indirect contact with human coronary artery smooth muscle cells, umbilical vein endothelial cells, and endothelial progenitor cells. γ-sterilization was demonstrated to guarantee safety of SLM-processed parts. From PLLA and PCL, stent prototypes were successfully generated and post-processing by spray- and dip-coating proved to thoroughly smoothen stent surfaces. In conclusion, for the first time, biodegradable polymers and the SLM technique were combined for the manufacturing of customized biodegradable coronary artery stent prototypes. SLM is advocated for the development of biodegradable coronary PLLA and PCL stents, potentially optimized for future bifurcation applications.
The long-term success of coronary stent implantation is limited by in-stent restenosis (ISR). In spite of a broad variety of animal models available, an ideal high-throughput model of ISR has been lacking. Apolipoprotein E (apoE) deficient rats enable the evaluation of human-sized coronary stents while at the same time providing an atherogenic phenotype. Whereas apoE deficient rats have been proposed as animal model of atherosclerosis, to date it is unknown whether they also develop pronounced ISR. We sought to assess ISR after abdominal aorta stent implantation in apoE deficient rats. A total of 42 rats (16 wildtype, 13 homozygous apoE−/− and 13 heterozygous apoE+/− rats) underwent abdominal aorta stent implantation. After 28 days blood samples were analyzed to characterize lipid profiles. ISR was assessed by histomorphometric means. Homozygous apoE−/− rats exhibited significantly higher total cholesterol and low-density cholesterol levels than wildtype apoE+/+ and heterozygous apoE+/− rats. ISR was significantly pronounced in homozygous apoE−/− rats as compared to wildtype apoE+/+ (p = <0.0001) and heterozygous apoE+/− rats (p = 0.0102) on western diet. Abdominal aorta stenting of apoE−/− rats is a reliable model to investigate ISR after stent implantation and thus can be used for the evaluation of novel stent concepts. Apolipoprotein E (apoE) deficient rats have been proposed as animal model of atherosclerosis. We investigated the development of restenosis 28 days after stent implantation into the abdominal aorta of wildtype apoE+/+, homozygous apoE−/− and heterozygous apoE+/− rats, respectively. Homozygous apoE−/− rats exhibited significantly higher LDL and significantly lower HDL cholesterol levels compared to wildtype apoE+/+ and heterozygous apoE+/− rats. Restenosis after stent implantation was significantly pronounced in western-diet-fed homozygous apoE−/− rats, accompanied by a significantly increased neointimal thickness. Thus, apoE knockout rats exhibit elevated restenosis and might provide a novel tool for testing of innovative stent concepts.
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