Angioplasty and stenting are standard treatment options for both stabile occlusive coronary artery disease and acute myocardial infarctions. Over the last years, several biodegradable stent systems have entered pre-clinical and clinical evaluation and into clinical practice. A strong supporting scaffold is necessary after angioplasty to prevent elastic recoil of the vessel but in the long term a permanent metallic stent will only impair normal physiology of the artery wall. Thus, the main advantage of a resorbable system is the potential for better vessel recovery and function in the long term. The new stent systems differ from traditional stents in size and biological responses and questions have risen regarding their mechanical strength and increased risk of stent thrombosis. Here, we present current treatment options with biodegradable scaffolds, discuss further key areas for improvements and review novel technological advances in the context of all up-to-date clinical trial information. New material choices are also covered as well as special considerations for pre-clinical testing.
<b><i>Aims:</i></b> Percutaneous coronary intervention is routinely performed to treat occlusive coronary artery disease. Coronary perforation is a potential complication and can be treated with a stent graft. Current stent grafts are associated with high restenosis rates. We tested the safety and feasibility of biodegradable stent grafts in pig and rabbit models. <b><i>Methods and Results:</i></b> Stent grafts were examined in pig coronaries with repeated OCT imaging for 42 days. Novel biodegradable coatings were applied on a bare metal stent by either an electrospinning (ES) or dip coating (DC) method. A completely biodegradable system was made by ES coating a magnesium-based stent. A commercially available stent graft served as a control. ES devices showed less restenosis (44.3 ± 8.8 vs. 59.1 ± 11.1% in controls, <i>p</i> < 0.05) and smaller reduction in minimum lumen area (44.3 ± 13.4 vs. 64.4 ± 13.6% in controls, <i>p</i> < 0.05) at day 42. DC devices occluded during follow-up. ES devices showed recanalization through the graft wall at day 42. Feasibility of the ES and DC devices was evaluated in pig coronary aneurysms and rabbit aortic perforation models and sealed aneurysms and perforations without complications. <b><i>Conclusions:</i></b> Recanalization of the graft wall improves biocompatibility. Biodegradable stent grafts may present an alternative to permanent implants by showing reduced restenosis at day 42.
Tissue microvasculature is known to remodel in response to ischemia. Yet, how this remodeling contributes to the process of post-ischemic recovery is still not completely understood. We studied how microvascular changes relate to post-ischemic muscle repair. Muscle-level microvascular alterations of blood flow and hemoglobin oxygenation, and post-ischemic myofiber and capillary responses were analyzed in aged, healthy C57Bl/6J mice (n = 48) and aged, hyperlipidemic LDLR−/−ApoB100/100 mice (n = 69) after induction of acute hindlimb ischemia using contrast ultrasound, photoacoustic imaging, and histological analyses, respectively. Microvascular responses leading to successful post-ischemic muscle repair in C57Bl/6J mice included an early capillary dilation phase preceding the return of arterial driving pressure followed by an increase in capillary density that further supported satellite cell-induced muscle regeneration. Failure of initial capillary enlargement due to a life-long moderate hypercholesterolemia in LDLR−/−ApoB100/100 mice led to inability to recover arterial driving pressure and resulted in an increase in distal necrosis, chronic tissue damage and a delay in overall recovery after ischemia. To conclude, these data reveal the important role of transient capillary enlargement in initiating a cascade of capillary events that are crucial for a successful post-ischemic muscle recovery. Essentially, the observed dynamic nature of the post-ischemic capillaries should be considered when designing novel treatments targeting the microvasculature in ischemic diseases.
This study aimed to show the significance of capillary function in post-ischemic recovery from the perspective of physiological parameters, such as blood flow, hemoglobin oxygenation and tissue regeneration. Muscle-level microvascular alterations of blood flow and hemoglobin oxygenation, and post-ischemic myofiber and capillary responses were analyzed in aged, healthy C57Bl/6J mice (n = 48) and aged, hyperlipidemic LDLR−/−ApoB100/100 mice (n = 69) after the induction of acute hindlimb ischemia using contrast ultrasound, photoacoustic imaging and histological analyses, respectively. The capillary responses that led to successful post-ischemic muscle repair in C57Bl/6J mice included an early capillary dilation phase, preceding the return of arterial driving pressure, followed by an increase in capillary density that further supported satellite cell-induced muscle regeneration. Initial capillary enlargement was absent in the LDLR−/−ApoB100/100 mice with lifelong moderate hypercholesterolemia and led to an inability to recover arterial driving pressure, with a resulting increase in distal necrosis, chronic tissue damage and a delay in the overall recovery after ischemia. To conclude, this manuscript highlights, beyond arterial collateralization, the importance of the proper function of the capillary endothelium in post-ischemic recovery and displays how post-ischemic capillary dynamics associate beyond tissue blood flow to both hemoglobin oxygenation and tissue regeneration.
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