Endothelial progenitor cells (EPCs) are a promising cell source for the treatment of several ischemic diseases for their potentials in neovascularization. However, the application of EPCs in cell‐based therapy has shown low therapeutic efficacy due to hostile tissue conditions after ischemia. In this study, a bio‐blood‐vessel (BBV) is developed, which is produced using a novel hybrid bioink (a mixture of vascular‐tissue‐derived decellularized extracellular matrix (VdECM) and alginate) and a versatile 3D coaxial cell printing method for delivering EPC and proangiogenic drugs (atorvastatin) to the ischemic injury sites. The hybrid bioink not only provides a favorable environment to promote the proliferation, differentiation, and neovascularization of EPCs but also enables a direct fabrication of tubular BBV. By controlling the printing parameters, the printing method allows to construct BBVs in desired dimensions, carrying both EPCs and atorvastatin‐loaded poly(lactic‐co‐glycolic) acid microspheres. The therapeutic efficacy of cell/drug‐laden BBVs is evaluated in an ischemia model at nude mouse hind limb, which exhibits enhanced survival and differentiation of EPCs, increased rate of neovascularization, and remarkable salvage of ischemic limbs. These outcomes suggest that the 3D‐printed ECM‐mediated cell/drug implantation can be a new therapeutic approach for the treatment of various ischemic diseases.

BACKGROUND: Although venoarterial extracorporeal membrane oxygenation (VA-ECMO) is beneficial for the treatment of profound cardiogenic shock, peripheral VA-ECMO cannulation can increase left ventricular afterload, thus compromising myocardial recovery. We investigated whether early routine left ventricular unloading can reduce 30-day mortality compared with the conventional approach in patients with cardiogenic shock undergoing VA-ECMO. METHODS: This randomized clinical trial involved 116 patients with cardiogenic shock undergoing VA-ECMO from March 2021 to September 2022 at Chonnam National University Hospital, Gwangju, South Korea. The patients were randomly assigned to undergo either early routine left ventricular unloading with transseptal left atrial cannulation within 12 hours after randomization (n=58) or the conventional approach, which permitted rescue transseptal left atrial cannulation in case of an increased left ventricular afterload (n=58). The primary outcome was all-cause mortality within 30 days. RESULTS: All 116 randomized patients (mean age, 67.6±13.5 years; 34 [29.3%] women) completed the trial. At 30 days, all-cause death had occurred in 27 (46.6%) patients in the early group and 26 (44.8%) patients in the conventional group (hazard ratio, 1.02 [95% CI, 0.59–1.74]; P =0.942). Crossover to rescue transseptal left atrial cannulation occurred in 29 patients (50%) in the conventional group according to a clear indication. Time to rescue transseptal cannulation in the conventional group was a median of 21.8 (interquartile range, 12.4–52.2) hours after randomization. There were no significant differences in other secondary outcomes between the 2 groups except for a shorter time to disappearance of pulmonary congestion in the early group (median, 3 [interquartile range, 2–6] versus 5 [interquartile range, 3–7] days; P =0.027). CONCLUSIONS: Among patients with cardiogenic shock undergoing VA-ECMO, early routine left ventricular unloading with transseptal left atrial cannulation did not reduce 30-day mortality compared with the conventional strategy, which permitted rescue transseptal left atrial cannulation. These findings should be cautiously interpreted until the results of multicenter trials using other unloading modalities become available. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04775472.

Kim Y, et al. Korean Circ J. 2018 Dec;48(12):1120-1130. https://doi.org/10.4070/kcj.2018.0181

Background: The role of intravascular ultrasound (IVUS)‐guided percutaneous coronary intervention (PCI) is still unclear in patients with acute myocardial infarction acute myocardial infarction. This study aimed to evaluate the long‐term impact of IVUS‐guided PCI in patients with acute myocardial infarction. Methods and Results: Among a total of 13 104 patients with acute myocardial infarction, enrolled in the Korea Acute Myocardial Infarction Registry‐National Institutes of Health, we selected patients who underwent PCI with second‐generation drug‐eluting stent implantation. The primary outcome was the risk of target lesion failure at 3 years. Among the study population, 1887 patients (21.0%) underwent IVUS‐guidance, and 7120 patients (79.0%) underwent angiography‐guidance for second‐generation drug‐eluting stent implantation. IVUS‐guided PCI was associated with a significantly lower risk of target lesion failure at 3 years (4.8% versus 8.0%; hazard ratio [HR], 0.59; 95% CI, 0.47 to 0.73; P <0.001) compared with angiography‐guided PCI. The difference was driven mainly by a lower risk of cardiac death and target vessel myocardial infarction. The results were consistent after confounder adjustment by multiple sensitivity analyses. Moreover, quartile analysis of volume of IVUS use showed that higher IVUS use was associated with a decreased risk of 3‐year target lesion failure (adjusted HR, 0.58; 95% CI, 0.45 to 0.75; P <0.001 for quartile 1 versus 4; P <0.001 for trend comparison across all quartiles). Conclusions: In patients with acute myocardial infarction who underwent PCI with second‐generation drug‐eluting stent implantation, the use of IVUS guidance was associated with a significant reduction in 3‐year target lesion failure, mainly driven by hard end points, such as cardiac death and target vessel myocardial infarction.

Drug-eluting stents (DESs) have been widely used as a treatment approach for coronary artery diseases. Generally, conventional DESs were fully covered with drugs and biodegradable polymers on both abluminal and luminal layers (i.e., conformal coating). However, uncontrolled drug release from the luminal drug-coating layer of the stent is known to inhibit re-endothelialization. Furthermore, the acidification of the surrounding tissue by the decomposed coating polymer causes inflammation, resulting in restenosis and late thrombosis. To overcome these limitations, here we demonstrated a functional DES coated with poly(lactic-co-glycolic acid) (PLGA), sirolimus (SRL), and magnesium hydroxide (Mg(OH)₂, MH) precisely only on the abluminal layer. The acidic neutralization effect of MH was elucidated by measuring the pH change of the fabricated film in PBS solution. In an in vitro cell study, the stent coated with MH exhibited higher compatibility with human coronary artery endothelial cells (ECs) and a lower inflammation score as compared to the control stent. Finally, in an in vivo large porcine model, the abluminal coated DES with SRL and MH showed excellent re-endothelialization and anti-inflammatory and anti-thrombotic effects. In conclusion, it is believed that this approach has great potential for the development of functional DES for the treatment of cardiovascular diseases.