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Background: Previous randomized controlled trials demonstrated a higher rate of stent thrombosis with bioresorbable vascular scaffold (BVS) implantation as compared with second-generation drug-eluting stent in selected patients/lesions. However, long-term outcomes of BVS implantations that utilize an optimized technique (OIT) in unselected patients/lesions are lacking. The aim of this study was to assess the real-world, long-term clinical outcomes of BVS (Absorb; Abbott Vascular) with OIT. Methods and results: In a cohort of 156 patients, a total of 347 BVS devices (435 lesions) were implanted, with intravascular ultrasound (IVUS) guidance utilized in 303 (87.3%) of the scaffolds. The primary efficacy endpoint was target-lesion revascularization (TLR) and the primary safety endpoint was scaffold thrombosis. Despite performing routine high-pressure postdilation, postintervention IVUS detected BVS underexpansion/malapposition in 53 scaffolds (28.7%), requiring further postdilation. At a median follow-up of 60 months (interquartile range, 45-73 months), TLR and scaffold thrombosis occurred in 16 patients (10.3%) and 1 patient (0.6%), respectively. At univariable analysis, IVUS-guided scaffold implantation was associated with lower TLR (odds ratio, 0.24; 95% confidence interval, 0.09-0.62; P

Stents have changed medicine and the treatment of obstructive vascular disease. Technology advancement and outcomes of numerous clinical trials have led to development of different generations of stents and other novel endovascular implants. Herewith, we briefly discuss the evolution of coronary intervention from balloon angioplasty to contemporary alternatives such as second-generation drug-eluting stents, bioresorbable scaffolds, drug-eluting balloons, and polymer-free stents. We briefly present clinical outcomes, solved/remaining challenges for each category, and accumulating evidence on effectiveness and safety of emerging therapies. With computational modeling playing an ever-increasing role in designing medical devices, we also review the impact of such models on understanding and optimizing drug delivery in stents. Interventional cardiology has made great strides because technological innovation has marched in lock step with advances in understanding the basic science of vascular repair. The continued evolution of endovascular therapies will rely on retaining this link between mechanistic insight and enlightened technical development.

Objectives To asses mid‐term clinical outcomes of bioresorbable vascular scaffolds (BVS) for the treatment of coronary artery disease in a large‐scale all‐comers population. Background Several clinical settings are underrepresented in randomized studies investigating BVS against drug‐eluting stents. Whether their results can be translated into the heterogeny patient population seen during daily routine requires further investigation. Methods The European ABSORB Consortium comprises the following European registries: GABI‐R, ABSORB UK Registry, ABSORB France, BVS RAI Registry, and REPARA BVS Registry, which all prospectively collected patient‐level data regarding outcomes following unrestricted BVS implantation. The primary endpoint of target lesion failure (TLF) includes cardiac death, target‐vessel myocardial infarction (TVMI) and target‐lesion revascularisation (TLR) at 12 months. The incidence of scaffold thrombosis (ST) according to ARC criteria was also assessed. Multivariable analysis was used to adjust for differences in patient and lesion characteristics. Results A total of 10,312 patients (mean age 58.4 ± 11.4 y) underwent BVS implantation during routine practice. The 12‐month follow‐up was complete in 95.5% of patients. At 12 months, the primary endpoint of TLF occurred in 3.6%; its components cardiac death, TVMI and TLR were documented in 1.2%, 1.8%, and 2.6%, respectively. The definite/probable ST rate was 1.7%. Absence of predilatation, discontinuation of DAPT and scaffold diameter below 3 mm were independent predictors of ST. Conclusions The EAC demonstrates reasonable real‐world clinical outcome data after BVS implantation. However, the rate of scaffold thrombosis remains high.

INTRODUCTION The concept of bioresorbable scaffolds (BRS) born with the aim to reduce the rate of late and very late cardiac events related to drug-eluting stents. However, first-generation BRS failed to prove their short-term safety and efficacy. Based on data derived from early investigations, new-generation BRS have been developed and tested in preliminary studies. The present review's focus is to summarize the mechanical characteristics of these new scaffolds and the clinical evidence of their safety and efficacy. EVIDENCE ACQUISITION This systematic review was performed following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). PUBMED, Google Scholar, and Biomed central databases were analyzed. Only papers published in English and in peer-reviewed journals were selected to summarize current evidence about new generation BRS, with CE mark approval. Overall, 23 studies were included. EVIDENCE SYNTHESIS Data obtained from selected studies assessing the safety and efficacy of new generation BRS are encouraging. This is thanks to the progressive development of scaffolds with a different backbone structure and struts thickness that guarantee higher radial strength, flexibility, and resistance to fracture. These characteristics led to low rates of major adverse cardiac events and device-oriented composite endpoint at follow-up. CONCLUSIONS New-generation BRS have a good safety profile in stable patients with simple lesions, supported by a meticulous implantation technique. The first studies were performed on a small population with short-term follow-up, therefore new randomized clinical trials and registries are needed to expand the preliminary findings.

In this review, we discuss about the reasons behind the failure of the Absorb bioresorbable vascular scaffold (BVS) device and about the challenges the future holds for the next generation of the bioresorbable scaffold (BRS) technology. Absorb BVS was burdened by intrinsic structural limitations which resulted in augmented rates of device thrombosis and clinical adverse events compared to current-generation metallic stent. Nevertheless, new generation devices with novel design and materials are in development. Second generation BRS have enhanced mechanical strength, smaller footprints, less thrombogenicity and modified bioresorption. These features, paired with proper patient and lesion selection and optimal “user-friendly” implant techniques, could possibly overcome the previous BRS generation limitations, rekindling physicians, and industry interest on this promising technology.

Background: Bioresorbable scaffolds (BRS) were considered to be beneficial for coronary bifurcation lesions regarding the avoidance of lateral branch opening incarceration after complete absorption. However, data is limited in this setting. The aim of this meta-analysis was to evaluate the short (6-month) and medium-term (1-year) outcomes of BRS in patients with coronary bifurcation lesions. Methods: PubMed, EMBASE, Web of Science, Cochrane library databases were searched to find the studies of BRS implantation in patients with coronary bifurcation lesions. The effective outcome was target lesion revascularization. The safety outcomes included major adverse cardiovascular events, target vessel revascularization, myocardial infarction, definite or probable scaffold thrombosis, and cardiac death. Results: A total of 1204 patients involved in 12 studies were included. The pooled estimate rate of target lesion revascularization as efficacy outcome was highly consistent between 6-month and 1-year follow-up, which was 4.74% (95% CI 2.36–9.54%, I 2 = 41.5%, p = 0.14) and 4.37% (95% CI 3.05–5.69%, I 2 = 4.6%, P = 0.39). The pooled estimated rate of major adverse cardiovascular events as safety outcome was 5.50% and 7.31% for both 6-month and 1-year follow-up. The pooled estimated rate of target vessel revascularization, myocardial infarction, definite or probable scaffold thrombosis, and cardiac death at 1-year follow-up was 5.92%, 2.52%, 1.69%, and 0.42%. Conclusions: The application of BRS for coronary bifurcation lesions is acceptable in efficacy outcome, but the high rate of scaffold thrombosis remains of concern (Registered by PROSPERO, CRD42019140341).

Bioresorbable scaffolds have emerged as a potential breakthrough for the treatment of coronary artery lesions. The need for drug release and plaque scaffolding is temporary, and leaving a permanent stent once the process of plaque recoil and vessel healing has ended might be superfluous or even deleterious exposing the patient to the risk of very late thrombosis, eliminating vessel reactivity, impairing non-invasive imaging and precluding possible future surgical revascularization. This long-term potential limitation of permanent bare metal stents might be overcome by using a resorbable scaffold. The metallic and antithrombotic properties make the resorbable magnesium scaffold an appealing technology for the treatment of coronary artery lesions. Notwithstanding this, its mechanical properties substantially differ from those of conventional bare metal stents, and previous experience using polymer-based scaffolds has shown that a standardized implantation technique and optimal patient and lesion selection are key factors for a successful implantation. A panel of expert cardiologists gathered to find a consensus on the best practices for Magmaris implantation in a selected patient population and to discuss the rationale for new potential future indications.

Percutaneous coronary intervention, which is safe, effective, and timely, has become an important treatment for coronary artery diseases and has been widely used in clinical practice. However, there are still some problems that urgently need to be solved. Permanent vessel caging through metallic implants not only prevents the process of positive vessel remodeling and the restoration of vascular physiology but also makes the future revascularization of target vessels more difficult. Bioresorbable scaffolds (BRSs) have been developed as a potential solution to avoid the above adverse reactions caused by permanent metallic devices. BRSs provide temporary support to the vessel wall in the short term and then gradually degrade over time to restore the natural state of coronary arteries. Nonetheless, long-term follow-up of large-scale trials has drawn considerable attention to the safety of BRSs, and the significantly increased risk of late scaffold thrombosis (ScT) limits its clinical application. In this review, we summarize the current status and clinical experiences of BRSs to understand the application prospects and limitations of these devices. In addition, we focus on ScT after implantation, as it is currently the primary drawback of BRS. We also analyze the causes of ScT and discuss improvements required to overcome this serious drawback and to move the field forward.

Background and aims: The impact of endothelial shear stress (ESS) on vessel remodeling in vessels implanted with bioresorbable scaffold (BRS) as compared to metallic drug-eluting stent (DES) remains elusive. The aim of this study was to determine whether the relationship between ESS and remodeling patterns differs in BRS from those seen in metallic DES at 3-year follow-up. Methods: In the ABSORB II randomized trial, lesions were investigated by serial coronary angiography and intravascular ultrasound (IVUS). Three-dimensional reconstructions of coronary arteries post-procedure and at 3 years were performed. ESS was quantified using non-Newtonian steady flow simulation. IVUS cross-sections in device segment were matched using identical landmarks. Results: Paired ESS calculations post-procedure and at 3 years were feasible in 57 lesions in 56 patients. Postprocedure, median ESS at frame level was higher in BRS than in DES, with marginal statistical significance (0.97 ± 0.48 vs. 0.75 ± 0.39 Pa, p = 0.063). In the BRS arm, vessel area and lumen area showed larger increases in the highest tercile of median ESS post-procedure as compared to the lowest tercile. In contrast, in DES, no significant relationship between median ESS post-procedure and remodeling was observed. In multivariate analysis, smaller vessel area, larger lumen area, higher plaque burden post-procedure, and higher median ESS post-procedure were independently associated with expansive remodeling in matched frames. Only in BRS, younger age was an additional significant predictor of expansive remodeling. Conclusions: In a subset of lesions with large plaque burden, shear stress could be associated with expansive remodeling and late lumen enlargement in BRS, while ESS had no impact on vessel dimension in metallic DES.

Aims Absorb bioresorbable scaffold (BRS) related events were noticed between 1 and 3 years – the approximate time of active scaffold bioresorption. This resulted in the recommendation for 3 year DAPT after Absorb BRS implantation. We aimed to evaluate the safety and efficacy of the Absorb BRS in comparison with Xience everolimus-eluting stent (EES) at 4 years follow-up in large unselected population. In addition, we aimed to assess the value of prolonged DAPT against scaffold thrombosis. Methods AIDA was an investigator-initiated, non-inferiority, multicenter, randomized, all-comers trial. Target vessel failure (a composite of cardiac death, target-vessel myocardial infarction and target-vessel revascularization) and device thrombosis at 4-year follow-up are the primary focus of this analysis. During the trial recommendation for DAPT was changed to up to 3-years post Absorb BVS implantation. Whether this adaption influenced the results after Absorb BVS will be assessed. Results Between August 2013 and December 2015, 1,845 patients were enrolled, of whom 924 were randomized to treatment with Absorb BRS and 921 to Xience EES. The baseline characteristics in the two study arms were well balanced. Of all patients, 18% had diabetes mellitus, more than 50% presented with ACS and the median SYNTAX score was 11. In the Absorb BRS arm, 97% of lesions were predilated and in 74% post-dilatation was performed. Four-year clinical outcomes are currently being adjudicated by an independent clinical event committee. The results will be available at EuroPCR 2020. Conclusions Absorb BRS is associated with higher rates of scaffold thrombosis throughout 3-year of follow-up. The performance of Absorb BRS beyond 3-years, in comparison with the Xience EES, in a large unselected population will be presented. (ClinicalTrials.gov Identifier: NCT01858077) Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Abbott

Background Bioresorbable scaffolds (BRS) were introduced to overcome the limitations of permanent metallic stent implantation. Optical coherence tomography (OCT) can provide important insights on vessel wall healing at follow-up. We compared OCT-assessed healing at 6 months after implantation of everolimus-eluting BRS and everolimus-eluting metallic stents (EES) in patients treated for acute myocardial infarction (AMI). Methods ISAR-Absorb MI is a multicentre, 2:1 randomized trial comparing outcomes of patients with AMI stented with BRS or conventional EES. Angiographic surveillance was planned for all patients at 6–8 months follow-up; surveillance with OCT at follow-up was discretionary. For the present analysis, patients with OCT follow-up were included and images analyzed at a core laboratory. Tissue characterization using grey-scale signal intensity (GSI) analysis was done for neointimal regions of interest (ROI) with thickness of 100 to 400 µm. ROI’s were classified as mature using a cut-off GSI score of 109.7. Generalized linear mixed model was used as appropriate. Results 70 patients in the BRS arm and 32 patients in the EES arm had OCT available for analysis at a median follow-up of 216 days. Minimum lumen area [5.13 (3.95, 6.70) vs. 4.93 (3.84, 6.99) mm2] and minimum stent area [5.78 (4.88, 7.34) vs. 6.39 (4.77, 7.45) mm2] were comparable between BRS and EES. In total 2,237 frames with 19,827 struts were assessed. Overall strut coverage was better with BRS compared to EES (97.5% vs. 90.9%, p Conclusions In selected patients undergoing OCT imaging at 6–8 months after implantation of BRS and conventional EES for AMI, we observed generally favorable healing characteristics with high rates of strut coverage and fewer areas of immature neointimal areas with BRS in comparison to EES.

Objective Present bench study aimed to evaluate whether technical characteristics of Fantom Encore® bioresorbable scaffold (BRS) allow to perform proximal optimization/side branch dilation/proximal optimization (POT-SB-POT) technique, as an adequate solution for bifurcation percutaneous coronary intervention. Methods Two Fantom Encore® BRS platforms (small with 3.0 mm nominal diameter, n = 7; and large with 3.5 mm nominal diameter, n = 7) were evaluated in bench models, which were designed according to Finet-law and fitted to nominal scaffold diameter in the distal main branch (MB) and fitted to indicated maximal expansion capacity in the proximal main branch (MB). Results were evaluated by (a) fluoroscopy, (b) optical coherence tomography (OCT) and (c) micro-computed tomography (μCT). Results All procedures were performed according to the protocol. Careful review of the fluoroscopic loops by an independent operator did not reveal any strut fracture or major deformation. By OCT the overall rate of perfectly apposed struts in the bifurcation area was 15 ± 6% after SB opening, that increased significantly but remained low with 22 ± 9% after final POT (p = .001). Compared to SB ballooning alone, significant benefit of final POT was found in rate of perfect apposition in the proximal MB (15 ± 12% vs. 26 ± 15%, respectively; p = .017) and at the abostial side of polygon of confluence (7 ± 9% vs. 16 ± 13%, respectively; p = .005). μCT analysis revealed a single strut fracture in one case with the small platform, while four cases showed single or multiple strut fractures with the large platform. Conclusion The mechanical characteristics of the device are not suitable for use of Conventional techniques for bifurcation PCI such as POT-SB-POT. The use of Fantom Encore® BRS for bifurcation PCI with relevant SB should not be encouraged.

Dutch researchers were among the first to perform clinical studies in bare metal coronary stents, the use of which was initially limited by a high incidence of in-stent restenosis. This problem was greatly solved by the introduction of drug-eluting stents (DES). Nevertheless, enthusiasm about first-generation DES was subdued by discussions about a higher risk of very-late stent thrombosis and mortality, which stimulated the development, refinement, and rapid adoption of new DES with more biocompatible durable polymer coatings, biodegradable polymer coatings, or no coating at all. In terms of clinical DES research, the 2010s were characterised by numerous large-scale randomised trials in all-comers and patients with minimal exclusion criteria. Bioresorbable scaffolds (BRS) were developed and investigated. The Igaki-Tamai scaffold without drug elution was clinically tested in the Netherlands in 1999, followed by an everolimus-eluting BRS (Absorb) which showed favourable imaging and clinical results. Afterwards, multiple clinical trials comparing Absorb and its metallic counterpart were performed, revealing an increased rate of scaffold thrombosis during follow-up. Based on these studies, the commercialisation of the device was subsequently halted. Novel technologies are being developed to overcome shortcomings of first-generation BRS. In this narrative review, we look back on numerous devices and on the DES and BRS trials reported by Dutch researchers.

Bioresorbable scaffolds (BRS) have been introduced in the last decade in percutaneous coronary interventions. Despite several advantages being postulated, the negative results from the mid-term follow-up of the Absorb trials have tempered enthusiasm for these innovative devices. The Absorb scaffold was associated with higher rates of target-lesion failure and scaffold thrombosis when compared to current metallic stents, and for this reason was withdrawn from the market. This failure has to be considered multifactorial, involving technical and technological aspects. Continuous engineering refinements in BRS technology, means newer-generation devices are available in clinical practice, and several more are under preclinical and clinical assessment. Thinner and smaller struts, associated with a faster resorption and reendothelialization process, are at the basis of promising preclinical results for new BRS. In this review we summarize the Absorb scaffold experience and focus on the latest evidence concerning emerging new BRS, to explore if a "BRS revival" is conceivable.

Aims Neoatherosclerosis is a frequent finding after implantation of permanent metallic stents. Bioresorbable scaffolds (BRS) are considered to reduce the incidence of neoatherosclerosis owing to their dissolution and consequent vascular restoration. The aim of this study was to evaluate the formation of neoatherosclerosis between magnesium-based BRS and thick-strut metallic drug-eluting stents (DES) in a rabbit model of neoatherosclerosis and in proportion to the effect of high-dose statin medication. Methods and results Fully bioresorbable magnesium scaffolds (BRS, n=45) and thick-strut permanent metallic DES of equivalent geometry and design (n=45) were implanted into the iliac arteries of New Zealand White rabbits (n=45) following endothelial balloon injury and exposure to a cholesterol diet. Endothelialisation was assessed in 12 animals after 35 days using scanning electron microscopy (SEM), showing significantly enhanced re-endothelialisation above struts in the BRS (n=13) compared to DES (n=10). Eleven (11) animals were terminated for baseline assessment after 91 days while the remaining 22 animals were randomised to receive high-dose statin treatment (3 mg/kg) or placebo. BRS-treated vessels showed a significant reduction in foam cell infiltration as a sign of early neoatherosclerosis by histology and OCT when compared to thick-strut DES-treated vessels. Statin treatment resulted in significant reduction of foam cell infiltration in BRS and DES by histology. Conclusions Our findings suggest reduced neoatherosclerosis formation in magnesium-based BRS relative to thick-strut DES. High-dose statin treatment may be a promising measure to reduce neoatherosclerosis progression, both on its own and in synergy with site-targeted device-based treatment.

Introduction An ancillary advantage of bioresorbable scaffolds is the possibility of non-invasive imaging assessment of the treated coronary segment. Cardiac computed tomography angiography (CCTA) studies of resorbable magnesium scaffolds (RMS) are scarce. Methods In this collaborative, international study, nine patients who had an RMS implanted underwent CCTA as part of follow-up assessment. Core-lab blinded quantitative and qualitative assessment was performed by an independent CCTA investigator. Results Eight studies were amenable for quantitative analysis, and the blinded CT investigator successfully located and evaluated patency of RMS in all cases. The CCTA follow-up in-scaffold percentage diameter stenosis and area stenosis was 22.2% (12.4–30) and 39.1% (0.23–0.50), in keeping with mild in-scaffold late loss and underlying plaque growth. Moreover, a detailed coronary plaque characterization at treated segments was feasible (fibrous plaque in 69.9%, fibrofatty in 17.13%, necrotic in 4.78% and calcium in 5.72%). As in 6 out of 8 cases, the presentation was an acute coronary syndrome, these preliminary results could suggest plaque stabilization and a good coronary vessel healing with RMS. Conclusion Non-invasive, follow-up assessment of RMS with CCTA is feasible. Further CCTA studies for either clinical or research purposes with the present and upcoming generation of resorbable magnesium scaffolds are warranted.

AIMS The MAGSTEMI trial showed larger endothelium-independent vasodilatation with magnesium-based bioresorbable scaffolds (MgBRS) than with sirolimus-eluting stents (SES). However, restenosis was more frequent with MgBRS. The aims of this study were to compare the healing pattern between MgBRS and SES and to describe the main causes of restenosis, as assessed by optical coherence tomography (OCT). METHODS AND RESULTS Ninety-five consecutive patients from the randomised MAGSTEMI trial (MgBRS=48, SES=47) underwent OCT imaging at one year. Healing and bioresorption pattern were categorised into four groups: 1) indiscernible struts were observed in 33.3% versus 0% of patients (p

Metallic drug-eluting stents have led to significant improvements in clinical outcomes but are inherently limited by their caging of the vessel wall. Fully bioresorbable scaffolds (BRS) have emerged in an effort to overcome these limitations, allowing a “leave nothing behind” approach. Although theoretically appealing, the initial experience with BRS technology was limited by increased rates of scaffold thrombosis compared with contemporary stents. This review gives a broad outline of the current BRS technologies and outlines the refinements in BRS design, procedural approach, lesion selection, and post-procedural care that resulted from early BRS trials.

AIMS Peripheral arteries are constantly exposed to deformation (elongation, twisting, shortening, compression) making bioresorbable scaffolds (BRS) a potentially attractive therapeutic alternative to metallic stents. We conducted a long-term pilot preclinical study of a novel sirolimus-eluting BRS in peripheral arteries. METHODS AND RESULTS Fourteen BRS were deployed in iliofemoral arteries of seven healthy Yucatan miniswine and examined with imaging, pharmacokinetic, histopathologic, and polymer degradation techniques at 0, 30, 90, 180 days, 1, 2, and 3.3 years. Angiographic late luminal loss remained unchanged at 30 and 180 days but significantly decreased from 1 to 3.3 years. optical coherence tomography (OCT) showed late increase in lumen area (1 year: 14.70 ± 3.58 mm2 , 2 years 22.04 ± 3.81 mm2 , and 3.3 years 23.45 ± 7.07 mm2 ; p

Background RENASCENT is a prospective, multi-center first-in-human clinical study to evaluate the clinical performance of the novel sirolimus-eluting 150-μm strut thickness FORTITUDE® BRS for percutaneous coronary intervention of single de novo coronary lesions. Methods FORTITUDE® BRS was tested in a prospective study in Italy and Colombia. Study objectives were in-scaffold angiographic late lumen loss (LLL) measured by quantitative coronary angiography and target vessel failure (TVF) defined as the composite rate of cardiac death, target vessel myocardial infarction or ischemia driven target lesion revascularization (TLR) at 9- and 24-months with clinical results up to 36-months. Results A total of 63 patients were enrolled. All patients underwent lesion pre-dilatation and 22 patients (34.9%) underwent post-dilatation. Clinical device and procedural success was 98.4% (62/63 patients) and 96.8% (61/63 patients) respectively. At 9-months, TVF occurred in 3/61 (4.9%) of the patients including 2 peri-procedural MI and one ischemia-driven TLR. Between 9- to 24-months, ischemia-driven TLR occurred in 3 additional patients (4.9%) including 1 patient who presented with very late ST after stopping all medications. There were no further TVF between 24- and 36-months. Conclusions In this multi-center prospective study, the FORTITUDE® BRS was shown to be safe and effective in the treatment of single coronary lesions with low levels of TVF and LLL at 9- and 24-months. It was shown to be clinically safe upto 36-months follow-up.

Exosomes derived from mesenchymal stem cells are extracellular vesicles released to facilitate cell communication and function. Recently, polylactic acid (PLA), calcium silicates (CaSi), and dicalcium phosphate dihydrate (DCPD) have been used to produce bioresorbable functional mineral-doped porous scaffolds-through thermally induced phase separation technique, as materials for bone regeneration. The aim of this study was to investigate the effect of mineral-doped PLA-based porous scaffolds enriched with exosome vesicles (EVs) on osteogenic commitment of human adipose mesenchymal stem cells (hAD-MSCs). Two different mineral-doped scaffolds were produced: PLA-10CaSi-10DCPD and PLA-5CaSi-5DCPD. Scaffolds surface micromorphology was investigated by ESEM-EDX before and after 28 days immersion in simulated body fluid (HBSS). Exosomes were deposited on the surface of the scaffolds and the effect of exosome-enriched scaffolds on osteogenic commitment of hAD-MSCs cultured in proximity of the scaffolds has been evaluated by real time PCR. In addition, the biocompatibility was evaluated by direct-contact seeding hAD-MSCs on scaffolds surface-using MTT viability test. In both formulations, ESEM showed pores similar in shape (circular and elliptic) and size (from 10&ndash, 30 &micro, m diameter). The porosity of the scaffolds decreased after 28 days immersion in simulated body fluid. Mineral-doped scaffolds showed a dynamic surface and created a suitable bone-forming microenvironment. The presence of the mineral fillers increased the osteogenic commitment of hAD-MSCs. Exosomes were easily entrapped on the surface of the scaffolds and their presence improved gene expression of major markers of osteogenesis such as collagen type I, osteopontin, osteonectin, osteocalcin. The experimental scaffolds enriched with exosomes, in particular PLA-10CaSi-10DCPD, increased the osteogenic commitment of MSCs. In conclusion, the enrichment of bioresorbable functional scaffolds with exosomes is confirmed as a potential strategy to improve bone regeneration procedures.

Bioresorbable vascular scaffolds (BVSs) were designed to overcome the limitations of metallic stents. Absorb BVS has provided information about strut thickness, scaffold degradation, vessel wall coverage, and their influence on thrombosis. Clinical trials have shown higher rates of target vessel myocardial infarction and stent thrombosis with the absorb BVS than with second-generation drug-eluting stents.

Aims: The aim of this study was to investigate clinical outcomes of patients at high risk of restenosis after implantation of a bioresorbable vascular scaffold (BVS). Methods and results: The COMPARE-ABSORB trial was an investigator-initiated, prospective randomised study. Patients at high risk of restenosis were randomly assigned to receive either a BVS or an everolimus-eluting stent (EES). A dedicated implantation technique was recommended for BVS. The primary endpoint was target lesion failure (TLF), defined as the composite of cardiac death, target vessel myocardial infarction (TVMI) or clinically indicated target lesion revascularisation at one year. The enrolment was discontinued prematurely because of a high thrombosis and TVMI rate in the BVS arm. A total of 1,670 patients were recruited (BVS 848 patients and EES 822 patients). TLF occurred in 43 patients (5.1%) of the BVS group and 34 patients (4.2%) of the EES group (absolute difference 0.9%, 95% confidence interval [CI]: −1.2%-3.0%, p non-inferiority

Aims Significant platelet activation after long stented coronary segments has been associated with periprocedural microvascular impairment and myonecrosis. In long lesions treated either with an everolimus-eluting bioresorbable vascular scaffold (BVS) or an everolimus-eluting stent (EES), we aimed to investigate (a) procedure-related microvascular impairment, and (b) the relationship of platelet activation with microvascular function and related myonecrosis. Methods and results Patients (n=66) undergoing elective percutaneous coronary intervention (PCI) in long lesions were randomised 1:1 to either BVS or EES. The primary endpoint was the difference between groups in changes of pressure-derived corrected index of microvascular resistance (cIMR) after PCI. Periprocedural myonecrosis was assessed by high-sensitivity cardiac troponin T (hs-cTnT), platelet reactivity by high-sensitivity adenosine diphosphate (hs-ADP)-induced platelet reactivity with the Multiplate Analyzer. Post-dilatation was more frequent in the BVS group, with consequent longer procedure time. A significant difference was observed between the two groups in the primary endpoint of ΔcIMR (p=0.04). hs-ADP was not different between the groups at different time points. hs-cTnT significantly increased after PCI, without difference between the groups. Conclusions In long lesions, BVS implantation is associated with significant acute reduction in IMR as compared with EES, with no significant interaction with platelet reactivity or periprocedural myonecrosis.

Aim To compare the long-term outcomes of patients implanted with Absorb bioresorbable scaffold (BRS) with optimal versus suboptimal technique. Methods and results All patients who received an Absorb between March 2012 and January 2016 were selected from 19 Italian centers databases to assess the impact of an optimal implantation technique (CIAO criteria) on long-term device-oriented composite end-point (DOCE) - including cardiac death (CD), target-vessel myocardial infarction (TV-MI) and ischemia-driven target lesion revascularization (ID-TLR) - on its single components and on scaffold thrombosis (ScT). CIAO criteria consist of predilation (balloon/vessel ratio 1:1), correct sizing (BRS/proximal reference vessel diameter -RVD- ratio 0.8–1.2) and high-pressure postdilation with non-compliant (NC) balloon (≥20 atm for balloon/BRS ratio 1:1 or ≥16 atm for a 0.25–0.5 mm oversized balloon). Among the 1.434 patients analyzed, 464 (32.4%) fulfilled all CIAO criteria for every BRS implanted (CIAO 3 group), while 970 (67.6%) did not in at least one of the received BRS (CIAO 0-1-2 group). At 31.0 (interquartile range -IQR- 24.8–38.5) months follow-up, CIAO criteria did not impact on DOCE (8.2% vs. 8.0%, p = 0.92), ID-TLR (6.9% vs. 7.1%, p = 0.72) or ScT (1.9% vs. 1.8%, p = 0.80) in the overall population. At multivariate analysis overall BRS length ( p = 0.001), severely calcified lesions (p = 0.03) and absence of CIAO criteria (CIAO 0, p = 0.005) were independent predictors of DOCE in long-term follow-up. Conclusion Our data suggest that strict application of an optimal Absorb implantation technique doesn't improve long-term DOCE or ScT but may mitigate the worse outcome of patients with calcific lesions.

Objectives: The aim of this study was to investigate the vascular responses and fates of the scaffold after bioresorbable vascular scaffold (BVS) implantation using multimodality imaging. Background: Serial comprehensive image assessments after BVS implantation in the context of a randomized trial have not yet been reported. Methods: In the ABSORB Japan trial, 400 patients were randomized to a BVS (n = 266) or a cobalt-chromium everolimus-eluting stent (n = 134). Through 3 years, patients underwent serial angiography and intravascular ultrasound or optical coherence tomography (OCT). Results: Luminal dimension at 3 years was consistently smaller with the BVS than with the cobalt-chromium everolimus-eluting stent (mean angiographic minimal luminal diameter 2.04 ± 0.63 mm vs. 2.40 ± 0.56 mm, mean difference −0.37 mm [95% confidence interval: −0.50 to −0.24 mm]; p < 0.001), mainly because of smaller device area (6.13 ± 2.03 mm2 vs. 7.15 ± 2.16 mm2, mean difference −1.04 mm2 [95% confidence interval: −1.66 to −0.42 mm2]; p < 0.001), and larger neointimal area (2.10 ± 0.61 mm2 vs. 1.86 ± 0.64 mm2, mean difference 0.24 mm2 [95% confidence interval: 0.06 to 0.43 mm2]; p = 0.01) by OCT. BVS-treated vessels did not show previously reported favorable vessel responses, such as positive vessel remodeling, late luminal enlargement, and restoration of vasomotion, although the OCT-based healing score was on average zero (interquartile range: 0.00 to 0.00). At 3 years, intraluminal scaffold dismantling (ISD) was observed in 14% of BVS. On serial OCT, ISD was observed in 6 lesions at 2 years, where the struts had been fully apposed at post-procedure, while ISD was observed in 12 lesions at 3 years, where 8 lesions were free from ISD on 2-year OCT. In 5 cases of very late scaffold thrombosis, strut discontinuities were detected in all 4 cases with available OCT immediately before reintervention. Conclusions: In this multimodality serial imaging study, luminal dimension at 3 years was smaller with the BVS than with the cobalt-chromium everolimus-eluting stent. ISD, suspected to be one of the mechanisms of very late BVS thrombosis, was observed in a substantial proportion of cases at 3 years, which developed between post-procedure and 2 years and even beyond 2 years. (AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 [Absorb™ BVS] in Japanese Population [ABSORB JAPAN]; NCT01844284)

Heterogeneous neointimal response has been observed after implantation of all generations of coronary stents. Our aim was assessing local factors of shear stress (SS) and plaque characteristics in neointimal response after implantation of bioresorbable scaffolds (BRS) in bifurcations. Ten patients from the BIFSORB pilot study were analysed. Follow-up optical frequency domain imaging (OFDI) was performed at 1 month and 2 years. Coronary lumen and BRS structure were reconstructed by fusion of OFDI and angiography and were used for subsequent flow simulation. Plaque arc degree and SS were quantified using post-procedural OFDI data and were matched with follow-up OFDI using anatomical landmarks. Strut-level and segment-level analysis were performed for 1-month and 2-year follow-up respectively. A total of 444 struts (54 jailing struts) were included at 1-month follow-up. Time-average SS (TASS) was significantly lower for covered struts than for uncovered struts in non-bifurcation segments (TASS: 1.81 ± 1.87 vs. 3.88 ± 3.72 Pa, p Heterogeneous neointimal response has been observed after implantation of all generations of coronary stents. Our aim was assessing local factors of shear stress (SS) and plaque characteristics in neointimal response after implantation of bioresorbable scaffolds (BRS) in bifurcations. Ten patients from the BIFSORB pilot study were analysed. Follow-up optical frequency domain imaging (OFDI) was performed at 1 month and 2 years. Coronary lumen and BRS structure were reconstructed by fusion of OFDI and angiography and were used for subsequent flow simulation. Plaque arc degree and SS were quantified using post-procedural OFDI data and were matched with follow-up OFDI using anatomical landmarks. Strut-level and segment-level analysis were performed for 1-month and 2-year follow-up respectively. A total of 444 struts (54 jailing struts) were included at 1-month follow-up. Time-average SS (TASS) was significantly lower for covered struts than for uncovered struts in non-bifurcation segments (TASS: 1.81 ± 1.87 vs. 3.88 ± 3.72 Pa, p

BACKGROUND/PURPOSE: To avoid long-term effects associated with permanent implants, bioresorbable vascular scaffolds were developed as they provide transient vessel support and disappear thereafter. The aim of the BIOSOLVE-II and -III studies was to assess the safety and performance of a magnesium based sirolimus-eluting scaffold; we report the clinical outcomes at 3 years, 2 years after scaffold resorption.METHODS/MATERIALS: BIOSOLVE-II and BIOSOLVE-III are international, prospective multi-center studies, including 184 patients with 189 de novo lesions and stable or unstable angina, or documented silent ischemia. Acute myocardial infarction, 3-vessel coronary artery disease and heavily calcified lesions were excluded. Antiplatelet therapy was recommended for 6-months.RESULTS: Patients were 65.5 ± 10.8 years old, and lesions were 12.1 ± 4.5 mm long and located in vessels with a diameter of 2.7 ± 0.4 mm. More than half of the lesions (56.5%) were type B2/C lesions. At 2 years, 92.5% (160/173) of patients were symptom-free and 91.5% (151/165) at 3 years; all the other patients had stable angina. At 3 years, target lesion failure occurred in 11 patients (6.3%), consisting of 4 cardiac deaths (2.3%), one target-vessel myocardial infarction (0.6%), and 6 clinically-driven target lesion revascularizations (3.4%). There was no definite or probable scaffold thrombosis.CONCLUSION: In a low-risk patient population, treatment with a sirolimus-eluting magnesium bioresorbable scaffold can be considered safe, in particular with no definite or probable scaffold thrombosis.ANNOTATED TABLE OF CONTENTS: BIOSOLVE-II- and III are prospective international, multi-center studies including 184 patients with de novo lesions. At 3 years, target lesion failure was 6.3%, consisting of 4 cardiac deaths (2.3%), one target-vessel myocardial infarction (0.6%), and 6 clinically-driven target lesion revascularizations (3.4%). There was no definite or probable scaffold thrombosis.