Waksman R.,MedStar Washington Hospital Center |
Zumstein P.,Biotronik AG |
Pritsch M.,Biotronik AG |
Wittchow E.,CVPath Institute Inc. |
And 4 more authors.
EuroIntervention | Year: 2017
Aims: The second-generation drug-eluting absorbable magnesium scaffold Magmaris, recently introduced for the treatment of obstructive coronary atherosclerotic lesions, suggests a good safety profile, but preclinical assessment is important for predicting clinical performance. The aim of the present study was to assess subacute and long-term safety as well as pharmacokinetic properties of the Magmaris compared with a current- generation metallic DES and an approved BRS in porcine and rabbit animal models. Methods and results: Ninety Magmaris scaffolds were implanted into non-diseased porcine and rabbit models. A bioresorbable vascular scaffold (Absorb) and a permanent drug-eluting stent (XIENCE Xpedition) served as controls. Scanning electron microscopy showed increased endothelialisation and decreased thrombus formation at three and 28 days in the Magmaris group compared with the Absorb group. In the XIENCE group, inflammation exceeded the level in the Magmaris group at 365 and 730 days. Neointimal growth was greater in the Magmaris group than in the XIENCE group. Late lumen loss decreased over time in both groups. Optical coherence tomography (OCT) showed stable luminal dimensions in both the Magmaris and XIENCE groups. Pharmacokinetic studies demonstrated a retarded elution profile in the Magmaris group with 69.4% of sirolimus released at 90 days. Conclusions: Preclinical results suggest that the Magmaris has a favourable safety profile with advanced healing relative to benchmark, low acute thrombogenicity, and absence of excessive lumen loss up to two years. These results support clinical application of Magmaris for human use. © Europa Digital & Publishing 2017.
Joner M.,Deutsches Herzzentrum Munich |
Byrne R.A.,Deutsches Herzzentrum Munich |
Lapointe J.-M.,AccelLAB Inc |
Radke P.W.,Universitatsklinik Schleswig Holstein |
And 3 more authors.
Thrombosis and Haemostasis | Year: 2011
The advent of drug-eluting balloon (DEB) therapy has represented an important development in interventional cardiology. Nevertheless, preclinical data with this technology remain scant, and comparative studies have not previously been published. Bare metal stents were implanted in the coronary arteries of 15 pigs followed by balloon angioplasty. Animals were allocated to treatment with a 60-second inflation of one of four different balloon catheters: a conventional untreated plain angioplasty balloon (PBA, Biotronik AG), the Pantera Lux DEB (3.0 μg/mm2 paclitaxel; BTHC excipient, Biotronik AG), the Elutax DEB (2.0 μg/mm2 paclitaxel; no excipient; Aachen Resonance), or the SeQuent Please DEB (3.0 μg/mm2 paclitaxel; iopromide excipient: B. Braun). Twenty-eight days following balloon deployment, animals underwent repeat angiography for quantitative coronary angiography analysis and euthanasia for histopathologic assessment. By histology, the mean neointimal thickness was 0.44 ± 0.19 mm with PBA, 0.35 ± 0.13 mm with Pantera Lux, 0.61 ± 0.20 mm with Elutax, and 0.47 ± 0.21 mm with SeQuent Please DEB (p=0.02). In comparison with PBA, deployment of the Pantera Lux or the SeQuent Please DEB resulted in delayed healing characterised by significant increases in fibrin, neointimal cell vacuity and delayed re-endothelialisation. In conclusion, investigation of comparative DEB performance in a porcine model of advanced coronary restenosis reveals significant heterogeneity of neointimal suppression between the devices tested with numerically lowest values seen in the Pantera Lux group. On the other hand, evidence of delayed healing was observed in the most effective DEB groups. © Schattauer 2011.
Durand E.,University of Paris Descartes |
Sharkawi T.,Institute Charles Gherardt |
Leclerc G.,AccelLAB Inc |
Raveleau M.,University of Paris Descartes |
And 3 more authors.
Circulation: Cardiovascular Interventions | Year: 2014
Background-We aimed to evaluate a new drug-free fully bioresorbable lactic acid-based scaffold designed to allow early dismantling synchronized with artery wall healing in comparison with a bare metal stent (BMS). Methods and Results-Twenty-three BMS (3.0×12 mm) and 36 lactic acid-based bioresorbable scaffolds (BRS, 3.0×11 mm) were implanted in porcine coronary arteries. QCA and optical coherence tomographic analyses were performed immediately after implantation and repeated after 1, 3, and 6 months. Microcomputed tomography was used to detect scaffold dismantling. Polymer degradation was evaluated throughout the study. The primary end-point was late lumen loss, and the secondary end-points were scaffold/stent diameter and acute recoil. Acute recoil was low and comparable between the BRS and the BMS groups (4.6±6.7 versus 4.6±5.1%; P=0.98). BRS outer diameter increased significantly from 1 to 6 months indicating late positive scaffold remodeling (P<0.0001), whereas BMS diameter remained constant (P=0.159). Late lumen loss decreased significantly from 1 to 6 months in the BRS group (P=0.003) without significant difference between BRS and BMS groups at 6 months (P=0.68). Microcomputed tomography identified BRS dismantling starting at 3 months, and weight-average molar masses of scaffold parts were 20% and 14% of their initial values at 3 and 6 months. Conclusions-BRS and BMS have similar 6-month outcomes in porcine coronary arteries. Interestingly, BRS dismantling was detected from 3 months and resulted in late lumen enlargement by increased scaffold diameter at 6 months. © 2014 American Heart Association, Inc.
Hutchens S.A.,Baxter Healthcare Corporation |
Campion C.,Baxter Healthcare Corporation |
Assad M.,AccelLAB Inc. |
Chagnon M.,AccelLAB Inc. |
Hing K.A.,Queen Mary, University of London
Journal of Materials Science: Materials in Medicine | Year: 2016
A synthetic bone graft substitute consisting of silicate-substituted calcium phosphate with increased strut porosity (SiCaP EP) was evaluated in an ovine distal femoral critical sized metaphyseal defect as a standalone bone graft, as an autologous iliac crest bone graft (ICBG) extender (SiCaP EP/ICBG), and when mixed with bone marrow aspirate (SiCaP EP/BMA). Defects were evaluated after 4, 8, and 12 weeks with radiography, decalcified paraffin-embedded histopathology, non-decalcified resin-embedded histomorphometry, and mechanical indentation testing. All test groups exhibited excellent biocompatibility and osseous healing as evidenced by an initial mild inflammatory response followed by neovascularization, bone growth, and marrow infiltration throughout all SiCaP EP-treated defects. SiCaP EP/ICBG produced more bone at early time points, while all groups produced similar amounts of bone at later time points. SiCaP EP/ICBG likewise showed more favorable mechanical properties at early time points, but was equivalent to SiCaP EP and SiCaP EP/BMA at later time points. This study demonstrates that SiCaP EP is efficacious as a standalone bone graft substitute, mixed with BMA, and as an autograft extender. © 2015, Springer Science+Business Media New York.
PubMed | AccelLAB Inc., Baxter Healthcare Corporation and Queen Mary, University of London
Type: Journal Article | Journal: Journal of materials science. Materials in medicine | Year: 2015
A synthetic bone graft substitute consisting of silicate-substituted calcium phosphate with increased strut porosity (SiCaP EP) was evaluated in an ovine distal femoral critical sized metaphyseal defect as a standalone bone graft, as an autologous iliac crest bone graft (ICBG) extender (SiCaP EP/ICBG), and when mixed with bone marrow aspirate (SiCaP EP/BMA). Defects were evaluated after 4, 8, and 12 weeks with radiography, decalcified paraffin-embedded histopathology, non-decalcified resin-embedded histomorphometry, and mechanical indentation testing. All test groups exhibited excellent biocompatibility and osseous healing as evidenced by an initial mild inflammatory response followed by neovascularization, bone growth, and marrow infiltration throughout all SiCaP EP-treated defects. SiCaP EP/ICBG produced more bone at early time points, while all groups produced similar amounts of bone at later time points. SiCaP EP/ICBG likewise showed more favorable mechanical properties at early time points, but was equivalent to SiCaP EP and SiCaP EP/BMA at later time points. This study demonstrates that SiCaP EP is efficacious as a standalone bone graft substitute, mixed with BMA, and as an autograft extender.
PubMed | AccelLAB Inc and Exogenesis
Type: | Journal: Journal of biomedical materials research. Part B, Applied biomaterials | Year: 2015
Polyetheretherketone (PEEK) is growing in popularity for orthopedic, spinal, and trauma applications but has potential significant limitations in use. PEEK is biocompatible, similar in elasticity to bone, and radiolucent, but is inert and therefore does not integrate well with bone. Current efforts are focusing on increasing the bioactivity of PEEK with surface modifications to improve the bone-implant interface. We used a novel Accelerated Neutral Atom Beam (ANAB) technology to enhance the bioactivity of PEEK. Human osteoblast-like cells seeded on ANAB-treated PEEK result in significantly enhanced proliferation compared with control PEEK. Cells grown on ANAB-treated PEEK increase osteogenic expression of ALPL (1.98-fold, p < 0.002), RUNX2 (3.20-fold, p < 0.002), COL1A (1.94-fold, p < 0.015), IBSP (2.78-fold, p < 0.003), and BMP2 (1.89-fold, p < 0.004). Cells grown on these treated surfaces also lead to an increased mineralization (6.4-fold at 21 days, p < 0.0005). In an ovine study, ANAB-treated PEEK implants resulted in enhanced bone-in-contact by 3.09-fold (p < 0.014), increased push-out strength (control 19591445 kPa; ANAB 40681197 kPa, p < 0.05), and evidence of bone ingrowth at both the early (4 weeks) and later (12 weeks) time points. Taken together, these data suggest that ANAB treatment of PEEK has the potential to enhance its bioactivity, leading to bone formation and significantly decreasing osseointegration time of orthopedic and spinal implants. ANAB treatment, therefore, may significantly enhance the performance of PEEK medical implants and lead to improved clinical outcomes. 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015.
Joner M.,TU Munich |
Radke P.W.,Universitatsklinik Schleswig Holstein |
Byrne R.A.,TU Munich |
Hartwig S.,BIOTRONIK SE and Co. KG |
And 3 more authors.
Journal of Biomaterials Applications | Year: 2013
Despite advances in contemporary stent technology, in-stent restenosis (ISR) remains the major limitation following revascularization procedures. We developed a porcine model of ISR to specifically investigate the preclinical outcomes of a novel drug-eluting balloon (DEB) in this particular setting. Fifteen pigs received bare metal stents in each of the major coronary arteries for 28 days to induce neointimal growth. Following repeat angiography, animals were allocated to fourdifferent treatment groups. The control group consisted of a bare angioplasty catheter, while the Pantera Lux™ (3.0 μg/mm2 paclitaxel) (30 s inflation) was compared to two consecutive deployments of the Pantera Lux™ (60 s inflation each) and the commercial SeQuent® Please balloon (60 s inflation). Twenty-eight days following balloon deployment, the animals underwent repeat angiography and were subsequently sacrificed for histopathologic assessment. There was a trend in reduction of percent diameter stenosis in the DEB group versus control (13.9% vs. 20.4%), while longer inflation duration or consecutive DEB deployment had no additional growth-limiting effect. Neointimal thickness was reduced from 0.38 ± 0.13 to 0.30 ± 0.09 mm in the control versus DEB group. All DEB groups showed delayed vascular healing characterized by dose-dependent increases in fibrin deposition and neointimal cell vacuity. Investigation of DEB in a porcine model of ISR is feasible and more accurately represents human disease conditions. The magnitude of neointima suppression is lower than that observed in non-diseased animal models and is accompanied by delayed vascular healing. © The Author(s) 2012.
Lapointe J.-M.,Accellab Inc |
Summers B.A.,Royal Veterinary College
Veterinary Pathology | Year: 2012
A 9-month-old female Yucatan pig was euthanized after acute onset of paraplegia. Gross and microscopic examination revealed dorsal dissection of the nucleus of the L2-L3 intervertebral disk through the annulus fibrosus, extrusion of nucleus pulposus material through the overlying dura mater and into the spinal cord, and associated acute spinal hemorrhage and necrosis. This is, to the authors' knowledge, the first reported case of intervertebral disk disease in swine. © The Author(s) 2012.
Wittchow E.,Biotronik SE and Co. KG |
Adden N.,Biotronik SE and Co. KG |
Riedmuller J.,Biotronik SE and Co. KG |
Savard C.,AccelLAB Inc. |
And 2 more authors.
EuroIntervention | Year: 2013
Aims: Among three versions of bioresorbable magnesium scaffolds featuring different paclitaxel-elution kinetics, we determined the best-performing scaffold and compared it with established, paclitaxel-eluting, permanent stents TAXUS Liberté and eucaTAX. Methods and results: Drug-elution kinetics in magnesium scaffolds were modulated by varying the composition of their bioresorbable poly(lactide-co-glycolide) coating loaded with paclitaxel. A 50:50 ratio of lactide to glycolide, or an 85:15 ratio and either high- or low-molecular-weight polymer was applied in the "50/50", "85/15H", and "85/15L" scaffolds, respectively. Seventy-three magnesium scaffolds (25 50/50, 24 85/15H, 24 85/15L) and 36 control stents (18 TAXUS Liberté, 18 eucaTAX) were implanted in coronary arteries of 50 Yucatan mini-pigs. Angiography, histomorphometry, and histopathology data were acquired at 28, 90 and 180 days. The best-performing magnesium scaffold, 85/15H, was equivalent to TAXUS Liberté and superior to eucaTAX regarding late luminal loss, intimal area, fibrin score, and endothelialisation. Intimal inflammation score was higher in 85/15H than in the control stents at 28 days, but this effect disappeared at later time points. Conclusions: By selecting suitable paclitaxel-elution kinetics, it was feasible to develop a bioresorbable magnesium scaffold whose efficacy and healing characteristics in a porcine coronary model are comparable with those of established paclitaxel-eluting permanent metallic stents.
Sheehy A.,Abbott Laboratories |
Hsu S.,Abbott Laboratories |
Bouchard A.,AccelLab Inc |
Lema P.,AccelLab Inc |
And 4 more authors.
Cardiovascular Diabetology | Year: 2012
Background: Diabetes remains a significant risk factor for restenosis/thrombosis following stenting. Although vascular healing responses following drug-eluting stent (DES) treatment have been characterized previously in healthy animals, comparative assessments of different DES in a large animal model with isolated features of diabetes remains limited. We aimed to comparatively assess the vascular response to paclitaxel-eluting (PES) and everolimus-eluting (EES) stents in a porcine coronary model of streptozotocin (STZ)-induced type I diabetes.Method: Twelve Yucatan swine were induced hyperglycemic with a single STZ dose intravenously to ablate pancreatic β-cells. After two months, each animal received one XIENCE V® (EES) and one Taxus Liberte (PES) stent, respectively, in each coronary artery. After three months, vascular healing was assessed by angiography and histomorphometry. Comparative in vitro effects of everolimus and paclitaxel (10-5 M-10-12 M) after 24 hours on carotid endothelial (EC) and smooth muscle (SMC) cell viability under hyperglycemic (42 mM) conditions were assayed by ELISA. Caspase-3 fluorescent assay was used to quantify caspase-3 activity of EC treated with everolimus or paclitaxel (10-5 M, 10-7 M) for 24 hours.Results: After 3 months, EES reduced neointimal area (1.60 ± 0.41 mm, p < 0.001) with trends toward reduced % diameter stenosis (11.2 ± 9.8%, p = 0.12) and angiographic late-loss (0.28 ± 0.30 mm, p = 0.058) compared to PES (neointimal area: 2.74 ± 0.58 mm, % diameter stenosis: 19.3 ± 14.7%, late loss: 0.55 ± 0.53 mm). Histopathology revealed increased inflammation scores (0.54 ± 0.21 vs. 0.08 ± 0.05), greater medial necrosis grade (0.52 ± 0.26 vs. 0.0 ± 0.0), and persistently elevated fibrin scores (1.60 ± 0.60 vs. 0.63 ± 0.41) with PES compared to EES (p < 0.05). In vitro, paclitaxel significantly increased (p < 0.05) EC/SMC apoptosis/necrosis at high concentrations (≥10-7 M), while everolimus did not affect EC/SMC apoptosis/necrosis within the dose range tested. In ECs, paclitaxel (10-5 M) significantly increased caspase-3 activity (p < 0.05) while everolimus had no effect.Conclusion: After 3 months, both DES exhibited signs of delayed healing in a STZ-induced diabetic swine model. PES exhibited greater neointimal area, increased inflammation, greater medial necrosis, and persistent fibrin compared to EES. Differential effects of everolimus and paclitaxel on vascular cell viability may potentially be a factor in regulating delayed healing observed with PES. Further investigation of molecular mechanisms may aid future development of stent-based therapies in treating coronary artery disease in diabetic patients. © 2012 Sheehy et al.