Clinical and Radiographic Evaluation of Autologous Platelet-Rich Fibrin With or Without Demineralized Bone Matrix in the Treatment of Grade II Furcation Defects.

Introduction This study aims to differentiate the employment of demineralized bone matrix (DMBM; Osseograft, Advanced Biotech Products (P) Ltd, Chennai, India) and platelet-rich fibrin (PRF) alone to a composite graft consisting of both materials in the surgical actions toward the anomalies of the human periodontal furcation imperfection. Methods In a split-mouth study, 30 patients with mandibular molars affected by the furcation were allocated without conscious choice to test (PRF + DMBM, n = 30) or control (PRF, n = 30) categories. At the starting point, three months after surgery, and six months later, the following modifiable factors were evaluated: probing pocket depth (PPD), full-mouth plaque scores, full-mouth gingival scores, radiographic defect depth, relative vertical clinical attachment level (RVCAL), and relative horizontal clinical attachment level (RHCAL). Results Results at three and six months demonstrated substantial differences between baseline values for both treatment methods in clinical and X-ray imaging appraisal. Nonetheless, the PRF/DMBM group manifests statistically significantly soaring changes observed in comparison to the PRF group. Overall, the probing depth (PD) in the test site was significantly lower than that in the control site, showing a reduction of 68% (95% CI=41%, 95%, p<0.001). Conclusion Clinical indications significantly improved with PRF and DMBM combined instead of PRF alone. On radiographs, the test group also showed higher bone fill.

Flap versus Flapless Immediate Implants with Bone Augmentation: A Novel Study.

Background: This study aimed to equate implants placed using a traditional flap elevation technique with implants placed using a flapless process regarding bone healing and success in clinical conditions. Materials and Methods: Sixty subjects were included in this research work. The participants were randomly divided into two groups. Patients in group A underwent implant placement with the flap elevation technique. Similarly, group B patients underwent implant placement without flap reflection. Parameters such as plaque index, wound healing index, crestal bone loss, and radiograph were considered to estimate the effectiveness of the two techniques. Results: Plaque indexes were improved in both groups. The modified gingival index also improved in all the phases of healing. The flapless method showed a better crestal bone. Conclusion: It can be concluded that this study showed that with the right augmentation techniques, implants could be successfully performed immediate extraction sockets, both with and without elevation of the mucoperiosteal flap.

Anesthetic Effect of 2% Amitriptyline Versus 2% Lidocaine: A Comparative Evaluation.

Introduction A common dental problem is the fear of pain during needle prick for giving local anesthesia (LA). The needle prick pain during dental procedures often varies with sex and age. Perception of pain depends on various factors, which can be psychological and biological. This perception of pain may change the behavior of patients toward dental treatments. Traditionally, lidocaine gel formulation was utilized before the parenteral dosage form. The lidocaine gel formulation is considered the drug of choice for LA in dental surgery. Currently, amitriptyline has been utilized in dental practice because of its beneficial pharmacology. Hence, the present study has been undertaken to compare the anesthetic ability of amitriptyline as an intraoral topical anesthetic agent with lidocaine gel. Methods This study was a comparative clinical study between two medications' anesthetic properties. This study included 120 patients indicated for bilateral orthodontics (the subdivision of dentistry that emphasizes identifying necessary interventions for the malocclusion of teeth) procedures. All the subjects were divided into amitriptyline and lidocaine groups. Both anesthetic gels were applied at separate sites before the injection of LA. The time of the onset of anesthesia was noted and analyzed. Patients were selected on the basis of inclusion and exclusion criteria. Individuals aged 18 to 30 years who were systemically healthy and orthodontically indicated for bilateral premolar extraction were included in this study. Again, patients with a history of neurological disorders and allergies to amitriptyline and lidocaine were excluded from the current study. Results Significant differences emerged between groups at five and 10 minutes, with amitriptyline-induced partial numbness (36.7% and 6.7%). At 40 and 45 minutes, both groups showed varied partial and complete numbness, with amitriptyline leading to partial recovery (23.3% and 73.3% complete numbness, 23.3% partial recovery) and lidocaine resulting in partial recovery (81.7%). When comparing the visual analog scale (VAS) scores, both groups exhibited a similar simultaneous effect at 15 minutes. Nonetheless, amitriptyline displayed significantly lower scores at 25 and 35 minutes (p < 0.001) in comparison to lidocaine. Similar observations were made when controlling for pain intensity. Conclusion It was concluded that amitriptyline holds both anesthetic and analgesic properties. Nevertheless, this study was unable to generalize the study findings because of the small sample size and being a single-center study. However, the VAS scores of anesthetic and analgesic pharmacodynamics properties of amitriptyline were statistically significantly lower than lidocaine, particularly at 25 and 35 minutes. Additionally, amitriptyline-induced anesthetic and analgesic pharmacology, especially pharmacokinetics properties, depends on the location and pattern of pain.

Experimental evaluation of the performance of large bore aspiration catheters.

BACKGROUND AND PURPOSE: Mechanical thrombectomy using an aspiration catheter (AC) is widely performed in patients with acute ischemic stroke due to large vessel occlusion. AC diameter directly impacts aspiration performance, which has led device companies to develop large bore ACs. The purpose of this study was to evaluate the in vitro performance of several commercially available large bore ACs. MATERIALS AND METHODS: We conceived an experimental set up to assess tracking force, aspiration flow rate, and distal end tensile force pre- and post-thrombectomy of ACs including Sofia 6 (Microvention Inc., California, USA), React 71 (Medtronic Neurovascular, Irvine, California, USA), Jet 7 (Penumbra Inc, Alameda, California, USA), Catalyst 7 (Stryker Neurovascular, Kalamazoo, Michigan, USA) and Embovac 071 (Johnson & Johnson Medical Ltd, UK). RESULTS: React 71 and Sofia 6 had significantly lower trackability force compared to the other ACs tested. Distal AC segment tensile force was highest for React 71 and lowest for Jet 7. Jet 7 had the highest internal diameter and the highest aspiration flow rate. CONCLUSION: The data from this comparative analysis may assist clinicians in selecting the appropriate AC and highlights the need for key performance criteria during the development of next-generation large-bore ACs for optimal AC performance.

Artificial intelligence in oral health surveillance among under-served communities.

A sizable percentage of the population in India still does not have easy access to dental facilities. Therefore, it is of interest to document the role of artificial intelligence (AI) in oral surveillance of underserved communities. Available data shows that AI makes it possible to screen, diagnose, track, prioritize, and monitor dental patients remotely via smart devices. As a result, dentists won't have to deal with simple situations that only require standard treatments; freeing them up to focus on more complicated cases. Additionally, this would allow dentists to reach a broader, more underprivileged population in difficult-to-reach places. AI fracture recognition and categorization performance has shown promise in preliminary testing. Methods for detecting aberrations are frequently employed in public health practise and research continues to be focused on them.

Biphasic Calcium Phosphate Versus Demineralized Freeze-Dried Bone Allograft in the Treatment of Periodontal Disease: A Clinical and Radiographical Evaluation.

 Aim The study aimed to clinically and radiographically evaluate the effect of biphasic calcium phosphate (BCP) versus demineralized freeze-dried bone allograft (DFDBA) in treating periodontal disease. Method The study consisted of 44 patients. The sites were randomly assigned to receive one of two treatment modalities (BCP at site 1 and demineralized freeze-dried bone at site 2) by a computerized method. All the clinical data were measured with the help of a University of North Carolina-15 (UNC-15) probe at the baseline, three months, and six months postoperatively. Radiovisiographs were taken using a Rinn XCP® (Dentsply/Rinn Corp, Elgin, IL) system and an oral grid using the paralleling technique. A manual calculation of the defect area was undertaken at the end of six months and was compared with the other groups. Result The linear bone growth recorded for site 1 at the end of six months was 3.8 ± 1.14 mm, and site 2 was 4.6 ± 1.07 mm. The intergroup comparison showed more remarkable linear bone growth in site 2, which was statistically insignificant, with a mean difference of 0.8 ± 1.23 mm and a p-value of 0.07. Conclusion Improvements were observed on all the documented parameters. However, the sites treated with DFDBA showed better periodontal regeneration.

Identifying Gingival Pigmentation Patterns and Skin Color and Its Co-relation With Serum Ferritin Levels in Thalassemic Patients.

BACKGROUND: Patients with ß-thalassemia major (ß-TM), a genetic issue due to hemoglobin (Hb) synthesis disorder, require life-long erythrocyte transfusion. The purpose of this study is to evaluate and compare gingival pigmentation and skin color with serum ferritin levels of patients with ß-TM, using the Dummett's oral pigmentation index (DOPI) and Fitzpatrick skin scale, respectively. METHODS: A total of 100 patients were monitored at a thalassemia care center. Each patient's gingival pigmentation and skin color were matched with DOPI and the skin scale under natural light. Serum ferritin levels, the interval of blood transfusions, and iron chelation medications were studied. A gingival pigmentation score and skin color type were compared with the serum ferritin. RESULTS: A significant correlation was found between age, serum ferritin, pigmentation score, and skin color, which means as serum ferritin level increases, gingival pigmentation score increases, and skin color darkens. CONCLUSION: This study evaluated the correlation between gingival pigmentation and skin color with serum ferritin levels and established gingival pigmentation as a sign of iron deposition in ß-TM patients. This is the simplest and least invasive method for evaluating serum ferritin level parameters in ß-TM patients.

In vitro methodology for medical device material thrombogenicity assessments: A use condition and bioanalytical proof-of-concept approach.

Device manufacturers and regulatory agencies currently utilize expensive and often inconclusive in vivo vascular implant models to assess implant material thrombogenicity. We report an in vitro thrombogenicity assessment methodology where test materials (polyethylene, Elasthane™ 80A polyurethane, Pebax®), alongside positive (borosilicate glass) and negative (no material) controls, were exposed to fresh human blood, with attention to common blood-contact use conditions and the variables: material (M), material surface modification (SM) with heparin, model (Mo), time (T), blood donor (D), exposure ratio (ER; cm2 material/ml blood), heparin anticoagulation (H), and blood draw/fill technique (DT). Two models were used: (1) a gentle-agitation test tube model and (2) a pulsatile flow closed-loop model. Thrombogenicity measurements included thrombin generation (thrombin-antithrombin complex [TAT] and human prothrombin fragment F1.2), platelet activation (ß-thromboglobulin), and platelet counts. We report that: (a) thrombogenicity was strongly dependent (p < .0001) on M, H, and T, and variably dependent (p < .0001 - > .05) on Mo, SM, and D (b) differences between positive control, test, and negative control materials became less pronounced as H increased from 0.6 to 2.0 U/ml, and (c) in vitro-to-in vivo case comparisons showed consistency in thrombogenicity rankings on materials classified to be of low, moderate, and high concern. In vitro methods using fresh human blood are therefore scientifically sound and cost effective compared to in vivo methods for screening intravascular materials and devices for thrombogenicity.

Longer 6-mm Diameter Stent Retrievers Are Effective for Achieving Higher First Pass Success with Fibrin-Rich Clots.

First pass success (FPS) can be defined as in vitro retrieval of clot in a single pass during mechanical thrombectomy (MT) for acute large vessel occlusion (LVO). Despite advancements in MT technology, retrieval of fibrin-rich clots remains a challenge. Therefore, the effect of stent retriever length on FPS for fibrin-rich clots was investigated by using SolitaireTM 6 × 40 versus 6 × 30 mm devices with a balloon guide catheter (BGC) or distal access catheter (DAC) and sheath, in an in vitro model of anterior circulation neurovascular anatomy. Additionally, vascular safety of the SolitaireTM 6 × 40 versus 6 × 30 mm devices was evaluated in a porcine model for differences in: luminal thrombus, inflammation, endothelial coverage, fibrin deposits, smooth muscle cell loss, elastic lamina and adventitia disruption, intimal hyperplasia, and lumen reduction, at 0, 30, and 90 days post-treatment. In vitro overall FPS was measured as: SolitaireTM 6 × 40 (95%) and SolitaireTM 6 × 30 (67%). FPS for clot location in middle cerebral artery was: (a) BGC (6 × 40 mm: 100%; 6 × 30 mm: 100%; n = 8); (b) DAC with 088 sheath (6 × 40 mm: 83%; 6 × 30 mm: 33%; n = 12). FPS for clot location in internal carotid artery was: (a) BGC (6 × 40 mm: 100%; 6 × 30 mm: 80%; n = 11); (b) DAC with 088 sheath (6 × 40 mm: 100%; 6 × 30 mm: 67%; n = 10). Stent length had a significant effect (Fisher's exact test; p < 0.05) on FPS. In vivo evaluation in the porcine model showed no difference in vascular safety parameters between the SolitaireTM 6 × 40 and 6 × 30 mm devices (p > 0.05) at all time points in the study. Longer stent retrievers may be safe and effective in improving FPS for fibrin-rich clots in in vitro and in vivo models of LVO.

Preclinical safety and efficacy evaluation of the Pipeline Vantage Embolization Device with Shield Technology.

BACKGROUND: The Pipeline Vantage Embolization Device with Shield Technology is a next generation flow diverter developed to improve aneurysm occlusion and implant endothelialization in addition to lowering thrombogenicity. We report here the in vivo biocompatibility and in vitro hemocompatibility performance of the Pipeline Vantage Embolization Device with Shield Technology (Vantage) compared with the Pipeline Flex Embolization Device (Flex). METHODS: Biocompatibility (via histology), aneurysm occlusion and vessel patency (via angiography), and endothelial coverage (via scanning electron microscopy (SEM)) for the Vantage and Flex devices were assessed in the rabbit elastase aneurysm model at 90 days (n=29) and 180 days (n=27). In vitro thrombogenicity for Flex and Vantage (n=16) was assessed using a human blood flow loop model at low heparin concentration (0.6 U/mL) with thrombin generation, platelet activation and thrombus visualization as outputs. RESULTS: Raymond Roy Occlusion Classification grade 1 was higher for Vantage (61%) compared with Flex (46%), but was not statistically significant (p>0.05). All branch vessels were patent. Histological measures for both devices were similar (p>0.05). Endothelial coverage of the implant was significantly better for Vantage compared with Flex (p<0.05). In vitro measurements of thrombin generation (thrombin-antithrombin complex (µg/mL): Vantage 0.49±0.45; Flex 10.57±9.84) and platelet activation (ß-thromboglobulin (IU/µl): Vantage 0.41±0.19; Flex 4.14±2.38) were both statistically lower (p<0.05) for Vantage compared with Flex. High resolution microscopy showed less accumulation of thrombus on Vantage as compared with Flex. CONCLUSION: Vantage improved aneurysm occlusion and implant endothelialization and had significantly lower thrombogenicity as compared with Flex, while preserving the biocompatibility safety profile of Flex.

In-vitro pliability assessment of embolization coils for intracranial aneurysm treatment.

BACKGROUND: Embolization coils have routinely been used to treat intracranial aneurysms via an endovascular approach. Soft coils are typically viewed as the best design for filling and finishing the aneurysms to achieve a higher packing density and are hypothesized to exert a lower force against the aneurysm wall during deployment. We report here an in vitro pliability test method to assess clinically relevant coil softness and compare these metrics for two commercially available framing and finishing coil products. METHODS: A force measurement sensor was affixed onto a side-wall synthetic aneurysm model to continuously measure forces on the aneurysm wall during coil deployment at a fixed delivery rate. A quantitative overall energy metric (average work number or AWN) was calculated from the force-displacement graph representing coil delivery into the aneurysm. Two groups of coils were evaluated: (a) finish coil group (N = 20 ea.): Axium™ Prime Extra Soft coil (ES) and Target™ 360 Nano coil (Nano), and (b) frame coil group (N = 20 ea.): Axium™ Prime FC coil (FC) and Target™ 360 Standard coil (Standard). RESULTS: (a) In the finish coil group, AWN was measured as: ES (0.53 ±â€¯0.09 gf-cm) and Nano (0.99 ±â€¯0.21 gf-cm). (b) In the frame coil group, AWN was measured as FC (2.54 ±â€¯0.53 gf-cm) and Standard (4.48 ±â€¯0.52 gf-cm). In both groups, Axium Prime coils had statistically lower measures of AWN and therefore higher pliability compared to Target coils (p < .001). CONCLUSIONS: The in-vitro pliability test method offers quantitative metrics to assess coil softness during deployment in a clinically relevant aneurysm model.

Safety and Efficacy Evaluation of Aspiration Thrombectomy With Large Bore Catheters in a Porcine Model.

OBJECTIVE: Thrombectomy with aspiration catheters has shown to be effective for treatment of intracranial large vessel occlusion (LVO). We present preclinical evaluation of the safety and efficacy of React68 and React71 (Medtronic PLC, Irvine, CA) catheters in animal models of LVO. METHODS: In vivo evaluation of catheter safety was performed in superficial cervical, internal maxillary, and renal arteries in a porcine model with or without clot (LVO). Animals were survived for 3 days and 30 days. Angiographic outcomes, usability, and histological parameters were compared for treatment with React68, React71, and ACE68 (Penumbra, Alameda, CA) catheters. RESULTS: The in vivo angiographic analysis in a porcine thrombectomy LVO model demonstrated that there was no statistically significant difference in the rate of Thrombolysis in Cerebral Infarction scale 2b/3 recanalization between React68, React71, and ACE68 catheters. There were no physical or neurologic deficits in any of the treated animals throughout the survival period. Histologic analysis showed statistically non-inferior safety profile of React68 and React71 catheters relative to ACE68 catheters, with minimal but similar mild internal elastic lamina disruption and smooth muscle loss, but a lack of inflammation, fibrin deposits, and changes in the adventitia at both time points examined. CONCLUSIONS: React68 and React71 aspiration catheters have an excellent safety, efficacy, and usability profile in animal models of LVO.

Hemodynamic differences between Pipeline and coil-adjunctive intracranial stents.

INTRODUCTION: Modern coil-adjunctive intracranial stent designs have increased metal surface coverage to construct putative 'flow diverter lights.' This is rooted in the assumption that flow diversion is linearly correlated with metal surface coverage rather than being a threshold to be reached by device porosity and design. OBJECTIVE: To evaluate this assumption, by performing computational flow analysis on three aneurysm models treated with low metal surface coverage stents (ATLAS and Enterprise), a Pipeline flow diverter, and the LVIS Blue stent. METHODS: Computational flow analysis was performed on virtual deployment models entailing deployment of an ATLAS, Enterprise, LVIS Blue, or Pipeline. The impact of device deployment on velocity vectors at the neck, maximum wall shear stress, inflow rate into the aneurysm, and turnover time was determined. RESULTS: Velocity vector plots demonstrated low magnitude, localized inflow jets for Pipeline only; asymmetric, selectively high inflow jets were seen for LVIS Blue, and broader velocity vector clusters were seen for Atlas and Enterprise. Reduction in wall shear stress as compared with baseline was significant for all devices and greatest for the Pipeline. Mean peak wall shear stress was significantly lower for LVIS Blue in comparison with ATLAS or Enterprise but significantly lower for Pipeline than for LVIS Blue. Reduction of inflow rate into the aneurysm was significant for LVIS Blue and Pipeline but significantly lower for Pipeline than for LVIS Blue. Turnover time was statistically similar for ATLAS, Enterprise, and LVIS Blue, but significantly increased for Pipeline. CONCLUSION: Considerable differences in peak wall shear stress, inflow rates, and turnover time between flow diverters, moderate- and low-porosity stents reinforce the assumption that effective flow diversion represents a threshold in device design, encompassing metal surface coverage only in part.

Thrombogenicity assessment of Pipeline, Pipeline Shield, Derivo and P64 flow diverters in an in vitro pulsatile flow human blood loop model.

Flow diversion is a disruptive technology for the treatment of intracranial aneurysms. However, these intraluminal devices pose a risk for thromboembolic complications despite dual antiplatelet therapy. We report the thrombogenic potential of the following flow diversion devices measured experimentally in a novel human blood in-vitro pulsatile flow loop model: Pipeline™ Flex Embolization Device (Pipeline), Pipeline™ Flex Embolization Device with Shield Technology™ (Pipeline Shield), Derivo Embolization Device (Derivo), and P64 Flow Modulation Device (P64). Thrombin generation (Mean ±â€¯SD; µg/mL) was measured as: Derivo (28 ±â€¯11), P64 (21 ±â€¯4.5), Pipeline (21 ±â€¯6.2), Pipeline Shield (0.6 ±â€¯0.1) and Negative Control (1.5 ±â€¯1.1). Platelet activation (IU/µL) was measured as: Derivo (4.9 ±â€¯0.7), P64 (5.2 ±â€¯0.7), Pipeline (5.5 ±â€¯0.4), Pipeline Shield (0.3 ±â€¯0.1), and Negative Control (0.9 ±â€¯0.7). We found that Pipeline Shield had significantly lower platelet activation and thrombin generation than the other devices tested (p < .05) and this was comparable to the Negative Control (no device, p > .05). High resolution scanning electron microscopy performed on the intraluminal and cross-sectional surfaces of each device showed the lowest accumulation of platelets and fibrin on Pipeline Shield relative to Derivo, P64, and Pipeline. Derivo and P64 also had higher thrombus accumulation at the flared ends. Pipeline device with Phosphorylcholine surface treatment (Pipeline Shield) could mitigate device material related thromboembolic complications.

Thrombogenicity assessment of Pipeline Flex, Pipeline Shield, and FRED flow diverters in an in vitro human blood physiological flow loop model.

Endovascular treatment of intracranial aneurysms with endoluminal flow diverters (single or multiple) has proven to be clinically safe and effective, but is associated with a risk of thromboembolic complications. Recently, a novel biomimetic surface modification with covalently bound phosphorylcholine (Shield Technology™) has shown to reduce the material thrombogenicity of the Pipeline flow diverter. Thrombogenicity of Pipeline Flex, Pipeline Shield, and Flow Redirection Endoluminal Device (FRED) in the presence of human blood under physiological flow conditions-in addition to relative increase in thrombogenicity with multiple devices-remains unknown and was investigated here. Thrombin generation (mean ± SD; µg/mL; thrombin-antithrombin complex or TAT) was measured as FRED (30.3 ± 2.9), Pipeline (13.9 ± 4.4), Pipeline Shield (0.4 ± 0.3), and negative control (no device; 0.1 ± 0.0). Platelet activation (mean ± SD; IU/µL; beta-thromboglobulin or ßTG) was measured as FRED (148 ± 45), Pipeline (92.8 ± 41), Pipeline Shield (16.2 ± 3.5), and negative control (2.70 ± 0.16). FRED was significantly more thrombogenic than Pipeline and Pipeline Shield (p < 0.05) for TAT. Additionally, Pipeline Shield had significantly lower TAT and ßTG than the other devices tested (p < 0.05) and these were comparable to the negative control (p > 0.05). TAT and ßTG scaled proportionately with multiple Pipeline devices (N = 6) but was unaffected by multiple Pipeline Shield (N = 6) devices-the latter being statistically similar to negative control (p > 0.05). © 2018 The Authors. Journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3195-3202, 2018.

Thrombogenicity of flow diverters in an ex vivo shunt model: effect of phosphorylcholine surface modification.

BACKGROUND: Flow diverters offer a promising treatment for cerebral aneurysms. However, they have associated thromboembolic risks, mandating chronic dual antiplatelet therapy (DAPT). Shield Technology is a phosphorylcholine surface modification of the Pipeline Embolization Device (PED) flow diverter, which has shown significant reductions in material thrombogenicity in vitro. OBJECTIVE: To compare the thrombogenicity of PED, PED with Shield Technology (PED+Shield), and the Flow-Redirection Endoluminal Device (FRED)-with and without single antiplatelet therapy and DAPT-under physiological flow. METHODS: An established non-human primate ex vivo arteriovenous shunt model of stent thrombosis was used. PED, PED+Shield, and FRED were tested without antiplatelet therapy, with acetylsalicylic acid (ASA) monotherapy, and with DAPT. Radiolabeled platelet deposition was quantified over 1 hour for each device and total fibrin deposition was also quantified. RESULTS: Cumulative statistical analysis showed significantly lower platelet deposition on PED compared with FRED. The same statistical model showed significant decreases in platelet deposition when ASA, clopidogrel, or Shield Technology was used. Direct comparisons of device performances within antiplatelet conditions showed consistent significant decreases in platelet accumulation on PED+Shield relative to FRED. PED+Shield showed significant reductions in platelet deposition compared with unmodified PED without antiplatelet therapy and with DAPT. PED accumulated minimal fibrin with and without Shield Technology. CONCLUSIONS: In this preclinical model, we have shown that the Shield Technology phosphorylcholine modification reduces the platelet-specific thrombogenicity of a flow diverter under physiologically relevant flow with and without DAPT. We have further identified increased fibrin-driven thrombogenicity associated with FRED relative to PED.

In-vitro thrombogenicity assessment of flow diversion and aneurysm bridging devices.

Endoluminal devices such as metallic flow diversion (FD) and aneurysm bridging (AB) stents are used for treatment of intracranial aneurysms. Treatments are associated with thrombogenic events mandating the use of dual antiplatelet therapy in all cases. In the current in vitro study, we utilize a slow binding fluorogenic thrombin specific substrate to measure the thrombin generation potential of six devices: four FD devices (Pipeline™ Flex embolization device, Pipeline™ Flex embolization device with Shield Technology™, SILK+, FRED™) and two AB devices (Solitaire™ AB, LEO+). We show that the Pipeline™ Flex embolization device with Shield Technology™ has significantly lower peak thrombin and takes significantly longer time to achieve peak thrombin (time to peak) compared to the other three FD devices (p < 0.05), with statistically similar results to the less thrombogenic AB devices. We conclude that surface modification of endoluminal stents could be an effective method to mitigate thrombogenic complications.

In-vitro thrombogenicity assessment of polymer filament modified and native platinum embolic coils.

BACKGROUND: Embolic coils have been used to treat intracranial aneurysms using an endovascular approach for more than two decades. However, significant aneurysm recanalization rates have been reported specifically in large and giant aneurysms. Adding filaments to bare Platinum coils is considered a modification and has been proposed to achieve higher aneurysm occlusion rates as compared to bare Platinum coils. Quantitative information - in terms of thrombin generation potential of these modifications - is however lacking. OBJECTIVE: We report here in vitro thrombogenicity of Platinum coils containing Nylon (Axium™ MicroFx™ Nylon coil) and PGLA (Axium™ MicroFx™ PGLA coil) filaments and compare them with equivalent bare Platinum Axium™ coils. METHOD: We utilize a quantitative method that tracks the formation of thrombin upon exposure of the test samples to human platelet rich plasma using a slow binding fluorogenic substrate. RESULTS: We report a significant increase in the total thrombin turnover, the peak thrombin amount and the rate of thrombin generation for the Axium™ MicroFx™ coils and filaments compared to the Axium™ coils and Platinum wire. CONCLUSION: Nylon and PGLA filaments added to bare Platinum coils increase thrombogenicity of coils. This study offers a robust quantitative method to compare thrombus formation efficacy of embolic coils under static conditions.

Comparative efficacy of in vitro and in vivo metabolized aspirin in the DeBakey ventricular assist device.

Ventricular assist devices (VADs) are implanted in patients with end-stage heart failure to provide both short- and long-term hemodynamic support. Unfortunately, bleeding and thromboembolic complications due to the severely disturbed, dynamic flow conditions generated within these devices require complex, long-term antiplatelet and anticoagulant therapy. While several studies have examined the effectiveness of one such agent, aspirin, under flow conditions, data comparing the efficacy of in vitro and in vivo metabolized aspirin is lacking. Two sets of studies were conducted in vitro with purified human platelets circulating for 30 min in a flow loop containing the DeBakey VAD (MicroMed Cardiovascular, Houston, TX, USA): (a) 20 µM aspirin was added exogenously in vitro to platelets isolated from aspirin-free subjects, and (b) platelets were obtained from donors 2 h (n = 14) and 20 h (n = 13) after ingestion of 1,000 mg aspirin. Near real-time platelet activation state (PAS) was measured with a modified prothrombinase-based assay. Platelets exposed to aspirin in vitro and in vivo (metabolized) showed 28.2 and 25.3 % reduction in platelet activation rate, respectively, compared to untreated controls. Our results demonstrate that in vitro treatment with antiplatelet drugs such as aspirin is as effective as in vivo metabolized aspirin in testing the effect of reducing shear-induced platelet activation in the VAD. Using the PAS assay provides a practical in vitro alternative to in vivo testing of antiplatelet efficacy, as well as for testing the thrombogenic performance of devices during their research and development.

Thromboresistance comparison of the HeartMate II ventricular assist device with the device thrombogenicity emulation- optimized HeartAssist 5 VAD.

Approximately 7.5 × 106 patients in the US currently suffer from end-stage heart failure. The FDA has recently approved the designations of the Thoratec HeartMate II ventricular assist device (VAD) for both bridge-to-transplant and destination therapy (DT) due to its mechanical durability and improved hemodynamics. However, incidence of pump thrombosis and thromboembolic events remains high, and the life-long complex pharmacological regimens are mandatory in its VAD recipients. We have previously successfully applied our device thrombogenicity emulation (DTE) methodology for optimizing device thromboresistance to the Micromed Debakey VAD, and demonstrated that optimizing device features implicated in exposing blood to elevated shear stresses and exposure times significantly reduces shear-induced platelet activation and significantly improves the device thromboresistance. In the present study, we compared the thrombogenicity of the FDA-approved HeartMate II VAD with the DTE-optimized Debakey VAD (now labeled HeartAssist 5). With quantitative probability density functions of the stress accumulation along large number of platelet trajectories within each device which were extracted from numerical flow simulations in each device, and through measurements of platelet activation rates in recirculation flow loops, we specifically show that: (a) Platelets flowing through the HeartAssist 5 are exposed to significantly lower stress accumulation that lead to platelet activation than the HeartMate II, especially at the impeller-shroud gap regions (b) Thrombus formation patterns observed in the HeartMate II are absent in the HeartAssist 5 (c) Platelet activation rates (PAR) measured in vitro with the VADs mounted in recirculation flow-loops show a 2.5-fold significantly higher PAR value for the HeartMate II. This head to head thrombogenic performance comparative study of the two VADs, one optimized with the DTE methodology and one FDA-approved, demonstrates the efficacy of the DTE methodology for drastically reducing the device thrombogenic potential, validating the need for a robust in silico/in vitro optimization methodology for improving cardiovascular devices thromboresistance.