Mechanical cues and substrate interaction affect the manner in which cells adhere, spread, migrate and form tissues. With increased interest in tissue-on-a-chip and co-culture systems utilizing porous membranes, it is important to understand the role of disrupted surfaces on cellular behavior. Using a transparent glass membrane with defined pore geometries, we investigated endothelial fibronectin fibrillogenesis and formation of focal adhesions as well as development of intercellular junctions. Cells formed fewer focal adhesions and had shorter fibronectin fibrils on porous membranes compared to non-porous controls, which was similar to cell behavior on continuous soft substrates with Young’s moduli seven orders of magnitude lower than glass. Additionally, porous membranes promoted enhanced cell-cell interactions as evidenced by earlier formation of tight junctions. These findings suggest that porous membranes with discontinuous surfaces promote reduced cell-matrix interactions similarly to soft substrates and may enhance tissue and barrier formation.

Typical in vitro barrier and co-culture models rely upon thick semi-permeable polymeric membranes that physically separate two compartments. Polymeric track-etched membranes, while permeable to small molecules, are far from physiological with respect to physical interactions with co-cultured cells and are not compatible with high-resolution imaging due to light scattering and autofluorescence. Here we report on an optically transparent ultrathin membrane with porosity exceeding 20%. We optimize deposition and annealing conditions to create a tensile and robust porous silicon dioxide membrane that is comparable in thickness to the vascular basement membrane (100–300 nm). We demonstrate that human umbilical vein endothelial cells (HUVECs) spread and proliferate on these membranes similarly to control substrates. Additionally, HUVECs are able to transfer cytoplasmic cargo to adipose-derived stem cells when they are co-cultured on opposite sides of the membrane, demonstrating its thickness supports physiologically relevant cellular interactions. Lastly, we confirm that these porous glass membranes are compatible with lift-off processes yielding membrane sheets with an active area of many square centimeters. We believe that these membranes will enable new in vitro barrier and co-culture models while offering dramatically improved visualization compared to conventional alternatives.

Porous substrates have gained increased usage in cell studies and tissue mimetic applications because they can partition distinct cell types while still allowing important biochemical crosstalk. In the presented work, we investigated how porous substrates with micron and submicron features influence early cell migration and the associated ECM establishment, which can critically affect the rate of cell coverage on the substrate and the ensuing tissue organization. We showed through time-lapse microscopy that cell speed and migratory distance on membranes with 0.5 μm pores were nearly two-fold of those observed on nonporous membranes, while values on membranes with 3.0 μm pores fell in between. Although the cell directionality ratio and the persistence time was unaffected by the presence of pores, the cells did exhibit directionality preferences based on the hexagonal pore patterning. Fibronectin fibrillogenesis exhibited a distinct inverse relationship to cell speed, as the fibrils formed on the nonporous control were significantly longer than those on both types of porous substrates. We further confirmed on a per cell basis that there is a negative correlation between fibronectin fibril length and cell speed. The observed trade-off between early cell coverage and ECM establishment thus warrants consideration in the selection or the engineering of the ideal porous substrate for tissue mimetic applications and may help guide future cell studies.

IntroductionFor patients undergoing mechanical thrombectomy, numerous (>3) thrombectomy passes may be harmful. However, non-recanalization leads to poor outcomes. For patients requiring multiple thrombectomy passes to achieve reperfusion, it remains unclear if the risk/benefit ratio favors recanalization.ObjectiveTo test the hypothesis that the benefits afforded by successful reperfusion outweigh the risk conveyed by the numerous passes required.MethodsWe retrospectively reviewed prospectively collected data for patients presenting to a comprehensive stroke center with anterior circulation large vessel occlusion (ACLVO) and undergoing thrombectomy requiring more than one pass over 24 months. We stratified patients into three groups: group 1 (successful reperfusion in 2–3 passes), group 2 (successful reperfusion in ≥4 passes), and group 3 (unsuccessful reperfusion).Results250 patients with ACLVO constituted the study cohort. Despite similar demographics, group 2 patients had better clinical outcomes than those in group 3 at 24 hours (National Institutes of Health Stroke Scale (NIHSS) score 13.5 vs 19.1, p<0.001) and at 90 days (modified Rankin Scale score 0–2 rates of 31.1% vs 0.0%, p=0.006) On multivariate logistic regression analysis, age (p=0.034), Alberta Stroke Program Early CT Score (p<0.01), NIHSS score (p=0.02), and parenchymal hematoma type 2 (p=0.015) were significant predictors of functional independence among those who achieved successful reperfusion, but the number of passes required did not predict outcome for these patients (p=0.74).ConclusionPatients who achieve successful reperfusion after many passes have better clinical outcomes than those who do not, despite the number of passes and procedural time required. The number of passes required to achieve successful reperfusion beyond the first pass is not a predictor of functional independence.

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IntroductionVarious large-bore catheters can be employed for manual aspiration thrombectomy (MAT); clinical differences are rarely explored.MethodsProspectively collected demographic, angiographic, and clinical data for patients with acute internal carotid artery, middle cerebral artery M1, or basilar occlusions undergoing MAT over 23 months at a comprehensive stroke center were reviewed. We excluded patients in stentriever-based randomized trials/registries. The four most commonly utilized aspiration catheters were analyzed, and multivariate logistic regression analyses were performed to determine the effect of primary aspiration catheter choice on first-pass success, final reperfusion, and modified Rankin Scale (mRS) score at 90 days.ResultsOf 464 large vessel thrombectomies, 180 were performed via MAT on the first pass with one of four catheters. First-pass success was achieved in 42% of cases overall; this rate did not differ significantly between catheters: 50% for Sofia, 45% for CAT6, 40% for 0.072 inch Navien, and 36% for ACE68, p=0.67. Final Thrombolysis in Cerebral Infarction 2b or 3 reperfusion was achieved in 94% of cases overall: 97% of cases with CAT6, 95% with Sofia, 92% with Navien, and 92% with ACE68, p=0.70. Mean number of passes for index thrombus (2.0 overall), median procedure time (32 min overall), 90-day good outcome (mRS 0–2, mean 36%), and 90-day mortality (mean 27%) did not differ significantly between patients treated with different initial catheters.ConclusionAmong large-bore aspiration catheters, catheter selection is not an independent predictor of first-pass success, final reperfusion, or clinical outcome.

OBJECTIVE Acute basilar artery occlusion (BAO) harbors a more guarded prognosis after thrombectomy compared with anterior circulation large-vessel occlusion. Whether this is a function of a greater proportion of atherosclerotic/intrinsic lesions is not well studied. The authors aimed to elucidate the prevalence and predictors of intracranial intrinsic atherosclerotic disease in patients with acute BAO and to compare angiographic and clinical outcomes between patients with BAO secondary to embolic versus intrinsic disease. METHODS A prospectively maintained stroke database was reviewed for all patients presenting between January 2013 and December 2019 to a tertiary care academic comprehensive stroke center with acute, nontandem BAO. Patient data were extracted, subdivided by stroke mechanism and treatment modality (embolic [thrombectomy only] and intrinsic [thrombectomy + stenting]), and angiographic and clinical results were compared. RESULTS Of 107 patients, 83 (78%) had embolic occlusions (thrombectomy only) and 24 (22%) had intrinsic disease (thrombectomy + stenting). There was no significant difference in patient age, presenting National Institutes of Health Stroke Scale score, time to presentation, selected medical comorbidities (hypertension, hyperlipidemia, diabetes, and atrial fibrillation), prior stroke, and posterior circulation Alberta Stroke Program Early CT Score. Patients with intrinsic disease were more likely to be active smokers (50% vs 26%, p = 0.04) and more likely to be male (88% vs 48%, p = 0.001). Successful recanalization, defined as a modified Thrombolysis in Cerebral Infarction (mTICI) grade of 2b or 3, was achieved in 90% of patients and did not differ significantly between the embolic versus intrinsic groups (89% vs 92%, p > 0.99). A 90-day good outcome (modified Rankin Scale [mRS] score 0–2) was found in 37% of patients overall and did not differ significantly between the two groups (36% vs 41%, p = 0.41). Mortality was 40% overall and did not significantly differ between groups (41% vs 36%, p = 0.45). CONCLUSIONS In the current study, demographic and clinical results for acute BAO showed that compared with intrinsic disease, thromboembolic disease is a more common mechanism of acute BAO, with 78% of patients undergoing thrombectomy alone. However, there was no significant difference in revascularization and outcome results between patients with embolic disease and those with intrinsic disease.

We received so many biographies of women neurosurgery leaders for this issue that only a selection could be condensed here. In all of them, the essence of a leader shines through. Many are included as “first” of their country or color or other achievement. All of them are included as outstanding—in clinical, academic, and organized neurosurgery. Two defining features are tenacity and service. When faced with shocking discrimination, or numbing indifference, they ignored it or fought valiantly. When choosing their life’s work, they chose service, often of the most neglected—those with pain, trauma, and disability. These women inspire and point the way to a time when the term “women leaders” as an exception is unnecessary.—Katharine J. Drummond, MD, on behalf of this month’s topic editors