Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

On-demand modulation of 3D-printed elastomers using programmable droplet inclusions

One of the key thrusts in three-dimensional (3D) printing and direct writing is to seamlessly vary composition and functional properties in printed constructs. Most inks used for extrusion-based printing, however, are compositionally static and available approaches for dynamic tuning of ink composition remain few. Here, we present an approach to modulate extruded inks at the point of print, using droplet inclusions. Using a glass capillary microfluidic device as the printhead, we dispersed droplets in a polydimethylsiloxane (PDMS) continuous phase and subsequently 3D printed the resulting emulsion into a variety of structures. The mechanical characteristics of the 3D-printed constructs can be tuned in situ by varying the spatial distribution of droplets, including aqueous and liquid metal droplets. In particular, we report the use of poly(ethylene glycol) diacrylate (PEGDA) aqueous droplets for local PDMS chemistry alteration resulting in significant softening (85% reduced elastic modulus) of the 3D-printed constructs. Furthermore, we imparted magnetic functionality in PDMS by dispersing ferrofluid droplets and rationally designed and printed a rudimentary magnetically responsive soft robotic actuator as a functional demonstration of our droplet-based strategy. Our approach represents a continuing trend of adapting microfluidic technology and principles for developing the next generation of additive manufacturing technology

Enhanced separation of aged RBCs by designing channel cross section.

Prolonged storage will alter the biophysical properties of red blood cells (RBCs), and it decreases the quality of stored blood for blood transfusion. It has been known that less deformable aged RBCs can be separated by margination, but the recognition of the storage time from the separation efficiency of the stiff RBCs is still a challenge. In this study, we realized enhanced separation of aged RBCs from normal RBCs by controlling the channel cross section and demonstrated that the storage time can be deduced from the percentage of the separated RBCs in the stored RBCs. This separation technology helps to reveal the regulation of time on the RBC aging mechanism and offer a new method to separate stiffened cells with high efficiency

Coated Gas Bubbles for the Continuous Synthesis of Hollow Inorganic Particles

We present a microfluidic approach for the controlled encapsulation of individual gas bubbles in micrometer-diameter aqueous droplets with high gas volume fractions and demonstrate this approach to making a liquid shell, which serves as a template for the synthesis of hollow inorganic particles. In particular, we find that an increase in the viscosity of the aqueous phase facilitates the encapsulation of individual gas bubbles in an aqueous droplet and allows control of the thickness of a thin aqueous shell. Furthermore, because such droplets contain a finite amount of water, uncontrolled hydrolysis reactions between reactive inorganic precursors and bulk water can be avoided. We demonstrate this approach by introducing reactive inorganic precursors, such as silane and titanium butoxide, for sol–gel reactions downstream from the formation of the bubble in a droplet and consequently fabricate hollow particles of silica or titania in one continuous flow process. These approaches provide a route to controlling double-emulsion-type gas–liquid microstructures and offer a new fabrication method for thin-shell-covered microbubbles and hollow microparticles

Surface-Bound Proteins with Preserved Functionality

Biocompatibility of materials strongly depends on their surface properties. Therefore, surface derivatization in a controllable manner provides means for achieving interfaces essential for a broad range of chemical, biological, and medical applications. Bioactive interfaces, while manifesting the activity for which they are designed, should suppress all nonspecific interaction between the supporting substrates and the surrounding media. This article describes a procedure for chemical derivatization of glass and silicon surfaces with polyethylene glycol (PEG) layers covalently functionalized with proteins. While the proteins introduce the functionality to the surfaces, the PEGs provide resistance against nonspecific interactions. For formation of aldehyde-functionalized surfaces, we coated the substrates with acetals (i.e., protected aldehydes). To avoid deterioration of the surfaces, we did not use strong mineral acids for the deprotection of the aldehydes. Instead, we used a relatively weak Lewis acid for conversion of the acetals into aldehydes. Introduction of α,ω-bifunctional polymers into the PEG layers, bound to the aldehydes, allowed us to covalently attach green fluorescent protein and bovine carbonic anhydrase to the surfaces. Spectroscopic studies indicated that the surface-bound proteins preserve their functionalities. The surface concentrations of the proteins, however, did not manifest linear proportionality to the molar fractions of the bifunctional PEGs used for the coatings. This finding suggests that surface-loading ratios cannot be directly predicted from the compositions of the solutions of competing reagents used for chemical derivatization

Bio-printing cell-laden Matrigel–agarose constructs

3D printing of biological architectures that mimic the structural and functional features of in vivo tissues is of great interest in tissue engineering and the development of transplantable organ constructs. Printable bio-inks that are compatible with cellular activities play critical roles in the process of 3D bio-printing. Although a variety of hydrogels have been used as bio-inks for 3D bio-printing, they inherit poor mechanical properties and/or the lack of essential protein components that compromise their performance. Here, a hybrid Matrigel-agarose hydrogel system has been demonstrated that possesses both desired rheological properties for bio-printing and biocompatibility for long-term (11 days) cell culture. The agarose component in the hybrid hydrogel system enables the maintenance of 3D-printed structures, whereas Matrigel provides essential microenvironments for cell growth. When human intestinal epithelial HCT116 cells are encapsulated in the printed Matrigel-agarose constructs, high cell viability and proper cell spreading morphology are observed. Given that Matrigel is used extensively for 3D cell culturing, the developed 3D-printable Matrigel-agarose system will open a new way to construct Matrigel-based 3D constructs for cell culture and tissue engineering

The effects of membrane cholesterol and simvastatin on red blood cell deformability and ATP release

It is known that deformation of red blood cells (RBCs) is linked to ATP release from the cells. Further, membrane cholesterol has been shown to alter properties of the cell membrane such as fluidity and bending stiffness. Membrane cholesterol content is increased in some cardiovascular diseases, for example, in individuals with acute coronary syndromes and chronic stable angina, and therefore, because of the potential clinical relevance, we investigated the influence of altered RBC membrane cholesterol levels on ATP release. Because of the correlation between statins and reduced membrane cholesterol in vivo, we also investigated the effects of simvastatin on RBC deformation and ATP release. We found that reducing membrane cholesterol increases cell deformability and ATP release. We also found that simvastatin increases deformability by acting directly on the membrane in the absence of the liver, and that ATP release was increased for cells with enriched cholesterol after treatment with simvastatin

Margination of Stiffened Red Blood Cells Regulated By Vessel Geometry

Abstract Margination of stiffened red blood cells has been implicated in many vascular diseases. Here, we report the margination of stiffened RBCs in vivo, and reveal the crucial role of the vessel geometry in the margination by calculations when the blood is seen as viscoelastic fluid. The vessel-geometry-regulated margination is then confirmed by in vitro experiments in microfluidic devices, and it establishes new insights to cell sorting technology and artificial blood vessel fabrication