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Abstract As the prospect of engineering primary B‐cells for cellular therapies in cancer, autoimmune diseases, and infectious diseases grows, there is an increasing demand for robust in vitro culture systems that effectively activate human B‐cells isolated from peripheral blood for consistent and efficient expansion and differentiation into various effector phenotypes. Feeder cell‐based systems have shown promise in providing long‐term signaling for expanding B‐cells in vitro. However, these co‐culture systems necessitate more rigorous downstream processing to prevent various feeder cell‐related contaminations in the final product, which limits their clinical potential. In this study, we introduce a microbead‐based CD40L‐presentation platform for stable and consistent activation of human naïve B‐cells. By employing a completely synthetic in vitro culture approach integrating B‐cell receptor, CD21 co‐receptor, toll‐like receptor (TLR‐9), and cytokine signals, we demonstrate that naïve B‐cells can differentiate into memory B‐cells (IgD‐CD38‐/lo + CD27+) and antibody‐secreting cells (IgD‐CD38++CD27+). During this process, B‐cells underwent up to a 50‐fold expansion, accompanied by isotype class switching and low levels of somatic hypermutation, mimicking physiological events within the germinal center. The reproducible generation of highly expanded and differentiated effector B‐cells from naïve B‐cells of multiple donors positions this feeder‐free in vitro synthetic niche as a promising platform for large‐scale production of effector B‐cell therapeutics.more » « lessFree, publicly-accessible full text available January 25, 2026
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The annual migration of monarch butterflies, Danaus plexippus, from their summer breeding grounds in North America to their overwintering sites in Mexico can span over 4000 kilometers. Little is known about the aerodynamic mechanism behind this extended flight. This study is motivated by the hypothesis that their flapping wing flight is enhanced by fluid-structure interactions. The objective of this study to quantify the aeroelastic performance of monarch butterfly wings and apply those values in the creation of an artificial wing with an end goal of creating a biomimetic micro-air vehicle. A micro-CT scan, force-deflection measurements, and a finite element solver on real monarch butterfly wings were used to determine the density and elastic modulus. These structural parameters were then used to create a monarch butterfly inspired artificial wing. A solidification process was used to adhere 3D printed vein structures to a membrane. The performance of the artificial butterfly wing was tested by measuring the lift at flapping frequencies between 6.3 and 14 Hz. Our results show that the elastic modulus of a real wing is 1.8 GPa along the span and 0.20 GPa along the chord, suggesting that the butterfly wing material is highly anisotropic. Real right forewings performed optimally at approximately 10 Hz, the flapping frequency of a live monarch butterfly, with a peak force of 4 mN. The artificial wing performed optimally at approximately 8 Hz with a peak force of 5 mN.more » « less