Jennifer A. Lewis

The design and synthesis of high permittivity polymers face a key challenge; namely, strong polarization requires concentrated dipoles that give rise to high thermal transition temperatures. The inverse relationship between permittivity and mobility limits the dielectric constant of all dipolar materials. Consequently, for pure polymers, the largest known dielectric constants are roughly 100 for vinylidene fluoride copolymers at the Curie temperature and 35 for room-temperature polymer melts. Here, we report the rational design and synthesis of a zwitterionic polysiloxane with a static dielectric constant of 420 at room temperature, the largest value achieved to date. This specific polysiloxane contains pendent zwitterionic dipoles with long, flexible spacers that simultaneously amplify dipole moment and dilute strong coulombic interactions, yielding a glass transition temperature Tg of-14 °C. This novel high-κ dielectric polymer overcomes the permittivity-mobility limitation thereby challenging the existing paradigm for dipolar polymer dielectrics.

Natural filaments, such as proteins, plant tendrils, octopus tentacles, and elephant trunks, can transform into arbitrary three-dimensional shapes that carry out vital functions. Their shape-morphing behavior arises from intricate patterning of active and passive regions, which are difficult to replicate in synthetic matter. Here, we introduce a filament-centric strategy for programmable shape morphing in which intrinsic curvature and twist are directly encoded within multimaterial elastomeric filaments during fabrication. By harnessing rotational multimaterial 3D printing, we directly prescribe the filament’s natural curvature–twist field κ(s) through controlled material distribution and helical liquid crystal mesogen alignment. When heated above their nematic-to-isotropic transition temperature ( T NI ), the helically aligned liquid crystal elastomer regions contract along their local director field, while passive regions remain essentially unchanged. This approach enables independent control of bending and torsion at every cross-section along the filament centerline: the principal natural curvatures of the filament along two orthogonal axes as well as the local twist. Next, we printed architected lattices composed of unit cells formed by sinusoidal filaments that either reversibly contract, expand, or exhibit out-of-plane deformations. Discrete elastic rod simulations of Janus filaments with different natural curvatures and twist, which are interconnected within the printed lattices, allow accurate prediction of their observed shape-morphing behavior. By integrating active–passive elastomers, additive manufacturing, and computational modeling, we have created shape-morphing matter with complex programmable responses for applications that rely on adaptive, robotic, or deployable architectures.

Natural filaments, such as proteins, plant tendrils, octopus tentacles, and elephant trunks, can transform into arbitrary three-dimensional shapes that carry out vital functions. Their shape-morphing behavior arises from intricate patterning of active and passive regions, which are difficult to replicate in synthetic matter. Here, we introduce a filament-centric strategy for programmable shape morphing in which intrinsic curvature and twist are directly encoded within multimaterial elastomeric filaments during fabrication. By harnessing rotational multimaterial 3D printing (RM-3DP), we directly prescribe the filament's natural curvature--twist field $\mathbf{k}(s)$ through controlled material distribution and helical liquid crystal mesogen alignment. When heated above their nematic-to-isotropic transition temperature ($T_\mathrm{NI}$), the helically aligned LCE regions contract along their local director field, while passive regions remain essentially unchanged. This approach enables independent control of bending and torsion at every cross-section along the filament centerline: the principal natural curvatures of the filament along two orthogonal axes as well as the local twist. Next, we printed architected lattices composed of unit cells formed by sinusoidal filaments that either reversibly contract, expand, or exhibit out-of-plane deformations. Discrete elastic rod simulations of Janus filaments with different natural curvatures and twist, which are interconnected within the printed lattices, allow accurate prediction of their observed shape-morphing behavior. By integrating active-passive elastomers, additive manufacturing, and computational modeling, we have created shape-morphing matter with complex programmable responses for applications that rely on adaptive, robotic, or deployable architectures.

Natural filaments, such as proteins, plant tendrils, octopus tentacles, and elephant trunks, can transform into arbitrary three-dimensional shapes that carry out vital functions. Their shape-morphing behavior arises from intricate patterning of active and passive regions, which are difficult to replicate in synthetic matter. Here, we introduce a filament-centric strategy for programmable shape morphing in which intrinsic curvature and twist are directly encoded within multimaterial elastomeric filaments during fabrication. By harnessing rotational multimaterial 3D printing (RM-3DP), we directly prescribe the filament's natural curvature--twist field $\mathbf{k}(s)$ through controlled material distribution and helical liquid crystal mesogen alignment. When heated above their nematic-to-isotropic transition temperature ($T_\mathrm{NI}$), the helically aligned LCE regions contract along their local director field, while passive regions remain essentially unchanged. This approach enables independent control of bending and torsion at every cross-section along the filament centerline: the principal natural curvatures of the filament along two orthogonal axes as well as the local twist. Next, we printed architected lattices composed of unit cells formed by sinusoidal filaments that either reversibly contract, expand, or exhibit out-of-plane deformations. Discrete elastic rod simulations of Janus filaments with different natural curvatures and twist, which are interconnected within the printed lattices, allow accurate prediction of their observed shape-morphing behavior. By integrating active-passive elastomers, additive manufacturing, and computational modeling, we have created shape-morphing matter with complex programmable responses for applications that rely on adaptive, robotic, or deployable architectures.

The design and synthesis of high permittivity polymers face a key challenge; namely, strong polarization requires concentrated dipoles that give rise to high thermal transition temperatures. The inverse relationship between permittivity and mobility limits the dielectric constant of all dipolar materials. Consequently, for pure polymers, the largest known dielectric constants are roughly 100 for vinylidene fluoride copolymers at the Curie temperature and 35 for room-temperature polymer melts. Here, we report the rational design and synthesis of a zwitterionic polysiloxane with a static dielectric constant of 420 at room temperature, the largest value achieved to date. This specific polysiloxane contains pendent zwitterionic dipoles with long, flexible spacers that simultaneously amplify dipole moment and dilute strong coulombic interactions, yielding a glass transition temperature Tg of-14 °C. This novel high-κ dielectric polymer overcomes the permittivity-mobility limitation thereby challenging the existing paradigm for dipolar polymer dielectrics.

ABSTRACT Light‐mediated 3D bioprinting methods hold great promise for the generation of biomimetic microvasculature networks for applications ranging from organ‐on‐chip models to vascularized tissue constructs. While printing microvascular channels (≤100 µm in diameter) within large hydrogel volumes (≥1 cm 3 ) is theoretically feasible, progress remains limited by the lack of suitable cytocompatible photoresins. Here, we report the development of an optimized photoresin based on fish gelatin and photoclick crosslinking chemistry for bioprinting perfusable, embedded microvascular networks via high‐resolution digital light processing (DLP). Specifically, our hydrogel matrix leverages the fast kinetics and negligible dark curing of thiol‐norbornene crosslinking as well as the low viscosity and thermal stability of fish gelatin. Using pulsed illumination and a biocompatible radical scavenger (DMPO), we further minimize radical diffusion‐induced blurring, enabling extended printing (>5 h). Finally, printing failures are reduced through the incorporation of a cytocompatible surfactant (Poloxamer‐188). Together, these advances open new avenues for printing perfusable biomimetic microvascular networks embedded in hydrogel matrices.

The rapid design and fabrication of soft robotic matter is of growing interest for shape morphing, actuation, and wearable devices. Here, we report a facile fabrication method for creating soft robotic materials with embedded pneumatics that exhibit programmable shape morphing behavior. Using rotational multimaterial 3D printing, asymmetrical core-shell filaments composed of elastomeric shells and fugitive channels are patterned in 1D, 2D, and 2.5D motifs. By precisely controlling the nozzle design, rotation rate, extrusion rate, and print path, one can control the local orientation, shape, and cross-sectional area of the patterned fugitive channel along each printed filament. Once the elastomeric matrix is cured, the fugitive ink is removed, leaving behind embedded channels that facilitate pneumatic actuation. Using a connected Fermat spiral pathing approach, one can automatically generate desired print paths required for more complex soft robots, such as hand-inspired grippers. Our integrated design and printing approach enables one to rapidly build soft robotic matter that exhibits myriad shape morphing transitions on demand.

Abstract Light-mediated 3D bioprinting methods hold great promise for the generation of biomimetic microvasculature networks for applications ranging from organ-on-chip models to vascularized tissue constructs. While printing microvascular channels (≤100 µm in diameter) within large hydrogel volumes (≥1 cm³) is theoretically feasible, progress remains limited by the lack of suitable biocompatible photoresins. Here, we report the development of an optimized photoresin based on fish gelatin and photoclick crosslinking chemistry for bioprinting perfusable, embedded microvascular networks via high-resolution digital light processing (DLP). Specifically, our biocompatible matrix leverages the fast kinetics and negligible dark curing of thiol-norbornene crosslinking as well as the low viscosity and thermal stability of fish gelatin. Using pulsed illumination and a biocompatible radical scavenger (DMPO), we further minimize radical diffusion-induced blurring, enabling extended printing (>5 h). Finally, printing failures are reduced through the incorporation of a biocompatible surfactant (Poloxamer-188). Together, these advances open new avenues for printing perfusable biomimetic microvascular networks embedded in biocompatible hydrogel matrices.

Background: Engineered kidney tissues are limited in part by a lack of collecting duct network and ureter to facilitate urine drainage and modification. Although protocols to derive ureteric bud (UB) and subsequently collecting duct organoids directly from human pluripotent stem cells (hPSCs) have recently been developed, these organoids are not perfusable, lacking both biophysical cues from luminal flow and a drainage outlet. Here, we develop a perfusable model of the UB and collecting duct derived from hPSCs. Methods: To fabricate our model, dissociated UB organoids were seeded into a 3D perfusable channel embedded within optimized extracellular matrix containing basement membrane matrix and collagen-I. We then differentiate UB tubules on-chip to collecting ducts in the presence of luminal flow. As a first step toward rapidly generating extensive tubular networks that can connect with a drainage outlet in bioengineered tissue, we bioprint UB cells adjacent to the perfusable UB channel and demonstrate fusion of the printed network to the drainage channel. Results: These UB cells on-chip form a confluent monolayer and maintain UB-like marker expression and morphology over several days to weeks. Notably, UB cells in the monolayer bud into the surrounding matrix while maintaining luminal interconnection with the central perfusable lumen resembling early branching morphogenesis observed in developing kidneys. We find that on chip collecting duct differentiation resulted in decreased UB markers and increased collecting duct markers relative to UB tubules. Moreover, we found differential marker expression is enhanced by luminal flow relative to static controls. Conclusion: This platform can facilitate fundamental understanding of development and disease in human collecting ducts and ultimately serve as a drainage channel upon integration with biomanufactured tissue. Funding: Other NIH Support - UC2DK126023, DK131821, Private Foundation Support, Government Support – Non-U.S.

This investigation, focused on analyzing the role of PIEZO1 mechanotransduction in maturing human induced pluripotent stem cell (iPSC)-derived ureteric bud (UB) and collecting duct (CD) kidney organoids, unexpectedly reveals developmentally regulated Ca 2+ oscillations and begins to dissect their mechanistic underpinnings. Specifically, transcriptomic analysis reveals that with time in culture and differentiation from UB to CD, organoids progressively acquire the molecular machinery necessary for complex Ca 2+ signaling dynamics. These results lead us to speculate that information encoded in oscillatory signals drives renal epithelial differentiation.

Aqueous organic redox flow batteries (AORFBs) represent a promising technology for large-scale energy storage due to their ability to decouple power and energy, potential low cost, and reliance on sustainably sourced molecules. Despite advancements, such as the introduction of inexpensive, abundant active materials and selective ion-exchange membranes, AORFBs require further development to achieve viability for grid-scale applications. Limited understanding of interactions between organic molecules and porous electrode fibers remains a key challenge. Porous carbonaceous electrodes— available as felts, cloths, and papers—play a critical role in energy storage systems like fuel cells and AORFBs. However, commercial carbon electrodes often exhibit heterogeneous performance(1), complicating efforts to distinguish structural effects from electrochemical effects. Integrating 3D-printed architected electrodes with electrochemical confocal fluorescence microscopy(2) enables direct visualization of interactions between fibers and electrochemical species. This approach reveals how porous electrode geometry influences AORFB performance. Architected electrodes isolate geometric contributions to diffusion and mass transport limitations of reduced species(3). A combination of physics-based modeling and experimental approaches allows for a detailed investigation of flow and electrochemical behavior. We derived 3D state-of-charge (SOC) maps from imaging to quantify reduced species concentrations within each voxel. Notably, both experiment and model reveal tails of electrolyte in the flow direction and mass transport limitations emerge near the outlet. This experimentally validated model facilitates the customization of electrodes for specific energy storage applications, paving the way for performance-based design and the development of next-generation electrodes that significantly outperform current commercial options. A. A. Wong, S. M. Rubinstein and M. J. Aziz, Cell Reports Physical Science , 2 , 100388 (2021). A.M. Graf, T. Cochard, K. Amini, M.S. Emanuel, S.M. Rubinstein, and M. J. Aziz. "Quantitative Local State of Charge Mapping by Operando Electrochemical Fluorescence Microscopy in Porous Electrodes" Energy Advances 3 , 2468 (2024). D. M. Barber et al., “Print-and-plate architected electrodes for electrochemical transformations under flow,” ChemRxiv(2024). This content is a preprint and has not been peer-reviewed. https://doi.org/10.26434/chemrxiv-2024-2hxnb Figure 1

Abstract Recent protocols have emerged to derive ureteric bud (UB) and collecting duct (CD) organoids directly from human induced pluripotent stem cells (hiPSCs). However, these 3D kidney tissues lack biophysical cues from luminal flow and a drainage outlet. To address these limitations, we have created perfusable 3D models of UB and CD tubules. UB organoids are first generated from hiPSCs followed by their dissociation into individual UB cells. Individual UB cells are then seeded onto a 3D perfusable channel embedded within an extracellular matrix composed of fragmented basement membrane matrix and collagen I, where they self-assemble into a confluent monolayer. During in vitro perfusion, these cells exhibit UB-like marker expression over several weeks, during which they undergo budding akin to early branching morphogenesis in developing kidneys. To further promote network formation, UB cells are bioprinted adjacent to a perfusable UB tubule, which form interconnections through luminal fusion. Finally, these 3D perfusable UB tubules are differentiated into collecting duct tubules under luminal flow. Our platform facilitates fundamental understanding of human collecting duct formation during renal development, while paving the way for using these physiologically relevant models for drug testing, disease modeling, and, ultimately, integration into bioprinted kidney tissues for therapeutic use.

Abstract Architected LCE lattices are fabricated with flow‐induced alignment via direct ink writing and systematically characterized their shape morphing, stiffness, and energy absorption behavior across strain rates spanning six orders of magnitude from 10 −3 to 10 3 s −1 . It is shown that architected liquid crystal elastomer (LCE) lattices exhibit superior energy absorption compared to their non‐mesogenic (silicone) counterparts. Importantly, the LCE‐to‐silicone energy absorption ratios are up to 18‐fold higher at the highest strain rate tested. A finite element model that captures their shape‐morphing response is developed, which exhibits excellent agreement with the experimental observations. The work opens new avenues for designing and fabricating LCE lattices with programmable alignment, shape morphing, and mechanics.

Traditional breast reconstruction methods, including synthetic implants and autologous tissue flaps, have limitations such as implant rupture, rejection, flap loss, and donor site morbidity. The ReConstruct Breast BioImplant, developed at the Wyss Institute in collaboration with BIDMC, offers a novel solution by utilizing a vascularized, living tissue implant engineered from autologous cells obtained through liposuction. This study aims to evaluate the feasibility and efficacy of the BioImplant in small animal models as a precursor to clinical application. The BioImplant was engineered using patient-derived cells obtained through liposuction. Bioprinting technology was employed to create 3-D printed vascularized soft tissue constructs with integrated cuffs for vascular attachment. BioImplants were surgically anastomosed to the femoral vessels of immunodeficient rats to allow immediate perfusion. Tissue viability, perfusion, and integration were assessed over nine days post-implantation; tissue viability was present at 9 days in a small animal model. The BioImplant successfully integrated with the animals’ circulatory systems, demonstrating immediate perfusion and sustained viability throughout the study period. The engineered tissue showed promising functionality and stability, suggesting its potential for clinical-scale production and application. The ReConstruct BioImplant presents a viable and effective approach for breast reconstruction, offering a safer, durable alternative to existing methods. Further studies in large animal models are planned to validate clinical efficacy and scale-up potential, advancing this technology toward clinical trials.

Ca 2+ signaling in metanephric mesenchymal (MM) cells contributes to key pattern forming events including branching morphogenesis in the embryonic rat kidney (Fontana et al., FASEB J, 2019). We previously reported that basolateral exposure of tubular structures isolated from MM-derived kidney organoids to the PIEZO1 channel agonist Yoda1 elicited a maturation stage-dependent elevation of intracellular Ca 2+ concentration, [Ca 2+ ] i (Carrisoza-Gaytán et al., AJP Cell Physiol, 2023). The aim of our current study is to explore whether tubular cells in human iPSC-derived UB and CD organoids exhibit similar developmental increases in PIEZO1 function.To investigate this, tubular structures from UB and CD organoids cultured for 34-35 or 61-65 d (4 tubules/group; n=38-40 cells/group) are loaded with the Ca 2+ -sensitive fluorophore Fura2-AM to measure [Ca 2+ ] i before and after basolateral exposure to Yoda1 (5 µM). Baseline [Ca 2+ ] i was 108.5±3.6 nM across all tubular cells studied, with no differences detected between UBs and CDs or days in culture. Subsequent exposure to Yoda1 induced an increase in [Ca 2+ ] i and appearance of Ca 2+ oscillations. The Yoda1-induced [Ca 2+ ] i signals of individually identified cells are then subject to spectral analysis using the multitaper method along with a harmonic F-test to identify predominant frequencies in the signal. We found that with advancing days in culture from 34-35 to 61-65 d: (i) Yoda1 induced an increase in [Ca 2+ ] i in UBs from 45.3±18.5 to 275.6±43.7 nM (p≤0.001) and in CDs from 61.7±16.1 to 254.3±56.2 nM (p≤0.001), (ii) the proportion of cells exhibiting Ca 2+ oscillations increased in UBs from 70 to 83% and in CDs from 75 to 84%, and (iii) the predominant oscillatory frequency fell by 50% in UBs and 30% in CDs from 15 mHz. These observations suggest that kidney organoids undergo a developmental increase in PIEZO1 abundance/activity and maturation of Ca 2+ signal transduction pathways, especially those involved in Ca 2+ oscillatory activity. Decoding Ca 2+ oscillations may unveil molecular mechanisms underlying maturation/differentiation. This work was supported by the NIH Re(Building) a Kidney Consortium (NIH UC2DK126023) and the Welcome LEAP Human Organs, Physiology and Engineering (HOPE) program. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

In one aspect, the present disclosure provides a nozzle for a 3D printing system. The nozzle may include a flowpath with a material inlet and a material outlet. The nozzle may further include a valve in fluid communication with the flowpath between the material inlet and the material outlet, where the valve includes a closed state and an open state, where in the closed state the valve obstructs the flowpath between the material inlet and the material outlet, and where in the open state the material inlet is in fluid communication with the material outlet. The nozzle may further include a compensator in fluid communication with the flowpath, where the compensator includes a contracted state associated with the open state of the valve and an expanded state associated with the closed state of the valve.

Abstract Flow cell electrodes are typically composed of porous carbon materials, such as papers, felts, and cloths. However, their random architecture hinders the fundamental characterization of electrode structure‐performance relationships during in situ operation of porous electrochemical flow systems. This work describes a “print‐and‐plate” method that combines direct ink writing of micro‐periodic lattices with a two‐step metal plating process that converts them into highly conductive (sheet resistance 40 mΩ sq −1 ) electrodes. Their operando performance is assessed in an anthraquinone disulfonic acid half‐cell using widefield electrochemical fluorescence microscopy, where output current and fluorescence intensity are in excellent agreement. The pressure drop associated with flow through three electrode designs is determined via simulations from which the most efficient design is identified and manufactured via print‐and‐plate. Confocal fluorescence microscopy is then used to create a 3D map of the state of charge (SOC) inside this print‐and‐plate electrode. The experimental state of the charge map is in good agreement with computational predictions. The rapid design, simulation, and fabrication of print‐and‐plate electrodes enable fundamental investigations of how architected porosity affects electrochemical performance under flow.

Cholesteric liquid crystal elastomers (CLCEs) hold great promise for mechanochromic applications in anti-counterfeiting, smart textiles, and soft robotics, thanks to the structural color and elasticity. While CLCEs are printed via direct ink writing (DIW) to fabricate free-standing films, complex 3D structures are not fabricated due to the opposing rheological properties necessary for cholesteric alignment and multilayer stacking. Here, 3D CLCE structures are realized by utilizing coaxial DIW to print a CLC ink within a silicone ink. By tailoring the ink compositions, and thus, the rheological properties, the cholesteric phase rapidly forms without an annealing step, while the silicone shell provides encapsulation and support to the CLCE core, allowing for layer-by-layer printing of self-supported 3D structures. As a demonstration, free-standing bistable thin-shell domes are printed. Color changes due to compressive and tensile stresses can be witnessed from the top and bottom of the inverted domes, respectively. When the domes are arranged in an array and inverted, they can snap back to their base state by uniaxial stretching, thereby functioning as mechanical sensors with memory. The additive manufacturing platform enables the rapid fabrication of 3D mechanochromic sensors thereby expanding the realm of potential applications for CLCEs.

Liquid crystal elastomers (LCEs) exhibit reversible shape morphing behavior when cycled above their nematic-to-isotropic transition temperature. During extrusion-based 3D printing, LCE inks are subjected to coupled shear and extensional flows that can be harnessed to spatially control the alignment of their nematic director along prescribed print paths. Here, we combine experiment and modeling to elucidate the effects of ink composition, nozzle geometry, and printing parameters on director alignment. From rheological measurements, we quantify the dimensionless Weissenberg number ( Wi ) for the flow field each ink experiences as a function of printing conditions and demonstrate that Wi is a strong predictor of LCE alignment. We find that director alignment in LCE filaments printed through a tapered nozzle varies radially when Wi < 1, while it is uniform when Wi ≫ 1. Based on COMSOL simulations and in operando X-ray measurements, we show that LCE inks printed through nozzles with an internal hyperbolic geometry exhibit a more uniform director alignment for a given Wi compared to those through tapered nozzles. Concomitantly, the stiffness along the print direction and actuation strain of printed LCEs increases substantially under such conditions. By varying Wi during printing through adjusting the flow rate “on the fly”, LCE architectures with uniform composition, yet locally encoded shape morphing transitions can be realized.

direct attractions. Each regime typically displays a distinctive mechanical response to changing colloid-nanoparticle size ratio, packing fractions, and the strength and spatial range of interparticle attractive and repulsive interactions. Small concentrations of nanoparticles can induce orders of magnitude elastic reinforcements typically involving single or double exponential growth with increasing colloid and/or nanoparticle packing fraction. Depending on the system, the elementary stress scale can be controlled by the colloid volume, the nanoparticle volume, or a combination of both. Connections between local microstructural organization and the mixture elastic shear modulus are established. The collective structure factor of the relatively dilute nanoparticle subsystem exhibits strong spatial ordering and large osmotic concentration fluctuations imprinted by the highly correlated dense colloidal subsystem. The relevance of the theoretical results for experimental mixtures with large size asymmetry, particularly in the context of 3D ink printing and additive manufacturing, are discussed.

NBA bonds can be exploited to crosslink pristine proteins, such as gelatin and fibrinogen, by targeting their primary amines. Since this approach does not require incorporation of photoreactive moieties along the backbone, the resulting crosslinked proteins are well suited for bioadhesives. Our photoinitiator-free platform provides a versatile approach for rapidly creating synthetic and biological hydrogels for applications ranging from tissue engineering to biomedical devices.

Liquid crystalline elastomers (LCEs) are anisotropic soft materials capable of large dimensional changes when subjected to a stimulus. The magnitude and directionality of the stimuli-induced thermomechanical response is associated with the alignment of the LCE. Recent reports detail the preparation of LCEs by additive manufacturing (AM) techniques, predominately using direct ink write printing. Another AM technique, digital light process (DLP) 3D printing, has generated significant interest as it affords LCE free-forms with high fidelity and resolution. However, one challenge of printing LCEs using vat polymerization methods such as DLP is enforcing alignment. Here, we document the preparation of aligned, main-chain LCEs via DLP 3D printing using a 100 mT magnetic field. Systematic examination isolates the contribution of magnetic field strength, alignment time, and build layer thickness on the degree of orientation in 3D printed LCEs. Informed by this fundamental understanding, DLP is used to print complex LCE free-forms with through-thickness variation in both spatial orientations. The hierarchical variation in spatial orientation within LCE free-forms is used to produce objects that exhibit mechanical instabilities upon heating. DLP printing of aligned LCEs opens new opportunities to fabricate stimuli-responsive materials in form factors optimized for functional use in soft robotics and energy absorption.

Flow cell electrodes are typically composed of porous carbon materials, such as papers, felts, and cloths. However, their random architecture hinders fundamental characterization of electrode structure-performance relationships during in situ operation of porous electrochemical flow systems. Here, we report a “print-and-plate” method that uses high-resolution direct ink writing to produce periodic lattices followed by a two-step metal plating process to convert these lattices into highly conductive (sheet resistance 40 milli-Ohm per square) electrodes. We assessed their in operando performance in an anthraquinone disulfonic acid half-cell using electrochemical fluorescence microscopy, where output current and fluorescence intensity are in excellent agreement. We then compared the pressure drop of three electrode designs simulated with a high-fidelity numerical solution to the governing PDEs. The most efficient design was then fabricated via the print-and-plate method and confocal fluorescence microscopy was used to generate a 3D map of the state of charge (SOC) inside the working electrode. The experimental state of charge map is in good agreement with our simulations. By unlocking programmable architectures, print-and-plate electrodes offer new opportunities for fundamental investigations relating porous electrode microstructure to performance and direct replication of simulated structures.

Methane (CH₄), an abundant greenhouse gas, is the second largest contributor to global warming after carbon dioxide (CO₂). In comparison to CO₂, CH₄ has a larger warming effect over a much shorter lifetime. While technologies to radically reduce global carbon dioxide emissions are materializing, rapid reductions in methane emissions are needed to limit near-term warming. Methane is primarily emitted as a byproduct from agricultural activities and energy extraction/utilization and is currently monitored via bottom-up (i.e., activity level) or top-down (via airborne or satellite retrievals) approaches. However, significant methane leaks remain undetected, and emission rates are challenging to characterize with current monitoring frameworks. In this report, we study methane leaks from oil and gas infrastructure using a tiered monitoring approach that combines bottom-up and top-down approaches in an integrated framework. We describe the individual advantages of bottom-up and top-down sensors in both stationary and mobile settings before characterizing how a fully integrated framework can improve predictions and uncertainties of potential leak locations and their emission rates. Further, we study the impact of different atmospheric (wind) conditions on integrated methane monitoring and develop a probabilistic approach to optimal sensor placement, thereby shortening detection times and improving monitoring capabilities. Last, we discuss how biogenic flux modeling can be used to improve assessment of background methane concentrations needed to fully assess the sensitivity of a tiered monitoring system.

The increasing scarcity of organs and the significant morbidity linked to dialysis require the development of engineered kidney tissues from human-induced pluripotent stem cells. Integrative approaches that synergize scalable kidney organoid differentiation, tissue biomanufacturing, and comprehensive assessment of their immune response and host integration are essential to accomplish this. Here, we create engineered human kidney tissues composed of organoid building blocks (OBBs) and transplant them into mice reconstituted with allogeneic human immune cells. Tissue-infiltrating human immune cells are composed of effector T cells and innate cells. This immune infiltration leads to kidney tissue injury characterized by reduced microvasculature, enhanced kidney cell apoptosis, and an inflammatory gene signature comparable to kidney organ transplant rejection in humans. Upon treatment with the immunosuppressive agent rapamycin, the induced immune response is greatly suppressed. Our model is a translational platform to study engineered kidney tissue immunogenicity and develop therapeutic targets for kidney rejection.

Direct ink writing, an extrusion‐based 3D printing method, is well suited for high‐mix low‐volume manufacturing. However, an iterative approach, using random selection or constant expert guidance, is still used to create printable inks and optimize printing parameters by expending significant amounts of time, materials, and effort. Herein, a machine learning (ML) model that estimates ink rheology in‐situ from a simple printed test pattern is reported. This ML model is trained with a rheologically diverse set of inks composed of different polymers. The model successfully correlated features of the simple printed test pattern to rheological properties, which could, in theory, inform both printed structures and future ink compositions. The behavior of this model is verified and analyzed with explainable artificial intelligence tools, linking printed feature importance to one's known physical understanding of the process.

Printing human tissues and organs replete with biomimetic vascular networks is of growing interest. While it is possible to embed perfusable channels within acellular and densely cellular matrices, they do not currently possess the biomimetic architectures found in native vessels. Here, coaxial sacrificial writing into functional tissues (co-SWIFT) is developed, an embedded bioprinting method capable of generating hierarchically branching, multilayered vascular networks within both granular hydrogel and densely cellular matrices. Coaxial printheads are designed with an extended core-shell configuration to facilitate robust core-core and shell-shell interconnections between printed branching vessels during embedded bioprinting. Using optimized core-shell ink combinations, biomimetic vessels composed of a smooth muscle cell-laden shell that surrounds perfusable lumens are coaxially printed into granular matrices composed of: 1) transparent alginate microparticles, 2) sacrificial microparticle-laden collagen, or 3) cardiac spheroids derived from human induced pluripotent stem cells. Biomimetic blood vessels that exhibit good barrier function are produced by seeding these interconnected lumens with a confluent layer of endothelial cells. Importantly, it is found that co-SWIFT cardiac tissues mature under perfusion, beat synchronously, and exhibit a cardio-effective drug response in vitro. This advance opens new avenues for the scalable biomanufacturing of vascularized organ-specific tissues for drug testing, disease modeling, and therapeutic use.

The ability to controllably perfuse kidney organoids would better recapitulate the native tissue microenvironment for applications ranging from drug testing to therapeutic use. Here, we report a perfusable, vascularized kidney organoid on chip model composed of two individually addressable channels embedded in an extracellular matrix (ECM). The channels are respectively seeded with kidney organoids and human umbilical vein endothelial cells that form a confluent endothelium (macrovessel). During perfusion, endogenous endothelial cells present within the kidney organoids migrate through the ECM towards the macrovessel, where they form lumen-on-lumen anastomoses that are supported by stromal-like cells. Once micro-macrovessel integration is achieved, we introduced fluorescently labeled dextran of varying molecular weight and red blood cells into the macrovessel, which are transported through the microvascular network to the glomerular epithelia within the kidney organoids. Our approach for achieving controlled organoid perfusion opens new avenues for generating other perfused human tissues.

The next 50 years of developmental biology will illuminate exciting new discoveries but are also poised to provide solutions to important problems society faces. Ten scientists whose work intersects with developmental biology in various capacities tell us about their vision for the future.

Intended use: Our technology is intended to be an agile tool to evaluate the design of a multi-tiered methane monitoring system.Under this work we evaluate different systems that utilize different types, quantities, and locations of sensors under a representative range of operating conditions.Driving Fundamental Science: We use advanced statistical methods to quantitatively evaluate monitoring network designs.Our evaluation framework is informed by atmospheric dispersion physics, realistic emission states, and reported measurement performance parameters. Relevant Past Work:We leverage past efforts that have performed this evaluation including: Modeling studies (e.g.see those cited in ROSES proposal) CHAMA (Sandia software for optimal sensor placement) Realistic emission inventories (e.g.Rutherford et al., 2021) Representative performance statistics

Abstract Printing human tissue constructs replete with biomimetic vascular networks is of growing interest for tissue and organ engineering. While it is now possible to embed perfusable channels within acellular and densely cellular matrices, they lack either the branching or multilayer architecture of native vessels. Here, we report a generalizable method for printing hierarchical branching vascular networks within soft and living matrices. We embed biomimetic vessels into granular hydrogel matrices via coaxial embedded printing (co-EMB3DP) as well as into bulk cardiac tissues via coaxial sacrificial writing into functional tissues (co-SWIFT). Each method relies on an extended core-shell printhead that promote facile interconnections between printed branching vessels. Though careful optimization of multiple core-shell inks and matrices, we show that embedded biomimetic vessels can be coaxially printed, which possess a smooth muscle cell-laden shell that surrounds perfusable lumens. Upon seeding these vessels with a confluent layer of endothelial cells, they exhibit good barrier function. As a final demonstration, we construct biomimetic vascularized cardiac tissues composed of a densely cellular matrix of cardiac spheroids derived from human induced pluripotent stem cells. Importantly, these co-SWIFT cardiac tissues mature under perfusion, beat synchronously, and exhibit a cardio-effective drug response in vitro. This advance opens new avenues for the scalable biomanufacturing of organ-specific tissues for drug testing, disease modeling, and therapeutic use.

An integrated design, modeling, and multi-material 3D printing platform for fabricating liquid crystal elastomer (LCE) lattices in both homogeneous and heterogeneous layouts with spatially programmable nematic director order and local composition is reported. Depending on their compositional topology, these lattices exhibit different reversible shape-morphing transformations upon cycling above and below their respective nematic-to-isotropic transition temperatures. Further, it is shown that there is good agreement between their experimentally observed deformation response and model predictions for all LCE lattice designs evaluated. Lastly, an inverse design model is established and the ability to print LCE lattices with the predicted deformation behavior is demonstrated. This work opens new avenues for creating architected LCE lattices that may find potential application in energy-dissipating structures, microfluidic pumping, mechanical logic, and soft robotics.

Rete ridges consist of undulations between the epidermis and dermis that enhance the mechanical properties and biological function of human skin. However, most human skin models are fabricated with a flat interface between the epidermal and dermal layers. Here, we report a micro-stamping method for producing human skin models patterned with rete ridges of controlled geometry. To mitigate keratinocyte-induced matrix degradation, telocollagen-fibrin matrices with and without crosslinks enable these micropatterned features to persist during longitudinal culture. Our human skin model exhibits an epidermis that includes the following markers: cytokeratin 14, p63, and Ki67 in the basal layer, cytokeratin 10 in the suprabasal layer, and laminin and collagen IV in the basement membrane. We demonstrated that two keratinocyte cell lines, one from a neonatal donor and another from an adult diabetic donor, are compatible with this model. We tested this model using an irritation test and showed that the epidermis prevents rapid penetration of sodium dodecyl sulfate. Gene expression analysis revealed differences in keratinocytes obtained from the two donors as well as between 2D (control) and 3D culture conditions. Our human skin model may find potential application for drug and cosmetic testing, disease and wound healing modeling, and aging studies.

Summary The increasing scarcity of organs and the significant morbidity linked to dialysis requires the development of engineered kidney tissues from human-induced pluripotent stem cells. To accomplish this, integrative approaches that synergize scalable kidney organoid differentiation, tissue biomanufacturing, and comprehensive assessment of their immune response and host integration are essential. Here, we create engineered human kidney tissues composed of kidney organoid building blocks (OBBs) and transplant them into mice reconstituted with allogeneic human immune cells. We assess their host vascular integration, in vivo maturation, and their ability to trigger human immune responses. Tissue-infiltrating human immune cells are composed of effector T cells and innate cells. This immune infiltration leads to kidney tissue injury characterized by reduced microvasculature, enhanced kidney cell apoptosis, and a unique inflammatory gene signature comparable to kidney organ transplant rejection in humans. Upon treatment with the immunosuppressive agent Rapamycin, the induced immune response is greatly suppressed. Our model serves as a translational platform to study engineered kidney tissue immunogenicity and develop novel therapeutic targets for kidney rejection.

T cell bispecific antibodies (TCBs) are the focus of intense development for cancer immunotherapy. Recently, peptide-MHC (major histocompatibility complex)-targeted TCBs have emerged as a new class of biotherapeutics with improved specificity. These TCBs simultaneously bind to target peptides presented by the polymorphic, species-specific MHC encoded by the human leukocyte antigen (HLA) allele present on target cells and to the CD3 coreceptor expressed by human T lymphocytes. Unfortunately, traditional models for assessing their effects on human tissues often lack predictive capability, particularly for “on-target, off-tumor” interactions. Here, we report an immune-infiltrated, kidney organoid-on-chip model in which peripheral blood mononuclear cells (PBMCs) along with nontargeting (control) or targeting TCB-based tool compounds are circulated under flow. The target consists of the RMF peptide derived from the intracellular tumor antigen Wilms’ tumor 1 (WT1) presented on HLA-A2 via a bivalent T cell receptor-like binding domain. Using our model, we measured TCB-mediated CD8 + T cell activation and killing of RMF-HLA-A2-presenting cells in the presence of PBMCs and multiple tool compounds. DP47, a non-pMHC-targeting TCB that only binds to CD3 (negative control), does not promote T cell activation and killing. Conversely, the nonspecific ESK1-like TCB (positive control) promotes CD8 + T cell expansion accompanied by dose-dependent T cell–mediated killing of multiple cell types, while WT1-TCB* recognizing the RMF-HLA-A2 complex with high specificity, leads solely to selective killing of WT1-expressing cells within kidney organoids under flow. Our 3D kidney organoid model offers a platform for preclinical testing of cancer immunotherapies and investigating tissue-immune system interactions.