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Advanced Materials Technologies

Wiley

Preprints posted in the last 90 days, ranked by how well they match Advanced Materials Technologies's content profile, based on 27 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.

1
Long-Lasting Electrohydrodynamically Printed Transparent Soft Microelectrode for Implantable Biointerfaces

Jo, H.; Lee, G.; Song, Y.; Kim, S. Y.; Kim, M.; Manna, R.; Choi, D.; Aderibigbe, A.; Suib, S. L.; Park, K.; Ahn, J.; Song, J.-H.; Kim, K.

2026-05-21 bioengineering 10.64898/2026.05.19.726391 medRxiv
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Reliable and scalable soft implantable neural interface fabrication remains a key challenge for chronic bioelectronic applications. Here, we present a transparent soft microelectrode fabricated with electrohydrodynamic (EHD) printing, utilizing the fluorinated polymer poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and poly (3, 4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS) to form seamless, selectively patterned multilayer structures with low impedance and long-term stability. Controlled in situ curing during printing yields dense, void-free substrate and encapsulation layers, suppressing interfacial defects and ionic pathways, while maintaining high optical transparency (>60%) with PEDOT:PSS. The printed microelectrodes exhibit low impedance, high charge storage and injection capacities, and stable electrochemical behavior under biomimetic conditions. In addition, the devices demonstrate robust mechanical and electromechanical stability under cyclic deformation in both dry and wet environments, as well as under prolonged electrical stimulation. Accelerated aging studies project multi-year operational lifetimes, and in vitro/in vivo biocompatibility assessments confirm excellent tissue integration. These results establish EHD-printed fluorinated polymer-based microelectrodes as a scalable and durable platform for chronic implantable biointerfaces. ToC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/726391v1_ufig1.gif" ALT="Figure 1"> View larger version (79K): org.highwire.dtl.DTLVardef@152c58aorg.highwire.dtl.DTLVardef@126f1f5org.highwire.dtl.DTLVardef@1d743cforg.highwire.dtl.DTLVardef@1a4d743_HPS_FORMAT_FIGEXP M_FIG C_FIG This report presents an electrohydrodynamically printed transparent soft microelectrode for chronic purposes. Electrohydrodynamic printing promotes seamless multilayer structures with selective deposition and long-term mechanical stability. The devices show low impedance, high charge capacity, and robust electrochemical/electromechanical properties. Accelerated aging projects [~]7.2 year lifetimes, and XPS/SEM-EDS confirm strong ion barrier properties and biocompatibility for chronic implantation.

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From Fabrication to Flow: Impact of Print Orientation on Surface Qualities and Capillary-Driven Flow in Laser SLA-based Open Microchannels

Lin, A.; Milton, L.; Chan, D. W. H.; Ghadge, N.; Tokihiro, J.; Brown, L.; Shin, A.; Toh, Y.-C.; Olanrewaju, A.; Berthier, E.; Berthier, J.; Theberge, A.

2026-04-14 bioengineering 10.64898/2026.04.10.717746 medRxiv
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Stereolithography (SLA) 3D printing has become increasingly popular for fabricating microfluidic devices, with applications including hydrogel patterning and tissue modeling. In open-channel systems with surface tension-driven flow, 3D-printer-induced discrepancies in channel surface texture can significantly impact fluid flow and device performance. While previous work has focused on comparing different 3D printing methods for microchannel fabrication, the effect of device orientation during SLA printing on microchannel morphology and capillary-driven flow has not been systematically evaluated. Furthermore, there is minimal research elucidating the influence of channel surface texture on the flow of biologically relevant hydrogel precursors commonly used in organ-on-a-chip applications. Herein, we investigated the impact of print orientation on channel morphology, fluid wetting behavior, and fluid flow by comparing laser SLA-based parts where the length of the channel was tilted at 0{degrees}, 15{degrees}, 45{degrees}, or 90{degrees} during printing. We demonstrated that channel floor surface texture is greatly affected by print orientation: the highest axial surface roughness was measured in 15{degrees} printed channels, and the highest axial surface tortuosity-which describes the real length along the surface-was measured in 45{degrees} printed channels. Print angles of 15{degrees} and 45{degrees} also resulted in asymmetric roughness of the channel floor, which caused asymmetric wetting of glycerol solution. Surface tension-driven flow of glycerol solution, agarose precursor solution, and collagen precursor solution was affected by print orientation, in which the 45{degrees} printed flow devices had slowest flow for all test fluids. Root mean square roughness was not a reliable predictor of slower flow; instead, surface tortuosity should be considered. Potential alternatives to better theoretically model how print angle-induced surface texture affects open-channel flow are discussed as well. These findings provide a framework of fabrication considerations for laser SLA printing of open microchannels that can also be applied to other layer-by-layer, vat photopolymerization-based 3D printing technologies.

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A robust and user-agnostic step-emulsion platform for scalable microgel fabrication

Pioche-Lee, D.; Yang, S.; Wang, X.; Ho, Y. Q.; Rahman, W.; Vartanian, A. C.; Pavlidis, D. I.; Zhang, I. W.; Vallier, J. E.; McCorkle, E.; Schaefer, A.; Putnam, A. J.; Shikanov, A. A.; DeForest, C. A.; Lesher-Perez, S. C.

2026-05-08 bioengineering 10.64898/2026.05.05.722106 medRxiv
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Over the past decade, the integration of microgel-based granular hydrogels in biomedical technologies has experienced substantial growth due to the numerous benefits microgels offer. However, the inability to easily adopt uniform microgel fabrication workflows at scale constitutes a major bottleneck, or in some cases, a barrier-to-entry that stunts further growth of the field. The gold-standard technique for emulsion-based microgel production is through microfluidic droplet-generating devices that produce liquid gel precursor droplets that gel post-production. However, traditional microfluidic workflows often require multiple independent flows and controlled pressure sources, along with a steep learning curve in using microfluidics to achieve uniform droplet sizes reproducibly and repeatedly. This difficulty in adopting microgel fabrication is further compounded by low throughput and the extensive flow rate calibration required when switching to new formulations (e.g., material type, droplet size). In this work, we present a step-emulsion system that bridges the gap by providing a robust and simple setup. We experimentally characterize and evaluate how flow and outlet channel dimension contribute to the generation of uniform droplet populations at specific sizes. With our large dataset consisting of various outlet channel dimensions, we evaluated outlet channel geometrical impacts (height, width, cross-sectional area, aspect-ratio, etc.) on gel precursor droplet size and generation throughput. We demonstrate robust, highly compatible, and repeatably uniform droplet generation from various gel precursor polymer backbones, users with varying microfluidics experience, and a wide viscosity range, including alginate solutions with 650 times the viscosity of water. Furthermore, we confirmed consistent gel precursor droplet generation outcomes driven by a constant flow source (syringe pump) and by direct manual injection as a simple and highly adoptable option for the generation of gel precursor droplets. This platform is ideal for researchers seeking rapid and easy microgel fabrication, regardless of microfluidics experience.

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Additive manufacturing of PEDOT:PSS electrodes on collagen substrates for soft and bioactive electronics

Liu, T.; Park, J.; Okafor, S. S.; Montgomery, S. K.; Goestenkors, A. P.; Semar, B. A.; Alvarez, R. M.; O'Hare, C. P.; Wu, Y.; Yu, J. S.; Vargas Espinoza, C. J.; Rutz, A. L.

2026-05-12 bioengineering 10.64898/2026.05.08.723335 medRxiv
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Traditional bioelectronic devices are limited by poor biointerfacing due to their substantial mismatch in mechanical and biochemical properties. In tissue engineering, soft and bioactive materials support biointegration by harnessing or mimicking the natural extracellular matrix (ECM). Building bioelectronic devices from ECM should improve their biointegration, yet there are limited methods to fabricate them due to current manufacturing approaches. An additive manufacturing strategy is presented here for collagen-based bioelectronic interfaces that integrates conducting polymer electrodes with ECM-based substrates or encapsulation layers. Addition of poly(ethylene glycol) diglycidyl ether (PEGDE) to poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) colloidal dispersions enables direct extrusion-based patterning under mild conditions compatible with collagen substrates, and forms aqueous stable and highly conducting printed patterns (2788 S m-{superscript 1}). The resulting interfaces maintain stable electrochemical performance over 7 days in physiological environments, and support primary human cell adhesion, viability, and proliferation across both material regions. A sacrificial patterning strategy using 3D printed cacao butter further enables spatial control of collagen encapsulation. This approach establishes a framework for fabricating functional bioelectronic devices based on ECM to further enhance device biointerfaces for tissue models and implantable systems.

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Extrusion-Printed Silicone Microarchitectures for Geometry-Controlled Flow in Lateral Flow Diagnostics and Paper Microfluidics

Alioglu, M. A.; Natarajan, S.; Skrodzki, D.; Colak, O.; Pan, D.

2026-05-21 bioengineering 10.64898/2026.05.19.726334 medRxiv
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Paper-based diagnostics such as lateral flow assays (LFAs) and microfluidic paper-based analytical devices ({micro}PADs) have attracted considerable attention because of their low cost, portability, and ease of use. Currently, to enable fabrication of {micro}PADs and improve LFA performance, hydrophobic blocks are patterned on paper substrates. However, fabrication of high-resolution hydrophobic barriers remains a major challenge. In this work, we developed a novel silicone extrudable ink for the fabrication of hydrophobic features on paper substrates. The ink was formulated using a vinyl-terminated polydimethylsiloxane (vPDMS) and polymethylhydrosiloxane (PMHS) system crosslinked through platinum-catalyzed hydrosilylation, and its rheological properties were tailored by incorporating silica fillers, obtaining a shear-thinning gel suitable for extrusion. The resulting formulation provided tunable properties, controlled deposition, and stable feature formation, enabling simple, low-cost, rapid, and robust fabrication of high-resolution hydrophobic barriers. Using this approach, we demonstrated improved fluid confinement and pattern fidelity on paper substrates, fabricated high-resolution paper microfluidic devices down to 150 {micro}m channel width, and enhanced the sensitivity of an LFA for a malaria diagnostic test. These results highlight the potential of this silicone ink platform as a practical and scalable strategy for advancing high-performance paper-based diagnostic technologies.

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Vitamin C-Induced Photo-Redox Threshold Enables High-Fidelity Volumetric Printing of Pristine Collagen

Wang, B.; Hasenauer, A.; Ivkovic, K.; Frind, A.-S.; Fercher, D.; Zenobi-Wong, M.

2026-04-16 bioengineering 10.64898/2026.04.13.717972 medRxiv
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Tomographic volumetric printing (TVP) enables rapid fabrication of complex, centimeter-scale 3D architectures. TVP of pristine proteins like collagen is attractive because it better preserves native bioactive motifs that regulate cell-matrix signaling. However, direct TVP of collagen remains challenging because dityrosine crosslinking, driven by visible-light-activated Ru(II)bpy32+/sodium persulfate (SPS), lacks an effective inhibitory mechanism. This results in near-immediate crosslinking upon exposure to light, which leads to an insufficient nonlinear threshold response that fails to suppress background curing. Here, we introduce vitamin C (L-ascorbic acid) as a biocompatible redox regulator to overcome this limitation. UV-Vis kinetics demonstrate that vitamin C suppresses Ru(III) accumulation and scavenges persulfate radicals within Ru/SPS system. This dual action generates a critical photo-redox and crosslinking threshold that inhibits dityrosine formation until vitamin C is depleted. Thereby the threshold response needed for TVP is successfully established, which enables high-fidelity volumetric printing of native collagen. Post-printing construct densification ([~]53% shrinkage) further improves feature resolution (80 {micro}m positive; 120 {micro}m negative) and yields mechanically stable and highly stretchable hydrogels (up to 180% strain). Collagen resin with vitamin C supports both cell seeding post-printing and cell-laden printing with high cell density and viability, enabling the rapid biofabrication of cell-instructive 3D microenvironments. Table of Contents (ToC) O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=37 SRC="FIGDIR/small/717972v1_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@742a83org.highwire.dtl.DTLVardef@930c06org.highwire.dtl.DTLVardef@1fa7f08org.highwire.dtl.DTLVardef@aa22bb_HPS_FORMAT_FIGEXP M_FIG C_FIG Tomographic volumetric printing (TVP) of native proteins is limited by uncontrolled background crosslinking. Here, vitamin C is introduced as a biocompatible redox-regulator to establish a tunable nonlinear polymerization threshold response for TVP. This strategy effectively suppresses background crosslinking and enables high-fidelity printing of pristine collagen. Subsequent post-print densification yields robust, elastic, and cell-compatible constructs with enhanced resolution for tissue engineering applications.

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A Heart-on-a-Chip Microdevice with Aligned Fibers for Cardiotoxicity Assessment

Murata, K.; Abulaiti, M.; Okama, R.; Kato, K.; Tanaka, Y.; Masumoto, H.

2026-05-04 bioengineering 10.64898/2026.04.30.721826 medRxiv
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Background and ObjectivesCardiovascular cells differentiated from human induced pluripotent stem cells (iPSCs), including cardiomyocytes, are valuable for evaluating human cardiac pharmacology and toxicity. Early assessment of cardiotoxicity, especially for novel drugs like anticancer agents, is essential for improving drug development efficiency and reducing costs. This study aimed to develop a highly sensitive bioassay system capable of evaluating the physiological function of human cardiac tissue in vitro. MethodsHuman iPSCs were differentiated into cardiovascular cell types (cardiomyocytes, vascular endothelial cells, and vascular mural cells) and assembled into a cardiac tissue model on aligned fiber device. This tissue was cultured dynamically to induce the formation of vascular network-like structure. By combining the fiber device with our previously developed heart-on-a-chip microdevice (HMD), we created a new model of HMD (Aligned Fiber-based HMD; AF-HMD) with improved throughput and stability. Pulsatile force changes induced by drug exposure were quantified by tracking the displacement of fluorescent microbeads within the microchannels. ResultsAF-HMD demonstrated functional responses to known cardiac agonists and toxicants, such as doxorubicin. The device also replicated clinically relevant cardiotoxic events, including the synergistic effects of trastuzumab and doxorubicin, showing marked reductions in contractile force and beat rate, mirroring clinical observations. ConclusionsThe AF-HMD system provides a sensitive and reproducible platform for evaluating cardiotoxicity in drug development. It offers a promising tool for preclinical screening, with potential applications in personalized medicine and predicting cardiotoxic risk in cancer therapy.

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Complementary multiphoton tools to create 3D architectures in soft hydrogels for epithelial tissue engineering.

Moser, S.; Hasenauer, A.; Shen, X.; Ramakrishna, S. N.; Isa, L.; Style, R.; Zenobi-Wong, M.

2026-04-02 bioengineering 10.64898/2026.03.31.715498 medRxiv
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Curvature provides essential mechanical cues for epithelial cells, playing a key role in cell differentiation and morphology. Repeatable manufacture of precisely controlled curvature in soft hydrogel materials is therefore essential to study epithelial mechanobiology and function. Multiphoton (MP) based biofabrication holds promise due to its high resolution and three-dimensional design flexibility. Here, we leverage MPs advantages while increasing print speed to develop two complementary tools based on replica molding and multiphoton ablation. These can provide scalable hydrogel curvatures with tunable surface properties relevant for epithelial tissue engineering. In replica molding, MP prints are transferred into PDMS used to pattern centimeter scale arrays in hydrogels. In multiphoton ablation, hydrogels are locally degraded to generate precisely controlled curvatures and surface topography. With both methods, we repeatably guide epithelial cells into alveolar and duct-like shapes. Concave alveolar-like surfaces are shown to enhance the formation of thicker epithelial layers. We observe that surface properties, controlled by both tools, could enhance cytoskeletal organization. Using these biofabrication techniques, individual effects of curvature, surface properties, hydrogel composition, and bulk stiffness on epithelial cells can be studied. Both approaches offer high curvature control and throughput, providing a viable alternative to traditional 3D culture and other printing methods.

9
Miniaturized wireless bioelectronics for electrically driven biohybrid robots

Tetsuka, H.; Ma, J.; Hirano, M.

2026-03-12 bioengineering 10.64898/2026.03.09.710657 medRxiv
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Although biohybrid robots offer the potential for soft, adaptive actuation by harnessing living muscle, practical operation in cell culture environments is often limited by the requirement of immersed leads or cumbersome stimulation equipment. Here, we present a thin, miniaturized, wireless bioelectronic stimulator that can electrically drive biohybrid robots while maintaining stability in aqueous cell culture media. Built on a 50-{micro}m liquid crystal polymer (LCP) substrate, the device integrates a planar receiving coil, interconnects, a diode-based rectifier, and a tank capacitor. This enables the device to convert an approximately 4.9-MHz radio-frequency (RF) input into pulsed direct current (DC), which is delivered through integrated stimulation electrodes. The stimulator has a footprint of [~]23 mm2 and a total thickness and mass of [~]100 {micro}m and [~]7 mg, respectively. We integrated the stimulator with a nanopatterned carbon nanotube (CNT)/gelatin hydrogel fin seeded with human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to generate propulsion through fin flapping. By optimizing the thickness of the polydimethylsiloxane (PDMS) encapsulation layer, the density was tuned, and the robot remained freely floating and retained shape integrity during operation. This produced autonomous forward locomotion of [~]70 {micro}m/s. The stimulator generated distance-dependent output voltage pulses of [~]2-6 V and reliably synchronized fin flapping rates of up to 2 Hz without an observable loss of cell attachment or sarcomeric organization. Together, these results establish a compact, media-compatible, wireless, bioelectronic interface suitable for closed-system biohybrid robotics.

10
Automated culture and monitoring of a high-throughput human heart-on-a-chip

Schellberg, B. G.; Burson, N. T.; Gomes, J.; Dai, G.; Koppes, A. N.; Koppes, R. A.

2026-03-14 bioengineering 10.64898/2026.03.11.711145 medRxiv
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Organ chips offer a disruptive innovation to study human diseases with tissue-specific resolution within a predictable and tunable in vitro environment. However, these platform technologies have for the most part failed to translate to broad use in the private sector due to a lack of high-throughput, user-friendly platforms. Here we present an automated high-throughput organ chip seeded with iPSC-derived cardiomyocytes transduced with GCaMP6f and interface with translational technologies to bridge the current academia-industry gap. Cardiomyocytes were seeded on-chip fully hands-free using an entry-level fluid handling robot to significantly reduce user handling requirements. Pipette interfaces were paramount to facilitating seeding and feeding through improved tolerances for establishing a functional connection to dispense and collect small fluidic volumes. Following successful seeding, GCaMP6f activity on-chip was monitored with our automated, non-invasive fiber-optic sensing platform. We show a significant decrease in cardiomyocyte beat rate in response to decreased ambient culture temperature using data collected with our optical sensing platform. This study provides a potential translational blueprint for academia-industry partnership toward broad adoption of organ chip technology in drug development and disease modeling.

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Open-source robotic chip-to-plate interface for high-throughput microfluidic generation of materials libraries

Navarro, I. B.; Datto, G.; Beni, L.; Barragan, D.; Mossburg, K. J.; Shen, S.; Hanna, A. R.; Cormode, D. P.; Issadore, D.

2026-05-14 bioengineering 10.64898/2026.05.12.724546 medRxiv
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Data-driven materials development requires large, well-characterized libraries of precisely defined formulations. While microfluidic platforms excel at generating highly controlled materials, their throughput is often limited by the challenge of efficiently interfacing device outputs with standard well plates. This bottleneck frequently necessitates manual transfer or non-microfluidic workflows, constraining both throughput and reproducibility. Here, we present LMNOP-bot (Libraries of Micro- and Nano-materials, OPen-source bot), an open-source robotic platform for the automated generation and collection of micro- and nanomaterial libraries from serial microfluidic outputs. Using synchronized, pressure-driven flow, LMNOP-bot enables continuous formulation and direct deposition into standard well plates. The system is low-cost (<$700, excluding pressure regulators), constructed from readily available or easily fabricated components, and designed for broad accessibility. LMNOP-bot collects [&ge;]30 {micro}L per formulation at a rate of one sample every four seconds, representing an approximately 50x increase in throughput over existing serial microfluidic workflows, and operates robustly for over 10,000 runs without maintenance. We demonstrate compatibility with both PDMS/glass and commercial polycarbonate devices, with seamless interfacing to 96- and 384-well plates. Repeated sampling confirms high precision and reproducibility. By removing a key bottleneck in microfluidic library generation, LMNOP-bot enables rapid, scalable, and accessible exploration of material design spaces.

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3D Printed Bioelectronic Scaffolds for Impedance-based Cytotoxicity Monitoring of In Vitro Cancer Models

Okafor, S. S.; Montgomery, S. K.; Park, J.; Liu, T.; Safrega, M.; Yu, J. S.; O'Hare, C. P.; Schab, A.; Goestenkors, A. P.; Vargas Espinoza, C. J.; Wu, Y.; Seanez, I.; Lomonosova, E.; Mullen, M. M.; Rutz, A. L.

2026-05-12 bioengineering 10.64898/2026.05.07.719019 medRxiv
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Cancer is a significant contributor to global mortality and places a substantial burden on healthcare systems, underscoring the need for improved strategies for developing and evaluating new therapies. Electrochemical impedance monitoring of in vitro cancer models is a promising technique for evaluating treatment effectiveness, particularly for evaluating how well a drug may kill cancer cells. This approach is advantageous over conventional end-point assays because it is non-destructive, label-free, and can provide temporal information on cell behavior and drug kinetics. However, traditional impedance devices are limited in that they do not support three-dimensional cell culture that has become standard in cancer studies. Typical devices are planar substrates that support monolayer culture, which has been shown to overestimate drug effectiveness. In this work, we propose 3D printed bioelectronic scaffold devices that provide 3D cancer cell culture while functioning as an on-chip readout for monitoring changes in cell characteristics via impedance. We describe device development and demonstrate reproducible fabrication, stable electrochemical properties, cell detection by impedance, and proof-of-concept monitoring of cytotoxicity in response to a chemotherapeutic drug. Overall, this technology offers a promising platform that could be further developed for compound screening as part of drug development or precision medicine.

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Integrating Electrical Components into a Printed Self-folding Cuff Electrode for Chronic Peripheral Nerve Interfaces

Hiendlmeier, L.; Tuezuen, D.; Tillert, H.; Dalichau, A.; Oetztuerk, M.; Guenzel, Y.; Zurita, F.; Al Boustani, G.; Zariffa, J.; Couzin-Fuchs, E.; Malliaras, G. G.; Guemes, A.; Wolfrum, B.

2026-03-18 neuroscience 10.64898/2026.03.16.712029 medRxiv
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Neuroelectronic thin-film implants hold promise for advancing fundamental understanding of the peripheral nervous system and offer potential for targeted treatments using specific stimulation. However, challenges in establishing robust and durable connections to soft and flexible implants limit their widespread adoption and long-term utility. Here, we present a novel method for integrating rigid electrical components, such as a standard USB-C connector, directly into a printed stretchable self-folding cuff electrode for chronic peripheral nerve interfacing. Our multi-material printing approach provides a gradual stiffness transition, effectively mitigating common failure points associated with mechanical stress at soft-rigid boundary. We demonstrate the integration of a wireless stimulation circuit and a robust USB-C implantable port, offering a plug- and-play solution for stable chronic electrophysiology experiments. Chronic implant studies in free-running locusts with USB-C connectors show reliable nerve recordings, capturing behavioral differences. The concept is further validated as a transcutaneous implanted port in rats for vagus nerve recordings. This work addresses a critical bottleneck in neurotechnology by enabling robust connectivity for implanted devices, which is essential for advancing peripheral nervous electrophysiology experiments in freely moving small vertebrates and insects.

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Extended perfused culture of cm-scale endocrine pancreatic tissues created through sacrificial embedded printing into alginate

Moeun, B.; Ebrahimi Orimi, H.; Lescot, T.; Brassard, J.; Paraskevas, S.; Lerouge, S.; Fortin, M.-A.; Leask, R.; Hoesli, C.

2026-04-10 bioengineering 10.64898/2026.04.07.715214 medRxiv
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Pluripotent stem cells represent a potentially unlimited cell source for the fabrication of human bioartificial tissues to study and treat degenerative conditions such as type 1 diabetes. Alginate is widely used for mammalian cell immobilization and the primary hydrogel studied for pancreatic islet encapsulation. Rheological properties of alginate solutions or fully gelled forms are unsuitable as support matrix for embedded 3D printing. We describe partially gelled self-healing alginate formulations tuned for embedded 3D printing. Perfusable multi-plane hierarchical networks branching into 10 parallel channels, obtained by 3D printing of Pluronic F127 into the alginate support, show high fidelity to computer-assisted models. Therapeutic {beta}-cell doses (40x106 cells/mL) within centimeter-thick perfusable constructs remained viable for at least 1 week of culture under flow, with rapid insulin secretion detected upon glucose challenges. Stem cell-derived islet clusters cultured in 5-channel contructs for 25 days differentiated towards functional insulin-expressing cells. We describe a novel approach to generate cm-scale perfusable endocrine pancreatic constructs using sacrificial embedded 3D printing into alginate. This approach offers an adaptable platform to engineer perfusable cm-scale functional endocrine pancreatic tissues and potentially other vascularized bioartificial tissues.

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Size Scaling of the Electrochemical Performance of Ti3C2Tx MXene Microelectrode Arrays for Electrophysiological Recording and Stimulation

Averbeck, S. R.; Garg, R.; Dong, R.; Hurwitz, D.; Apollo, N. V.; Beauchamp, M. S.; Vitale, F.

2026-03-23 bioengineering 10.64898/2026.03.19.712102 medRxiv
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Miniaturized neural interfaces for research, diagnostics, and neuromodulation therapies require electrode materials that maintain low impedance and high charge injection capacity as device dimensions shrink to ensure high-quality recordings and safe stimulation. Conventional interfaces rely on metals like platinum (Pt), which are limited by intrinsically high impedance and low charge transfer capacity, reducing their performance in sub-100 {micro}m applications. Ti3C2Tx MXene has emerged as a promising alternative for high-density recording and stimulation interfaces, though the fundamental charge transfer mechanisms governing its performance remain poorly understood. This study evaluates Ti3C2Tx MXene microelectrodes across a range of diameters (25 - 500 {micro}m) and systematically elucidates the mechanisms governing their recording and stimulation capabilities. Electrochemical impedance spectroscopy, cyclic voltammetry, and voltage transient measurements - supported by equivalent-circuit modeling - revealed enhanced recording and stimulation capabilities of the MXene microelectrodes over size-matched Pt microelectrodes, attributed to reduced charge-transfer resistance and increased double-layer capacitance. Finally, varying the volume and concentration of the spray-coated Ti3C2Tx films showed that increased MXene concentration and volume enhanced performance by creating thicker, rougher interfaces. Together, these results establish Ti3C2Tx MXene as a promising electrode material with exceptional performance at the microscale.

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Online characterization of surrogate metrics for metabolic phenotype in human induced pluripotent stem cell bioprocessing

Colter, J.; Kallos, M.; Murari, K.

2026-05-12 bioengineering 10.64898/2026.05.08.723750 medRxiv
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Human induced pluripotent stem cells (hiPSCs) are the most accessible source material for derivation of stem-cell-based therapies at scale. However, a disconnect exists between quality characteristics of phenotype in the pluripotent state, and downstream metrics for efficacy and safety. Bridging this gap is a major challenge. Given hiPSC plasticity, environmental conditioning plays a crucial role in guiding phenotype. This work presents a parallelizable scale-down approach, acquiring real-time data to inform hiPSC phenotype throughout biomanufacturing. We developed an optoelectronic instrumentation suite capable of measuring pH, dissolved oxygen, and cell density as important surrogates for phenotype in a scale-down expansion bioprocess. We were successful in obtaining continuous, integrated parametric data throughout cultivation and estimating metabolic characteristics of hiPSC phenotype. This system functions as a proof-of-concept tool for development of predictive models and monitoring strategies around the elucidation of phenotypic dynamics within hiPSC biomanufacturing. We have demonstrated a feasible open-source multivariate continuous monitoring approach at research scale that combines common process parameters with a scattering measurement against aggregate density. The combination of these parameters enables surrogate measurement of a metric for metabolic phenotype. This contribution emphasizes monitoring how the bioprocess influences variables important in the context of cell state, in broader pursuit of better understanding the link to downstream functionality and global optima in hiPSC biomanufacturing for regenerative medicine.

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3D Droplet-Based Bioprinting of Customized In Vitro Head and Neck Cancer Tumor Microenvironment Models

Messuri, V.; Ha, A.; Cruz, L. A.; Harrington, D.

2026-03-31 bioengineering 10.64898/2026.03.27.714925 medRxiv
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In vitro models are increasingly critical for interrogating cancer biology and therapeutic response, however, accurately recapitulating the tumor microenvironment (TME) remains a persistent challenge, particularly in head and neck cancers (HNC) characterized by complex cell-matrix interactions and heterogeneity. Current models often lack independent tunability of biochemical and biophysical cues, limiting systematic investigation of microenvironmental cues in a high-throughput format. Here, we establish a 3D droplet-based bioprinting platform for the fabrication of customizable in vitro TME models using poly(ethylene glycol) (PEG) hydrogels. Human HNC cell lines (FaDu and 2A3) with differing HPV statuses were bioprinted into PEG matrices spanning physiologically relevant stiffnesses (0.7-4.8 kPa) and compositions, including non-functionalized PEG and peptide-functionalized PEG (PEGfnc: RGD, YIGSR, CNYYSNS) and cultured for 7 days. Cluster growth, cell viability, and cluster morphology were assessed across multiple time points, matrix compositions, and matrix stiffnesses. Proliferation and endpoint phenotype expression were visualized using confocal microscopy through immunofluorescence. Results indicated enhanced cell viability in PEGfnc matrices, compared to non-functionalized matrices, while effect of matrix stiffness was less prominent. Median cluster size reached 40-50 m by day 7, and linear mixed-effects modeling identified how changes in cluster surface area, volume, and tumoroid complexity varied with cell type, matrix, and stiffness. By decoupling and systematically varying key TME parameters, this approach provides a robust and scalable framework for dissecting tumor-matrix interactions and advancing physiologically relevant in vitro models for cancer research and therapeutic screening.

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Spatial control of light-responsive proteins and optogenetics within hydrogels via volumetric bioprinting

Ribezzi, D.; Catala, P.; Nijssen, O.; Florczak, S.; Groessbacjer, G.; Nijenhuis, W.; Bernal, P.; Nijhoff, B.; Delrot, P.; Malda, J.; Hierholzer, A.; Fussenegger, M.; Kapitein, L.; Levato, R.

2026-04-13 bioengineering 10.64898/2026.04.09.717404 medRxiv
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Spatiotemporal control over cell fate and behaviour within bioprinted constructs remains a key challenge in tissue engineering. Optogenetics offers versatile potential for non-invasive regulation of biological processes. Yet, its integration within large-scale, cell-laden bioprinted materials is still limited, especially considering spatial constraints of existing light delivery methods. In this study, we introduce a novel approach that repurposes tomographic volumetric bioprinting to enable post-printing stimulation of photosensitive protein-switches and optogenetic circuits in cells deep within hydrogel constructs. By converging different bioprinting approaches, computer vision, context-aware model generation, and synthetic biology and cell engineering, we demonstrated selective activation of a fluorescent, light-responsive protein probe within multi-material centimeter-scale constructs. Moreover, leveraging a multi-wavelength volumetric bioprinter, we further demonstrate this concept by selectively stimulating cells expressing a near-infrared optogenetic system that triggers gene expression and the induction of pancreas-specific transcription factors. The described methods provide platforms for remote, repeatable, and localized control of biological events in volumetric constructs, opening new possibilities for advanced tissue models, and dynamic tuning of cell-mediated protein production in engineered living systems.

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Modular Integration of Impedance Sensing for Real-Time Assessment of Barrier Integrity

Farajollahi, S.; Mansouri, M.; De Silva, D.; Hsu, M.-C.; Chen, K.; Hughes, A.; Esmaili, P.; Goyal, K.; Day, S. W.; McGrath, J. L.; Abhyankar, V. V.

2026-03-10 bioengineering 10.64898/2026.03.08.703312 medRxiv
Top 0.1%
3.9%
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Microphysiological systems (MPS) are essential for modeling tissue barriers, yet integrating electrical readouts often requires permanently sealed microfluidic architectures that limit access to open-well (direct-access) workflows used in bioscience laboratories. To resolve this issue, we present a modular approach in which functional components are added and removed from a standard MPS core using a magnetic interface. This design preserves compatibility with established open-well protocols for seeding and downstream analysis, while microfluidic perfusion or electrical sensing capabilities are added only when needed. We demonstrate this approach with an impedance-sensing module that enables continuous impedance measurements to assess barrier function. By fitting spectra to an equivalent circuit model, we quantify junctional and non-junctional electrical contributions to barrier integrity over time, alongside conventional single-frequency TEER, and complementary permeability and imaging readouts. We apply this platform across three representative use cases, including LPS-induced disruption, shear stress-mediated strengthening, and compatibility with barrier models formed above a 3D hydrogel matrix.

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Damping nonlinearity in agarose hydrogels under relative humidity: balancing network stiffness and energy dissipation

Obojo, I.; Dedola, M.; Nelms, K.; de Kergariou, C.; Patrick, I.; Cademartiri, L.; Armstrong, J.; Perriman, A. W.; Scarpa, F.

2026-05-06 bioengineering 10.64898/2026.05.02.722420 medRxiv
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3.8%
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Sustainable, biodegradable elastomers are needed to replace fossil-based alternatives and reduce the environmental impact of traditional vibration damping materials. We investigate agarose-based hydrogels as eco-friendly vibration absorbers, examining the combined effects of polymer concentration (1-7 wt%), relative humidity (55-98%), and mechanical pre-stress on their dynamic mechanical properties. Frequency-dependent viscoelastic and vibration transmissibility tests, supported by Gaussian Process Regression (GPR), reveal that increasing agarose concentration enhances the storage modulus (E') by over an order of magnitude, reaching[~] 5 MPa depending on humidity and applied prestress. Remarkably, the damping efficiency--characterised by the loss factor (tan(d))--exhibits a highly non-monotonic trend. Maximum energy dissipation is observed at intermediate network densities, with tan(d) up to 0.21 and a loss modulus of[~] 515 kPa at 5 w% and 75% relative humidity, comparable to synthetic elastomers. GPR analysis shows that prestress controls nonlinear stiffening and transmissibility resonance behavior, while shifting peak damping from 5 wt% to 1 wt% agarose as prestress increases. These findings underscore the mechanical tunability and sustainability of agarose hydrogels, providing potential design guidance for biodegradable vibration mitigation materials.