bims-enlima Biomed News
on Engineered living materials
Issue of 2025–10–19
48 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool
  1. Applications of synthetic polymers directed toward living cells.
  2. Sonicated inks and focused-ultrasound writing enable deep-penetration acoustic volumetric printing.
  3. Self-Assembly of Heterogeneous Hydrogels Enabled by Molecular Bridges.
  4. Hijacking a bacterial ABC transporter for genetic code expansion.
  5. Adaptive 3D printing.
  6. Electrochromic DNA-based bioink with rapid interfacial gelation for bioprinting applications.
  7. ATP-Powered Signaling Between Artificial and Living Cells.
  8. Multiscale interface engineering in biohybrid composites for biomedical applications.
  9. Spatially Programmable Electroadhesive Enables In Situ Site-Selective Functional Coupling.
  10. A recursive enzymatic competition network capable of multitask molecular information processing.
  11. Programmable promoter editing for precise control of transgene expression.
  12. StreptoCAD: An Open-Source Software Toolbox Automating Genome Engineering Workflows in Streptomycetes.
  13. Fabrication of Protein-Polysaccharide-Based Hydrogel Composites Incorporated with Magnetite Nanoparticles as Acellular Matrices.
  14. Empathi: embedding-based phage protein annotation tool by hierarchical assignment.
  15. Wearable disposable electrotherapy.
  16. Semi-crystalline and amorphous materials via multi-temperature 3D printing from one formulation.
  17. Actin Polymerizing Motors to Assist Cytoskeleton-like Networks Formation in Artificial Cells.
  18. Beyond Packaging: A Perspective on the Emerging Applications of Biodegradable Polymers in Electronics, Sensors, Actuators, and Healthcare.
  19. Ultrasoft Zwitterionic Eutectogels for Adaptive and Durable Sensing at Dynamic Skin Interfaces.
  20. In vivo mechano-tissue engineering by hydrogels capable of transmitting intercellular mechanical stress.
  21. Harnessing precision in hydrogel architectures through reversible-deactivation radical polymerisation techniques.
  22. Seaweed Derived Polysaccharides as Sustainable Biomaterials for Tissue Engineering Applications.
  23. Reprocessable and Recyclable Cellulosic Network Polymers with Intrinsic Flame Retardancy via Dynamic Covalent Cross-Linking.
  24. Long-range optical coupling with epsilon-near-zero materials.
  25. Designing around immune memory to counter PEG immunogenicity.
  26. Synergistic Effects of Dynamic and Stable Networks on the Mechanical Behavior of Poly(vinyl alcohol) Hydrogels.
  27. Injectable Hydrogels for Programmable Nanoparticle Release.
  28. A tumor-on-a-chip for in vitro study of CAR-T cell immunotherapy in solid tumors.
  29. Bubble-driven cell detachment.
  30. A compact model of Escherichia coli core and biosynthetic metabolism.
  31. Automated Microfluidic Platform for Single Spheroid Culture and Extracellular Vesicle Isolation: Application to Spheroid Transcriptomic Profiling.
  32. Engineered 3D immuno-glial-neurovascular human miBrain model.
  33. Hermetic stretchable seals enabled by a viscoplastic surface effect.
  34. Laser-assisted electrohydrodynamic printing of sub-microscale 3D conductive features on low-melting-point polymeric substrates.
  35. Durable, pure water-fed, anion-exchange membrane electrolyzers through interphase engineering.
  36. Architects of molecular cages win Chemistry Nobel.
  37. Soft and Strong: Elastic Conductors with Bio-Inspired Self-Protection.
  38. Piezo1 regulates the mechanotransduction of soft matrix viscoelasticity.
  39. Reagentless Real-Time ATP Monitoring with New DNA Aptamers.
  40. Inhibition of bacterial growth by antibiotics: a minimal model.
  41. Invasin-functionalized PIC hydrogels enable long-term 3D culture of epithelial organoids.
  42. Light-gated redox switching and actuation in polymer hydrogels.
  43. Scaling Laws for Passive Polymer Dynamics in Active Turbulence.
  44. Design, Synthesis, and Screening of COFs for CO2 Adsorption by Gaussian Process.
  45. Predicting sequence-specific amplification efficiency in multi-template PCR with deep learning.
  46. Directed evolution.
  47. Characterisation of cuticle mechanical properties: analysing stiffness in layered living systems to understand surface buckling patterns.
  48. Activity-based selection for enhanced base editor mutational scanning.
  1. Nat Synth. 2024 Aug;3(8): 943-957
    Applications of synthetic polymers directed toward living cells.
    Anqi Zhang, Spencer Zhao, Jonathan Tyson, Karl Deisseroth, Zhenan Bao.
      Cells execute remarkable functions using biopolymers synthesized from natural building blocks. Engineering cells to leverage the vast array of synthesizable abiotic polymers could provide enhanced or entirely new cellular functions. In this review, we discuss the applications of in situ synthesized abiotic polymers in three distinct domains: intracellular polymerization, cell surface polymerization, and extracellular polymerization. These advances have led to novel applications in various areas, such as cancer therapy, cell imaging, cellular activity manipulation, cell protection, and electrode assembly. Examples of these synthetic approaches can be applied across all domains of life, ranging from microbes and cultured mammalian cells to plants and animals. Finally, we discuss challenges and future opportunities in this emerging field, which could enable new synthetic approaches to influence biological processes and functions.
    DOI:  https://doi.org/10.1038/s44160-024-00560-2
  2. Nat Protoc. 2025 Oct 15.
    Sonicated inks and focused-ultrasound writing enable deep-penetration acoustic volumetric printing.
    Xiao Kuang, Qiangzhou Rong, Saud Belal, Nanchao Wang, Tri Vu, Abigail Herrera-Ruiz, Zebang Zhang, Yu Shrike Zhang, Junjie Yao.
      Volumetric printing is an emerging additive manufacturing technique that builds 3D constructs with enhanced printing speed and surface quality by forgoing the stepwise ink renewal. Existing volumetric printing techniques almost exclusively rely on light energy to trigger photopolymerization in transparent inks, limiting the material choice, build size, cell density and in vivo printability. Sonicated ink (or sono-ink) and focused-ultrasound (FUS) writing have been developed for deep-penetration acoustic volumetric printing (DAVP) within optically scattering media and beneath soft tissues. This technology uses rapid sono-thermal heating to induce material solidification at the FUS focal region, constructing 3D objects without the need for a build platform. Here, we describe two procedures necessary to achieve DAVP. First, we provide a step-by-step guide for preparing and characterizing multicomponent viscoelastic self-enhancing sono-inks. The lower critical solution temperature polymers are synthesized as a phase-transition reversible acoustic absorber to formulate the sono-inks. We characterize the rheological, acoustic and cytocompatibility properties of the sono-inks. We then detail the procedure for building a 3D FUS printer by integrating an FUS transducer with a 3D printing platform. The development of the 3D FUS printer needs basic knowledge of the ultrasound system, FUS physics and volumetric printing. Using the sono-inks and the 3D FUS printer, we further provide guidance to evaluate the sono-thermal heating effect and characterize the volumetric printing resolutions. We demonstrate the printing of volumetric constructs through optically scattering materials such as centimeter-thick biological tissues. The procedures require ~470 h to complete.
    DOI:  https://doi.org/10.1038/s41596-025-01258-1
  3. ACS Appl Mater Interfaces. 2025 Oct 16.
    Self-Assembly of Heterogeneous Hydrogels Enabled by Molecular Bridges.
    Yidi Lu, Xi Chen, Jingda Tang, Guogao Zhang.
      Synthetic hydrogels typically exhibit homogeneous microstructures, which are formed through the polymerization of aqueous hydrogel precursors. While the aqueous nature of hydrogel precursors enables diverse processing methods, it concurrently presents a challenge: hydrogel precursors are immiscible with hydrophobic constituents. This limitation hinders efforts to develop heterogeneous microstructures in synthetic hydrogels. Here, we demonstrate that a common hydrogel monomer can function as a molecular bridge between a water molecule and a hydrophobic polymer, enabling the formation of a stable, homogeneous precursor solution of hydrophobic polymer, hydrogel monomer, and water. Upon polymerization of the hydrogel monomer, the bridging effect diminishes, rendering the hydrophobic polymer insoluble and inducing phase separation. The phase separation is arrested during polymerization, yielding self-assembled microstructures. The self-assembled heterogeneous hydrogels exhibit significantly enhanced mechanical performance compared to conventional homogeneous hydrogels. This strategy is broadly applicable to various hydrogel systems, providing a versatile approach for engineering heterogeneous microstructures in synthetic hydrogels.
    Keywords:  heterogeneous microstructures; hydrogel; molecular bridges; phase separation; self-assemble
    DOI:  https://doi.org/10.1021/acsami.5c17363
  4. Nature. 2025 Oct 15.
    Hijacking a bacterial ABC transporter for genetic code expansion.
    Tarun Iype, Maximilian Fottner, Paul Böhm, Carlos Piedrafita, Yannis Möller, Michael Groll, Kathrin Lang.
      The site-specific encoding of non-canonical amino acids (ncAAs) provides a powerful tool for expanding the functional repertoire of proteins1-4. Its widespread use for basic research and biotechnological applications is, however, hampered by the low efficiencies of current ncAA incorporation strategies. Here we reveal poor cellular ncAA uptake as a main obstacle to efficient genetic code expansion and overcome this bottleneck by hijacking a bacterial ATP-binding cassette (ABC) transporter5 to actively import easily synthesizable isopeptide-linked tripeptides that are processed into ncAAs within the cell. Using this approach, we enable efficient encoding of a variety of previously inaccessible ncAAs, decorating proteins with bioorthogonal6 and crosslinker7 moieties, post-translational modifications8,9 and functionalities for chemoenzymatic conjugation. We then devise a high-throughput directed evolution platform to engineer tailored transporter systems for the import of ncAAs that were historically refractory to efficient uptake. Customized Escherichia coli strains expressing these evolved transporters facilitate single and multi-site ncAA incorporation with wild-type efficiencies. Additionally, we adapt the tripeptide scaffolds for the co-transport of two different ncAAs, enabling their efficient dual incorporation. Collectively, our study demonstrates that engineering of uptake systems is a powerful strategy for programmable import of chemically diverse building blocks.
    DOI:  https://doi.org/10.1038/s41586-025-09576-w
  5. Nat Mater. 2025 Oct 14.
    Adaptive 3D printing.
    Alison Stoddart.
      
    DOI:  https://doi.org/10.1038/s41563-025-02387-4
  6. Nanoscale Horiz. 2025 Oct 13.
    Electrochromic DNA-based bioink with rapid interfacial gelation for bioprinting applications.
    Yoonbin Ji, Taehyeon Kim, Iksoo Jang, Jong Bum Lee.
      Recent advances in biofabrication demand bioinks that are not only biocompatible and mechanically suitable for tissue engineering, but also responsive to dynamic biological and electrical cues. Here, we introduce a DNA-viologen hybrid bioink system that rapidly forms a structurally defined hydrogel through interfacial gelation, enabling precise spatial control of gelation without requiring external triggers. The resulting hydrogel exhibits a hollow capsule morphology, tunable viscoelasticity, and excellent printability, making it suitable for soft tissue-direct patterning applications. Beyond its mechanical properties, this system integrates reversible electrochromic functionality, allowing dynamic optical responses under electrical stimulation. Taken together, this proof-of-concept study highlights how the integration of electroactive behavior with the programmability of DNA can open opportunities for multifunctional soft materials. The combination of rapid formation, structural adaptability, and electrical responsiveness underscores its promise in emerging applications, including wearable devices, biosensors, and stimuli-responsive platforms.
    DOI:  https://doi.org/10.1039/d5nh00488h
  7. Angew Chem Int Ed Engl. 2025 Oct 18. e202517843
    ATP-Powered Signaling Between Artificial and Living Cells.
    Soumya Sethi, Charu Sharma, Andreas Walther.
      ATP is the energy currency of life and is overabundant in the tumor microenvironment, where it has been suggested as a target for cancer therapy. We introduce ATP-dissipative delivery of DNA signals from artificial cells to living cells by exploiting an ATP-driven reaction network that transiently ejects DNA Signal strands from the shielded artificial cell interior to the extracellular medium of living cells. We customize the Signal for intracellular uptake or for extracellular instruction using a cytokine-ssDNA chimera that can trigger efficient intracellular downstream signaling programs. Our study discusses details of system design on a timer circuit and artificial cell level, system integration challenges, and how ATP concentrations regulate the transient delivery. The strategy can be extended to deliver therapeutic oligonucleotides for applications in gene therapy and gene silencing. For cancer therapy, it can use naturally enhanced ATP levels to induce selective delivery of therapeutic oligonucleotides.
    Keywords:  ATP‐fueled reaction network; ATP‐responsive biomaterials; Artificial cell signaling; Artificial cell–living cell communication; Dissipative reaction network
    DOI:  https://doi.org/10.1002/anie.202517843
  8. Mater Today Bio. 2025 Dec;35 102382
    Multiscale interface engineering in biohybrid composites for biomedical applications.
    Yi Wang, Tingyu Wang, Ran Tang, Dongtao Wang, Xianglong Zhang, Hiromi Nagaumi, Bowen Yang, Xu Ren, Jin Huang, Yingjie Zhang, Jiming Hao, Qiang Ma.
      Multiscale composites with engineered interfaces have emerged as a cornerstone in the development of next-generation biomedical materials. This review provides a comprehensive and structured overview of interface design strategies spanning nano-to macro-scales, emphasizing their role in modulating mechanical performance, biological signaling, and adaptive functionality. We categorize key approaches into three synergistic domains: hierarchical structuring for mechanical and cellular control, stimuli-responsive interfaces for dynamic biomedical functions, and bioinspired or living systems that mimic and integrate with biological environments. Advanced fabrication techniques-including additive manufacturing, surface nanofunctionalization, and layer-by-layer assembly-are reviewed alongside multiscale characterization tools for structural and interfacial analysis. We further link these interface strategies to a range of biomedical applications, such as osteochondral scaffolds, vascularized implants, antibacterial coatings, smart drug delivery carriers, and neural-integrated electronics. Biological interactions, including protein adsorption, mechanotransduction, and immune modulation, are explored to elucidate how engineered interfaces influence cellular fate and integration. Finally, we outline key challenges-such as manufacturing scalability, long-term biocompatibility, and regulatory approval-and propose forward-looking solutions enabled by AI-driven materials design and organ-on-chip validation. This review serves as a conceptual and technical roadmap for researchers developing multifunctional biomaterials through the lens of multiscale interface engineering.
    Keywords:  Hierarchical design; Interface engineering; Living biomaterials; Multiscale composites; Stimuli-responsive systems
    DOI:  https://doi.org/10.1016/j.mtbio.2025.102382
  9. Adv Mater. 2025 Oct 14. e11039
    Spatially Programmable Electroadhesive Enables In Situ Site-Selective Functional Coupling.
    Yuting Guo, Zhuoming Liang, Guoshi Xu, Zhen Gu, Yuheng Xu, Michael Raphael Panganiban, Xue Cai, Jet Yong Kiat Lim, Jiguang Zhang, Jingxiu Huang, Tingting Fan, Qi Gu, Yuxin Liu.
      Precise intraoperative integration of bioelectronic devices with wet tissue surfaces remains a challenge due to the limited spatial control of adhesion sites. Here, an in situ spatially programmable electrical bioadhesive (termed "STICH") is reported that enables site-selective adhesion and functional coupling via light-activated bonding with wet biological tissue. Upon irradiation with patterned green light, Rose Bengal in a chitosan/silver nanowire hydrogel matrix generates singlet oxygen, which oxidizes amino acid residues into carbonyl groups on the tissue surface. The covalent bonding is then formed between the newly formed reactive carbonyl group and amine groups on chitosan. The spatially programmable adhesive allows robust tissue bonding with a lap-shear strength of 160 kPa and precise adhesion regions at ≈2 µm resolution. The light-patternable adhesive enables spatially resolved mechanical coupling for directional electromechanical sensing on ex vivo cardiac tissue. The low impedance adhesive interface also provides spatially programmed electrical coupling for in vivo neuromuscular stimulation on intraoperatively selected muscle groups. This platform advances microscale device-tissue integration and paves the way for reconfigurable bioelectronic therapies.
    Keywords:  bioadhesive interfaces; mechanical and electrical coupling; spatially programmable
    DOI:  https://doi.org/10.1002/adma.202511039
  10. Nat Chem. 2025 Oct 17.
    A recursive enzymatic competition network capable of multitask molecular information processing.
    Souvik Ghosh, Mathieu G Baltussen, Anna C Knox, Rianne Haije, Quentin Duez, Anastasia T Tsitsimeli, Man Him Chak, Jonathon E Beves, Wilhelm T S Huck.
      Living cells understand their environment by combining, integrating and interpreting chemical and physical stimuli. Despite considerable advances in the design of enzymatic reaction networks that mimic hallmarks of living systems, these approaches lack the complexity to fully capture biological information processing. Here we introduce a scalable approach to design complex enzymatic reaction networks capable of reservoir computation based on recursive competition of substrates. This protease-based network can perform a broad range of classification tasks based on peptide and physicochemical inputs and can simultaneously perform an extensive set of discrete and continuous information processing tasks. The enzymatic reservoir can act as a temperature sensor from 25 °C to 55 °C with 1.3 °C accuracy, and performs decision-making, activation and tuning tasks common to neurological systems. We show a possible route to temporal information processing and a direct interface with optical systems by demonstrating the extension of the network to incorporate sensitivity to light pulses. Our results show a class of competition-based molecular systems capable of increasingly powerful information-processing tasks.
    DOI:  https://doi.org/10.1038/s41557-025-01981-y
  11. Nat Biotechnol. 2025 Oct 13.
    Programmable promoter editing for precise control of transgene expression.
    Sneha R Kabaria, Yunbeen Bae, Mary E Ehmann, Brittany A Lende-Dorn, Adam M Beitz, Emma L Peterman, Kasey S Love, Deon S Ploessl, Kate E Galloway.
      Subtle changes in gene expression direct cells to distinct cellular states. Identifying and controlling dose-dependent transgenes require tools for precisely titrating expression. Here, we develop a highly modular, extensible framework called DIAL for building editable promoters that allow for fine-scale, heritable changes in transgene expression. Using DIAL, we increase expression by recombinase-mediated excision of spacers between the binding sites of a synthetic zinc finger transcription factor and the core promoter. By nesting varying numbers and lengths of spacers, DIAL generates a tunable range of unimodal setpoints from a single promoter. Through small-molecule control of transcription factors and recombinases, DIAL supports temporally defined, user-guided control of transgene expression that is extensible to additional transcription factors. Lentiviral delivery of DIAL generates multiple setpoints in primary cells and induced pluripotent stem cells. As promoter editing generates stable states, DIAL setpoints are heritable, facilitating mapping of transgene levels to phenotype and fate in direct conversion to induced motor neurons. The DIAL framework opens opportunities for tailoring transgene expression and improving the predictability and performance of gene circuits across diverse applications.
    DOI:  https://doi.org/10.1038/s41587-025-02854-y
  12. ACS Synth Biol. 2025 Oct 14.
    StreptoCAD: An Open-Source Software Toolbox Automating Genome Engineering Workflows in Streptomycetes.
    Lucas Levassor, Christopher M Whitford, Søren D Petersen, Kai Blin, Tilmann Weber, Rasmus J N Frandsen.
      Streptomycetes hold immense potential for discovering novel bioactive molecules for applications in medicine or sustainable agriculture. However, high-throughput exploration is hampered by the current Streptomyces genetic engineering methods that involve the manual design of complex experimental molecular biological engineering strategies for each targeted gene. Here, we introduce StreptoCAD, an open-source software toolbox that automates and streamlines the design of genome engineering strategies in Streptomyces, supporting various CRISPR-based and gene overexpression methods. Once initiated, StreptoCAD designs all necessary DNA primers and CRISPR guide sequences, simulates plasmid assemblies (cloning) and the resulting modification of the genomic target(s), and further summarizes the information needed for laboratory implementation and documentation. StreptoCAD currently offers six design workflows, including the construction of overexpression libraries, base-editing, including multiplexed CRISPR-BEST plasmid generation, and genome engineering using CRISPR-Cas9, CRISPR-Cas3, and CRISPRi systems. In addition to automating the design process, StreptoCAD further secures compliance with the FAIR principles, ensuring reproducibility and ease of data management via standardized output files. To experimentally demonstrate the design process and output of StreptoCAD, we designed and constructed a series of gene overexpression strains, and performed CRISPRi knockdowns in Streptomyces Gö40/10, underscoring the tool's efficiency and user-friendliness.. This tool simplifies complex genetic engineering tasks and promotes collaboration through standardized workflows and design parameters. StreptoCAD is set to transform genome engineering in Streptomyces, making sophisticated genetic manipulations accessible for all and accelerating natural product discovery.
    Keywords:  CRISPR-Cas systems; FAIR principles; genome engineering; overexpression libraries; streptomyces; synthetic biology
    DOI:  https://doi.org/10.1021/acssynbio.5c00261
  13. Int J Mol Sci. 2025 Sep 24. pii: 9338. [Epub ahead of print]26(19):
    Fabrication of Protein-Polysaccharide-Based Hydrogel Composites Incorporated with Magnetite Nanoparticles as Acellular Matrices.
    Anet Vadakken Gigimon, Hatim Machrafi, Claire Perfetti, Patrick Hendrick, Carlo S Iorio.
      Hydrogels with protein-polysaccharide combinations are widely used in the field of tissue engineering, as they can mimic the in vivo environments of native tissues, specifically the extracellular matrix (ECM). However, achieving stability and mechanical properties comparable to those of tissues by employing natural polymers remains a challenge due to their weak structural characteristics. In this work, we optimized the fabrication strategy of a hydrogel composite, comprising gelatin and sodium alginate (Gel-SA), by varying reaction parameters. Magnetite (Fe3O4) nanoparticles were incorporated to enhance the mechanical stability and structural integrity of the scaffold. The changes in hydrogel stiffness and viscoelastic properties due to variations in polymer mixing ratio, crosslinking time, and heating cycle, both before and after nanoparticle incorporation, were compared. FTIR spectra of crosslinked hydrogels confirmed physical interactions of Gel-SA, metal coordination bonds of alginate with Ca2+, and magnetite nanoparticles. Tensile and rheology tests confirmed that even at low magnetite concentration, the Gel-SA-Fe3O4 hydrogel exhibits mechanical properties comparable to soft tissues. This work has demonstrated enhanced resilience of magnetite-incorporated Gel-SA hydrogels during the heating cycle, compared to Gel-SA gel, as thermal stability is a significant concern for hydrogels containing gelatin. The interactions of thermoreversible gelatin, anionic alginate, and nanoparticles result in dynamic hydrogels, facilitating their use as viscoelastic acellular matrices.
    Keywords:  biomaterials; hydrogel composites; mechanical stability; nanoparticles; protein–polysaccharide; self-healing; tissue engineering
    DOI:  https://doi.org/10.3390/ijms26199338
  14. Nat Commun. 2025 Oct 14. 16(1): 9114
    Empathi: embedding-based phage protein annotation tool by hierarchical assignment.
    Alexandre Boulay, Audrey Leprince, François Enault, Elsa Rousseau, Clovis Galiez.
      Bacteriophages, viruses infecting bacteria, are estimated to outnumber their cellular hosts by 10-fold, acting as key players in all microbial ecosystems. Under evolutionary pressure by their host, they evolve rapidly and encode a large diversity of protein sequences. Consequently, the majority of functions carried by phage proteins remain elusive. Current tools to comprehensively identify phage protein functions from their sequence either lack sensitivity (those relying on homology for instance) or specificity (assigning a single coarse grain function to a protein). Here, we introduce Empathi, a protein-embedding-based classifier that assigns functions in a hierarchical manner. New categories were specifically elaborated for phage protein functions and organized such that molecular-level functions are respected in each category, making them well suited for training machine learning classifiers based on protein embeddings. Empathi outperforms homology-based methods on a dataset of cultured phage genomes, tripling the number of annotated homologous groups. On the EnVhogDB database, the most recent and extensive database of metagenomically-sourced phage proteins, Empathi doubled the annotated fraction of protein families from 16% to 33%. Having a more global view of the repertoire of functions a phage possesses will assuredly help to understand them and their interactions with bacteria better.
    DOI:  https://doi.org/10.1038/s41467-025-64177-5
  15. Nat Commun. 2025 Oct 13. 16(1): 9060
    Wearable disposable electrotherapy.
    Mohamad FallahRad, Kyle Donnery, Mojtaba Belali Koochesfahani, Zeeshan Chaudhry, Rayyan Bhuiyan, Benjamin Babaev, Matthew Saw, Tiffany Liu, Miguel R Diaz Uraga, Mahdi Zaman, Kisholoy Saha, Osvaldo Velarde, Ayman Rddad, Niranjan Khadka, Myesha Thahsin, Alexander Couzis, Marom Bikson.
      We design and validate an electrotherapy platform without electronic components, using printed, abundant, environmentally benign materials. Whereas existing electrotherapy devices use an independent power source and electronics to generate and control stimulation currents, our design eliminates the need for these components. Device production relies only on scalable additive manufacturing and common materials, minimizing cost and environmental impact. The disposable single-use platform (as discreet as adhesive bandages) is activated simply by placement on the body. A prescribed electrotherapy dose is regulated by a flexible 3D electrochemical architecture tailored to each application by a bespoke operational theory. The single-dose usability of this platform is a categorical shift from existing approaches with durable equipment that require programming and assembly to disposable electrodes for each use. Our Wearable Disposable Electrotherapy technology can be distributed like pharmacotherapy, with indications spanning neuromodulation of brain disorders, skin health and wound healing, transcutaneous drug delivery, and bioelectronic medicine.
    DOI:  https://doi.org/10.1038/s41467-025-64101-x
  16. Nat Commun. 2025 Oct 15. 16(1): 8961
    Semi-crystalline and amorphous materials via multi-temperature 3D printing from one formulation.
    Michael Göschl, Dominik Laa, Thomas Koch, Evan Constable, Xin Liu, Andrei Pimenov, Jürgen Stampfl, Robert Liska, Katharina Ehrmann.
      Multi-material 3D printing concerns the use of two or more 3D printable materials within a single printed part. The result is a composite that benefits from the combined properties of the individual 3D printed materials. Typically, a distinct differentiation between material properties can only be achieved using multiple feedstocks and advanced engineering solutions. In this work, we create multi-material 3D printed photopolymer parts from a single monomer mixture through simple adjustments in printing temperature and light intensity. We achieve this by employing a liquid crystalline (LC) monomer that forms a highly stable LC phase in conjunction with a trifunctional thiol crosslinker. A drastic change in mechanical and optical properties was achieved depending on the presence of an LC phase during polymerization. The proof of principle from bulk experiments could be translated fully into 3D printing, achieving pixel-to-pixel resolution of the material properties solely guided by changing the printing parameters temperature and light intensity. The versatility of produced multi-material composite parts is demonstrated in shape memory applications and methods for chemical data storage and encryption.
    DOI:  https://doi.org/10.1038/s41467-025-64092-9
  17. ACS Nano. 2025 Oct 16.
    Actin Polymerizing Motors to Assist Cytoskeleton-like Networks Formation in Artificial Cells.
    Miguel A Ramos Docampo, Cathrine Abild Meyer, Cecilie Ryberg, Daniel E Otzen, Christian Hirsch, Brigitte Städler.
      Artificial cells are man-made systems that imitate specific functions of biological cells to study or harness cellular behavior. Biological cells can respond to external forces and signals by altering their shape, undergoing deformation, and generating the mechanical forces required for their movement. The cytoskeleton orchestrates this process through the coordinated action of actin filaments, intermediate filaments, and microtubules. Examples of artificial cells that sense and adapt to changes in their environment owing to cytoskeleton rearrangement have extensively been explored. These efforts focus on the use of biomolecules that stochastically self-assemble in the lumen of an artificial cell. Here, we employ actin polymerizing nanomotors to assist cytoskeleton formation inside artificial cells. Nano- and micromotors are a class of active colloids that can self-propel outperforming Brownian motion. Inspired by natures' way of leveraging biopolymerization reactions to sustain locomotion in microorganisms or in organelles within cells, we imitate the mechanism of motion of the food-born bacteria Listeria monocytogenes. Specifically, we coat polystyrene particles with an actin recruiting protein that allows for actin filament polymerization in a mammalian cell lysate environment. This polymerization results in up to a 3-fold increase in the propulsion of the motors compared to their Brownian motion. Lastly, we show that these motors can be encapsulated inside hybrid vesicle-based artificial cells made of amphiphilic block copolymers and phospholipids, forming actin filaments that assemble into a cytoskeleton-like network. Taken together, this effort highlights the synergistic integration of bottom-up synthetic biology and active matter, demonstrating how their convergence can advance the design of life-like systems.
    Keywords:  ActA; actin polymerization; artificial cells; nanomotors; synthetic cytoskeleton
    DOI:  https://doi.org/10.1021/acsnano.5c12624
  18. Materials (Basel). 2025 Sep 26. pii: 4485. [Epub ahead of print]18(19):
    Beyond Packaging: A Perspective on the Emerging Applications of Biodegradable Polymers in Electronics, Sensors, Actuators, and Healthcare.
    Reshma Kailas Kumar, Chaoying Wan, Paresh Kumar Samantaray.
      Biopolymers have emerged as a transformative class of materials that reconcile high-performance functionality with environmental stewardship. Their inherent capacity for controlled degradation and biocompatibility has driven rapid advancements across electronics, sensing, actuation, and healthcare. In flexible electronics, these polymers serve as substrates, dielectrics, and conductive composites that enable transient devices, reducing electronic waste without compromising electrical performance. Within sensing and actuation, biodegradable polymer matrices facilitate the development of fully resorbable biosensors and soft actuators. These systems harness tailored degradation kinetics to achieve temporal control over signal transduction and mechanical response, unlocking applications in in vivo monitoring and on-demand drug delivery. In healthcare, biodegradable polymers underpin novel approaches in tissue engineering, wound healing, and bioresorbable implants. Their tunable chemical architectures and processing versatility allow for precise regulation of mechanical properties, degradation rates, and therapeutic payloads, fostering seamless integration with biological environments. The convergence of these emerging applications underscores the pivotal role of biodegradable polymers in advancing sustainable technology and personalized medicine. Continued interdisciplinary research into polymer design, processing strategies, and integration techniques will accelerate commercialization and broaden the impact of these lower eCO2 value materials across diverse sectors. This perspective article comments on the innovation in these sectors that go beyond the applications of biodegradable materials in packaging applications.
    Keywords:  biodegradable polymers; bioresorbable implants; resorbable biosensors; soft actuators; transient electronics
    DOI:  https://doi.org/10.3390/ma18194485
  19. ACS Appl Mater Interfaces. 2025 Oct 12.
    Ultrasoft Zwitterionic Eutectogels for Adaptive and Durable Sensing at Dynamic Skin Interfaces.
    Yufan Wang, Han Shen, Yu Zhang, Zhenchuan Yu, Jiqiang Wang.
      Zwitterionic hydrogels have attracted considerable interest as promising candidates for next-generation bioelectronic interfaces due to their intrinsic antifouling characteristics and efficient ionic conductivity. However, their practical use is often limited by low mechanical compliance, poor adhesion to biological substrates, and environmental vulnerability. Herein, we report a new class of zwitterionic eutectogels synthesized through a one-pot photopolymerization of zwitterionic and polar monomers in a deep eutectic solvent (DES). The DES phase not only serves as a nonvolatile medium but also promotes multivalent hydrogen bonding and electrostatic coordination, resulting in a skin-compliant yet tough polymer network. The resulting eutectogels exhibit an ultralow modulus (∼10 kPa), toughness of 160 kJ m-3, stretchability of 850%, and ionic conductivity of 70 mS m-1. Crucially, they also maintain environmentally tolerant and strain-adaptive interfacial adhesion, enabling reliable and conformal contact with dynamically deforming skin. These features collectively enable robust electrophysiological signal acquisition and high-fidelity strain sensing, highlighting their potential as a versatile platform for wearable bioelectronics and soft human-machine interfaces.
    Keywords:  eutectogels; hydrogels; ionic skins; self-adhesion; stretchable electronics
    DOI:  https://doi.org/10.1021/acsami.5c16633
  20. Nat Commun. 2025 Oct 15. 16(1): 8847
    In vivo mechano-tissue engineering by hydrogels capable of transmitting intercellular mechanical stress.
    Natsumi Ueda, Hayato Okazaki, Akihiro Mikuma, Ayane Kunieda, Soma Kawashima, Takeru Torii, Keiko Kawauchi, Masatake Matsuoka, Tomohiro Onodera, Norimasa Iwasaki, Koji Nagahama.
      Integrating the latest insights from mechanobiology into tissue engineering could lead to innovative technologies. Here we show a method to effectively elicit the regenerative response of transplanted cells by utilizing mechanical stress generated in vivo. The essential feature of our method is that it does not use specific ligands for the vital mechanosensor integrins to mechanically activate them. In our method, azide groups are introduced into the integrin, and the hydrogel is modified with cyclooctyne (DBCO) groups. Thus, bioorthogonal click reaction between the azide groups and the DBCO groups forms direct, stable, irreversible covalent bonds between the cellular integrin and the hydrogel. We demonstrate that the integrin-hydrogel linkage is in ON state regardless of the intensity of the stress, the cell cycle, or the extracellular environment, so that mechanical stress is rapidly and reliably transmitted to the nucleus through the linkage in vivo, resulting in regenerative response of the transplanted cells.
    DOI:  https://doi.org/10.1038/s41467-025-64656-9
  21. Mater Horiz. 2025 Oct 17.
    Harnessing precision in hydrogel architectures through reversible-deactivation radical polymerisation techniques.
    Amit Kumar, Pratibha Sharma, Andrew B Lowe.
      Hydrogels, featuring unique three-dimensional network structures and excellent compatibility with diverse biological environments, have attracted widespread interest for applications in biomedicine, drug delivery, soft robotics, tissue engineering, and bioelectronics. Hydrogels are traditionally synthesised through radical polymerisation of functional monomers, during which both chain propagation and crosslinking occur. This process forms a three-dimensional network, with a pore-like structure determined by the crosslinking density and the organisation of any template used. Traditional radical polymerisation leads to random chain propagation, limiting control over the structural features of the resulting hydrogel. Reversible-deactivation radical polymerisation (RDRP) techniques, such as reversible addition-fragmentation chain transfer (RAFT) polymerisation, atom transfer radical polymerisation (ATRP), and nitroxide-mediated polymerisation (NMP), are powerful tools for the precise synthesis of hydrogels. These methods enable molecular-level control over network architecture and ensure uniform distribution of functional groups, resulting in materials with tailored swelling behaviour, mechanical properties and functional performance. The significant progress achieved by researchers in this field has inspired us to review recent advances in the application of RDRP techniques for hydrogel synthesis, emphasising their advantages over hydrogels synthesised by conventional polymerisation methods. Additionally, we discuss the underlying design strategies for integrating functional monomers, crosslinking elements, and stimuli-responsive features into hydrogel systems. We conclude by highlighting studies that explore hydrogels with controlled architectures for applications in self-healing systems, multi-responsive materials, bioactive hydrogels and other advanced functions.
    DOI:  https://doi.org/10.1039/d5mh00947b
  22. ACS Biomater Sci Eng. 2025 Oct 15.
    Seaweed Derived Polysaccharides as Sustainable Biomaterials for Tissue Engineering Applications.
    Pradnya Ghalsasi, Gobinath Chithiravelu, Binata Joddar.
      The integration of marine-derived biomaterials has given new directions for fabricating scaffolds that support and influence tissue engineering. Among these, seaweed-derived polysaccharides, such as alginate, agarose, carrageenan, ulvan, laminarin, and fucoidan, present a distinctive combination of structural diversity, functional versatility, and natural abundance. Unlike many synthetic biomaterials, these polysaccharides possess inherent bioactivity, including antioxidant properties and cell signaling cues. These properties can be further tailored through chemical or physical modifications or by combination with other natural or synthetic polymers to suit specific regenerative applications. Fabrication techniques such as 3D printing, electrospinning, microbeads, and hydrogel casting are used to improve the functional outcomes of the scaffolds. Moreover, macroalgae-derived polysaccharides have low-cost production and are environmentally sustainable, making them a preferred choice for clinical applications. This review elaborates on recent advances in the use of seaweed-derived polysaccharide scaffolds for soft and hard tissue engineering. Future efforts should focus on enhancing their clinical translation through deeper biological insights and scalable fabrication.
    Keywords:  agarose; alginates; biofabrication; bioprinting; carrageenan; electrospinning; extracellular matrix; hydrogel; regenerative medicine; seaweed-derived polysaccharides; stimuli-responsive materials
    DOI:  https://doi.org/10.1021/acsbiomaterials.5c01301
  23. ACS Nano. 2025 Oct 16.
    Reprocessable and Recyclable Cellulosic Network Polymers with Intrinsic Flame Retardancy via Dynamic Covalent Cross-Linking.
    Guowen Zhou, Zhixing Huang, Ruotong Du, Zepeng Lei, Xiaohui Wang.
      Developing sustainable, high-performance biobased materials is critical for reducing dependence on petroleum-derived plastics. Cellulose is the most abundant and renewable polymer resource, yet current cellulose-based materials often suffer from limitations such as flammability, water sensitivity, limited processability, and recyclability in practical use. Herein, we propose an integrated strategy to reconfigure cellulose's hydrogen-bonded network into a dynamic covalent architecture while incorporating flame-retardant units in situ. The resulting thermo-processable cellulosic network polymers (CAA-DDPNs) exhibit high tensile strength (46-65 MPa), self-extinguishing behavior, and resistance to both water and common organic solvents. Compared with several engineering plastics, CAA-DDPN films demonstrate higher thermal stability (onset 281-301 °C) and an ultralow coefficient of thermal expansion (0.9-1.8 ppm K-1). More importantly, the dynamic linkers enable efficient chemical depolymerization to recover monomers, thereby overcoming the limited chemical recyclability of prior cellulose materials. The combination of mechanical robustness, thermal and chemical resilience, flame retardancy, and circularity makes CAA-DDPNs a viable, eco-friendly alternative to conventional petroleum-based plastics.
    Keywords:  cellulosic network polymers; dynamic covalent chemistry; flame retardance; plastic substitute; recyclability
    DOI:  https://doi.org/10.1021/acsnano.5c16164
  24. Nat Commun. 2025 Oct 16. 16(1): 9172
    Long-range optical coupling with epsilon-near-zero materials.
    Danqing Wang, Zheyu Lu, Sorren Warkander, Niharika Gupta, Qingjun Wang, Penghong Ci, Ruihan Guo, Jiachen Li, Ali Javey, Jie Yao, Feng Wang, Junqiao Wu.
      Long-range resonant quantum tunneling of electrons happens across potential barriers when the wavefunction interferes constructively outside the barrier. Here we demonstrate an analogy in optical systems based on epsilon-near-zero materials, achieving phase-modulated, long-range optical interactions between transparent semiconducting oxide layers beyond the evanescent photonic coupling. Distinct from weak thin-film interference, intense electromagnetic fields confined within the epsilon-near-zero thin films show anti-correlated intensity oscillations as a function of interlayer separation up to hundreds of microns. The oscillatory, anti-correlated electromagnetic field intensities were probed by second harmonic generation from wedged indium tin oxide multilayers. Such a system that hosts subwavelength mode footprint and simultaneously long-range radiative coupling offers prospects for long-distance optical communication, large-scale photonic circuits, and hybrid quantum photonic systems.
    DOI:  https://doi.org/10.1038/s41467-025-64504-w
  25. Nat Mater. 2025 Oct 15.
    Designing around immune memory to counter PEG immunogenicity.
    Namit Chaudhary, Kathryn A Whitehead.
      
    DOI:  https://doi.org/10.1038/s41563-025-02383-8
  26. ACS Appl Mater Interfaces. 2025 Oct 17.
    Synergistic Effects of Dynamic and Stable Networks on the Mechanical Behavior of Poly(vinyl alcohol) Hydrogels.
    Ming-Ke Zhang, Xiang Luo, Rui Huang, Yan Zhang, Yue Yin, Ming-Ming Chen, Dong Liu, Kun Song.
      We investigate the effects of dynamic and stable network structures on the mechanical behavior of poly(vinyl alcohol) hydrogels prepared through diverse methods, including freeze-thawing (F), salting out (S), dry annealing (A), and their combinations (F-S, F-A, F-S-A). Utilizing in situ small-angle X-ray/neutron scattering (SAXS/SANS) and rheometry, we elucidate the structural evolution and mechanical response mechanisms of these hydrogels. Salting out induces a dynamic network (generally refers to the network with highly reversible cross-link points such as hydrogen bonds), enhancing energy dissipation and self-healing, while annealing forms a stable network (generally refers to the network with low-reversibility cross-link points such as crystals), improving strength and stiffness. The synergistic effect of salting out and annealing achieves a balanced network structure, optimizing crystal formation, uniformity, and mechanical performance. This tunable network design offers a universal strategy for adaptive hydrogels in biomedical devices. Additionally, the process of fracture and recrystallization of crystals within the structure is closely related to the yielding, hardening, fracture, and other behaviors of the sample, revealing a direct correlation between microstructural evolution and macroscopic mechanical properties.
    Keywords:  dynamic network; in situ small-angle scattering; poly(vinyl alcohol) hydrogel; stable network; synergistic effect
    DOI:  https://doi.org/10.1021/acsami.5c14757
  27. Adv Funct Mater. 2025 Jan 02. 35(1):
    Injectable Hydrogels for Programmable Nanoparticle Release.
    Wenting Shi, Ying Xi, Xinyi Sheng, Soumen Das, Dongjing He, Kasie Collins, Yuhang Hu, M G Finn.
      Injectable hydrogels represent a promising strategy for the extended release of biological molecules, thereby reducing the frequency of injections. This study introduces a novel system based on Michael addition of dextran and polyethylene glycol (PEG) polymers functionalized with oxanorbornadiene (OND) and thiol groups, respectively. Reliable control over gelation speed allows administration by injection using a simple syringe-to-syringe mixing protocol that entrains more than 95% of virus-like particle (VLP) cargo. A combination of retro-Diels-Alder and hydrolytic ester bond cleavage gives rise to programmable release of the VLPs. Different release profiles, including burst, linear, and delayed release over a two-week period, are engineered using different OND linkages, and rheological characterization shows the hydrogels to be well within the desired range of stiffness for subcutaneous use. The modular nature of this system offers a generalizable platform for developing degradable materials aimed at sustained release biomedical applications.
    Keywords:  degradable hydrogels; programmable release; virus-like particles
    DOI:  https://doi.org/10.1002/adfm.202409796
  28. Nat Biotechnol. 2025 Oct 17.
    A tumor-on-a-chip for in vitro study of CAR-T cell immunotherapy in solid tumors.
    Haijiao Liu, Estela Noguera-Ortega, Xuanqi Dong, Won Dong Lee, Jeehan Chang, Sezin Aday Aydin, Yumei Li, Yonghee Shin, Xinyi Shi, Maria Liousia, Marina C Martinez, Joshua J Brotman, Soyeon Kim, Zeyu Chen, Anni Wang, Zirui Ou, Jungwook Paek, Ju Young Park, Aidi Liu, Haonan Hu, Zebin Xiao, Dora Maria Racca, Se-Jeong Kim, G Scott Worthen, Wei Guo, Ellen Puré, Taewook Kang, Joshua D Rabinowitz, E John Wherry, Edmund K Moon, Steven M Albelda, Dan Dongeun Huh.
      Our limited understanding of cancer-immune interactions remains a critical barrier to advancing chimeric antigen receptor (CAR)-T cell therapy for solid malignancies. Here, we present a microengineered system that enables vascularization of human tumor explants and their controlled perfusion with immune cells to model the activity of CAR-T cells in the tumor microenvironment. Using vascularized human lung adenocarcinoma tumors, we first demonstrate the ability of our tumor-on-a-chip system to simulate, visualize and interrogate CAR-T cell function. We then test a chemokine-directed CAR-T cell engineering strategy in a model of malignant pleural mesothelioma and validate our findings in a matching in vivo mouse model. Finally, we describe a potential therapeutic target that can be pharmacologically modulated to increase the efficacy of CAR-T cells in lung adenocarcinoma, for which we present biomarkers identified by global metabolomics analysis. Our microphysiological system provides promising in vitro technology to advance the development of adoptive cell therapies for cancer and other diseases.
    DOI:  https://doi.org/10.1038/s41587-025-02845-z
  29. Sci Adv. 2025 Oct 17. 11(42): eadu3708
    Bubble-driven cell detachment.
    Bert Vandereydt, Baptiste Blanc, Kripa K Varanasi.
      On-demand cell detachment is of great importance in various applications in biosensitive environments. Existing methods such as enzymatic treatments and mechanical scraping are often time-consuming, labor-intensive, and harmful to cells. In this work, we demonstrate a method of detaching cells from substrates using electrochemical bubble generation without biocide generation. We demonstrate that shear stress generated by fluid flow beneath a rising bubble is the primary mechanism for cell detachment. This strategy, relying solely on physical forces and independent of cell or surface chemistry, can therefore work with a large range of the media, surfaces, and cells. We successfully implement this discovery at the lab-scale by designing a prototype for on-demand cell detachment that maintains high cell viability. The developed principle could find applications in high-throughput culture settings, such as algae photobioreactors or cell culture environments.
    DOI:  https://doi.org/10.1126/sciadv.adu3708
  30. PLoS Comput Biol. 2025 Oct;21(10): e1013564
    A compact model of Escherichia coli core and biosynthetic metabolism.
    Marco Corrao, Hai He, Wolfram Liebermeister, Elad Noor, Arren Bar-Even.
      Metabolic models condense biochemical knowledge about organisms in a structured and standardised way. As large-scale network reconstructions are readily available for many organisms, genome-scale models are being widely used among modellers and engineers. However, these large models can be difficult to analyse and visualise, and occasionally generate predictions that are hard to interpret or even biologically unrealistic. Of the thousands of enzymatic reactions in a typical bacterial metabolism, only a few hundred form the metabolic pathways essential to produce energy carriers and biosynthetic precursors. These pathways carry relatively high flux, are central to maintaining and reproducing the cell, and provide precursors and energy to engineered metabolic pathways. Focusing on these central metabolic subsystems, we present iCH360, a manually curated medium-scale model of energy and biosynthesis metabolism for the well-studied bacterium Escherichia coli K-12 MG1655. The model is a sub-network of the most recent genome-scale reconstruction, iML1515, and comes with an updated layer of database annotations and a range of metabolic maps for visualisation. We enriched the stoichiometric network with extensive biological information and quantitative data, including thermodynamic and kinetic constants, enhancing the scope and applicability of the model. In addition, we assess the properties of this model in comparison to its genome-scale parent and demonstrate the use of the network and supporting data in various scenarios, including enzyme-constrained flux balance analysis, elementary flux mode analysis, and thermodynamic analysis. Overall, this model holds the potential to become a reference medium-scale metabolic model for E. coli.
    DOI:  https://doi.org/10.1371/journal.pcbi.1013564
  31. Small. 2025 Oct 14. e08115
    Automated Microfluidic Platform for Single Spheroid Culture and Extracellular Vesicle Isolation: Application to Spheroid Transcriptomic Profiling.
    Marie Hut, Josiane Denis, Frédéric Bottausci, Myriam Cubizolles, Patricia Laurent, Joris Kaal, Mahfod Benessalah, François Boizot, Nadia Cherradi, Yves Fouillet, Vincent Agache.
      Extracellular vesicles (EVs) are key mediators of intercellular communication and carry molecular information that reflects the state of their cell of origin. 3D cell cultures more accurately reflect the in vivo microenvironment and the biogenesis of extracellular vesicles compared to 2D cultures. Despite these advantages, studying EVs in 3D systems such as spheroids remains technically challenging. Conventional EV isolation and characterization methods often require pooling multiple spheroids to obtain sufficient material, which masks the intrinsic heterogeneity between individual spheroids and limits applications in precision medicine. To overcome these challenges, this work develops an automated microfluidic platform capable of single-spheroid culture, continuous secretion collection, and high-efficiency EV isolation. The platform incorporates 200 nm filtration and immunomagnetic capture targeting CD63/CD81-positive EVs, achieving a 60% recovery yield. Using adrenocortical carcinoma spheroids as a model, this work demonstrates that inhibiting β-catenin signaling selectively reduces the levels of EV-derived miR-139-5p and miR-483-5p, consistent with prior findings from 2D culture studies. This platform represents a groundbreaking approach to EV profiling at the single-spheroid level, unlocking new opportunities for personalized medicine, drug discovery, and targeted therapies by enabling the analysis of cellular heterogeneity and scarce biological samples such as patient-derived organoids.
    Keywords:  extracellular vesicles; microfluidics; microphysiological systems; precision medicine; single‐spheroid
    DOI:  https://doi.org/10.1002/smll.202508115
  32. Proc Natl Acad Sci U S A. 2025 Oct 21. 122(42): e2511596122
    Engineered 3D immuno-glial-neurovascular human miBrain model.
    Alice E Stanton, Adele Bubnys, Emre Agbas, Benjamin James, Dong Shin Park, Alan Jiang, Rebecca L Pinals, Liwang Liu, Nhat Truong, Anjanet Loon, Colin Staab, Oyku Cerit, Hsin-Lan Wen, David Mankus, Margaret E Bisher, Abigail K R Lytton-Jean, Manolis Kellis, Joel W Blanchard, Robert Langer, Li-Huei Tsai.
      Patient-specific, human-based cellular models integrating a biomimetic blood-brain barrier, immune, and myelinated neuron components are critically needed to enable accelerated, translationally relevant discovery of neurological disease mechanisms and interventions. To construct a human cell-based model that includes these features and all six major brain cell types needed to mimic disease and dissect pathological mechanisms, we have constructed, characterized, and utilized a multicellular integrated brain (miBrain) immuno-glial-neurovascular model by engineering a brain-inspired 3D hydrogel and identifying conditions to coculture these six brain cell types, all differentiated from patient induced pluripotent stem cells. miBrains recapitulate in vivo-like hallmarks inclusive of neuronal activity, functional connectivity, barrier function, myelin-producing oligodendrocyte engagement with neurons, multicellular interactions, and transcriptomic profiles. We implemented the model to study Alzheimer's Disease pathologies associated with APOE4 genetic risk. APOE4 miBrains differentially exhibit amyloid aggregation, tau phosphorylation, and astrocytic glial fibrillary acidic protein. Unlike the coemergent fate specification of glia and neurons in other organoid approaches, miBrains integrate independently differentiated cell types, a feature we harnessed to identify that APOE4 in astrocytes promotes neuronal tau pathogenesis and dysregulation through crosstalk with microglia.
    Keywords:  biomaterials; brain organoid; microphysiological system; neuro-immune; neurovascular
    DOI:  https://doi.org/10.1073/pnas.2511596122
  33. Nat Mater. 2025 Oct 17.
    Hermetic stretchable seals enabled by a viscoplastic surface effect.
    Rui Xia, Chun Li, Yan Shao, Dong He, Jianfeng Yan, Mao Yu, Kangjie Chu, Huanhuan Yang, Daohang Cai, Guoli Chen, Yaqi Du, Guangfu Luo, Weishu Liu, Fuzeng Ren, Zhubing He, Yanhao Yu.
      Elastic seals safeguard stretchable electronics from reactive species in the surrounding environment. However, elastic contact with device modules and the intrinsic small-molecule permeability of elastomers limit the hermeticity of devices. Here we present a viscoplastic surface effect in polymeric elastomers for deriving sealing platforms with high hermeticity and large stretchability, made possible by controlling phase separations of partially miscible polar plastics within the near-surface region of block copolymer elastomers. The resulting viscoplastic surface allows the elastomer to form defect-free interfaces regardless of their size, materials chemistry and geometry. This capability facilitates the airtight integration of device modules to mitigate side leakage and enable the seamless assembly of high-potential gas barriers to prevent bulk penetration. A multilayer seal that incorporates scavenging components demonstrates properties that are as hermetic as aluminium foil while being stretchable like a rubber band. This breakthrough extends the operational lifetime of perovskite optoelectronics, hydrogel thermoelectrics and implantable bioelectronics without sacrificing their stretchability or efficiency.
    DOI:  https://doi.org/10.1038/s41563-025-02386-5
  34. Nanoscale. 2025 Oct 13.
    Laser-assisted electrohydrodynamic printing of sub-microscale 3D conductive features on low-melting-point polymeric substrates.
    Jiaxin Li, Jinke Chang, Yuhua Chen, Qihang Ma, Kun Yu, Yi Ding, Dichen Li, Jiankang He.
      Electrohydrodynamic (EHD) printing stands as a promising and cost-effective method for crafting intricate metallic structures at the micro/nanoscale, boasting diverse applications. Yet, conventional EHD-printed features often require high-temperature sintering (120-400 °C) for conductivity, limiting their integration and application on most polymeric substrates with low melting points (<300 °C). Here, we introduce an innovative laser-assisted EHD printing technique, which selectively melts the as-printed gold nanoparticles and expels residual solvents and surfactants, without damaging the substrates. This enables damage-free fabrication of highly conductive sub-microscale 3D structures on polymeric substrates at ambient temperature. Our printed features, as small as 604 ± 27 nm, exhibit a low resistivity of 2.54 ± 0.38 × 10-7 Ω m. Furthermore, we demonstrate the versatility of this approach by printing complex patterns and multimaterial structures on various substrates, including PET and human hair. The technique represents a significant advancement in EHD printing of electronics, offering exceptional precision and conductivity across diverse substrates and opening avenues for a wide array of applications in flexible electronics, biosensors, wearable devices, and biomedical implants.
    DOI:  https://doi.org/10.1039/d5nr03296b
  35. Science. 2025 Oct 16. 390(6770): 294-298
    Durable, pure water-fed, anion-exchange membrane electrolyzers through interphase engineering.
    Shujin Hou, Archana Sekar, Yang Zhao, Minkyoung Kwak, Juhyun Oh, Kelvin Kam-Yun Li, Peiyao Wu, Ryan T Hannagan, Valeria Cartagena, Anthony C Ekennia, Hui Duan, Michael J Zachman, Joelle Frechette, Gregory M Su, Balsu Lakshmanan, Yushan Yan, Thomas F Jaramillo, Shannon W Boettcher.
      Anion-exchange membrane water electrolyzers (AEMWEs) promise scalable, low-cost hydrogen production but are limited by the electrochemical instability of their anode ionomers. We report interphase engineering using inorganic-containing molecular additives that coassemble with ionomer, enabling pure water-fed AEMWEs to operate with a degradation rate <0.5 millivolt per hour at 2.0 amperes per square centimeter and 70°C-a >20-fold durability improvement. Analysis of different additives and ionomers shows that the stabilization mechanism involves cross-links between metal oxo/hydroxo oligomers and ionomers. Under operation, the inorganic additive enriches, forming an interphase near the water-oxidation catalyst that passivates the anode ionomer against continuous degradation while maintaining mechanical integrity and hydroxide conductivity. This additive-based interphase-engineering strategy provides a path to durable AEMWEs that operate without supporting electrolytes and is adaptable across diverse catalysts and ionomers for electrochemical technologies.
    DOI:  https://doi.org/10.1126/science.adw7100
  36. Science. 2025 Oct 16. 390(6770): 226-227
    Architects of molecular cages win Chemistry Nobel.
    Daniel Clery, Catherine Offord.
      Spongelike materials called metal-organic frameworks can separate and store gases.
    DOI:  https://doi.org/10.1126/science.aed1023
  37. Adv Mater. 2025 Oct 16. e12471
    Soft and Strong: Elastic Conductors with Bio-Inspired Self-Protection.
    Chenglong Zhang, Xiulun Yin, Chris Zhou, Xin Lu, Siying Wu, Ying Li, Addie Bahi, Sukhneet Kaur Dhillon, Orlando J Rojas, Jinhua Jiang, Nanliang Chen, Frank K Ko, John D W Madden.
      Skin is soft yet strong - a combination achieved by integrating compliant elastin with stiff but wavy collagen, producing non-linear mechanical properties. Inspired by this structure, stiff conductive wires are engineered into sinusoidal patterns and mechanically interlocked them with highly elastic fibers using a reimagined woven fabric approach. The result is a highly conducting and stretchable yarn that also has high tensile strength - a combination that is attractive for wearable applications where comfort and durability are valued. With a diameter of ≈1 mm-comparable to many commercial yarns-the fabric-based yarn exhibits low stiffness across a broad strain range (up to 270% under 2 N of force) while demonstrating a self-protective transition to high stiffness and strength (up to 30 MPa) as it nears failure. Additionally, this yarn offers excellent flexibility, high strain tolerance (exceeding 500%), inherent breathability, and superior weavability. By tuning the number of elastic fibers and electrode fibers, it can further tailor these stretchable conductive yarns into strain-insensitive connecting yarns (low impedance at MHz frequencies, GF = 0.0003) and mechanical sensing yarns with dual strain and proximity sensing capabilities. The integration of these functional yarns enables system-level smart textile applications, such as wristband controllers.
    Keywords:  carbon nanotube fiber; machine learning; stretchable electronics; wearable sensors
    DOI:  https://doi.org/10.1002/adma.202512471
  38. Nat Commun. 2025 Oct 15. 16(1): 9155
    Piezo1 regulates the mechanotransduction of soft matrix viscoelasticity.
    Mariana A G Oliva, Giuseppe Ciccone, Gotthold Fläschner, Jiajun Luo, Jonah L Voigt, Patrizia Romani, Paul Genever, Oana Dobre, Sirio Dupont, Massimo Vassalli, Pere Roca-Cusachs, Manuel Salmeron-Sanchez.
      Mechanosensitive ion channels such as Piezo1 have fundamental roles in sensing the mechanical properties of the extracellular matrix. However, whether and how Piezo1 senses time-dependent matrix mechanical properties, that is, viscoelasticity, remains unknown. To address this question, we combine an immortalised mesenchymal stem cell line, in which Piezo1 expression can be silenced, with soft and stiff viscoelastic hydrogels that have independently tuneable elastic and viscous moduli. We demonstrate that Piezo1 is a regulator of the mechanotransduction of viscoelasticity in soft matrices, both experimentally and through simulations incorporating Piezo1 into a modified viscoelastic molecular clutch model. Using RNA sequencing, we also identify the transcriptomic responses of mesenchymal stem cells to matrix viscoelasticity and Piezo1 activity, identifying gene signatures that reflect their mechanobiology in soft and stiff viscoelastic hydrogels.
    DOI:  https://doi.org/10.1038/s41467-025-64185-5
  39. Small. 2025 Oct 16. e08898
    Reagentless Real-Time ATP Monitoring with New DNA Aptamers.
    Adara Bacon, Obtin Alkhamis, Caleb Byrd, Jacob Perry, Juan Canoura, Yi Xiao.
      Adenosine triphosphate (ATP) is essential to numerous biological processes, and there is considerable interest in methods for measuring this molecule in real time. Current ATP sensors have fundamental shortcomings that limit their utility, such as poor specificity, the need for exogenous reagents, or assay complexity. Aptamer-based biosensors have shown great promise for ATP detection, but existing aptamers have modest affinity and poor specificity that limit their practical utility. Here, the systematic evolution of ligands by exponential enrichment (SELEX) process is used to discover new DNA aptamers that bind ATP with unprecedentedly high affinity and specificity. The best-performance aptamer, ATP18-13, displays at least tenfold greater affinity for ATP relative to previously reported aptamers, with far superior capacity to discriminate against analogs including adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine. ATP18-13 is used to develop a fluorescent beacon sensor that achieves a limit of detection of 125 nm ATP in buffer and 1 µm ATP in cell culture medium. The capability of this sensor is demonstrated to achieve real-time, seconds-scale monitoring of deoxyATP consumption during DNA polymerase-mediated template extension. The aptamers and sensors developed here can thus prove useful for monitoring ATP in a variety of biological contexts.
    Keywords:  ATP; SELEX; aptamers; monitoring; sensors
    DOI:  https://doi.org/10.1002/smll.202508898
  40. Phys Biol. 2025 Oct 14.
    Inhibition of bacterial growth by antibiotics: a minimal model.
    Barnabé Ledoux, David Lacoste.
      Growth in bacterial populations generally depends on the environment (availability and quality of nutrients, presence of a toxic inhibitor, product inhibition..). Here, we build a minimal model to describe the action of a bacteriostatic antibiotic, assuming that this drug inhibits an essential autocatalytic cycle of the cell metabolism. The model recovers known growth laws, can describe various types of antibiotics and confirms the existence of two distinct regimes of growth-dependent susceptibility, previously identified only for ribosome targeting antibiotics. We introduce a proxy for cell risk, which proves useful to compare the effects of various types of antibiotics. We also develop extensions of our model to describe the effect of combining two antibiotics targeting two different autocatalytic cycles or a regime where cell growth is inhibited by a waste product.
    Keywords:  antibiotics; autocatalysis; cells; growth; growth laws; ribosomes
    DOI:  https://doi.org/10.1088/1478-3975/ae1343
  41. Proc Natl Acad Sci U S A. 2025 Oct 21. 122(42): e2507500122
    Invasin-functionalized PIC hydrogels enable long-term 3D culture of epithelial organoids.
    Joost J A P M Wijnakker, Sangho Lim, Robin Schreurs, João Ferreira Faria, Jeroen Korving, Harry Begthel, Kirti K Iyer, Paul H J Kouwer, Hans Clevers.
      Tissue stem cell (TSC)-derived epithelial organoids are typically cultured in Matrigel [T. Sato et al., Nature 459, 262-265 (2009)], an extracellular matrix-like hydrogel produced from Engelbreth-Holm-Swarm sarcoma cells. This tumor is grown in the mouse abdomen [R. W. Orkin et al., J. Exp. Med. 145, 204-220 (1977)]. Previously, we demonstrated that the Yersinia membrane protein Invasin, coated on transwells, replaces Matrigel by activating β1-integrins, allowing long-term expansion of primary epithelial cells as 2D organoid sheets [J. J. A. P. M. Wijnakker et al., Proc. Natl. Acad. Sci. U.S.A. 122, e2420595121 (2025)]. Here, we functionalize a synthetic polyisocyanide (PIC) hydrogel with the integrin-activating domain of Invasin (INV). PIC hydrogels are soluble at 4 °C and form a gel at 37 °C [P. H. J. Kouwer et al., Nature 493, 651-655 (2013)]. When INV is covalently linked to PIC, the resulting hydrogel supports multipassage 3D growth of human intestinal and airway organoids. Self-renewal, polarization, and differentiation are maintained. The 3D swelling assay for cystic fibrosis drug testing (S. F. Boj et al., J. Vis. Exp. (2017), 10.3791/55159] was validated using PIC-INV. With PIC-INV hydrogels, we establish a fully defined and animal-free system for 3D TSC-derived organoid culture.
    Keywords:  Invasin; PIC; biomaterials; organoid; stem cells
    DOI:  https://doi.org/10.1073/pnas.2507500122
  42. Nat Commun. 2025 Oct 14. 16(1): 9106
    Light-gated redox switching and actuation in polymer hydrogels.
    Roza R Weber, Robert Hein, Alexander Ryabchun, Yohan Gisbert, David Garcia Romero, Maria Antonietta Loi, Ben L Feringa.
      Stimuli-responsive materials based on molecular switches, introducing life-like properties such as adaptive behavior in an aqueous environment, are fascinating, providing numerous opportunities to control functions and enable future applications like actuators and soft robotics. Light-responsive molecular systems are receiving particular attention, due to the non-invasive stimulus and distinctive spatio-temporal control possible with photoswitches. In contrast, redox-switching is quantitative, non-volatile and associated with significant changes in material properties, but lacks spatio-temporal precision. Herein we address this challenge in the first proof-of-principle demonstration of light-gated redox switching of polymer hydrogel materials, thereby combining the advantages of both strategies. We present a unique approach where irradiation controls the intrinsic redox properties of the system. This is enabled by the reversible and versatile light- and redox-responsive bisthioxanthylidene switch embedded in a polymer hydrogel, whose two-electron oxidation potential is strongly modulated by light. As a result, oxidation of the material, which is associated with large changes in color, fluorescence, swelling and actuation can be carried out in water with high precision in space and time by photo-masking. This light-gated redox-patterning of the material can be exploited for numerous functions including, as demonstrated here, complex motion and reversible surface texturing.
    DOI:  https://doi.org/10.1038/s41467-025-64123-5
  43. Phys Rev Lett. 2025 Sep 26. 135(13): 138301
    Scaling Laws for Passive Polymer Dynamics in Active Turbulence.
    Zahra K Valei, Tyler N Shendruk.
      Biological systems commonly combine intrinsically out-of-equilibrium active components with passive polymeric inclusions to produce unique material properties. To explore these composite systems, idealized models-such as polymers in active fluids-are essential to develop a predictive theoretical framework. We simulate a single, freely jointed passive chain in two-dimensional active turbulence. Active flows advect the polymer, producing a substantially enhanced diffusivity. Our results reveal that the dimensionless diffusivity obeys scaling laws governed by the Péclet, Weissenberg, and Ericksen numbers, which paves the way for designing active/polymeric hybrid materials with predictable properties that differ significantly from those of nondeformable inclusions.
    DOI:  https://doi.org/10.1103/w3gp-knnp
  44. ACS Appl Mater Interfaces. 2025 Oct 13.
    Design, Synthesis, and Screening of COFs for CO2 Adsorption by Gaussian Process.
    Jian Guan, Zhenhua Dai, Hang Zhou, Zejiang Huang, Xuelu Wang, Wenlong Zhang, Xiaohong Guan, Mengshuai Liu, Haitao Lv, Shifa Zhong.
      Effective CO2 capture requires careful design of Covalent Organic Frameworks (COFs). Current computational approaches often rely solely on simulated properties, neglecting critical chemical and synthetic factors that determine real-world COF performance. We present an integrated computational-experimental framework combining machine learning with experimental validation. Our study analyzes 240 unique COFs (617 samples) with experimentally measured CO2 adsorption capacities across varied synthesis conditions. Gaussian Process and CatBoost models were developed to predict CO2 adsorption by simultaneously considering chemical structures, synthesis parameters, and measurement protocols. The GP model demonstrates improved generalization and uncertainty quantification compared to CatBoost. SHAP analysis reveals the model's focus on COF type and synthesis conditions. Using a database of 181 building blocks, we generated 5557 COF structures with synthesis condition recommendations based on experimental similarity. Experimental validation confirmed the predictions for three synthesized COFs, demonstrating the framework's practical utility for COF design and optimization.
    Keywords:  CO2 adsorption; COF design; Gaussian process; machine learning; synthesis condition recommendation
    DOI:  https://doi.org/10.1021/acsami.5c11762
  45. Nat Commun. 2025 Oct 16. 16(1): 9187
    Predicting sequence-specific amplification efficiency in multi-template PCR with deep learning.
    Andreas L Gimpel, Bowen Fan, Dexiong Chen, Laetitia O D Wölfle, Max Horn, Laetitia Meng-Papaxanthos, Philipp L Antkowiak, Wendelin J Stark, Beat Christen, Karsten Borgwardt, Robert N Grass.
      Multi-template polymerase chain reaction (PCR) is a critical technique enabling the parallel amplification of diverse DNA molecules, thereby facilitating applications in fields from quantitative molecular biology to DNA data storage. However, non-homogeneous amplification due to sequence-specific amplification efficiencies often results in skewed abundance data, compromising accuracy and sensitivity. In this study, we address amplification efficiency in complex amplicon libraries by employing one-dimensional convolutional neural networks (1D-CNNs) to predict sequence-specific amplification efficiencies, based on sequence information alone. Trained on reliably annotated datasets derived from synthetic DNA pools, these models achieve a high predictive performance (AUROC: 0.88, AUPRC: 0.44), thereby enabling the design of inherently homogeneous amplicon libraries. We further introduce CluMo, a deep learning interpretation framework that identifies specific motifs adjacent to adapter priming sites as closely associated with poor amplification. This insight leads to the elucidation of adapter-mediated self-priming as the major mechanism causing low amplification efficiency, challenging long-standing PCR design assumptions. By addressing the basis for non-homogeneous amplification in multi-template PCR, our deep-learning approach reduces the required sequencing depth to recover 99% of amplicon sequences fourfold, and opens new avenues to improve the efficiency of DNA amplification in fields such as genomics, diagnostics, and synthetic biology.
    DOI:  https://doi.org/10.1038/s41467-025-64221-4
  46. Nat Biotechnol. 2025 Oct;43(10): 1618
    Directed evolution.
      
    DOI:  https://doi.org/10.1038/s41587-025-02840-4
  47. Soft Matter. 2025 Oct 15.
    Characterisation of cuticle mechanical properties: analysing stiffness in layered living systems to understand surface buckling patterns.
    Chiara A Airoldi, Chao Chen, Humberto Herrera-Ubaldo, Hongbo Fu, Carlos A Lugo, Udhaya Ponraj, Alfred J Crosby, Beverley J Glover.
      Development of a living organism is a highly regulated process during which biological materials undergo constant change. De novo material synthesis and genetically-regulated changes in mechanical properties of materials are key for organ development. However, few studies have attempted to produce quantitative measurements of the mechanical properties of biological materials during growth. Such quantitative analysis is particularly challenging where the material is layered, and yet layering of materials with different mechanical properties may be essential to morphogenetic pattern formation. This is the case for the Hibiscus trionum flower petal, where buckling of the cuticle on top of the epidermal cell wall forms ridges, producing an iridescent effect. This ridge formation is hypothesised to be due to mechanical instability, which directly depends upon the mechanical properties of the individual layers of cuticle and cell wall. We set out to develop methods to measure the mechanical properties of the surface layers of plant epidermal cells through atomic force microscopy (AFM). To ensure that our results were reproducible and represented the most appropriate combination of experimental parameters, we used the uniaxial tensile tester for ultrathin films (TUTTUT) to provide independent measurement of cuticle stiffness. We explored mechanical properties of the upper cuticle and lower cuticular layer of the epidermal cell surface across growth stages. In addition to offering technical approaches to explore the stiffness of living layered materials, our findings suggest that temporal changes in biological material properties are key to understanding the development of biological surface patterns.
    DOI:  https://doi.org/10.1039/d4sm01406e
  48. Nat Genet. 2025 Oct 14.
    Activity-based selection for enhanced base editor mutational scanning.
    Eleanor G Kaplan, Ryan J Steger, Spencer T Shah, Laura M Drepanos, Audrey L Griffith, Ganna Reint, John G Doench.
      Base editing is a CRISPR-based technology that enables high-throughput, nucleotide-level functional interrogation of the genome that is essential for understanding the genetic basis of human disease and informing therapeutic development. Base editing screens have emerged as a powerful experimental approach, yet significant cell-to-cell variability in editing efficiency introduces noise that may obscure meaningful results. Here we develop a co-selection method that enriches for cells with high base editing activity, substantially increasing editing efficiency at a target locus. We evaluate this activity-based selection method against a traditional screening approach by tiling guide RNAs across TP53, demonstrating its enhanced capacity to pinpoint specific mutations and protein regions of functional importance. We anticipate that this modular selection method will enhance the resolution of base editing screens across many applications.
    DOI:  https://doi.org/10.1038/s41588-025-02366-0
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