bims-enlima Biomed News
on Engineered living materials
Issue of 2026–08–09
thirty-one papers selected by
Rahul Kumar, Tallinna Tehnikaülikool
  1. Interactions between fungi, algae, and bacteria: multispecies engineered living materials leverage function and structure.
  2. SCHEPHERD: A modular, programmable, direct current platform to control cell behavior.
  3. Model-Assisted Prioritization of Gelatin Methacryloyl (GelMA) Hydrogel Formulations for Three-Dimensional Cell Culture.
  4. Reconciling Granular Hydrogel Microstructure and Mechanics via a Temporary Thermo-Responsive and Cell-Invadable Matrix.
  5. Black yeasts are efficient heterologous hosts for the production of a wide range of fungal polyketides.
  6. Self-assembled contacts for high-yield molecular devices.
  7. Single Atoms Functioning as Catalysts Inside Living Matter.
  8. Ionizable Lipid-Dependent Optimization of Steroid Lipid Nanoparticles With Tunable Immunomodulatory Properties.
  9. Designing DNA nanostar hydrogels for sequence-specific degradation and antibody release.
  10. Strategic enhancement of Cas9 nickase-driven gene amplification.
  11. Generative design of bacteriophages with genome language models.
  12. Engineered yeast that make cancer drugs could spare a rare flower.
  13. Programmable continuous gradient bioprinting for engineering spatially heterogeneous microenvironments.
  14. Bioprinted cell-instructive lung-dECM constructs for reconstructing an immuno-regenerative pulmonary microenvironment.
  15. Transient culture of adult human hepatocytes as organoids improves engineered liver engraftment.
  16. Calcium tunes snail mucus-based materials to multiple functions.
  17. Enhancing the Versatility of Polyethylene Terephthalate (PET) Through Strategic Biomolecular Functionalization.
  18. Microdroplets jam together to mimic soft tissues.
  19. Biphasic Polyampholyte Hydrogel for Rewritable 3D Encryption Enabled Via Pressure and Solvent Exchange.
  20. From Caffeine to Aspirin: Everyday Molecules as Triggers for Genetically Encoded Proximity Systems.
  21. A covalent PFKL activator suppresses tumor growth.
  22. Modular PEG coatings for engineering a biomimetic glycocalyx on lipid membranes.
  23. A metabolite morphogen coordinates multicellular development in Bacillus subtilis.
  24. Antiviral defence is a conserved function of diverse bacterial DNA glycosylases.
  25. Inspiration from nature for fiber materials and fiber electronics.
  26. Structured adhesives: inspiration, modeling, engineering and applications.
  27. Twisting light the Weyl way.
  28. Entangled glycerol hydrogels for wave modulation of Rayleigh-SAW devices.
  29. Programmable Functional Silicification of DNA Origami Nanostructures.
  30. A Universal Multifunctional Zinc Ionic Semi-Interpenetrating Network Hydrogel Coating on Polymer Surfaces.
  31. Molecular engineering of self-assembled layers.
  1. Curr Opin Microbiol. 2026 Aug 05. pii: S1369-5274(26)00100-1. [Epub ahead of print]93 102806
    Interactions between fungi, algae, and bacteria: multispecies engineered living materials leverage function and structure.
    Marc Kessels Solé, Hannelore Wilssens, Elise Elsacker, Lien De Wannemaeker, Marjan De Mey.
      The need for materials that have a limited impact on the environment has led to the development of engineered living materials (ELMs), which integrate living organisms and material applications to generate functional matter. Filamentous fungi offer a promising scaffold to design ELMs, which can be produced from the bottom up, but the possibilities for introducing dynamic functionalities are limited. To solve this, multispecies ELMs can be designed, using bacteria and algae to introduce biological functions in the material. The amenability of bacteria for synthetic biology offers a suitable platform to develop novel functions, while algae can endow the material with photosynthetic properties. Due to the preexisting natural interactions between these organisms and fungi, such as lichens and fungal highways, the establishment of a consortium-based bottom-up ELM becomes feasible. In this review, we summarize the natural mutualistic interactions between fungi, algae, and bacteria and how they can be harnessed for the design and implementation of engineered living materials, using filamentous fungi as their structural backbone. Furthermore, we review the role of such interactions in industrial processes, where they have been engineered for wastewater treatment and biotechnological production. Lastly, we discuss the current challenges of engineered living materials, the advantages of consortia-based solutions, and their future perspectives.
    DOI:  https://doi.org/10.1016/j.mib.2026.102806
  2. Sci Adv. 2026 Aug 07. 12(32): eaed5802
    SCHEPHERD: A modular, programmable, direct current platform to control cell behavior.
    Yubin Lin, Jeremy S Yodh, Celeste Rodriguez, Paul Kreymborg, Daniel J Cohen.
      Spanning frogs, fish, and humans, direct current (dc) bioelectric cues play critical roles beyond neuromuscular function, such as modulating morphogenesis, immune response, and healing through electrotaxis-electrically directed cell migration. Harnessing this potential requires dedicated, versatile tools. However, standardized, accessible, and reproducible infrastructure capable of dc stimulation remains a challenge. We present SCHEPHERD: a universal, electrobioreactor integrating eight stimulation channels and modular inserts to enable most electrotaxis assays in one device (cells, monolayers, and 3D spheroids) while enabling powerful, expanded capabilities. SCHEPHERD revealed through parameter sweeps that dc fields act like a "steering wheel and gas pedal" for cell migration. We then used live confocal imaging to observe electrically reprogrammed F-actin dynamics. Last, our multipolar inserts generated complex spatial electrical patterns that reorganize engineered tissue dynamics. By substantially improving accessibility through modularity and an open-source, graphically programmed, stand-alone stimulator, we hope that SCHEPHERD can help broaden the community studying these important dc bioelectric phenomena.
    DOI:  https://doi.org/10.1126/sciadv.aed5802
  3. ACS Appl Mater Interfaces. 2026 Aug 05. 18(30): 40536-40553
    Model-Assisted Prioritization of Gelatin Methacryloyl (GelMA) Hydrogel Formulations for Three-Dimensional Cell Culture.
    Peisong Yin, Xin Wang, Suqing Liu, Yujun Huang, Meiyi Huang, Yu Zhang, Ruijun Peng, Jingwen Sun, Yaobin Wu, Ling Wang.
      Owing to highly tunable mechanics, gelatin methacryloyl (GelMA) hydrogels are widely exploited for three-dimensional (3D) cell culture, whereas limited experimental sampling restricts efficient formulation screening. In this work, we developed a BNN-based modeling pipeline to map GelMA hydrogels with various cross-linking parameters toward linear viscoelastic moduli and nonlinear critical stress, thereby categorizing all tested formulations into low/intermediate/high stable mechanical windows. Calibration on C2C12 myoblast morphologies confirmed that nonlinear critical stress complements linear rheological parameters to refine the screening priority of cell-compatible hydrogel recipes. Subsequent validation with primary cardiomyocytes demonstrated consistent morphological trends matching the predefined mechanical windows, alongside ambiguous boundary formulations. Our findings construct a bounded prioritization strategy to rapidly select GelMA compositions under sparse experimental conditions, with further prospective validations demanded before generalized predictive use for diverse tissue engineering scenarios.
    Keywords:  Gelatin methacryloyl (GelMA); Hydrogels; Mechanical windows; Rheology; Three-dimensional cell culture
    DOI:  https://doi.org/10.1021/acsami.6c11606
  4. Small. 2026 Aug 06. e75043
    Reconciling Granular Hydrogel Microstructure and Mechanics via a Temporary Thermo-Responsive and Cell-Invadable Matrix.
    Jun Kim, Soyeon Kwon, Taimoor H Qazi.
      Granular hydrogels are biomaterials composed of densely packed microparticles forming microporous structures. Their architecture can be controlled by tuning microparticle size, shape, and packing density. However, the mechanical properties of granular hydrogels mainly depend on interparticle interactions, whereby increasing the separation distance between microparticles to improve void volume weakens overall mechanical properties and induces unjamming, severely limiting their design and applicability. This study develops Thermo-Responsive Granular Hydrogels (TRGHs) with adjustable interparticle spacing and preserved mechanical integrity through incorporating a temporary thermo-responsive and cell-invadable interstitial matrix. It is shown that the interstitial space can be increased by more than 150% and the storage modulus can be increased by 4 orders of magnitude from 5 to 8900 Pa and maintained at this level by first processing at 5°C and then increasing the temperature to 37°C. Crucially, TRGHs show improved extrudability and structural integrity after 3D printing, support enhanced in vitro cell migration from embedded spheroids, and permit uninhibited in vivo cell and vessel invasion after subcutaneous injection. By addressing the trade-off between interparticle space and mechanical properties, these advanced biomaterials broaden the design possibilities for granular hydrogels in biofabrication, in vitro disease modeling, and tissue repair.
    Keywords:  injectable hydrogels; microgels; microparticles; tissue engineering; wound healing
    DOI:  https://doi.org/10.1002/smll.75043
  5. Nat Chem Biol. 2026 Aug 03.
    Black yeasts are efficient heterologous hosts for the production of a wide range of fungal polyketides.
    Adrian E Gadar-Lopez, Ana Calheiros de Carvalho, Xiaowei Li, Daniela Rago, Linda Ahonen, Charlotte H Gotfredsen, Marie V Lukassen, Carolina Cano-Prieto, Ling Chen, Sidharth Jayachandran, Jeppe S Brogaard, Miriam von Bargen, Laasya Bhagavan, Tomas Strucko, Adrian Krummenacher-Frey, Dushica Arsovska, Erin C Carr, Sheila I Jensen, Steven D Harris, Uffe H Mortensen, Jay D Keasling, Pablo Cruz-Morales.
      Fungal polyketides are a rich source of bioactive molecules. Their biosynthesis is often activated by environmental conditions that are hard to reproduce under laboratory conditions. Heterologous expression bypasses native regulation, enabling systematic polyketide discovery. The most widely used fungal hosts are the highly tractable Saccharomycotina yeasts with a narrow product scope and the metabolically robust but less tractable filamentous Eurotiomycetes. Here we established yeasts of the genera Exophiala and Knufia as hosts for polyketide production. These hosts are genetically tractable and robust, allowing us to heterologously produce six fungal polyketides with different domain architectures: 6-methylsalicylic acid, YWA1, monocillin II, farinosone B and monacolin J. Our findings demonstrate that these yeast hosts can efficiently produce complex polyketides allowing systematic polyketide synthase expression.
    DOI:  https://doi.org/10.1038/s41589-026-02282-2
  6. Nat Nanotechnol. 2026 Aug 03.
    Self-assembled contacts for high-yield molecular devices.
    Sarah O Spector, Peter F Satterthwaite, Maxwell Conte, Teddy Hsieh, Eduard O Bobylev, Kieran Dunn, Weikun Zhu, Jinwoo Sim, Jeremiah A Johnson, Farnaz Niroui.
      With their atomic precision and synthetically tailorable properties, molecules offer new possibilities for emerging computing, sensing, optical and quantum technologies. However, the scalable, damage-free integration of molecules into active devices with atomic-scale control remains a critical challenge due to incompatibility with existing top-down fabrication processes. Here we introduce self-assembled contacts, a strategy in which device structures are first fabricated using standard semiconductor manufacturing processes and subsequently transformed through engineered surface interactions to form self-aligned, pristine interfaces with molecules. We validate this approach by fabricating over 1,000 electrically active metal-molecule-metal devices with yields of up to 99% and stable operation over 105 measurement cycles, even for molecular layers thinner than 1 nm. In situ Raman measurements verified the preservation of molecular integrity. Beyond individual devices, the platform supports system-level integration, which we demonstrate through vector-matrix multiplication, a fundamental operation in neuromorphic computing, implemented in a crossbar array of self-rectified molecular memory devices. Our results establish self-assembled contacts as a scalable platform for integrating molecular functionalities into devices, bridging self-assembly and top-down manufacturing.
    DOI:  https://doi.org/10.1038/s41565-026-02227-9
  7. Adv Mater. 2026 Aug 06. e74564
    Single Atoms Functioning as Catalysts Inside Living Matter.
    Xue Zhou, Tianhang Feng, Zhiquan An, Zimeng Huang, Yingjie Zhang, Zhonghai Zhang.
      Single-atom catalysts represent the ultimate limit of materials miniaturization, yet their functionality has been confined to well-defined abiotic environments. Whether atomically dispersed metal centers can preserve catalytic identity within the chemically crowded, dynamically regulated milieu of living matter remains unknown. Here we show that Fe-Nx single atoms embedded in graphene quantum dots operate as catalytic entities inside the cytoplasm of bacteria. Following cellular internalization, these isolated sites establish a light-driven intracellular redox cycle that accelerates NADH oxidation while maintaining cellular viability. Time-resolved fluorescence measurements reveal pronounced excited-state quenching in the biohybrid, supporting close material-cell coupling and light-driven charge consumption within the cellular environment. The resulting perturbation propagates through endogenous biochemical networks, producing a programmable redistribution of reducing equivalents and enhanced succinate biosynthesis without genetic modification. Structural analyses confirm that atomic dispersion of Fe centers is preserved under biological conditions. These findings demonstrate that atomically defined materials can function within living systems while retaining both structural integrity and catalytic activity, thereby extending single-atom catalysis from abiotic interfaces to biological environments. Living matter thus emerges as a viable reaction field for atomic-scale materials, opening opportunities for designing functional materials capable of operating within complex biological settings.
    Keywords:  co2‐to‐chemicals conversion; intracellular single‐atom catalysis; microbial redox programming; photocatalytic microfluidic bioreactor; succinate production
    DOI:  https://doi.org/10.1002/adma.74564
  8. Adv Mater. 2026 Aug 06. e74301
    Ionizable Lipid-Dependent Optimization of Steroid Lipid Nanoparticles With Tunable Immunomodulatory Properties.
    Ajay S Thatte, Benjamin E Nachod, Julia Baena, Jenna Muscat-Rivera, Lesley Chaboub, Hannah C Safford, Hannah C Geisler, Hannah M Yamagata, Melgious J Y Ang, Michael Kegel, Alexandre Poirier, Elaine R Tong, Zhe Zhong, Qiangqiang Shi, Jinjin Wang, Elisa Battistini, Ye Zeng, Alex G Hamilton, Kelsey L Swingle, Drew Weissman, Jilian R Melamed, Michael J Mitchell.
      Lipid nanoparticles (LNPs) are a leading platform for nucleic acid delivery, yet their intrinsic adjuvanticity poses a significant materials design challenge for applications requiring immunological quiescence. Here, we report a modular engineering strategy that incorporates FDA-approved corticosteroids into LNP formulations, creating a new class of steroid LNPs with tunable anti-inflammatory properties. Through systematic screening of steroid and cholesterol substitution ratios, we establish structure-property relationships governing mRNA encapsulation efficiency, physicochemical characteristics, and inflammation suppression. Triamcinolone (TRI) emerges as our lead steroid, with 50% cholesterol substitution in SM-102 LNPs preserving physicochemical characteristics. Importantly, we show that optimal substitution ratios are ionizable lipid-dependent-80% for MC3 and 50% for SM-102 and ALC-0315-revealing fundamental design principles for these dual-functional LNPs. In an endotoxemia mouse model, TRI LNPs administered intramuscularly maintain mRNA delivery efficacy while reducing inflammatory cytokines by ∼4-fold compared to SM-102 LNPs. In a multiple sclerosis mouse model, TRI LNPs delivering therapeutic mRNA promote antigen-specific tolerance in spinal cord tissue and protect against paralysis. Compared to SM-102 LNPs, TRI LNPs reduce inflammatory cytokines by ∼3-fold and prolong protection against paralysis. Together, our work introduces a generalizable materials design strategy for engineering LNPs with tunable immunomodulatory properties to expand their therapeutic utility.
    Keywords:  autoimmune disease; immunomodulatory materials; lipid nanoparticles; nanomaterials design; nanotechnology; nucleic acid delivery
    DOI:  https://doi.org/10.1002/adma.74301
  9. Soft Matter. 2026 Aug 05.
    Designing DNA nanostar hydrogels for sequence-specific degradation and antibody release.
    Giorgia Palombo, Christine A Merrick, Jennifer Harnett, Susan Rosser, Davide Michieletto, Yair Augusto Gutiérrez Fosado.
      DNA nanostar (DNAns) hydrogels are promising materials for in vivo applications, including tissue regeneration and drug and antibody delivery. However, a systematic and quantitative understanding of the design principles controlling their degradation is lacking. Here, we investigate hydrogels made of three-armed DNAns with varying flexible joints, arm lengths, and mesh sizes and use restriction enzymes (RE) to cut the DNAns structures while monitoring the gel's degradation. We discover that (i) removing flexible joints, (ii) increasing arm length, or (iii) relocating the RE site along a DNA linker markedly accelerates hydrogel degradation. In contrast, non-specific endonucleases, e.g. DNaseI, quickly degrade DNAns hydrogels regardless of design. Importantly, the release of antibodies from DNAns hydrogels can be modulated by the action of sequence-specific enzymes, confirming that design-dependent susceptibility to sequence-specific enzymatic degradation can be leveraged for responsive drug-delivery systems. These findings provide new design principles for engineering DNAns hydrogels with tailored material properties, sequence-specific enzymatic susceptibility, and controlled cargo release.
    DOI:  https://doi.org/10.1039/d6sm00563b
  10. Cell Rep Methods. 2026 Aug 06. pii: S2667-2375(26)00245-6. [Epub ahead of print] 101544
    Strategic enhancement of Cas9 nickase-driven gene amplification.
    Hiroaki Takesue, Satoshi Okada, Takashi Ito.
      Gene amplification plays a critical role in evolution and disease and is widely utilized to overexpress valuable gene products in biotechnology. To broaden these applications, we previously developed break-induced replication (BIR)-mediated tandem repeat expansion (BITREx), a method utilizing Cas9 nickase (nCas9) to amplify genetic sequences by driving tandem array expansion through ectopic BIR. Since BITREx efficiency depends on the guide RNA (gRNA) recruiting nCas9 to the array's flanking regions, here we develop a plasmid-based reporter system in budding yeast for the rapid identification of high-performing gRNAs. Furthermore, we introduce BITREx 2.0, a dual-nicking strategy that targets both sides of the gene array. We demonstrate that BITREx 2.0 is effective for both natural and synthetic arrays, enhancing expansion efficiency by up to an order of magnitude compared to the original single-nicking format. These advancements significantly broaden the applicability and efficiency of nCas9-mediated gene amplification across diverse biological and biotechnological contexts.
    Keywords:  BITREx; CP: biotechnology; CP: genetics; break-induced replication; genome editing; reporter gene; tandem repeat
    DOI:  https://doi.org/10.1016/j.crmeth.2026.101544
  11. Science. 2026 Aug 06. 393(6811): eaec2657
    Generative design of bacteriophages with genome language models.
    Samuel H King, Claudia L Driscoll, David B Li, Daniel Guo, Aditi T Merchant, Garyk Brixi, Max E Wilkinson, Brian L Hie.
      Many important biological functions arise not from single genes but from complex interactions encoded by entire genomes. We report the first generative design of complete bacteriophage genomes using genome language models. We generated viable bacteriophages with target host tropism, using the phage ΦX174 as our design template. Experimental testing yielded 16 phages with diverse fitness profiles in laboratory conditions. Cryo-electron microscopy confirmed that a generated phage utilizes an evolutionarily distant DNA packaging protein in its capsid. A cocktail of generated phages rapidly overcomes ΦX174-resistant Escherichia coli strains, demonstrating a path toward artificial intelligence-generated phage therapies against rapidly evolving bacterial pathogens. This work provides a blueprint for the design of diverse synthetic bacteriophages and useful biological systems at the genome scale.
    DOI:  https://doi.org/10.1126/science.aec2657
  12. Nature. 2026 Aug 04.
    Engineered yeast that make cancer drugs could spare a rare flower.
      
    Keywords:  Synthetic biology
    DOI:  https://doi.org/10.1038/d41586-026-02428-1
  13. Mater Today Bio. 2026 Aug;39 103475
    Programmable continuous gradient bioprinting for engineering spatially heterogeneous microenvironments.
    Taekyung Choi, Hyungseok Lee.
      Native tissues exhibit spatial heterogeneity in mechanical, cellular, and biochemical properties, yet reproducing such gradients in extrusion-based bioprinting remains challenging. Existing multi-material bioprinting approaches can create spatial variations in material composition, but often rely on discrete material transitions rather than continuous gradients. Here, we present a dual ball-valve mixing module that generates continuous gradients through real-time control of the mixing ratio between two precursor inks within a single-nozzle configuration. Complementary actuation of paired ball valves continuously adjusts the mixing ratio while maintaining constant extrusion conditions, transforming gradient formation into a programmable feature of the printing process. The versatility of the platform was demonstrated through gradients in mechanical stiffness, cell density, and biochemical cues. Continuous mixing enabled gradual transitions in material properties, reducing abrupt interfacial changes associated with discrete material deposition. Spatially defined cell-density distributions and graded two-population cellular interfaces were achieved while maintaining cell viability comparable to conventional extrusion bioprinting. Furthermore, a TGF-β1 gradient induced location-dependent epithelial-mesenchymal transition responses, demonstrating the ability to translate programmed biochemical gradients into spatially regulated cellular behavior. Consequently, this work establishes dynamic bioink mixing as an effective strategy for generating continuous and spatially programmable gradients, enabling the integration of material composition, cellular organization, and biochemical signaling within a single extrusion-based bioprinting process.
    Keywords:  Ball valve flow control; Extrusion bioprinting; Functionally graded bioink; Tissue microenvironment engineering
    DOI:  https://doi.org/10.1016/j.mtbio.2026.103475
  14. Biomaterials. 2026 Jul 28. pii: S0142-9612(26)00532-6. [Epub ahead of print]337 124508
    Bioprinted cell-instructive lung-dECM constructs for reconstructing an immuno-regenerative pulmonary microenvironment.
    Soham Ghosh, Falguni Pati.
      Pulmonary tissue engineering requires scaffolds that combine parenchymal mechanical compliance with extracellular matrix-bound instructive cues, yet soft materials often lack print fidelity. Here, we developed decellularized lung matrix (dLM) bioinks using an osmotic decellularization strategy designed to preserve sulfated glycosaminoglycans (sGAGs) and basement membrane proteins and benchmarked them against conventionally detergent-processed dLM. Rather than inferring printability from bulk viscosity without shear history, we standardized extrusion conditions by defining flow windows through print-matched thixotropy testing that incorporates nozzle residence time and wall shear stress to predict post-extrusion structural recovery. This framework revealed distinct structure-function tradeoffs, collagen-dominant dLM inks supported superior vertical layer stacking through higher viscosity and proportionate elastic and viscous recovery, whereas sGAG preserved polyelectrolyte rich matrices exhibited faster viscosity rebuild with rapid gelation after extrusion. Resultant dLM hydrogels maintained lung parenchymal viscoelasticity ranges and retained cytocompatibility through bioprinting. Printed dLM scaffolds directed mesenchymal stem cell fate in a spatially dependent manner; surface-seeding induced epithelial markers, including cytokeratin and tight junction proteins, and surfactant-associated transcripts, whereas encapsulated cells developed α-SMA expression, consistent with an interstitial myogenic phenotype. Macrophages cultured within sGAG-rich dLM scaffolds adopted anti-inflammatory polarization with elevated mannose receptor expression and regulatory cytokine production that persisted under inflammatory stimulation. Together these results show that strategic preservation of lung ECM components can yield printed scaffolds that reconcile pulmonary mechanics, high printing fidelity, regenerative niche-specific cell responses, and sustained in vitro immunomodulation, requirements that collectively establish a compositionally validated bioink platform for engineering lung tissue.
    Keywords:  Decellularized extracellular matrix bioink; Extrusion bioprinting; Immunomodulatory biomaterials; Lung tissue engineering; Macrophage polarization; Mesenchymal stem cell differentiation
    DOI:  https://doi.org/10.1016/j.biomaterials.2026.124508
  15. Biomaterials. 2026 Jul 23. pii: S0142-9612(26)00489-8. [Epub ahead of print]337 124465
    Transient culture of adult human hepatocytes as organoids improves engineered liver engraftment.
    Sarah H Saxton, Inkyung Kang, Shannon Mitchell, Jeremy Lotto, Aditya Upadhyay, Chenhui Zou, Corrine Quirk, Tara N McCray, Olivia Prado, Fredrik Johansson, Chelsea L Fortin, Dorice L Goune, Ekaterini D Zacharis, Ludovic Vallier, Ype P de Jong, Kelly R Stevens.
      Bioengineered livers could serve as a bridge or alternative to whole organ transplantation for patients suffering from liver disease. However, identifying cellular configurations that promote adult human hepatocyte survival after tissue transplantation remains a critical hurdle. We hypothesized that transient culture of adult hepatocytes in 3D as organoids would enhance engraftment of these cells in bioengineered tissues in vivo. Here, we established an organoid system that supports culture of adult human hepatocytes from eight different human adult donors aged 19-49. These organoids support retention of human hepatocyte morphology found in the mature liver, express an adult liver transcriptome, and exhibit mature functions such as inducible cytochrome activity. Importantly, adult human hepatocyte organoids (AHHO) improved engraftment of hepatocytes up to 25-fold in vivo in engineered tissues compared to previous hepatocyte models. Thus, 'priming' human cells in organoids could have a major impact on translational bioengineered tissue applications.
    Keywords:  Bioengineered liver; Hepatocyte organoids; Tissue engraftment
    DOI:  https://doi.org/10.1016/j.biomaterials.2026.124465
  16. Science. 2026 Aug 06. 393(6811): 596-600
    Calcium tunes snail mucus-based materials to multiple functions.
    Mariella Gabler, Emeline Raguin, Ernesto Scoppola, Barbara Steigenberger, Assa Yeroslaviz, Peter Werner, Peter Fratzl, Franziska Jehle.
      Mucus is known as a viscous fluid; yet, snails manufacture various mucus-based materials with much higher cohesion and tailored to different and even antagonistic functions, including lubrication, adhesion, protection, and defense. To gain insight into this versatility, we use a multidisciplinary approach to investigate five different mucus-based materials produced by the snail Cepaea nemoralis. Our results demonstrate that snails use collagen VI as a main structural component and add amorphous calcium carbonate (ACC) during mucus secretion. ACC functions as an ion source in wet mucus types, most likely for cross-linking, or as a mineral precursor in dry mucus types. These findings shed light on the versatility of these viscoelastic materials, which are able to switch between very different properties on the basis of calcium and protein content.
    DOI:  https://doi.org/10.1126/science.adx7367
  17. Angew Chem Int Ed Engl. 2026 Aug 05. e26115
    Enhancing the Versatility of Polyethylene Terephthalate (PET) Through Strategic Biomolecular Functionalization.
    Bhumrapee Eiamthong, Thanate Srimora, Rawiporn Amornloetwattana, Chayasith Uttamapinant.
      As biocatalytic strategies for PET recycling reach maturation, insights gained from PET hydrolase research can be leveraged to inform the design of proteins and surface-functionalization strategies that promote stable association of functional proteins with PET surfaces, enabling the development of functional protein-plastic hybrid materials. Herein, we examine recent developments in biofunctionalization strategies of PET and related materials, with a focus on chemical biology approaches that offer more precise control of the orientation of proteins on PET and related materials. Biophysical insights from protein-polymer interface chemistry studies can inform protein selection, design, and engineering approaches to minimize denaturation and maximize function of proteins upon attachment to surfaces. Finally, we highlight applications of protein-functionalized PET and related synthetic polymers, including for biomedical applications and scalable biocatalysis, showcasing the potential of integrating biological activity into durable synthetic polymers.
    Keywords:  biofunctionalization; click chemistry and biology; immobilization; plastic; polyethylene terephthalate (PET)
    DOI:  https://doi.org/10.1002/anie.202526115
  18. Nat Mater. 2026 Aug 06.
    Microdroplets jam together to mimic soft tissues.
    Yuyan Su, Yujia Zhang.
      
    DOI:  https://doi.org/10.1038/s41563-026-02701-8
  19. Small. 2026 Aug 02. e75030
    Biphasic Polyampholyte Hydrogel for Rewritable 3D Encryption Enabled Via Pressure and Solvent Exchange.
    Jianhua Hu, Xuefeng Yang, Guowen Zhou, Chunyu Chang.
      3D encryption is an advanced cryptographic technique that integrates concurrent information and shape encryption in a single unit. However, traditional 3D encryption systems suffered complex decryption proces with multiple triggers for decryption, due to their separated keys for shape decryption and information decryption. Herein, we propose polyampholyte hydrogels with biphasic structures for rewritable 3D encryption. The phase separation of polyampholyte hydrogel was triggered by pressure and solvent exchange, resulting in opaque patterns. Owing to the sea-island structure of quaternized polyrotaxane-modified polyampholyte (QRPA) hydrogel, 3D encryption could be achieved by shaping the patterned hydrogel and fixing in DMSO. Importantly, the one-step decryption was accomplished by immersing the 3D encrypted hydrogel in water, where the deformed hydrogel reverted to its original shape and simultaneously displayed the hidden patterns. Besides, the QRPA hydrogels were rewritable and multiple-shape programmable for complex 3D encryption. We constructed a new 3D encryption system that can be decrypted with a single step or multilevel security, showcasing its potential in advanced encryption.
    Keywords:  3D encryption; phase separation; polyampholyte hydrogel; polyrotaxane; solvent exchange
    DOI:  https://doi.org/10.1002/smll.75030
  20. Chemistry. 2026 Aug 03. e71530
    From Caffeine to Aspirin: Everyday Molecules as Triggers for Genetically Encoded Proximity Systems.
    Mingguang Cui, Tianlu Wang, Yaoyu Han, Yun Huang, Tien-Hung Lan, Yunbin Zhou.
      Chemically induced proximity (CIP) enables programmable control of gene expression, protein activity, cellular signaling, and engineered cell functions using small molecules. Yet many classical CIP platforms rely on ligands that may limit therapeutic translation owing to unfavorable biosafety profiles, off-target activity, incomplete reversibility, dosing constraints, and potential immunogenicity of engineered components. This perspective highlights dietary small molecule- and OTC drug-responsive CIP systems as emerging platforms for translational chemogenetic control. We focus on two complementary design strategies. One exploits nanobody-derived binders against familiar small molecules, as exemplified by synthetic anti-caffeine nanobody-based systems. The other adapts naturally evolved ligand-binding proteins through rational protein engineering, as illustrated by salicylate-responsive platforms derived from plant salicylic acid (SA)-binding receptors for reversible proximity control and aspirin-responsive gene regulation. Together, these engineered systems demonstrate how familiar molecules such as caffeine, SA, and aspirin can be transformed into programmable biological inputs. We further discuss how artificial intelligence (AI)-guided protein engineering may expand this design space by enabling de novo construction and functional reprogramming of ligand-responsive modules, leading to safer and clinically compatible proximity-control systems.
    Keywords:  artificial intelligence; chemical induced proximity; immunotherapy; nanobody; over‐the‐counter drugs
    DOI:  https://doi.org/10.1002/chem.71530
  21. Nat Chem Biol. 2026 Aug 05.
    A covalent PFKL activator suppresses tumor growth.
    Xiaoding Jiang, Eric M Lynch, Congcong Lyu, Crystal N Wilson, Lauren E Salay, Hayden T Hess, Scott N Lyons, Mu-Jie Lu, Shuangyu Luo, Gibae Kim, Hsin-Ru Chan, Wesley J Wolfe, Lauren G Zacharias, Thomas P Mathews, Yi-Chih Lin, Bradley A Webb, Justin M Kollman, Xiaolu A Cambronne, Ku-Lung Hsu.
      Glycolysis fuels vital cellular functions, and its dysregulation has been implicated in cancer, neurodegeneration, antibiotic resistance and diabetes. The glycolytic dependency of cancer, known as the Warburg effect, represents a key vulnerability for development of targeted anticancer agents; however, the development of such agents remains challenging owing to metabolic heterogeneity and resistance. Here we developed a covalent phosphofructokinase-1 liver type (PFKL) activator that couples glycolytic activation with delivery of a cytotoxic carnitine palmitoyltransferase 2 (CPT2)-targeting payload to cancer cells in vitro and in vivo. The electrophile-drug conjugate site-specifically and proteome-wide selectively modifies K677 in the allosteric effector site to stabilize the R-state tetramer of PFKL, while concomitantly releasing a CPT2-selective inhibitor to destabilize cell metabolism. The delivery mechanism of electrophile-drug conjugates is analogous to that of antibody-drug conjugates, but differentiated by their selective covalent targeting of intracellular proteins.
    DOI:  https://doi.org/10.1038/s41589-026-02289-9
  22. Soft Matter. 2026 Aug 03.
    Modular PEG coatings for engineering a biomimetic glycocalyx on lipid membranes.
    Marco Halbeisen, Svetozar Gavrilović, Yusuf Qutbuddin, Juan Heredero, Petra Schwille.
      Engineering synthetic cells with biomimetic surface architectures requires precise control over the spatial organization and mechanical properties of the membrane surface. Inspired by the protective and regulatory functions of the natural glycocalyx, we present a modular platform for constructing hierarchical, crosslinked PEG networks on fluid lipid membranes. Through spatially controlled, sequential strain-promoted azide-alkyne cycloaddition (SPAAC), we assemble a tunable, multilayered PEG mesh that mimics the dynamic, dense, and mechanically resilient architecture of the glycocalyx. By incorporating linear PEG lipids as defined anchors at controlled densities (0.25-1 mol%), we establish a reactive scaffold on the membrane surface. Sequential conjugation with eight-arm PEG-DBCO and eight-arm PEG-azide enables the formation of a covalently crosslinked, multilayered PEG mesh with tunable thickness, connectivity, and mechanical robustness. The multivalency of the eight-arm architecture allows each first-layer PEG to act as a branching node, enabling high-density network formation and exceeding the surface coverage achievable with linear PEG chains. Crucially, the phase-dependent partitioning of the lipid anchor enables a spatially confined network assembly within the liquid-disordered (Ld) domains of phase-separated membranes, allowing for domain-specific functionalization. Once formed, the crosslinked network exhibits persistent spatial organization, retaining its footprint even after thermal mixing of the underlying lipid phase-a hallmark of mechanical stability and functional memory. Quantitative analysis via QCM-D and FRAP reveals that network connectivity and lateral mobility are governed by anchor density and PEG architecture. The resulting mesh acts as a tunable steric barrier, effectively attenuating receptor-ligand interactions in a stepwise, assembly-dependent manner. This work demonstrates a powerful strategy for engineering programmable, adaptive, and mechanically resilient surface architectures on model membranes, a critical step toward interfacing functional synthetic cells with intelligent nanocarriers of spatiotemporally regulated functionality.
    DOI:  https://doi.org/10.1039/d6sm00474a
  23. Sci Adv. 2026 Aug 07. 12(32): eaee6610
    A metabolite morphogen coordinates multicellular development in Bacillus subtilis.
    Taylor B Updegrove, Vani Pande, Fukang She, Michael C Gilmore, Vivek Anantharaman, David M Stevenson, Daniel Amador-Noguez, L Aravind, Felipe Cava, Jiji Chen, Jue D Wang, Kumaran S Ramamurthi.
      The transition from unicellular to multicellular growth requires diversification of cellular functions within genetically identical populations. In Bacillus subtilis, biofilm formation is historically viewed as a developmental precursor to sporulation along a linear pathway. Here, we show that biofilm formation and sporulation instead diverge along a branched pathway. A subpopulation that first initiates sporulation catabolizes lipoteichoic acid through the sequential action of the enzymes ShfP (Sporulation heterogeneity factor Poison) and PhoA (alkaline phosphatase A), leading to the release of millimolar concentrations of glycerol. This glycerol impedes sporulation by disrupting cell wall synthesis and cytoplasmic pH, necessitating counteraction by another protein, ShfA (Sporulation heterogeneity factor Antidote). The extracellular glycerol, however, acts as a morphogen that directs neighboring cells to initiate biofilm formation, which we directly visualize in developing populations of cells. Thus, B. subtilis multicellularity emerges through a branched developmental program in which sporulating cells generate the cue that creates the biofilm-producing lineage via cell-cell communication through repurposing of a canonical intracellular metabolite.
    DOI:  https://doi.org/10.1126/sciadv.aee6610
  24. Nat Microbiol. 2026 Aug 06.
    Antiviral defence is a conserved function of diverse bacterial DNA glycosylases.
    Landon J Getz, Amy L Qian, Y Vivian Liu, Sam R Fairburn, Mahnoor S Butt, Yan-Jiun Lee, Peter R Weigele, Karen L Maxwell.
      Bacteria are frequently attacked by viruses, known as phages, and rely on diverse defence systems to survive. While phages can evade defences by covalently modifying their DNA, these non-canonical nucleobases create molecular signatures that bacteria can exploit. Here, using structure-guided discovery, we identified two widespread families of anti-phage DNA glycosylases, Dag1 and Dag2. Although DNA glycosylases are classically associated with DNA repair, Dag1 and Dag2 act as antiviral effectors that selectively target phages carrying modified guanine bases. Guided by the conserved glycosylase fold, we uncovered numerous defence-associated glycosylases that collectively form a diverse repertoire of enzymes targeting chemically modified phage DNA. We further identified a distinct glycosylase superfamily that protects against phages carrying modified thymidine bases. Together, these findings establish DNA glycosylases as a versatile class of bacterial immune proteins and highlight structure-guided discovery as a powerful strategy for uncovering hidden antiviral defences.
    DOI:  https://doi.org/10.1038/s41564-026-02441-0
  25. Mater Horiz. 2026 Aug 03.
    Inspiration from nature for fiber materials and fiber electronics.
    Hao Guo, Wang Li, Qingquan Han, Chunlei Dong, Xuemei Sun, Huisheng Peng, Songlin Zhang.
      Natural fibers have evolved through optimized biosynthetic pathways to achieve an exceptional combination of strength, toughness, and compliance. Although these biological systems have inspired rapid advances in biomimetic fiber materials and fiber electronics, existing studies remain largely fragmented across biological principles, fabrication strategies, structural design, and device applications. To bridge these disconnected areas, this review proposes a bioinspiration-processing-structure-function (BPSF) conceptual framework that establishes a unified design pathway for bioinspired fiber materials and fiber electronics. Guided by this framework, we first summarize the transferable design principles derived from fibrous and non-fibrous biological systems. We then discuss how biomimetic processing strategies translate these biological principles into controllable fiber structures. Building on this processing-structure relationship, we further examine how structural engineering controls load transfer, interfacial coupling, and electromechanical stability, and highlight how these structural advantages enable reliable sensing, actuation, and adaptation in integrated fiber electronic systems. Finally, we discuss the key challenges and opportunities. This review establishes a cross-level design paradigm that links biological inspiration with processing, structural engineering, and device functionality, providing a perspective for advancing bioinspired fibers from passive structural mimics toward robust, adaptive, and intelligent fiber electronic systems.
    DOI:  https://doi.org/10.1039/d6mh00875e
  26. Mater Horiz. 2026 Aug 03.
    Structured adhesives: inspiration, modeling, engineering and applications.
    Xiaohang Luo, Di Tan, Longjian Xue.
      Nature has evolved a remarkable diversity of structured adhesives that enable organisms to achieve robust, reversible, and adaptive attachment in natural environments. Unlike conventional chemical glues, these biological adhesives exhibit strong yet controllable adhesion with residue-free detachment, self-cleaning capabilities, and environmental adaptability, which are primarily enabled by their evolutionarily optimized hierarchical architectures. Deciphering the structural and mechanical principles underlying these systems is therefore essential for the rational design of next-generation bioinspired reversible adhesives. This review examines how biological adhesion principles can be translated into engineered structured adhesives by linking biological archetypes, interfacial mechanics, structural design, and functional integration within a unified framework. We discuss the physical mechanisms governing biological adhesion and the theoretical models that have shaped the current understanding of structured adhesive contacts. We then survey fabrication technologies and design strategies to gain enhanced adhesion, detachment regulation, and improved structural adaptability. Furthermore, we highlight emerging design paradigms, including interfacial stress regulation, internally heterogeneous architectures, programmable reversibility, and adhesion-sensing integration, that are shifting structured adhesives from static attachment structures toward adaptive, multifunctional, and intelligent interfaces. Finally, we outline the persistent challenges in structural design, scalable manufacturing, environmental adaptability, and system integration, while offering perspectives on future opportunities for advanced bioinspired adhesives in robotics, wearable systems, and biomedical applications.
    DOI:  https://doi.org/10.1039/d6mh00861e
  27. Nat Mater. 2026 Aug 06.
    Twisting light the Weyl way.
    A Akrap, M Orlita.
      
    DOI:  https://doi.org/10.1038/s41563-026-02709-0
  28. Mater Horiz. 2026 Aug 05.
    Entangled glycerol hydrogels for wave modulation of Rayleigh-SAW devices.
    Zhipeng Du, Yuwei Han, Tianji Fei, Tao Wang, Kun Jia.
      Surface acoustic wave (SAW) devices, particularly of the Rayleigh type, harness nanoscale-amplitude vibrations on a piezoelectric substrate to sense, actuate and process various targets. SAW modulation in selected areas is essential for high-performance devices. Here, we develop a highly entangled glycerol hydrogel as a compact, high-efficiency absorber for wave modulation of Rayleigh-SAW devices. A high glycerol content of 50 wt% ensures strong Rayleigh-SAW attenuation and suppresses dehydration, whereas the dense chain entanglements preserve network stiffness despite inhibited radical polymerization at high glycerol fractions. The highly entangled glycerol hydrogel shows a SAW-attenuation coefficient of 1110 m-1 (113.5% higher than that of the widely adopted absorber polydimethylsiloxane, PDMS) together with a stiffness of ∼100 kPa, enabling a 52.9% reduction in the characteristic absorber length relative to PDMS. Moreover, it adheres strongly to a LiNbO3 substrate without surface treatment, delivering an adhesion energy of up to 50 J m-2 (400% higher than that of PDMS). We also demonstrate two SAW-based microfluidic applications of the highly entangled glycerol hydrogel absorber. Compared with PDMS, the glycerol hydrogel absorber increases the streaming velocity by 36.8% in droplet stirring and the collection rate by 56.9% in particle enrichment. The highly entangled glycerol hydrogel absorber offers a space-efficient route toward further miniaturization and integration of SAW devices.
    DOI:  https://doi.org/10.1039/d6mh00842a
  29. Adv Mater. 2026 Aug 05. e74516
    Programmable Functional Silicification of DNA Origami Nanostructures.
    Anna V Baptist, Lasse Guericke, Philipp Mauker, Oliver Thorn-Seshold, Amelie Heuer-Jungemann.
      The silicification of DNA origami nanostructures offers a powerful strategy for enhancing their mechanical stability and resistance against detrimental environmental conditions. In the past years, several studies have investigated key aspects of the silicification process, resulting in a variety of established protocols. However, until now, the silica coating generally served as a passive protective layer or as the base for the further deposition of inorganic materials, but it did not carry any additional functionality itself. Here, we introduce two complementary, programmable approaches for the direct fabrication of functionalized silica coatings of DNA origami nanostructures. First, we synthesized a fluorescein-bearing silica precursor which imparts fluorescence to the silica coating of both individual DNA origami nanostructures and crystals, enabling intracellular tracking of silica-stabilized structures. Second, we employed a silica precursor containing a disulfide bridge to generate a redox responsive silica coating that degrades in a reducing environment. By introducing functionality at the precursor level, our approach establishes silicification as a modular platform for constructing responsive and traceable DNA-based hybrid materials. These strategies expand the chemical scope of DNA nanotechnology and facilitate future applications in drug delivery and advanced materials science.
    Keywords:  DNA origami; cellular uptake; dissolvability; fluorescence; silicification
    DOI:  https://doi.org/10.1002/adma.74516
  30. Small. 2026 Aug 05. e75009
    A Universal Multifunctional Zinc Ionic Semi-Interpenetrating Network Hydrogel Coating on Polymer Surfaces.
    Yu-Qing Wei, Baisong Zhao, Meng-Han Bai, Jun-Yang Wang, Yu-Xin Zong, Zhefeng Kang, Zhi-Guo Wang, Rui Hong, Lisha Yi, Jia-Zhuang Xu, Zhong-Ming Li.
      Integration of hydrogel coatings onto medical devices holds great promise to mitigate tissue-device contact issues, yet achieving robust interfacial bonding and multifunctionality remains challenging. Here, a universal multifunctional zinc ionic semi-interpenetrating network hydrogel coating (Zn-SIHC) is developed onto polymer surfaces for tissue-friendly interventions. Zn-SIHC is generated in situ through surface-initiated polymerization of acrylamide (AM) as the primary covalent network. Chitosan is uniformly dispersed within this network, where zinc ions act as the cross-linkers to establish a complementary ionic network. Incorporation of zinc ions enhances both tensile strength (fourfold increase) and peeling strength (uo tp ∼900 N/m) due to ionic reinforcement and ensures good antibacterial capability. Meanwhile, Zn-SIHC exhibits favorable hydrophilic lubricity (CoF = 0.05), transparency (91%), antifouling properties, and biocompatibility. The clinical applicability of Zn-SIHC in alleviating intubation-related side effects is verified using an in vivo tracheal intubation model in cynomolgus monkeys. The potential mechanism by which Zn-SIHC inhibits intubation injury-induced inflammation and apoptosis is preliminarily deciphered. This work opens a new avenue for surface engineering of medical intervention devices.
    Keywords:  hydrated lubrication; hydrogel coating; intubation injury; ionic semi‐interpenetrating network; mechanical reinforcement
    DOI:  https://doi.org/10.1002/smll.75009
  31. Nat Mater. 2026 Aug 04.
    Molecular engineering of self-assembled layers.
    Ceylan Doyranli, Jovana V Milić.
      
    DOI:  https://doi.org/10.1038/s41563-026-02664-w
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