bims-enlima Biomed News
on Engineered living materials
Issue of 2026–07–19
forty-nine papers selected by
Rahul Kumar, Tallinna Tehnikaülikool
  1. Integrating microchannels and flows into 3D printable granular hydrogel matrices.
  2. PEG-Based Living Hydrogels Engineered for Tunable Production of Bioactive Lipopeptides.
  3. De novo design of orthogonal far-red, orange, and green fluorophore-binding proteins for multiplexed imaging.
  4. Self-Growing and Mechanically Tunable Living Materials with Paenibacillus mucilaginosus Extracellular Polymeric Substances.
  5. Bound water as a kinetic crosslinker for bio-inspired impact-stiffening polymers.
  6. Engineered E. coli swarming for binary and analog input recording.
  7. Stress-Adaptive Biomaterials With Tunable Yielding Architectures Regulate Organoid Morphogenesis.
  8. An optogenetic smart microscopy platform reveals signaling dynamics-dependent control over collective cell migration.
  9. Controlled Peptide Capture and Release in 3D-Printed Multimaterial Microstructures.
  10. Restoring intracellular homeostasis disrupted by synthetic nanoassemblies.
  11. Cryogenic silicification enables nongenetic functional continuity across mammalian cell generations.
  12. High-resolution reconstruction of cell-type-specific transcriptional regulatory processes from bulk sequencing samples.
  13. The Hidden Cost of Fusion: Intrinsic Asymmetry in Vesicle Fusion Restricts Synthetic Cell Growth.
  14. Bridging stimulus-responsive and dissipative peptide assemblies to build complex interactive biomaterials.
  15. SABER bioprinting: a temporal platform for multiday assembly of engineered tissues.
  16. Diarylcyclopropenones: Modular, Tetherable, Light-Triggerable Reservoirs of Carbon Monoxide in Crosslinked Hydrogels.
  17. Dynamic global acetylation remodeling during the yeast heat shock response.
  18. Bioinspired organic materials for seamless neurohybrid interfaces: from material design to living electronics.
  19. Spatiotemporally controlled matrix softening facilitates deterministic crypt formation in human intestinal organoids.
  20. Synthetic Intrinsically Disordered Proteins Enable Soluble Expression of Disulfide-Rich Therapeutics in E. coli.
  21. Too big, too small, too O2: the Pandoro Effect from oxygen gradients in tomographic volumetric additive manufacturing.
  22. A Facile Fabrication Process for Handmade Fully Polymeric Neural Interfaces.
  23. Multistage microrobots with pH-responsive release of platelet membrane-coated nanoparticles.
  24. Screen-Printed Biochar-Derived Graphene Solid-Contact Ion-Selective Electrodes for Nutrient Monitoring in Hydroponic Solutions.
  25. Xeno-Free Peptide-Functionalized Hydrogels Support hiPSC Encapsulation and In Situ Differentiation into Structurally Mature Cardiomyocytes.
  26. From sound sensing to neural control.
  27. Bacillus subtilis cells can escape biofilms by producing a hydrogel that ejects them.
  28. Simultaneous measurements of translation rate and transcriptome uncovers linked regulation within an active bacterial cell population.
  29. Guanine-Rich DNA Aptamers for Selective Binding to Agarose Hydrogels.
  30. Programmable CRISPRtune dissects the transcriptional repressive activity of MeCP2.
  31. Ultrasoft, adhesive, pH-tunable hydrogel based on in situ functionalized laser-induced graphene for through-hair concurrent biosensing.
  32. Flavin-Decorated Proteins and Bacteria Enable Photoenzymatic Amine Valorisation.
  33. Bridging solar harvesting technologies using hydrogels towards sustainability.
  34. Programmable regenerative tissues: Converging mammalian synthetic biology and tissue engineering.
  35. Pathway remodeling and adaptive evolution enable efficient co-utilization of glucose and xylose in Escherichia coli.
  36. Immobilised enzyme reactors for post-production glycan modification of purified glycoproteins.
  37. Self-Assembled Living Microreactors for Selective Microcystin Removal via Cascade Sieving, Adsorption and Biodegradation.
  38. Chemical recycling and repolymerization of poly(ethylene terephthalate), poly(ethylene furanoate), and their copolyesters.
  39. Illuminating new pathways: beyond conventional photochemistries for multi-photon 3D laser printing.
  40. AI-powered the toughest biohydrogels.
  41. Digintel metasurface of extensive reprogrammable morphing.
  42. Engineering aptamer dimers (apdimers) for optimization of synthetic riboswitches.
  43. Nanopore-Mediated Assembly Enables Precise and Continuous Synthesis of mRNA-Encapsulated Lipid Nanoparticles for COVID-19 Vaccines.
  44. Chitosan-Based Hydrogels in Vascular Tissue Engineering Applications.
  45. Selectivity Emerges from Indiscriminate Photoreduction.
  46. Two parallel phosphorus economies.
  47. Establishment of SRLC: a multiplex genome editing technology for Saccharomyces cerevisiae and its application in metabolic engineering of malonyl-CoA pathway.
  48. Programming fracture resistance in metamaterials via elastic instabilities.
  49. Tuning Hydrogel Mechanics and Microstructure to Maximize Extracellular Vesicle Production from Mesenchymal Stem Cells.
  1. Lab Chip. 2026 Jul 15.
    Integrating microchannels and flows into 3D printable granular hydrogel matrices.
    Emily Ferrarese, Emily Swanekamp, Thuy-Vi Bui, Matthew J Lazzara, Christopher B Highley.
      Microfluidic systems incorporating or contained within hydrogels are important in creating microphysiological systems (MPSs). Often naturally-derived hydrogels are used, as their inherent bioactivity supports dynamic cellular behaviors. Hydrogel biomaterials that are partly or fully synthetic are desirable in engineering systems with specific, designed properties, though they typically lack bioactive features of natural materials without additional molecular design. In particular, engineering synthetic biomaterials to support physiologically relevant, dynamic cellular behaviors is an important design goal. Granular hydrogels inherently permit dynamic cellular activity, owning to porosity between particles and dynamic material properties in the absence of interparticle crosslinking. However, using dynamic granular hydrogels in MPSs requires stable channels to perfuse fluid in these dynamic systems. Here, we establish channels within granular hydrogels to enable perfusion through spatially controlled interparticle crosslinking. Selective crosslinking allowed for the formation of stable channels while allowing hydrogel microparticles between two channels to remain uncrosslinked. This allowed spatiotemporal control of signals within an environment established from microparticles without interparticle crosslinking. Fluorescently tagged molecules allowed for the visualization of controlled soluble gradients between two channels within the device. Additionally, embedded 3D printing processes can be used to specify material composition within the system, demonstrating integrated technology for engineering well-defined hydrogel systems. Integrated microfluidic-based control over soluble signals in a system that is compatible with 3D printing processes will establish a basis for building MPSs for broad applications, and the ability to maintain granular systems in culture without interparticle crosslinking will enable design of synthetic hydrogels that access unique dynamic properties within these systems.
    DOI:  https://doi.org/10.1039/d5lc00219b
  2. ACS Appl Polym Mater. 2026 Jul 10. 8(13): 10210-10222
    PEG-Based Living Hydrogels Engineered for Tunable Production of Bioactive Lipopeptides.
    Jeffrey A Reed, Moises M Gutierrez, Douglas A Dougherty, Asad Bin Zaman, Ryan R Hansen.
      Encapsulation of microbial cells within nanoporous hydrogels creates dynamic and responsive living materials well-suited for biotherapeutic applications. Bacillus subtilis is a promising microbe in this application as it is generally regarded as safe, can be sporulated for long-term stability and resistance to nonideal environments, and can produce antimicrobial and anticancer molecules such as the cyclic lipopeptide surfactin. Here, we examine the growth of B. subtilis cells and corresponding production of surfactin after encapsulation within poly-(ethylene glycol) (PEG) hydrogels at varied levels of nanoconfinement. Encapsulation was achieved through Michael-type addition reactions between PEG diacrylate and PEG tetrathiol macromers, where macromer molecular weight was systematically varied to generate hydrogels across a range of average mesh sizes (9-19 nm). Hydrogels had varied Young's modulus (7.3 ± 1.7 kPa to 16.4 ± 0.7 kPa) and provided a 7-fold range in small molecule diffusivity. In-situ cellular growth monitoring and surfactin quantification revealed that all hydrogels stimulated the production of surfactin with verified antibacterial activity and in a manner tunable with mesh size. Smallest mesh sizes drove highest surfactin production, a ∼5-fold increase relative to equivalent cultures of unconfined cells. Cell loading was then varied in 9 nm mesh size hydrogels to reveal that low cell loading (0.1-1 × 104 cells per μL hydrogel) promoted sustained growth and surfactin production proportional to the number of cells loaded. Conversely, hydrogels loaded with excessive cells (2.5-7.5 × 104 cells per μL hydrogel) resulted in unsustained growth and diminished surfactin production. Finally, to develop a more robust material, B. subtilis endospores were encapsulated into hydrogels at optimized conditions. Spore-laden hydrogels retained the capability to produce surfactin after exposure to dehydration and temperature stress. These results indicate that hydrogel encapsulation stimulates B. subtilis surfactin production according to the level of nanoconfinement to achieve a tunable engineered living material for production of bioactive molecules.
    Keywords:  bacteria; biotherapeutics; engineered living materials; hydrogels; poly(ethylene glycol); surfactin; wound dressings
    DOI:  https://doi.org/10.1021/acsapm.6c00761
  3. Science. 2026 Jul 16. eaeb0822
    De novo design of orthogonal far-red, orange, and green fluorophore-binding proteins for multiplexed imaging.
    Long Tran, Steffen Klein, David Juergens, Shajesh Sharma, Justin Decarreau, Gyu Rie Lee, Yujia Wang, Wei Chen, Asim K Bera, Alex Kang, Jon Woods, Emily Joyce, Dionne K Vafeados, Nicole Roullier, Xinting Li, Bingxu Liu, Yang Bo, Edin Muratspahić, Tim A Brown, Jonathan B Grimm, Ronak Patel, Luke D Lavis, Julia Mahamid, Linna An, David Baker.
      Fluorescent proteins and small-molecule dyes offer complementary advantages for biological imaging: proteins are amenable to genetic tagging, whereas dyes provide superior brightness and photostability. To combine these strengths, we used de novo protein design to generate small, nanomolar-affinity, high-selectivity binders (NovoTags) for three cell-permeable dyes spanning the visible spectrum. We show that the NovoTag fluorescent lifetimes can be tuned and demonstrate their application in lifetime and wavelength-based multiplexed fluorescence imaging. We further design a two-chain NovoTag that functions as a chemically induced dimerization system with fluorescent readout in living cells, or as a minimally perturbing proximity probe in fixed cells. Our approach combines the advantages of fluorescent proteins and small-molecule dyes, expanding the toolkit for cellular imaging.
    DOI:  https://doi.org/10.1126/science.aeb0822
  4. ACS Appl Polym Mater. 2026 Jul 10. 8(13): 10300-10311
    Self-Growing and Mechanically Tunable Living Materials with Paenibacillus mucilaginosus Extracellular Polymeric Substances.
    Yifan Cui, Stéphane Bernhard, Mathias Steinacher, Nika Petelinsek, Lorenzo Minervini, Stefan Mommer, Mark W Tibbitt.
      Engineered living materials (ELMs) typically embed functional cells in nonliving matrices, limiting growth, remodeling, and long-term adaptation at the material level. Here, we introduce extracellular polymeric substances (EPS) produced by Paenibacillus mucilaginosus as a living carrier matrix for ELMs. P. mucilaginosus EPS possesses suitable rheological behavior, such as shear thinning and elastic recovery, required for extrusion-based fabrication. Its mechanical properties can be further tuned through dynamic covalent cross-linking via boronate ester formation or physical reinforcement with Laponite or xanthan gum. With boronate ester cross-linking (18 mM), the storage modulus increased from 100 to 800 Pa. The inclusion of 0.5 w/v % Laponite further increased the modulus to 1300 Pa. Uniquely, a living matrix comprised ofP. mucilaginosus EPS provides a substrate for material growth. As a proof of concept, we manufactured photosynthetic living materials by embedding a photosynthetic cyanobacterium strain,Synechococcus sp. PCC 7002, in the EPS matrix and printed into defined architectures. Both P. mucilaginosus and cyanobacterium PCC 7002 remained viable and grew over 30 days. Matrix outgrowth and microbial colonization enabled the expansion of the living constructs within the printed structure. This work establishes P. mucilaginosus EPS as a candidate living scaffold for self-growing and mechanically tunable ELMs.
    Keywords:  carbon capture; dynamic covalent chemistry; extracellular polymeric substances; living materials; self-growing
    DOI:  https://doi.org/10.1021/acsapm.6c01028
  5. Nat Commun. 2026 Jul 17.
    Bound water as a kinetic crosslinker for bio-inspired impact-stiffening polymers.
    Siyu Jin, Zhaoming Zhang, Menghao Ji, Jiheng Hu, Dianteng Zhao, Yichen Huang, Jiajia Xue, Hang Zhao, Bo Zheng, Xuzhou Yan, Lingyan Gao.
      Developing high-performance impact-stiffening polymers that are broadly applicable across chemical systems remains a key challenge, as existing designs rely on meticulously engineered molecular motifs. Inspired by water's role in biological impact resistance, we introduce a generalizable biomimetic paradigm. We transform water-commonly considered a property-limiting plasticizer-into an active, rate-sensitive cross-linker by structurally confining bound-water networks within proton-rich polymer scaffolds. Programming their dissociation kinetics enables a sharp, reversible soft-to-rigid transition under impact via kinetic freezing. This design, demonstrated in a poly(thioctic acid)-based system, concurrently achieves outstanding energy dissipation, self-healing, and strong adhesion. Crucially, it bypasses de novo synthesis of specialized motifs and is applicable across diverse polymer backbones, establishing programmable water dynamics as a versatile principle for adaptive polymeric materials.
    DOI:  https://doi.org/10.1038/s41467-026-75737-8
  6. Mol Syst Biol. 2026 Jul 16.
    Engineered E. coli swarming for binary and analog input recording.
    Marian Shaw, Sadhya Garg, Julia Kirby, Samuel Schmidgall, Filippo Liguori, Anjali Doshi, Tao Tu, Tal Danino.
      Many bacterial species form self-organized macroscale patterns through swarming. Despite its extensive genetic tractability, Escherichia coli remains underexplored for robust, applied control of swarming. Here we develop a set of E. coli strains that generate centimeter-scale swarming patterns to spatially record environmental inputs. Specifically, we modulate the expression of swarming-related genes in response to chemical and optical signals, reshaping baseline swarm patterns in analog or binary-like fashions. To decode bacterial patterns across space and time, we develop scalable computational methods incorporating feature extraction, regression, and deep-learning models. Time-lapse imaging reveals that colonies record inputs dynamically, enabling early-stage classification. This work establishes a strategy for spatial information recording in E. coli and expands the toolkit for programming emergent microbial behaviors at macroscopic scales.
    DOI:  https://doi.org/10.1038/s44320-026-00232-7
  7. Small. 2026 Jul 11. e74538
    Stress-Adaptive Biomaterials With Tunable Yielding Architectures Regulate Organoid Morphogenesis.
    James P W Reeves, Sabra Rostami, Mostafa Rammal, Andrei Bocan, Paula Lépine, Matthew J Harrington, Thomas M Durcan, Christopher Moraes.
      The yield stress at which biomaterials undergo plastic deformation limits the stresses that can be developed in encapsulated growing tissues. While matrix mechanical properties such as stiffness and viscoelasticity have a profound effect on cells, the role of yield stress has remained challenging to define. Here, we design a granular hydrogel platform with supramolecular host-guest dynamic crosslinkers to precisely and quantitatively tune the stress at which the matrix repeatedly yields and reconfigures around tissues as they grow. Designed to provide similar mechanical constraints as a mesh stress ball, matrix yield stresses can be tuned between 12 and 370 Pa, while maintaining a storage modulus below ∼0.1 kPa. Our study suggests that this range of yield stress is sufficient to promote or limit peripheral shedding in a model of non-adhesive cancer migration, and that early development of midbrain organoids is exquisitely sensitive to these matrix mechanics. Yield stresses of only 25 Pa promoted bud-like protrusions and large, luminized neural rosettes, while variations as small as 10 Pa limited these phenotypes. These studies indicate that morphogenesis and tissue organization can be controlled via the material's yield stress, suggesting a new mechanical parameter to target in designing biomaterials for disease modeling and regenerative medicine.
    Keywords:  3D culture; development; granular gel; growth‐induced stress; mechanical plasticity; mechanobiology; midbrain; rosette; yield stress
    DOI:  https://doi.org/10.1002/smll.74538
  8. Cell Syst. 2026 Jul 16. pii: S2405-4712(26)00156-0. [Epub ahead of print] 101674
    An optogenetic smart microscopy platform reveals signaling dynamics-dependent control over collective cell migration.
    Harrison R Oatman, Beena C Lad, Long Nguyen, Justin H Gubbens, Jared E Toettcher.
      In cell biology, optical techniques can measure cells' internal states (biosensors) and stimulate cellular responses (optogenetics). Yet the design of all-optical experiments is often manual: a predetermined stimulus pattern is applied to cells, biosensors are measured over time, and data are processed offline. Here, we develop PyCLM, a Python-based suite enabling closed-loop measurement, image segmentation, and optogenetic control of thousands of cells per experiment. We showcase PyCLM on diverse applications, including performing feedback control on single cells and delivering developmental signaling patterns to Drosophila embryos. We compare single-cell versus tissue-scale optogenetic control of epithelial migration, revealing that fast and slow waves of receptor tyrosine kinase activity determine the direction of tissue movement, matching prior in vivo observations in zebrafish and mouse. PyCLM enables simple setup of dynamic experiments to probe cell and tissue properties and provides a first step toward real-time control of single-cell states at the tissue scale.
    Keywords:  cell migration; closed-loop microscopy; feedback control; optogenetics; receptor tyrosine kinase signaling; smart microscopy
    DOI:  https://doi.org/10.1016/j.cels.2026.101674
  9. Adv Sci (Weinh). 2026 Jul 16. e76505
    Controlled Peptide Capture and Release in 3D-Printed Multimaterial Microstructures.
    Niklas Schwegler, Thomas Heim, Philipp Mainik, Eva Blasco, Franziska Thomas.
      High-resolution two-photon laser printing has revolutionized the fabrication of complex 3D micro- and nanostructures across a wide range of materials. However, the implementation of engineered biomolecules as functional, stimuli-responsive units remains underexplored. In this study, we present a method for fabricating 3D-printed hydrogel microstructures that contain de novo designed heterodimeric coiled-coil peptides to allow controlled peptide capture and release. Covalent incorporation of one coil strand into the 3D-printed network was combined with fluorescent labelling of the complementary strand. Controlling the assembly and disassembly of the coiled coil enabled selective binding and subsequent programmable release of the fluorescently labelled peptide using various external stimuli, such as pH, ionic strength, temperature, or peptide competitors. Using a set of orthogonal coiled-coil peptides, we fabricated multimaterial microstructures in which spatially resolved coiled-coil functionalization was achieved. Under complete spatiotemporal control, it was shown that the complementary coil strands could be captured and released selectively. This work demonstrates the use of discretely folded, chemically synthesizable peptides for 2PLP fabrication for the first time. Utilizing coiled-coil interactions as molecular handles enables the production of stimuli-responsive and reconfigurable hydrogel microstructures. This approach opens up possibilities for dynamic biomaterials, programmable drug delivery, and biochemical process engineering at the microscale.
    Keywords:  3D printing; coiled‐coils; hydrogels; peptides; stimuli‐responsive materials; two‐photon laser printing
    DOI:  https://doi.org/10.1002/advs.76505
  10. Nat Chem Biol. 2026 Jul 17.
    Restoring intracellular homeostasis disrupted by synthetic nanoassemblies.
    Jiaqi Xing, Xiaoran Zheng, Yong Ren, Maximilian Schuler, David Y W Ng, Tanja Weil, Seraphine V Wegner, Christopher V Synatschke.
      Cells have evolved to defend against perturbations by maintaining their intrinsic homeostasis to survive. However, no intrinsic pathway exists for them to expel new-to-biology synthetic nanostructures. Here we establish crosstalk between supramolecular transformations and genetic responses, achieving programmable influx-efflux cycles of nanoassemblies in living bacterial cells to restore redox and energy homeostasis. Specifically, a model photosensitizer-peptide conjugate undergoes multiple redox cycles between methionine and methionine sulfoxide (MetO), resulting in reversible morphological transformations between nanofibers (NFs) and nanoparticles (NPs). Upon irradiation, the oxidized peptide NPs are internalized into bacteria. To counteract the perturbations caused by internalized NPs, engineered bacteria activate the expression of MetO reductases in response to photo-oxidative stress. The internalized NPs are intracellularly enzymatically reduced such that they are expelled as reduced NFs, setting the stage for subsequent cycles. The concept presented here paves the way for the interlinked network between dynamic supramolecular assemblies and cellular regulatory behaviors.
    DOI:  https://doi.org/10.1038/s41589-026-02279-x
  11. Proc Natl Acad Sci U S A. 2026 Jul 21. 123(29): e2604560123
    Cryogenic silicification enables nongenetic functional continuity across mammalian cell generations.
    Jiangfan Cao, Ting Ruan, Zeyu Li, Zhouping Tian, Sishi Guo, Junxian Yang, Qi Lei, Lingxiang Jiang, Jimin Guo, C Jeffrey Brinker, Wei Zhu.
      Mammalian cells are intrinsically soft, with Young's moduli typically ranging from 0.1 to 10.0 kPa depending on the organization of the F-actin cytoskeleton, rendering them highly susceptible to mechanical and environmental stresses. This inherent fragility severely constrains their manipulation and functional deployment under nonphysiological conditions. Here, we report a cryogenic dormancy-enabled silicification strategy that achieves deep integration of inorganic silica reinforcement within living mammalian cells while preserving cell viability and proliferative capacity. Transient membrane permeability during cryogenic dormancy allows intracellular accumulation of silicic acid, which subsequently undergoes protein-mediated condensation to form a conformal amorphous silica network spanning both extracellular and intracellular compartments. The resulting silica-cell hybrids, termed Silicacytes, exhibit substantially enhanced mechanical robustness and resistance to a broad range of environmental stresses. Notably, this materials-mediated reinforcement is neither permanent nor genetic in nature: silica structures are progressively partitioned during cell division, conferring a pseudoheritable enhancement that persists for two to three generations before gradually dissipating. By enabling a reversible and temporally bounded extension of cellular robustness without altering genetic identity, cryosilicification establishes a nongenetic mode of functional continuity across cell generations. This work expands the conceptual framework of material-cell interactions and provides a general strategy for transient cellular reinforcement, with implications for cell engineering, immune cell manipulation, and the development of adaptive biohybrid systems.
    Keywords:  biohybrid materials; cellular mechanics; nongenetic inheritance; silica–cell interactions; stress tolerance
    DOI:  https://doi.org/10.1073/pnas.2604560123
  12. Nat Biotechnol. 2026 Jul 13.
    High-resolution reconstruction of cell-type-specific transcriptional regulatory processes from bulk sequencing samples.
    Li Yao, Sagar R Shah, Abdullah Ozer, Yutong Zhu, Xiuqi Pan, Tianyu Xia, Junke Zhang, Alden King-Yung Leung, Meihan Wei, John T Lis, Haiyuan Yu.
      Single-cell sequencing methods such as scRNA-seq and scATAC-seq have advanced our understanding of individual cellular functions but experimentally adapting genome-wide assays measuring other genomic features to achieve single-cell resolution remains a technical challenge. Here we introduce deep-learning-based deconvolution of tissue profiles with accurate interpretation of locus-specific signals (DeepDETAILS), a quasisupervised framework performing cross-modality deconvolution using scATAC-seq reference libraries for other bulk datasets. DeepDETAILS enables base-pair-resolution mapping of genomic signals across diverse cell types, with great versatility for various omics datasets, including nascent transcript sequencing (such as PRO-cap and PRO-seq) and ChIP-seq for chromatin modifications. Using DeepDETAILS, we generated a compendium of high-resolution nascent transcription and histone modification signals across 39 diverse human tissues and 86 distinct cell types. Furthermore, we applied our compendium to fine-map risk variants associated with primary sclerosing cholangitis, a progressive cholestatic liver disorder, and revealed a potential etiology of the disease.
    DOI:  https://doi.org/10.1038/s41587-026-03218-w
  13. Biophys J. 2026 Jul 13. pii: S0006-3495(26)00493-5. [Epub ahead of print]
    The Hidden Cost of Fusion: Intrinsic Asymmetry in Vesicle Fusion Restricts Synthetic Cell Growth.
    Rafael B Lira, Rafaela M Cavalcanti, Karin A Riske, Rumiana Dimova.
      Membrane fusion is essential for signaling, cargo delivery, and synthetic cell growth, yet its mechanical consequences remain poorly defined. How fusion-driven membrane growth can be sustained without compromising compartment stability remains an unresolved challenge. Here, we established a minimal reconstituted system where content-loaded small liposomes fuse with single cell-sized giant unilamellar vesicles (GUVs), combining micropipette delivery, electrodeformation, and live imaging. Fusion outcomes were quantified through lipid and content mixing assays, GUV electrodeformation to track area and tension, and phase contrast imaging to monitor leakage. GUVs incorporated lipids and cargo from hundreds of thousands of vesicles at unprecedented efficiency rates, enabling substantial growth. However, accumulation of leaflet asymmetries induced curvature and tension, driving budding, rupture and leakage. Hemifusion amplified these destabilizing effects. Lipid number asymmetries emerge as a dominant mechanical cost of fusion, highlighting how cells may regulate these processes and guiding the design of therapeutic delivery systems and synthetic cells capable of robust and stable growth.
    Keywords:  Compartment growth; artificial cell; budding; charge-mediated fusion; giant unilamellar vesicles; leaflet asymmetry; membrane fusion; membrane pores
    DOI:  https://doi.org/10.1016/j.bpj.2026.07.012
  14. Nat Rev Chem. 2026 Jul 15.
    Bridging stimulus-responsive and dissipative peptide assemblies to build complex interactive biomaterials.
    Maximilian Schuler, Ayan Chatterjee, David Y W Ng, Tanja Weil.
      Self-assembling peptides are versatile building blocks for biomaterials owing to their programmable sequences and ability to form complex supramolecular architectures. Designing systems that operate dynamically at the biological interface is particularly compelling, as living systems rely on both stimulus responsiveness and continuous energy dissipation to regulate structure and function. However, most synthetic peptide assemblies remain confined to near-equilibrium behaviour, whereas chemically fuelled dissipative systems often lack compatibility with biological environments. In this Review, we discuss recent advances in stimulus-responsive and dissipative peptide assemblies, highlighting their distinct design principles and functional capabilities. We compare sequence-encoded and trigger-based strategies with chemically fuelled reaction networks that enable transient assembly. Finally, we outline emerging strategies to bridge these approaches, including improving bioorthogonality, tuning concentration regimes, and integrating cellular processes. Together, these concepts provide a framework for developing interactive peptide biomaterials with life-like functions.
    DOI:  https://doi.org/10.1038/s41570-026-00846-3
  15. Biofabrication. 2026 Jul 14.
    SABER bioprinting: a temporal platform for multiday assembly of engineered tissues.
    Joshua R Gershlak, Shoaib A Goraya, Marie Billaud, Farhad R Nezami, Harald C Ott.
      Current bioprinting approaches are constrained to single-session fabrication, limiting the scale, temporal complexity, and biological maturation achievable in engineered constructs. Here, we demonstrate the feasibility of Sequential Additive Biofabrication Extended over Real-time (SABER), a bioprinting strategy that introduces time as an explicit design variable by enabling multi-day additive fabrication of soft-hydrogel constructs supported by continuous perfusion culture. SABER integrates a thermoresponsive methylcellulose-agarose support material, which allows high-fidelity collagen deposition at low temperatures and mechanical stabilization at culture temperatures, with a custom bioreactor that permits direct through-tissue perfusion. We demonstrate feasibility of multi-day fabrication of layered constructs, nested geometries, suspended internal features, a miniaturized acellular human heart model with preserved architectural fidelity, and a 10-layer approximately 1 cm thick construct demonstrating scalability beyond single-session practical limits. SABER supports perfusion culture of thick cell-laden constructs, enabling printed cardiac tissues to remain viable and contractile after one week of perfusion culture and permitting in situ differentiation of bioprinted iPS cells into cardiomyocytes. These findings establish SABER as a proof-of-concept platform for time-resolved, perfused bioprinting of soft hydrogel constructs, introducing time as an explicit design variable in biofabrication and providing a foundation for future work exploring multi-day fabrication workflows at scales and with temporal complexity not supported by existing single-session approaches.
    Keywords:  Bioprinting; Bioreactor; Cardiac Tissue Engineering; Perfusion; Stem Cell Differentiation; Temporal Bioprinting
    DOI:  https://doi.org/10.1088/1758-5090/ae8a86
  16. ACS Appl Bio Mater. 2026 Jul 13.
    Diarylcyclopropenones: Modular, Tetherable, Light-Triggerable Reservoirs of Carbon Monoxide in Crosslinked Hydrogels.
    Mckenna G Hanson, Noah R DuBois, Vivian C Lawless, Arghya Sarkar, Riya Joshi, Ram Ambre, Renee R Frontiera, Brady T Worrell.
      Carbon monoxide (CO) is an endogenously produced gasotransmitter with established anti-inflammatory and cytoprotective effects, yet its therapeutic exploration and application remain limited by challenges associated with controlled delivery. We recently demonstrated that diphenylcyclopropenone (DPCP) serves as a highly efficient, visible-light-triggered CO-generating motif when incorporated into polymeric micelles. Here, we investigate whether DPCP functions as a modular CO source by integrating it into chemically diverse crosslinked hydrogel networks. Hydrogels were selected as a representative solid biomaterial platform due to their widespread use in implants, tissue engineering, and cell culture. We demonstrate that DPCP-mediated CO generation is preserved across a range of hydrogel compositions, and that hydrogels allow for spatiotemporal control over CO release. However, CO release into solution depends on hydrogel network properties and chemistry. These results establish diarylcyclopropenones as a modular, tetherable, light-triggerable reservoir of CO gas and hydrogels as a tunable platform for its use.
    Keywords:  CO releasing molecules; carbon monoxide; hydrogels; photochemistry; polymer chemistry
    DOI:  https://doi.org/10.1021/acsabm.6c00933
  17. Genome Biol. 2026 Jul 17. pii: 229. [Epub ahead of print]27(1):
    Dynamic global acetylation remodeling during the yeast heat shock response.
    Rebecca E Hardman-Kavanaugh, Aaron J Storey, Tara N Stuecker, Stephanie E Hood, Gregory A Barrett-Wilt, Venkata R Krishnamurthi, Yong Wang, Stephanie D Byrum, Samuel G Mackintosh, Rick D Edmondson, Wayne P Wahls, Alan J Tackett, Jeffrey A Lewis.
       BACKGROUND: All organisms experience stress and must rapidly respond to changing conditions. Thus, cells have evolved sophisticated rapid-response mechanisms such as post-translational protein modification to rapidly and reversibly modulate protein activity. One such post-translational modification is reversible lysine acetylation, where proteomic studies have identified thousands of acetylated proteins across diverse organisms. While the sheer size of the 'acetylome' is striking, the function of acetylation for the vast majority of proteins remains largely obscure.
    RESULTS: Here, we find that global acetylation plays a previously unappreciated role in the heat shock response of Saccharomyces cerevisiae. Dysregulated acetylation renders cells heat sensitive, and the acetylome is globally remodeled during heat shock over time, with ~ 400 high-confidence acetyl marks across ~ 200 proteins significantly changing. Proteins with significant acetylome changes strongly overlap with genes induced or repressed by heat shock. Intriguingly, we find nearly 40 proteins with at least two acetyl marks that significantly change in the opposite directions. These proteins are strongly enriched for chaperones and ribosomal proteins, suggesting that these two key processes are coordinately regulated by protein acetylation during heat shock.
    CONCLUSIONS: Our results suggest that protein acetylation helps activate induced proteins and inactivate repressed proteins during heat shock. We hypothesize that the same type of activating and inactivating marks that exist on histones may be a general feature of proteins regulated by acetylation. Overall, this work has identified a new layer of post-translational regulation that likely augments the classic heat shock response.
    DOI:  https://doi.org/10.1186/s13059-026-04194-9
  18. Mater Horiz. 2026 Jul 18.
    Bioinspired organic materials for seamless neurohybrid interfaces: from material design to living electronics.
    Nevena Stajković, Anna Manukânc, Matilde Trilli, Jan Steinkühler, Valeria Criscuolo, Francesca Santoro.
      The brain architecture is multi-layered, with billions of neurons organized into intricate neural networks that communicate via synapses. Since synapse dysfunction is a main hallmark of neurological disorders, understanding the mechanisms underlying their failure is necessary for designing novel treatments. Neuroelectronic devices are powerful tools for recording and stimulating brain activity. Therefore, they can be used to understand and potentially treat neurological disorders. Achieving this requires the seamless integration of neurohybrid interfaces into neural tissue, enabling bidirectional communication. This focus article highlights the roles of organic mixed ionic-electronic conductors, advanced polymer chemistry, and soft materials with tunable properties in enabling seamless integration. Drawing inspiration from the dynamic structure of neurons, we cover materials that mimic neuron structure and function. We explore novel approaches, including in vivo polymerization and synthetic biology, that hold promise for realizing living neuroelectronics and advancing the frontiers of neuroscience, bioengineering, and clinical medicine.
    DOI:  https://doi.org/10.1039/d6mh00280c
  19. Proc Natl Acad Sci U S A. 2026 Jul 21. 123(29): e2533029123
    Spatiotemporally controlled matrix softening facilitates deterministic crypt formation in human intestinal organoids.
    Michael R Blatchley, Kaustav Bera, Nolan R Petrich, Bruce E Kirkpatrick, F Max Yavitt, Patrick S McGrath, Peter J Dempsey, Kristi S Anseth.
      Spatially controlling morphogenesis is a challenge for many organoid systems that manifests as a limited understanding of self-organization of differentiating cells and leads to a high degree of heterogeneity in organoid morphometrics. Current methods to grow organoids rely on temporal presentation of soluble cues that are not controllably delivered, and little is known about the role of the extracellular microenvironment in this process. Here, we present a material-based strategy to spatiotemporally control morphogenesis of human intestinal organoids (HIOs) with predictable crypt morphometrics and cell composition that match their in vivo tissue counterparts. We first optimize culture conditions to generate more reproducible HIOs with predictable growth in phototunable poly (ethylene glycol)-based hydrogels, and then systematically investigate the role of light-mediated matrix softening in guiding crypt formation. The light dose delivered to crypt-sized regions adjacent to growing organoids is a key factor in maintaining organoid cell viability, as well as crypt budding and elongation. With optimized light doses, predictable epithelial shape changes result in programmable crypt formation, confirmed by the presence of proliferative (Ki67+) and niche-defining Paneth (Lyz+) cells. This methodology could be readily adopted for other budding and branching organoids to facilitate controllable changes in morphogenesis or cell migration. Sequential patterning approaches and more complex pattern designs could further open the parameter space to facilitate modeling of a wide array of engineered tissues for applications ranging from fundamental biology to disease modeling and translational medicine.
    Keywords:  hydrogels; morphogenesis; organoids; photopatterning
    DOI:  https://doi.org/10.1073/pnas.2533029123
  20. ACS Synth Biol. 2026 Jul 16.
    Synthetic Intrinsically Disordered Proteins Enable Soluble Expression of Disulfide-Rich Therapeutics in E. coli.
    Yulia Shmidov, Parul Sirohi, Jonathan C Su, Joy Shijia Tong, Rohit Suresh, Joshua J Milligan, Daniel M Shapiro, Ashutosh Chilkoti.
      We previously reported the de novo design of three small (<20 kDa), highly soluble synthetic intrinsically disordered proteins (SynIDPs) and demonstrated their utility as solubility tags for proteins and antifouling agents. Building on this work, we now show that these hypersoluble SynIDPs significantly enhance the soluble expression of disulfide-rich proteins (DRPs) of therapeutic relevance, including fibroblast growth factor 21 (FGF-21), interleukin-15 (IL-15), and bovine pancreatic trypsin inhibitor (BPTI). Through SynIDP fusions, we achieve soluble recombinant production of functionally active DRPs containing a single disulfide bond in the E. coli strain BL21(DE3) and up to three nonconsecutive disulfide bonds in the E. coli SHuffle T7 Express strain, without the need for refolding. The resulting SynIDP-DRP fusion proteins retain biological activity, confirming correct folding and disulfide-bond formation with minimal interference from the SynIDP tag, which obviates the need for tag removal. Collectively, these findings highlight the versatility and utility of SynIDPs as molecular tools to advance the production and development of protein therapeutics.
    Keywords:  disulfide-rich proteins; interleukin-15; recombinant expression; solubility tags; synthetic intrinsically disordered proteins
    DOI:  https://doi.org/10.1021/acssynbio.6c00115
  21. Biofabrication. 2026 Jul 14.
    Too big, too small, too O2: the Pandoro Effect from oxygen gradients in tomographic volumetric additive manufacturing.
    Riccardo Rizzo, Felix Wechsler, Qianyi Zhang, Christophe Moser.
      Tomographic Volumetric Additive Manufacturing (TVAM) enables rapid, layerless biofabrication; however, its application to thermoreversible hydrogels is often compromised by complex chemical kinetics. In this study, we identify and characterize a recurrent printing artifact -termed thePandoro effect-manifesting as a truncated-cone distortion caused by premature polymerization at the vial bottom and inhibition at the top. We demonstrate that this phenomenon originates from a vertical oxygen gradient driven by the thermal hysteresis of resin preparation: heating depletes dissolved oxygen, while subsequent cooling induces diffusion-limited re-oxygenation from the air-resin interface. To mitigate this, we present a multi-tiered strategy. First, we introduce a coupled ray optical and photochemical optimization model that rigorously accounts for spatially heterogeneous inhibitor concentrations. Unlike conventional threshold-based approaches, this differentiable framework explicitly simulates the spatiotemporal reaction-diffusion dynamics of oxygen depletion, allowing the inverse solver to predictively compensate for local inhibition gradients. Complementing this algorithmic correction, we validate two process-based interventions: the elimination of the air-resin interface and the control of headspace atmosphere. We demonstrate that these strategies effectively suppress thePandoro effect, and are compatible with cell-laden resins. This work establishes guidelines for reproducible volumetric bioprinting and expands our open-source Dr.TVAM platform with advanced polymerization modeling capabilities.
    Keywords:  Biofabrication; Bioprinting; Oxygen diffusion; Oxygen inhibition; Photochemistry; Photopolymerization; Tomographic volumetric additive manufacturing
    DOI:  https://doi.org/10.1088/1758-5090/ae8a84
  22. ACS Appl Bio Mater. 2026 Jul 11.
    A Facile Fabrication Process for Handmade Fully Polymeric Neural Interfaces.
    Angela Braccia, Ciro Zinno, Alice Giannotti, Filippo Castellani, Anar Dushpanova, Valentina Casieri, Khatia Gabisonia, Fabio Bernini, Vincenzo Lionetti, Stephanie Lacour, Silvestro Micera, Eugenio Redolfi Riva.
      Conventional neural interfaces are typically manufactured by photolithographic micromachining using thermoplastic insulators and noble-metal conductors. Although effective, these approaches require costly, time-intensive infrastructure, restrict material selection, and often produce devices with substantial mechanical and interfacial mismatch relative to soft neural tissue, limiting long-term performance. Here, we introduce CASPER (CAsted and Screen-Printed polymeric ElectRodes), a cleanroom-free and low-cost benchtop strategy for the fully manual fabrication of implantable neural interfaces from biocompatible polymeric materials. By combining polymer casting with manual screen printing and reusable molds, CASPER enables rapid electrode fabrication without specialized microfabrication equipment. As a proof of concept, we developed CASPER-cuff, a fully polymeric cuff electrode tailored to the swine cervical vagus nerve, integrating PDMS insulation with metal-free PEDOT:PSS conductive hydrogel active sites. CASPER-cuff exhibited tissue-compliant mechanical properties (E < 1 MPa), together with competitive electrochemical performance (|Z|@1 kHz = 3.58 ± 1.78 kΩ; cCSC = 74.98 ± 20.27 mC cm-2), demonstrating that marked simplification of manufacturing does not compromise device function. In vivo implantation further showed stable nerve coupling and reliable stimulation and recording of evoked compound action potentials, consistent with vagal B-fiber recruitment. CASPER establishes an accessible route toward customizable, fully polymeric soft neural interfaces for bioelectronic medicine.
    Keywords:  benchtop; bioelectronic medicine; cuff electrode; fully polymeric; neural interfaces
    DOI:  https://doi.org/10.1021/acsabm.6c00736
  23. Sci Adv. 2026 Jul 17. 12(29): eaee6534
    Multistage microrobots with pH-responsive release of platelet membrane-coated nanoparticles.
    Rujie Sun, Junyoung Kim, Yixuan Leng, Yuyang Zuo, Jungmin Kim, Ruoxiao Xie, Tao Yang, Liyun Ma, Xin Song, Jiaxiang Ma, Jinmyoung Joo, Yoon-Kyoung Cho, Molly M Stevens.
      Targeted drug delivery in the gastrointestinal tract remains challenging because therapeutics must overcome multiple hierarchical barriers before reaching diseased tissue. Here, we present a multistage delivery platform that integrates magnetic microrobots, a pH-responsive protective coating, and platelet membrane-coated nanoparticles (PNPs) in one platform. A fillable design enables the formation of an internal magnetic layer for microrobot actuation, while the pH-responsive coating protects the cargo during transit and selectively degrades upon pH change, releasing cancer cell-targeting PNPs. In an in vitro colon cancer model that reproduces key gastrointestinal features, including flow, pH variation, and villi-like structures, this strategy increased nanoparticle retention and enhanced cancer cell cytotoxicity compared to nanoparticles administered alone. Ex vivo studies in porcine stomach and intestine further demonstrated robust locomotion on compliant and folded tissue surfaces. These results establish an environment-responsive hierarchical delivery strategy for more precise oral delivery in complex gastrointestinal settings.
    DOI:  https://doi.org/10.1126/sciadv.aee6534
  24. ACS Appl Mater Interfaces. 2026 Jul 13.
    Screen-Printed Biochar-Derived Graphene Solid-Contact Ion-Selective Electrodes for Nutrient Monitoring in Hydroponic Solutions.
    Gustavo L Milião, Janan Hui, Raquel R A Soares, Haoyang You, Kayla Vittore, Cicero C Pola, Ethan H Leung, DoKyoung Lee, Stuart J Rowan, Carmen L Gomes, Mark C Hersam, Jonathan C Claussen.
      Scalable manufacturing of graphene-based solid-contact ion-selective electrodes (SC-ISEs) is constrained by reliance on mined graphite and on patterning methods that are costly, energy-intensive, or poorly suited to high-throughput production. Here, we present a sustainable, manufacturing-ready approach in which graphene derived from hardwood biochar is formulated into printable inks and patterned by high-throughput screen printing to produce bioderived graphene solid-contact ion-selective electrodes (BioG-SC-ISEs). Unlike prior biomass-derived electrodes based on amorphous or activated carbons, this work demonstrates the conversion of biochar into graphene-like nanosheets compatible with scalable printing. By functionalizing the screen-printed electrodes with poly(vinyl chloride) (PVC)-based ion-selective membranes doped with distinct ionophores, we produced sensors capable of selectively monitoring six plant nutrients (K+, Na+, NH4+, Ca2+, Mg2+, and NO3-). The resulting sensors exhibited near-Nernstian sensitivities with detection limits between 0.064 and 0.526 mg·L-1 with wide sensing ranges (10-6 to 10-1 M for monovalent ions, 10-5 to 10-1 M for Mg2+, and 10-5 to 10-2 M for Ca2+). As an application-relevant demonstration, K+ BioG-SC-ISEs tracked progressive potassium depletion across modified Hoagland formulations (100%, 50%, and 25% K+), achieving a sensitivity of 57.4 ± 0.7 mV·dec-1 and a detection limit nearly three orders of magnitude below typical hydroponic potassium levels, with measurements in close agreement with inductively coupled plasma optical emission spectrometry (ICP-OES). Overall, this work establishes a sustainable strategy for scalable SC-ISE manufacturing and provides a versatile platform for high-performance ion sensing with direct implications for hydroponic agriculture, environmental monitoring, and other electrochemical sensing applications requiring selective ion detection.
    Keywords:  bioderived graphene; hydroponic nutrient monitoring; potentiometric sensing; screen printing; solid-contact ion-selective electrodes; sustainable materials
    DOI:  https://doi.org/10.1021/acsami.6c08370
  25. bioRxiv. 2026 Jul 10. pii: 2026.07.08.737331. [Epub ahead of print]
    Xeno-Free Peptide-Functionalized Hydrogels Support hiPSC Encapsulation and In Situ Differentiation into Structurally Mature Cardiomyocytes.
    Mohammadjafar Hashemi, Nongmaithem Debeni Devi, Yasaman Kargar Gaz Kooh, Charlotte Chen, Bahareh Bahmani, Ganesh Malayath, Julia Victor, Nathaniel Huebsch.
      While defined synthetic substrates can replace Matrigel for human induced pluripotent stem cell (hiPSC) culture and hiPSC-derived cardiomyocyte (hiPSC-CM) production, existing approaches culture cells on two-dimensional surfaces and yield structurally immature cardiomyocytes, limiting their use in disease modeling and regenerative medicine. Here, we developed a xeno-free, fully-defined cyclic RGD (cRGD)-functionalized alginate platform in which we encapsulated hiPSCs to support their expansion and in situ cardiac differentiation. cRGD functionalization was essential for hiPSC survival and pluripotency, with maximal support achieved at a low ligand density (25 µM). In the presence of cRGD, hiPSC encapsulation into softer gels made from lower molecular weight alginates led to enhanced hiPSC expansion and improved cardiogenesis. Strikingly, differentiation in situ with 3D gels led to hiPSC-CM with higher structural maturity, including a markedly increased proportion of Desmin-positive cardiomyocytes. Finally, after enzymatic retrieval from hydrogels, cardiomyocytes derived from softer gels formed tissue-engineered myocardium with superior contractile force compared to tissue fashioned from hiPSC-CM derived from more rigid gels. Together, these results demonstrate the promise of this defined, tunable platform for biomanufacturing of structurally mature cardiomyocytes from hiPSC.
    DOI:  https://doi.org/10.64898/2026.07.08.737331
  26. Nat Mater. 2026 Jul 14.
    From sound sensing to neural control.
      
    DOI:  https://doi.org/10.1038/s41563-026-02657-9
  27. Nat Microbiol. 2026 Jul 16.
    Bacillus subtilis cells can escape biofilms by producing a hydrogel that ejects them.
      
    DOI:  https://doi.org/10.1038/s41564-026-02430-3
  28. Sci Adv. 2026 Jul 17. 12(29): eadz1707
    Simultaneous measurements of translation rate and transcriptome uncovers linked regulation within an active bacterial cell population.
    Christopher Baumann, Molly Hydorn, Samuel F Cooke, Jonathan Dworkin, Adam Z Rosenthal.
      Cell-to-cell variation within clonal bacterial populations provides bacterial communities with important advantages including opportunities for bet-hedging and metabolic division of labor. In recent years, the extent of bacterial heterogeneity has been documented both at the transcriptome level and with physiological measurements of cell growth rate and translation rate. However, methods that link physiological parameters to a single cell's full transcriptomic state are lacking, making it difficult to identify the regulatory mechanisms that couple physiology and transcriptional output. Here, we introduce a method that combines click chemistry-enabled labeling of nascent polypeptides to measure translation rates in single cells alongside microfluidic encapsulation and single-cell transcriptomic measurements, providing a tandem measurement of translation rate and transcriptome in thousands of single Bacillus subtilis cells. In a culture experiencing nutrient limitation, we identified a subpopulation of cells with a higher rate of protein translation that overexpresses genes for several metabolic processes including acetoin production and arginine synthesis. Using a genetic approach informed by the gene expression in this subpopulation, we identified a regulatory mechanism that couples the increase in protein abundance of a transcriptional regulator AlsR with the expression of alsR-regulated genes in this subpopulation.
    DOI:  https://doi.org/10.1126/sciadv.adz1707
  29. Bioconjug Chem. 2026 Jul 13.
    Guanine-Rich DNA Aptamers for Selective Binding to Agarose Hydrogels.
    Yibo Liu, Juewen Liu.
      Although DNA-functionalized hydrogels have been widely explored for sensing, controlled release, and smart materials, the potential for strong, noncovalent recognition between DNA and hydrated polymer networks remains largely unexplored. Here, we report the selection of DNA aptamers that specifically bind agarose hydrogels. Using a structured DNA library and agarose beads as the target, a dominant guanine-rich sequence, Agar-1, emerged after 11 rounds of selection. Quantitative PCR and fluorescence assays confirmed that the enriched sequences bind agarose substantially more strongly than a random DNA library. Truncation yielded a 42-nucleotide aptamer that retained binding activity, whereas further truncation that preserved only the guanine-rich region abolished binding, indicating a strict structural requirement. Notably, binding required Mg2+ and was inhibited by K+, suggesting a non-G-quadruplex recognition mechanism. In contrast to previously reported C/T-rich sequences that bind microplastics, the G-rich agarose aptamers highlight the versatility of DNA-polymer interactions and demonstrate how simple changes in sequence composition can drive recognition of distinct materials. These findings establish the feasibility of evolving aptamers against hydrogels and provide a foundation for engineering programmable DNA-hydrogel interfaces for biosensing, responsive materials, and controlled-release applications.
    DOI:  https://doi.org/10.1021/acs.bioconjchem.6c00242
  30. bioRxiv. 2026 Jul 10. pii: 2026.07.08.737375. [Epub ahead of print]
    Programmable CRISPRtune dissects the transcriptional repressive activity of MeCP2.
    Jinna I Brim, Izaiah J Ornelas, Peter J Colias, Nikita S Divekar, Da Xu, Justin P Lubin, Sophia I Ferrel, Luis Galán Palma, Mitzi G Hernández Zamora, Rithu K Pattali, Jameel J McDaniel, Sarah E Chasins, James K Nuñez.
      The ability to control the expression of human genes is a major goal in synthetic biology, enables dissection of gene function, and can be harnessed for therapeutic applications. Advances in genome editing and transcriptional engineering often result in complete gene inactivation or full transcriptional repression. However, programmable tools to dial transcription at intermediate levels remain challenging. Here, we present CRISPRtune - a synthetic fusion of MeCP2 to catalytically dead dCas9 that tunes down transcription of endogenous genes in human cells by harnessing the mild repressor activity of MeCP2. Using pooled genome-scale CRISPR screens, we tune the expression of thousands of endogenous genes and define the targeting rules of CRISPRtune in human cells. With a platform to target MeCP2 at defined genomic sites, we show the direct epigenetic changes induced by MeCP2 at gene promoters and we identify its genetic dependency partners for productive transcriptional repression. Rett syndrome-associated mutations of MeCP2 show defects for transcriptional repression due to their failure to remodel the local epigenetic landscape of target genes. Together, we present a programmable method for transcriptional tuning in mammalian cells and offer an orthogonal platform to dissect the mechanistic function of chromatin regulators in living cells.
    DOI:  https://doi.org/10.64898/2026.07.08.737375
  31. Sci Adv. 2026 Jul 17. 12(29): eaee5890
    Ultrasoft, adhesive, pH-tunable hydrogel based on in situ functionalized laser-induced graphene for through-hair concurrent biosensing.
    Fatema Tuz Zohra, Abu Musa Abdullah, Yangbo Yuan, Yuqi Wang, Jirong Lin, Wanqing Zhang, Kazi Safowan Shahed, Xianzhe Zhang, Md Abu Sayeed Biswas, Bowen Li, Xiaojun Lian, Su Yan, Huanyu Cheng.
      This work reports a printable, ultrasoft, highly stretchable, adhesive, breathable hydrogel engineered that is radically tuned by controlling the precursor pH level for simultaneous biosignal monitoring. The hydrogel based on porous laser-induced graphene composites synthesized using in situ laser reduction with polydopamine and tannic acid exhibits ultrasmall Young's modulus of 1.08 kilopascal, super high stretchability of ~8000%, and desirable conductivity and adhesive strength for through-hair signal monitoring even in the presence of sweat. The excellent skin conformability of the hydrogel provides the resulting electrodes with low skin contact impedance at both wet and dry conditions, a high signal-to-noise ratio, and motion artifact-free monitoring of electrophysiological signals. Combined with electrodermal activity and strain sensing from the facile patterning/printing of the reusable and storable gel, the proof-of-concept demonstration of the device platform is showcased for anxiety monitoring and nerve rehabilitation studies.
    DOI:  https://doi.org/10.1126/sciadv.aee5890
  32. ACS Synth Biol. 2026 Jul 13.
    Flavin-Decorated Proteins and Bacteria Enable Photoenzymatic Amine Valorisation.
    Vasco F Batista, Christian Å Ringsmose, Erik D Hedegård, Henrik Karring, Changzhu Wu.
      The search for more sustainable catalytic methods, such as biocatalysis and photocatalysis, has greatly contributed to a sustainable future of synthetic chemistry. Within photocatalysis, flavin-type heterocycles are powerful tools for oxidative transformations but often suffer from poor water solubility, photostability, and limited reusability. Here, we provide a proof-of-concept strategy to bridge the gap between photocatalysis and biocatalysis through the development of artificial flavin biomolecules. A 7-/8-carboxyflavin derivative was synthesized and covalently attached to protein surfaces via a biocompatible amide coupling reaction, creating an artificial flavin-decorated protein with oxidative properties. This biophotocatalyst operates efficiently in water under mild conditions, enabling the photooxidation of primary amines without external oxidants. It was also integrated into one-pot, sequential cascade reactions with whole-cell biocatalysts to achieve the enantioselective synthesis of (R)-benzoin and chiral secondary alcohols. Furthermore, the flavin photocatalyst was immobilized on the surface of Escherichia coli cells through a similar process, creating a recyclable, heterogeneous cellular photocatalyst. These modified bacteria exhibited high activity in amine oxidation, could be easily recycled, and maintained performance over multiple reaction cycles without evidence of catalyst leaching. Overall, this work establishes a versatile framework for constructing hybrid biophotocatalytic systems and showcases how they can contribute to environmentally sustainable synthesis through reactions in water and catalyst recycling.
    Keywords:  biocatalysis; bioconjugation; cascade reactions; flavin photocatalysis; photocatalysis
    DOI:  https://doi.org/10.1021/acssynbio.6c00218
  33. Chem Soc Rev. 2026 Jul 12.
    Bridging solar harvesting technologies using hydrogels towards sustainability.
    Xinglong Pan, Weixin Guan, Wanheng Lu, Yuanming Zhang, Wei Li Ong, Zhiqun Lin, Guihua Yu, Ghim Wei Ho.
      The utilization of solar energy has been integral to biological evolution, industrial revolution, and humanity's journey across the past, present, and future, shaping both natural ecosystems and technological advancements. Effectively harnessing this sustainable energy is crucial for addressing the escalating and coupled global energy-water-environment crises. This tutorial review advances an integration paradigm in which hydrogels serve as adaptable and scalable matrices enabling cost-effective solar harvesting that aligns with sustainability and economic feasibility. We first summarize the challenges inherent in existing solar technologies and extrinsic factors beyond material design that influence their sustainable development. Next, we highlight the transformative potential of integrating hydrogels into advanced solar systems through hierarchical energy utilization, multifunctional coordination, and enhanced environmental adaptability and stability. Finally, we assess the broader technological and societal implications of integrated solar harvesting systems by considering regional economic disparities, local resource availability, societal needs, and environmental impacts. By offering a pragmatic perspective on hybrid solar technologies, this tutorial review bridges academic innovation and practical application, charting pathways toward high-efficiency, cost-effective solar energy utilization, with hydrogels serving as a versatile integration platform. These advancements not only foster sustainable development but also contribute to aquatic and terrestrial ecosystem resilience while driving progress toward more resilient, eco-friendly societies.
    DOI:  https://doi.org/10.1039/d6cs00055j
  34. Cell Syst. 2026 Jul 15. pii: S2405-4712(26)00154-7. [Epub ahead of print]17(7): 101672
    Programmable regenerative tissues: Converging mammalian synthetic biology and tissue engineering.
    Alexander E Vlahos.
      Synthetic biology can program cellular behavior but remains underused in regenerative medicine. This commentary argues that integrating synthetic biology with tissue engineering should target vascularization and immune integration through compact, context-aware circuits. Embedded within engineered tissues, these circuits could enable adaptive grafts that sense stress and coordinate regenerative responses.
    DOI:  https://doi.org/10.1016/j.cels.2026.101672
  35. mBio. 2026 Jul 14. e0115026
    Pathway remodeling and adaptive evolution enable efficient co-utilization of glucose and xylose in Escherichia coli.
    Xiaoxu Tan, Yichun Hu, Kai Li, Wensi Meng, Kaiyu Gao, Qiaoyue Yang, Lingru Gong, Leilei Guo, Mengyao Hao, Hongxu Zhang, Yidong Liu, Zhaoqi Kang, Cuiqing Ma, Chao Gao, Qianjin Kang, Chuanjuan Lü, Ping Xu.
      Efficient co-utilization of glucose and xylose is critical for microbial bioconversion of lignocellulosic hydrolysates. However, carbon catabolite repression prevents simultaneous sugar consumption in conventional industrial strains such as Escherichia coli. Here, we blocked the Embden-Meyerhof-Parnas and pentose phosphate pathways in E. coli MG1655 by deleting pgi and gnd, generating strain E. coli MD0 that metabolizes glucose exclusively via the Entner-Doudoroff pathway. Adaptive laboratory evolution yielded mutant E. coli MDE with superior glucose-xylose co-utilization, outperforming E. coli MG1655ΔptsG. Genomic analysis identified gntR and xylR mutations as key contributors to this phenotype. Similar engineering in Klebsiella oxytoca also enhanced glucose and xylose co-utilization. Seven byproduct genes were deleted in E. coli MDE, and efficient production of pyruvate from straw hydrolysate was achieved by using the constructed strain E. coli MDE-6. Further introducing the budRABC operon in E. coli MDE-6 resulted in 2,3-butanediol generation from straw hydrolysate. This study establishes E. coli MDE as a robust chassis for lignocellulose biorefinery.IMPORTANCEThe inability of industrial microbes to co-utilize glucose and xylose severely limits lignocellulosic biomass valorization in bioproduction. Here, we combined pathway separation and adaptive laboratory evolution to develop an Escherichia coli mutant MDE capable of simultaneous glucose and xylose utilization. Strain E. coli MDE was engineered to efficiently produce pyruvate and 2,3-butanediol from straw hydrolysate and showed robust sugar co-utilization at various ratios. We identified two key beneficial mutations enabling this phenotype. When introduced into Klebsiella oxytoca alongside the pathway separation strategy, these mutations also conferred efficient glucose-xylose co-utilization. This study provides a generalizable strategy for engineering simultaneous sugar utilization in diverse microbial chassis.
    Keywords:  2,3-butanediol; Escherichia coli; carbon catabolite repression; lignocellulosic hydrolysate; pyruvate
    DOI:  https://doi.org/10.1128/mbio.01150-26
  36. bioRxiv. 2026 Jul 10. pii: 2026.07.09.737398. [Epub ahead of print]
    Immobilised enzyme reactors for post-production glycan modification of purified glycoproteins.
    Nicholas J DeBono, Joel Cain, Chi-Hung Lin, Nicolle H Packer, Edward S X Moh.
      Controlling protein glycosylation as a critical quality attribute of biopharmaceuticals remains challenging when glycosylation is coupled to cellular production systems. Here, we present a proof-of-concept glycosyltransferase immobilised enzyme reactor (IMER) housed within a 3D-printed column that enables directed post-production glycan modification of purified glycoproteins. Using β-1,4-galactosyltransferase (β4GalT1-IMER) and α-2,6-sialyltransferase (ST6Gal1-IMER) immobilised on Ni-NTA resin, the IMER achieved near-complete galactosylation and substantial sialylation of partially deglycosylated bovine fetuin N-glycans with their respective substrates with a maximum substrate-enzyme contact time of four minutes. Isomeric-level analysis revealed arm-specific addition preferences for both enzymes, consistent with known specificities. The modular IMER design permits sequential connection of individual enzyme chambers, potentially offering a scalable, plug-and-play platform for constructing defined glycan structures on recombinant glycoprotein therapeutics.
    DOI:  https://doi.org/10.64898/2026.07.09.737398
  37. Small. 2026 Jul 17. e74690
    Self-Assembled Living Microreactors for Selective Microcystin Removal via Cascade Sieving, Adsorption and Biodegradation.
    Lixun Zhang, Xuewu Shen, Han Hu, Shengyin Tang, Sunny Jiang, Yuntao Guan.
      Microcystin contamination caused by harmful cyanobacterial blooms is a growing global challenge for water safety. Here we reported a self-assembled living microreactor that encapsulated microcystin-degrading bacteria within a biochar-reinforced double-network hydrogel, enabling integrated molecular sieving, adsorption, and enzymatic degradation. The system exhibited size- and charge-selective removal of microcystin over coexisting organic matters, while maintaining high degradation efficiency under harsh stress conditions, including pH (5-9), inorganic ions (10-200 mg/L), and natural organic matters (5-20 mg/L). The microreactor demonstrated excellent mechanical stability, negligible cell leakage, and high bioactivity, and achieved nearly complete removal of microcystin-LR during five repeated operation cycles and continuous biofiltration in environmental water, confirming its scalable application potential. Mechanistic investigations revealed a cascade process involving shell-confined molecular sieving, adsorption-mediated toxin enrichment on biochar, and localized biodegradation within the living core. This work establishes a generalizable design paradigm for programmable living materials, offering new opportunities for selective biodegradation and remediation in complex aqueous systems.
    Keywords:  biochar adsorption; biodegradation; harmful algal blooms; hydrogel encapsulation; microcystin; selective cascade sieving
    DOI:  https://doi.org/10.1002/smll.74690
  38. RSC Adv. 2026 Jul 06.
    Chemical recycling and repolymerization of poly(ethylene terephthalate), poly(ethylene furanoate), and their copolyesters.
    Lauri Välinen, Hossein Baniasadi, Jukka Niskanen.
      Replacing fossil-based plastics with bio-based ones is vital for future sustainability. However, bio-based plastics are not recycled within current recycling feeds, as polymers generally do not mix. Hence, mixing bio-based polymers with existing mechanical recycling feeds would yield materials of poor quality. For efficient recycling and as drop-in alternatives, bio-based polymers must have similar properties to the polymers in the feed they are mixed with. Chemical recycling and repolymerization can overcome incompatibility challenges by yielding copolymers. However, the question is: are the properties of the copolymers similar to those of the virgin homopolymers? Poly(ethylene furanoate) (PEF), a bio-based polymer, has similar properties to poly(ethylene terephthalate) (PET), such as high melting temperature, thermal stability, crystallinity, and gas-barrier properties. Both PEF and PET can be chemically recycled by solvolytic methods, and the obtained monomers can be repolymerized into copolymers that have similar properties to the virgin polymers. We have chemically recycled PET and PEF, repolymerized the recyclates into homo- and copolymers, and investigated the properties of the resulting polymers. We were able to repolymerize high-molecular weight polymers (M w 63.5-123.4 kg mol-1) with good mechanical properties (up to 43.2 MPa). Collecting PEF and PET waste in the same recycling feed and chemically recycling them make the utilization of bio-based plastic feasible on a global scale, while utilizing existing recycling streams.
    DOI:  https://doi.org/10.1039/d6ra02625g
  39. Mater Horiz. 2026 Jul 17.
    Illuminating new pathways: beyond conventional photochemistries for multi-photon 3D laser printing.
    Pia S Klee, Samantha O Catt, Eva Blasco.
      In the expanding field of multi-photon 3D laser printing (MPLP), new chemistries for facilitating photocrosslinking have been slowly emerging alongside the currently predominant (meth)acrylate-based systems. Expanding the selection of available photochemistries is crucial for precisely tailoring inks to their respective applications. In this review, we present chemistries beyond established (meth)acrylates that have been adapted for MPLP. Firstly, intermolecularly photoinitiated systems that require a photoinitiator are discussed. We then further highlight chemistries that are intramolecularly initiated without the need for a photoinitiator, while discussing the impact the network architecture has on the properties and on potential applications.
    DOI:  https://doi.org/10.1039/d6mh00856a
  40. Bioact Mater. 2026 Dec;66 339-351
    AI-powered the toughest biohydrogels.
    Jiameng Yang, Tao Fu, Ke Yao, Weicheng Kong, Bokun Li, Wanqing Xu, Zhou Zhu, Ximin Yuan, Yong He.
      Hydrogel soft materials hold immense promise for applications ranging from bionic soft robots to flexible human-machine interfaces, but realizing this potential critically depends on excellent mechanical properties. While substantial progress has been made in toughening hydrogels, concurrently achieving a significant enhancement in strength remains a formidable challenge, thereby limiting their functional use. This work introduced a CPTR (centrifugation - progressive training - restorative soaking) strategy, which prestructured the material through centrifugation, continuously evolved and optimized the structure through progressive training, and further refined and locked the structure through soaking. The mechanical properties were improved through the three processes synergistically. By inputting the process parameters and corresponding mechanical test results, the AI model analyzed feature importance, ranked optimal performance combinations, and recommended new schemes. Through such iterative cycles, a CPTR hydrogel with an outstanding tensile strength of 134.31 MPa and toughness of 10.25 MJ/m3 was achieved, currently the highest strength among biohydrogels. Its excellent mechanical performance and processability allowed the hydrogel to be constructed into fibers and network structures, opening new avenues for developing next-generation soft actuators, robust controllable release systems, and other advanced functional materials.
    Keywords:  3D printing; Biological hydrogel; Biomanufacturing; Salting-out effect; Tough hydrogel
    DOI:  https://doi.org/10.1016/j.bioactmat.2026.07.002
  41. Sci Adv. 2026 Jul 17. 12(29): eaef3895
    Digintel metasurface of extensive reprogrammable morphing.
    Wanqing Lin, Lang Qin, Qingfeng Wang, Lei Liu, Yingbo Yan, Huasong Qin, Yilun Liu.
      Programmable surface morphing is reshaping geometrical matter from static, prespecified forms into systems capable of adaptive, on-demand control, yet precise and extensive reprogrammable morphing of complex surfaces remains a central challenge through external stimulated material response. Here, we present a reprogrammable digital-intelligent (digintel) metasurface (DMS) built from digitally addressable bistable unit cells whose stable configuration switching generates local eigenstrain, as well as the digitally programmable surface morphing. By digitally encoding the stable state of unit cells, DMS exhibits extensive reprogrammable morphing with the complexity and type of surface morphology exponentially increasing with the number of unit cells. To precisely design the target surface, we further develop a machine learning-assisted inverse-design framework that maps the target surface to digital state codes, enabling deterministic reconstruction of complex surfaces. Experiments and finite element analyses validate the mechanical response of the unit cell and DMS, manifested as state-dependent stiffness, stability margins, load-bearing capacity, and morphing-enabled flow-field modulation across reconfigured geometries. This work establishes a generalizable platform for digintel engineering of reconfigurable functional surfaces, with potential impact on robotics, medical assistance, and aerospace morphing structures.
    DOI:  https://doi.org/10.1126/sciadv.aef3895
  42. Nucleic Acids Res. 2026 Jul 03. pii: gkag702. [Epub ahead of print]54(13):
    Engineering aptamer dimers (apdimers) for optimization of synthetic riboswitches.
    Vera Hedwig, Elisabeth Müller, Stephanie Ketterer, Isabel Lang, Matthias Klugmann, Jörg S Hartig.
      Riboswitches are compact RNA-based regulatory elements capable of modulating gene expression in response to small molecules, without the need for additional proteins. Various synthetic riboswitches have been engineered using in vitro-generated tetracycline and theophylline aptamers. However, many of these constructs exhibit suboptimal switching efficiency and background expression. Moreover, efforts to enhance their performance often involve time-consuming and costly screening processes. Here we report that artificial riboswitches can be efficiently optimized by engineering fusion aptamers that contain two binding pockets (apdimers). Following this rational approach, we generated cooperativity between both binding pockets, resulting in the improved performance of splicing-based and ribozyme-based synthetic riboswitches. We finally combined optimized tetracycline switches, yielding dynamic ranges exceeding 1000-fold with minimal background expression in the OFF state. In addition, we show that the optimized tetracycline riboswitches can be used to efficiently induce AAV-mediated transgene expression in mice. The presented strategy offers a straightforward and effective approach for the optimization of existing synthetic riboswitches and the design of novel riboswitches.
    DOI:  https://doi.org/10.1093/nar/gkag702
  43. ACS Nano. 2026 Jul 16.
    Nanopore-Mediated Assembly Enables Precise and Continuous Synthesis of mRNA-Encapsulated Lipid Nanoparticles for COVID-19 Vaccines.
    Zhixiang Liu, William Stewart, Yilong Teng, Yufeng Song, Maoping Tang, Yuxuan Guo, Xue-Qing Zhang, Kamalesh K Sirkar, Xiaoyang Xu.
      RNA therapeutics are reshaping modern medicine, as exemplified by the rapid deployment of lipid nanoparticle (LNP)-based mRNA vaccines during the COVID-19 pandemic. However, the ability to reproducibly generate LNPs with precisely defined physicochemical properties at scale remains a critical challenge, particularly as the particle size and size distribution strongly influence biodistribution, cellular uptake, and therapeutic efficacy. Conventional mixing technologies ensure reproducibility but offer limited control over interfacial mixing and nanoparticle assembly, constraining both tunability and scalability. We present a hollow fiber membrane (HFM)-based platform that leverages dense arrays of nanoscale pores to mediate uniform, highly localized interfacial mixing, enabling controlled lipid self-assembly and RNA encapsulation. This nanopore-mediated architecture allows continuous, high-throughput synthesis of LNPs with tunable particle sizes, narrow size distributions, and high encapsulation efficiencies, with particle characteristics directly correlated to the membrane pore size. HFM-derived LNPs exhibit robust in vitro transfection and potent in vivo immune responses and are compatible with multiple lipid chemistries and nucleic acid payloads, including mRNA vaccine constructs. Together, this work establishes HFM-based nanopore assembly as a versatile and scalable approach for producing well-defined LNPs, with direct relevance to the current and future mRNA vaccine and therapeutic development.
    Keywords:  RNA therapeutics; continuous manufacturing; hollow fiber membrane; lipid nanoparticles; mRNA vaccines
    DOI:  https://doi.org/10.1021/acsnano.6c00729
  44. Materials (Basel). 2026 Jun 24. pii: 2715. [Epub ahead of print]19(13):
    Chitosan-Based Hydrogels in Vascular Tissue Engineering Applications.
    Lauren Taylor, Shih-Feng Chou.
      The development of biocompatible materials has gained traction due to the increasing clinical demands for customizable and functional medical devices. Chitosan, a deacetylated derivative of chitin, is a naturally occurring biopolymer with strong antimicrobial properties, immunocompatibility, and structural adaptability, making it a promising candidate for biomedical applications. Through mechanisms such as crosslinking, ionic bonding, gas formation, and UV radiation, the mechanical properties and stimulus responses of chitosan-based hydrogels can be tailored for drug delivery at specific sites or under specific pH, light, or electrical conditions. Beyond drug delivery, chitosan hydrogels have shown considerable potential for vascular tissue repair. The porous structure of chitosan allows patient specific vascular scaffolding to be created that promotes the recovery rate veins and stenting procedures. Thermally sensitive hydrogels can deliver drugs to target regions to further assist in vascular healing. Furthermore, recent developments with composite polymers and coatings engineered to self-assemble within veins provide scaffolds for vascular tissue growth. This manuscript reviews chitosan hydrogel fabrication methods and their corresponding materials properties, with particular emphasis on drug delivery to vascular tissues. Furthermore, relevant findings from clinical trials are summarized to support the potential of chitosan hydrogels for future clinical use. Challenges of chitosan hydrogels, such as insufficient mechanical strength, high degradation rates, and complex manufacturing, remain as areas for research break-through.
    Keywords:  chitosan; hydrogels; polymer cross-linking; stents; vascular repair
    DOI:  https://doi.org/10.3390/ma19132715
  45. Nature. 2026 Jul 15.
    Selectivity Emerges from Indiscriminate Photoreduction.
    Joseph M Edgecomb, Arindam Sau, Niket Manoj, Matthew D Resmini, Alissia F Meyer, Robert S Paton, Niels H Damrauer, Zachary K Wickens.
      Single electron transfer (SET) reduction is amongst the most fundamental strategies for the activation of organic compounds. The design of selective reactions that leverage SET is grounded by the premise that differences in substrate redox potentials predict relative rates of SET, with more favorable reductions occurring faster.1 However, across the diverse modes of redox catalysis,2,3 devising reactions that require SET to the harder-to-reduce of two reactants remains challenging. This restriction all but precludes coupling reactions when targeting substrates that are thermodynamically difficult to reduce or oxidize.4,5 Here, we introduce an alternative selectivity paradigm for outer sphere SET that is divorced from substrate redox potentials. We show that super-potent photoreductants render substrate redox potentials irrelevant through diffusion-limited SET, allowing a new selectivity profile to emerge from competition between downstream chemical steps and back electron transfer (BET). We validate these principles in the context of radical annulation reactions between cyclopropyl ketones and easier-to-reduce alkenes. While these mismatched redox potentials previously precluded such reactions, we promote selective radical annulation even as the requisite ketone reduction becomes disfavored by a volt. More broadly, these studies offer a general blueprint for the design of SET reactions that require violation of redox potential control.
    DOI:  https://doi.org/10.1038/s41586-026-10897-7
  46. Nat Mater. 2026 Jul 14.
    Two parallel phosphorus economies.
    Paul Westerhoff, Jacob L Jones.
      
    DOI:  https://doi.org/10.1038/s41563-026-02687-3
  47. Microb Cell Fact. 2026 Jul 16.
    Establishment of SRLC: a multiplex genome editing technology for Saccharomyces cerevisiae and its application in metabolic engineering of malonyl-CoA pathway.
    Wentao Zheng, Miao Wang, Qiang Tu, Xiaoying Bian, Youming Zhang, Xue Wang.
      The development of advanced genome engineering tools is crucial for optimizing metabolic pathways in Saccharomyces cerevisiae and achieving efficient biomanufacturing. This study proposes an enhancing multiplex genome editing strategy in S. cerevisiae by employing Escherichia coli-derived single-stranded annealing proteins (SSAPs) combined with S. cerevisiae-derived homologous recombinases (Rad51 and Rad52). The strategy utilizes an SSAP-Rad-Linearized CRISPR (SRLC) platform, which supports efficient simultaneous editing of multiple genomic loci without constructing complex multi-gRNA expression vectors. Co-overexpressing Rad51/Rad52 and E. coli SSAP proteins significantly enhances homologous recombination (HR), allowing precise multi-locus genome editing mediated by short homologous arms. Furthermore, SRLC employs a linearized CRISPR-Cas system to stimulate homologous recombination and enable counter-selection in S. cerevisiae, thereby improving precise multiplex genome editing efficiency. We applied SRLC to engineer the malonyl-CoA metabolic pathway in S. cerevisiae. Through a single round of editing and screening, we constructed a chassis strain with 9 targets simultaneously modification and achieved a 9.6-fold increase in intracellular malonyl-CoA. Using this chassis, 3-hydroxypropionic acid production increased 4.5-fold relative to wild-type S. cerevisiae. This platform offers a robust and scalable tool for S. cerevisiae manipulation and a practical pathway-engineering strategy for building for malonyl-CoA-derived factories.
    DOI:  https://doi.org/10.1186/s12934-026-03068-w
  48. Nature. 2026 Jul 15.
    Programming fracture resistance in metamaterials via elastic instabilities.
    Yujia Wang, Yangchengyi Liu, Kunlin Wu, Xuan Zhang, Hanzheng Xing, Songyan Zhang, Changhong Linghu, Yifan Wang, Xiaoyan Li, Huajian Gao.
      The design of fracture-resistant materials has long been hindered by the complexity of toughening mechanisms across multiple length scales1,2. Mechanical metamaterials offer a promising platform to address this challenge, yet existing research has largely focused on passively characterizing fracture in conventional lattice architectures3-8. Recent studies have demonstrated the potential of elastic instabilities to enhance functionalities in architected materials9-18; however, their connection to fracture resistance remains unexplored. Here we demonstrate that fracture behaviours in mechanical metamaterials can be actively programmed by exploiting elastic instabilities, thereby bridging the two traditionally disconnected failure modes. Through a combination of experiments and simulations, we show that controlled manipulation of the inelastic zone size in pseudoplastic metamaterials enables a transition from intrinsic to extrinsic fracture behaviour, accompanied by up to a one-order-of-magnitude increase in fracture energy. This work represents a shift from passive observation to active control of fracture mechanics, establishing a new framework for designing metamaterials with tailored fracture resistance. Our findings not only advance the fundamental understanding of instability-fracture interactions in metamaterials but also suggest a broadly applicable route for programming fracture behaviours through instability design.
    DOI:  https://doi.org/10.1038/s41586-026-10804-0
  49. Cell Mol Bioeng. 2026 Jun;19(3): 375-386
    Tuning Hydrogel Mechanics and Microstructure to Maximize Extracellular Vesicle Production from Mesenchymal Stem Cells.
    Riddhesh B Doshi, Bethany Yee, Nicolas Warburton, Juanfang Ruan, Richard Tilley, Kuldip Sidhu, Kristopher A Kilian.
       Background: The secretory output from mesenchymal stem cells (MSCs) have emerged as promising therapeutics with extracellular vesicles (EVs) gaining prominence due to solution stability and optimal size for overcoming biological barriers during delivery. However, reproducible and scalable production of EVs for therapeutic use remains a challenge in biotechnology. Here we demonstrate optimization of EV production from MSCs using soft hydrogel microcarriers.
    Methods: Gelatin methacryloyl (GelMA) hydrogels were prepared at a range of concentrations for the culture of two sources of MSCs: adipose derived stem cells (ADSCs) and induced pluripotent stem cell derived MSCs (iMSCs). The mechanical properties of the hydrogels were evaluated using shear rheology. EVs were isolated and analyzed for physical and biological characteristics using electron microscopy, nanoparticle tracking, proteomics, and functional assays for wound healing and angiogenesis.
    Results: Both cell types were responsive to hydrogel stiffness (0.3-16 KPa), showing optimal EV secretion from cultures on 10 KPa hydrogels, with a further 18-fold increase when formulated as microcarriers compared to traditional monolayer culture. Proteomics analysis and functional assays revealed that EVs from microcarrier culture displayed increased wound healing and regenerative properties.
    Conclusion: This study demonstrates the advantages of hydrogel microcarriers in the production of cell-derived products, with optimized design parameters to guide scaleup and translation to manufacturing, in support of biotechnology and biomedical applications.
    Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-026-00917-x.
    Keywords:  Biomaterials; Extracellular vesicles; Mesenchymal stem cell; Microcarriers
    DOI:  https://doi.org/10.1007/s12195-026-00917-x
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