bims-enlima Biomed News
on Engineered living materials
Issue of 2026–01–25
39 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool



  1. Trends Biotechnol. 2026 Jan 20. pii: S0167-7799(25)00536-0. [Epub ahead of print]
      Image-guided volumetric bioprinting allows for the adaptive fabrication of complex structures for tissue engineering. Seminal work by Florczak et al. introduces Generative, Adaptive, Context-Aware 3D Printing, a workflow that uses computer vision to automatically generate functional, vascular-like networks that conform to living cells within hydrogels, improving their functionality.
    Keywords:  adaptive; biofabrication; volumetric
    DOI:  https://doi.org/10.1016/j.tibtech.2025.12.015
  2. ACS Appl Mater Interfaces. 2026 Jan 20.
      Dynamic extracellular matrix mechanics regulate fundamental cellular processes, yet precise control over spatiotemporal rigidity modulation remains challenging. Protein-based photoresponsive hydrogels offer a unique solution by coupling molecular conformational changes to macroscopic mechanics; however, the mechanisms governing this multiscale transition remain unclear. Here, we present a quantitative framework bridging single-molecule protein mechanics to bulk modulus modulation using photoactive yellow protein hydrogels. By engineering two cysteine linkage geometries, we show that anisotropic unfolding landscapes yield distinct rigidity change amplitudes under light/dark cycling. Using data from single-molecule atomic force microscopy, swelling equilibrium, and worm-like chain modeling, we develop a predictive model incorporating unfolding probabilities to explain these differences. Importantly, our model's control of amplitude reveals that fibroblast-to-myofibroblast transdifferentiation is coregulated by the frequency and magnitude of rigidity cycles. These results establish a mechanistic foundation for designing protein hydrogels with programmable dynamics and reveal how frequency-specific mechanical cues shape cell fate.
    Keywords:  cyclic mechanical stimulation; fibroblast-to-myofibroblast transdifferentiation; mechanical properties; mechanobiology; mechanotransduction; photoactive yellow protein; phototunable hydrogel; switchable hydrogel
    DOI:  https://doi.org/10.1021/acsami.5c23033
  3. Curr Opin Biotechnol. 2026 Jan 19. pii: S0958-1669(25)00179-X. [Epub ahead of print]97 103435
      This review explores the reconceptualisation of microbial colonisation on buildings: from a detrimental process (biofouling) to a source of beneficial, programmable biocatalysis. Strategies for embedding microbial and fungal communities into architectural materials to perform functions such as bioremediation, biomineralisation, and energy generation are explored. The analysis includes the multiscalar design of bioreceptive substrates, engineered living paints, mycelium composites, and probiotic surfaces, which transform passive structures into metabolically active interfaces. These approaches are regarded as Engineered Eco-Ornamentation, where surface design intentionally supports microbial ecology and urban metabolism. The integration of these living systems with computational modelling and digital fabrication to create adaptive building systems is considered. Key challenges include scaling biological processes for architectural application, ensuring long-term material durability, and aligning metabolic activity with practical construction constraints. Addressing these challenges positions functionally designed biocatalytic surfaces as a foundational research field for more regenerative and ecologically integrated architecture.
    DOI:  https://doi.org/10.1016/j.copbio.2025.103435
  4. Adv Mater. 2026 Jan 21. e16809
      Designing soft materials that autonomously respond to complex physiological environments remains a fundamental challenge in biomedical systems engineering. Here, we report on a 3D-printed hybrid protein-polymer hydrogel actuator that operates via endogenous biochemical logic, enabling fully autonomous dual-stage shape morphing and enzyme-triggered drug release in gastric-mimicking environments. The actuator comprises a bilayer structure: an active layer based on bovine serum albumin-poly (ethylene glycol) diacrylate (BSA-PEGDA), and a passive PEGDA layer. In acidic gastric fluid, the BSA-PEGDA layer undergoes rapid conformational swelling, followed by delayed softening from pepsin-mediated degradation, autonomously driving reversible shape transitions without manual intervention. By embedding doxorubicin (DOX) within the BSA-PEGDA hydrogel network, the system achieves site-specific, enzyme-gated drug release that is tunable using pepstatin A as a biochemical inhibitor. High-resolution digital light processing (DLP) printing enables the fabrication of complex autonomous actuators and microneedle-equipped grippers capable of mucosal adhesion, catch-and-release behavior, and controlled delivery. This work establishes a materials design strategy where biochemical cues are used as programmable inputs to drive mechanical and therapeutic outputs, offering a robust platform for bioresponsive soft robotics and in situ drug delivery.
    Keywords:  autonomous actuators; biochemical logic; endogenous biochemical cues; hydrogels; protein‐driven materials
    DOI:  https://doi.org/10.1002/adma.202516809
  5. Adv Mater. 2026 Jan 22. e16741
      The design of hydrogels that combine mechanical robustness with dynamic reconfigurability remains a fundamental challenge, as increasing crosslink dissociation rates compromise network integrity. This limitation is addressed through the incorporation of an associative crosslink exchange into DNA-based supramolecular hydrogels, enabling the decoupling of network relaxation behavior from crosslink stability. The hydrogels are constructed from enzyme-synthesized single-stranded DNA that self-assembles via hybridization between complementary domains. These crosslinks can reorganize through dissociative melting or associative strand displacement reaction, yielding networks with tunable relaxation timescales spanning over three orders of magnitude. Rheological measurements and thermodynamic modeling confirm that associative exchange facilitates efficient stress dissipation without diminishing rupture strength or thermal stability. In contrast, dissociative systems inherently trade increased dynamics with mechanical weakening. This decoupling is achieved through the implementation of a catalytic reorganization pathway governed by the composition of the sample, independently of the crosslink strength. These findings establish the mechanism of reorganization as a key design parameter for engineering adaptive soft materials that combine resilience and responsiveness.
    Keywords:  DNA hydrogels; associative reorganizations; relaxations; rheology; rupture mechanics; supramolecular networks
    DOI:  https://doi.org/10.1002/adma.202516741
  6. ACS Appl Mater Interfaces. 2026 Jan 22.
      Digital light processing (DLP) three-dimensional (3D) printing has been considered one of the most sustainable additive manufacturing methods for high-speed and high-resolution construction. As 3D printing technology advances, a continuous printing process is achieved, which brings controllable parameters along with printing. Herein, we propose a refilling-driven particle redistribution mechanism during continuous printing, enabling the simultaneous control of microparticle distribution and 3D functionalization. The microparticle properties (dimension, wettability, and quantity ratio) and printing speed influenced the microparticle moving tendency and distribution law, which are versatile for different kinds of microparticles. Based on the single-microparticle distribution law, the motion of multidimensional microparticles along the resin refilling process can be controlled, through which microparticles can be controlled to locate inside different parts of the cured structure or inside the liquid resin. Selective microparticle separation from multidimensional mixed microparticles can be realized, with the special characteristics of small microparticle extraction from mixed microparticles. In addition, one-step printing of a two-dimensional (2D) or 3D wetting pattern can thus be realized by regulating the location of microparticles with different wettabilities and ratios. The 3D wetting patterns of the outer surfaces of structures and microfluidic inner surfaces can be one-step-printed, which satisfies the urgent demand for functionality beyond simple structural fabrication and expands the application scope of continuous 3D printing.
    Keywords:  continuous 3D printing; microparticles distribution; one-step printing; selective separation; wetting patterning
    DOI:  https://doi.org/10.1021/acsami.5c22187
  7. ACS Synth Biol. 2026 Jan 21.
      Protein liquid-liquid phase separation underlies the formation of membraneless organelles in cells and plays a key role in the assembly process of natural materials such as the assembly of tropoelastin into elastic fibers. Here, we engineered a series of charged elastin-like polypeptides (ELPs) that form complex coacervates, providing a rapid method of concentrating proteins into a fluid state. Compared with coacervates formed via simple coacervation, complex coacervates exhibited greater fluidity, likely due to differences between electrostatic interactions and hydrophobic forces. We designed these ELPs to further contain cross-linking domains compatible with tyrosinase or transglutaminase and found that cross-linking was enhanced when proteins were in a condensed state compared to free in solution. Cross-linking the ELP complex coacervates led to the formation of gels with distinct properties dependent on the nature of the cross-linking. This work expands the design space of protein hydrogels, offering a novel strategy for forming cross-linked networks from complex coacervates and providing opportunity for future use in tissue engineering and biocompatible biomaterials applications.
    Keywords:  biomaterials; biosynthesis; coacervation; enzymatic cross-linking; microrheology; protein engineering
    DOI:  https://doi.org/10.1021/acssynbio.5c00592
  8. Mater Today Bio. 2026 Feb;36 102643
      Purely protein-based hydrogels are widely used in tissue engineering for their biomimicry and biocompatibility, yet remain challenging to tailor with precision and predictability at biological and mechanical levels. To overcome this, synthetic self-assembling peptide amphiphiles (PAs) offer opportunities for supramolecular customization, both as single-phase materials and co-assembled with proteins to create hybrid nanocomposites with emerging functionalities. Similarly, contactless, sound-guided bioassembly techniques using liquid-phase hydrogel precursors are emerging as strategic tools for obtaining structured and functional hydrogels. Leveraging these advances, here a fast, contactless, 'one-pot' bioassembly strategy merging supramolecular PA self-assembly with sound-guided patterning to fabricate hybrid peptide-protein hydrogels with predictable, shape-dependent functionality is presented. Using fibrin as proof-of-concept, material performance is biologically enhanced by incorporating growth factor-binding PAs, while inorganic microparticles are embedded and spatially organized via acoustic fields to tune mechanical properties. This strategy allows predictable tuning of composite stiffness and architecture by adjusting sound wave frequency, with acoustic fields guiding material organization from nano-to-macroscale. Composite hydrogels result highly permissive to cell infiltration in vitro and versatile platforms to tune immune cell-material interactions. This modular biofabrication platform integrating supramolecular and sound-guided processes can be generalized to other building blocks, opening unique opportunities for scalable, tunable, and hierarchically-organized biomaterials.
    Keywords:  Biofabrication; Bottom-up; Composite; Multiscale; Peptide amphiphiles; Proteins; Sound-based bioassembly
    DOI:  https://doi.org/10.1016/j.mtbio.2025.102643
  9. Nat Biotechnol. 2026 Jan 19.
      Engineering bacteria to secrete gut therapeutics has been limited by their poor autonomous sensing of pathological cues and inability to sustain localized, long-term therapeutic activity. Here we engineer nonpathogenic Escherichia coli with a blood-inducible gene circuit that secretes the barnacle-derived adhesive protein CP43K and the therapeutic gut-barrier-healing factor TFF3 in response to gastrointestinal bleeding, an indicator of severe inflammatory bowel disease (IBD). Adhesive production enables sustained bacterial attachment to inflamed tissues for up to 10 days or 7 days following a single rectal or oral administration, respectively. This effect depends on bleeding-induced adhesion. Using two mouse models of IBD, the colitis model induced by dextran sulfate sodium and the interleukin-10-knockout mouse model, we demonstrate improved weight recovery, reversed colonic shortening and reduced intestinal bleeding. Additionally, the treatment decreases intestinal inflammation, promotes mucosal repair and restores gut barrier integrity, demonstrating comprehensive therapeutic efficacy.
    DOI:  https://doi.org/10.1038/s41587-025-02970-9
  10. Proc Natl Acad Sci U S A. 2026 Jan 27. 123(4): e2517323123
      Synthetic cells aim to emulate living systems by reconstituting essential cellular processes within lipid-bound architectures. However, their functional complexity remains constrained by a key challenge: the synthesis and correct integration of hydrophobic membrane proteins via cell-free approaches. Here, inspired by natural cells, we developed a spatially regulated translation strategy in which membrane-anchored mRNAs recruit ribosomes to drive the cotranslational insertion of membrane proteins into lipid bilayers. This design enables efficient in situ synthesis and integration of multiple transmembrane proteins within giant unilamellar vesicles, supporting selective small-molecule transport across membranes. Importantly, the method allows for precise stoichiometric control of membrane protein composition. Together, this work establishes a minimal yet versatile framework for the direct synthesis and integration of membrane proteins, advancing the construction of functional synthetic cells.
    Keywords:  cell-free protein synthesis; membrane proteins; synthetic cells
    DOI:  https://doi.org/10.1073/pnas.2517323123
  11. Small. 2026 Jan 19. e11065
      Molecular patterning at single-molecule resolution could significantly advance biomolecular analysis and the engineering of functional surfaces by enabling precise control over the spatial arrangement and mechanical accessibility of individual biomolecules. Such control is particularly valuable for multiplexed single-molecule assays, which reveal molecular mechanisms, non-equilibrium behavior, and nanoscale mechanical properties through the application of mechanical force. Standard surface functionalization methods, however, often lack sufficient precision, programmability, or accessibility, resulting in random or sparse biomolecular arrangements. To address this, we have developed a light-guided surface patterning method that can covalently organize oligonucleotides (oligos) without the need for lithographic equipment. Oligos with 3-cyanovinylcarbazole (CNVK) nucleoside are crosslinked in precise spatial arrangements defined by UV patterns projected through a digital micromirror device (DMD), with beads arranged accordingly. We demonstrate compatibility with established single-molecule methods by performing single-molecule force spectroscopy experiments on patterned coverslips, using magnetic tweezers and hydrodynamic-based approaches. Our light-guided method provides a scalable and accessible platform for biomolecular patterning that allows precise control over molecular identity and spatial positioning, enabling high-throughput single-molecule manipulation and mechanical characterization.
    Keywords:  DNA nanotechnology; biomaterials; biophysics; bio‐lithography; surface functionalization
    DOI:  https://doi.org/10.1002/smll.202511065
  12. ACS Appl Mater Interfaces. 2026 Jan 22.
      The ocean's extreme environments demand robust materials for next-generation exploration tools. Here, we report a multifunctional poly(vinyl alcohol) hydrogel (PVA-H) fabricated via universal solvent-induced crystallization for bioinspired robotic fish skins. Alkaline solvent induction triggers intrachain crystallization within concentrated PVA solutions, yielding hydrogels with exceptional mechanical strength (compressive strength up to 2.6 MPa, tensile strain >450%), environmental tolerance (resilience to 1 M acetic acid/NaOH, seawater, 3 M NaCl), and optical transparency (>80%). The material demonstrates efficient recyclability (>90% recovery over 10 cycles) and biocompatibility (hemolysis rate <1.5%). Ionic compounding enables stable underwater conductivity and antifreezing performance at -20 °C. Hydrophilicity-driven interfacial water layers inhibit >70% protein adsorption, which confers antifouling properties. Integration of ice templating and solvent crystallization facilitated scalable fabrication of biomimetic fish skins, validated through sustained underwater operation. This work establishes a versatile platform for durable, eco-adaptive marine robotics operating in chemically, thermally, and biologically hostile environments.
    Keywords:  biomimetic materials; extreme environments; hydrogels; marine robotics; solvent-induced crystallization
    DOI:  https://doi.org/10.1021/acsami.5c22380
  13. Small. 2026 Jan 20. e10964
      Next-generation microelectronic devices and energy systems will require fabrication techniques that enable the rapid spatial arrangement of 1D and 2D functional nanomaterials. Arranging atomically thin 2D nanosheets in three-dimensional (3D) space, however, is challenging due to the need for additives or support materials required for their spatial build-up. Here, we report an advanced fabrication technique that can arrange nanometer-thick micron-sized Ti3C2Tx MXene 2D nanosheets in self-supporting three-dimensional structures in a single printing step. This additive-free approach leverages aerosol jet 3D nanoprinting (AJP), where fluid dynamics of rapidly evaporating aerosol droplets is used to achieve precise, support-free, freestanding 3D geometries of 2D nanosheets. A real-time thickening effect during printing and van der Waals interactions between MXene nanosheets are identified as the basis of robust structure formation in 3D, offering a pathway to use 2D materials in device applications. The versatility and impact of this technique are demonstrated by constructing 3D microsupercapacitors (MSCs) with finely patterned 3D MXene electrodes. These devices exhibit a breakthrough areal capacitance of 375 mF·cm-2 at a current density of 1.5 mA·cm-2 (equivalent electrode capacitance of 1500 mF·cm-2) and an energy density of 11.04 µWh·cm-2 at a power density of 0.40 mW·cm-2. This electrochemical performance far exceeds that of MSCs fabricated by other high-resolution patterning methods. This work paves the way for the use of 2D materials in micron-sized device systems.
    Keywords:  2D materials; 3D Printing architected materials; MXene; energy storage; microsupercapacitors
    DOI:  https://doi.org/10.1002/smll.202510964
  14. Small. 2026 Jan 21. e12844
      Lipid exchange between membranes is fundamental to biological function and technological applications, from drug delivery and vesicle trafficking to the design of biomimetic materials. Yet, quantitative prediction of both activation energies and timescales has remained elusive due to complex energy landscapes. Here, we present a thermodynamic-kinetic framework inspired by glassy dynamics to address this challenge. Using a single, experimentally accessible parameter-the thermal expansion coefficient of lipid vesicles-we apply the Collective Small Displacements (CSD) model to predict activation energies and transfer timescales without adjustable parameters. Our label-free quartz crystal microbalance experiments validate these predictions across multiple lipid systems. We demonstrate that lipid exchange proceeds through rare, cooperative molecular events analogous to those governing relaxation in amorphous materials. By connecting a simple equilibrium thermodynamic property to interfacial transport dynamics, this work provides a versatile predictive tool for engineering lipid-based materials and transport kinetics at the nanoscale, with broad implications for soft matter physics, synthetic biology, and nanobiotechnology.
    Keywords:  charged lipid membranes; glassy dynamics; interfacial processes; lipid transfer kinetics; thermodynamics
    DOI:  https://doi.org/10.1002/smll.202512844
  15. Small. 2026 Jan 21. e10329
      Porous materials have garnered extensive interest for applications in catalysis, energy storage, and biomedicine. However, there is a general difficulty that higher porosity typically leads to lower mechanical strength. Natural porous structures, developed and evolved in complex environments, exhibit remarkable mechanical properties and multifunctionality, offering crucial inspiration for developing strong and tough functional porous materials. In this paper, some representative structures of natural porous materials are taken as examples, and they are grouped and discussed from the perspectives of structural characteristics and mechanical design, aiming to refine the general principles of mechanical robustness of porous materials. Based on these design principles, manufacturing strategies for bioinspired strong and tough porous materials are summarized. Finally, recent advances in the application of biomimetic tough porous materials in the fields of energy absorption, bone tissue engineering, and energy/sensing are explored. By mimicking the natural multi-scale porous structure, it is possible to make synthetic porous materials with both comprehensive mechanical properties and multifunctionality, which brings a new direction for the development of porous materials.
    Keywords:  biomimetic porous materials; natural porous materials; porous structures; strong and tough properties
    DOI:  https://doi.org/10.1002/smll.202510329
  16. Bioact Mater. 2026 May;59 595-606
      Granular microgels are attractive bioinks for bioprinting due to their injectability, printability, modularity, and enhanced macroporosity compared to conventional nanoporous hydrogels. Despite the potential of microgels for bioprinting, most previous work has relied on spherical microgels and produced isotropic tissues, whereas many native tissues are inherently anisotropic. While emerging studies have explored non-spherical microgels for bioprinting, there remains a need for bioinks that support cell alignment and tunable niche cues. Microribbons (μRB) are anisotropic ribbon-shaped microgels, but the potential of μRBs as bioinks for printing 3D anisotropic tissues remains unexplored. Here, we report the development of μRBs with tunable stiffness as bioinks for extrusion-based bioprinting and demonstrate that μRB bioinks maintain excellent printability and align during extrusion. μRB bioinks support alignment of MSCs and endothelial cells, with greater alignment as μRB stiffness increases. Increasing μRB stiffness also accelerates mesenchymal stromal cell osteogenesis in 3D. Finally, we demonstrate the potential of μRB bioinks for modeling breast cancer-bone metastasis, which features spatial patterning of multiple cell types to model cancer cell invasion at the tissue interface. Together, these results establish ribbon-shaped microgels as a new class of anisotropic bioinks, offering a versatile platform to support a broad range of bioprinting applications.
    Keywords:  3D bioprinting; Alignment; Anisotropic; Cancer invasion; Differentiation; Microgels; Ribbon-shape
    DOI:  https://doi.org/10.1016/j.bioactmat.2025.12.040
  17. Nat Phys. 2026 ;22(1): 123-130
      Organisms use specialized sensors to measure their environments, but the principles governing their accuracy are unknown. The bacterium Escherichia coli climbs chemical gradients at speeds bounded by the amount of information it receives from its environment. However, it remains unclear what prevents E. coli cells from acquiring more information. Past work argued that chemosensing by E. coli is limited by the stochastic arrival of molecules at their receptors by diffusion, without providing direct evidence. Here we show instead that E. coli encode two orders of magnitude less information than this physical limit. We develop an information-theoretic approach to quantify how accurately chemical signals can be estimated from observations of molecule arrivals as the physical limit and of chemotaxis signalling activity for E. coli cells, and then we measure the associated information rates in single-cell experiments. Our findings demonstrate that E. coli chemosensing is limited by internal noise in signal processing rather than molecule arrival noise, motivating investigations of the physical and biological constraints that shaped the evolution of this prototypical sensory system.
    Keywords:  Biological physics; Cellular motility; Statistical physics
    DOI:  https://doi.org/10.1038/s41567-025-03111-4
  18. Nat Chem Biol. 2026 Jan 20.
      Mammalian cells receive signaling instructions through interactions on their surfaces. Proteoglycans are critical to these interactions, carrying long glycosaminoglycans that recruit signaling molecules. Biosynthetic redundancy in the first glycosylation step by two xylosyltransferases XT1/2 complicates annotation of proteoglycans. Here we develop a chemical genetic strategy that manipulates the glycan attachment site of cellular proteoglycans. Through a bump-and-hole tactic, we engineer the two isoenzymes XT1 and XT2 to specifically transfer the chemically tagged xylose analog 6AzGlc to target proteins. The tag contains a bioorthogonal functionality, allowing to visualize and profile target proteins in mammalian cells. Unlike xylose analogs, 6AzGlc is amenable to cellular nucleotide-sugar biosynthesis, establishing the XT1/2 bump-and-hole tactic in cells. The approach allows pinpointing glycosylation sites by mass spectrometry and exploiting the chemical handle to manufacture proteoglycans with defined glycosaminoglycan chains for cellular applications. Engineered XT enzymes permit an orthogonal view into proteoglycan biology through conventional techniques in biochemistry.
    DOI:  https://doi.org/10.1038/s41589-025-02113-w
  19. Macromol Rapid Commun. 2026 Jan 22. e00797
      Herein, a novel approach to create macroscale lower critical solution temperature (LCST) thermoresponsive hydrogels in a controlled manner using living cationic polymerization and a subsequent radical reaction is presented. By using a crosslinker capable of orthogonal reactions, 4-(vinyloxy)butyl methacrylate (VBM), which contains both vinyl ether and methacrylate moieties that react via cationic polymerization and radical reactions respectively, tremendous control over both the synthesis of the polymer structure as well as the hydrogel structure and its macroscale size and shape, by a post-polymerization UV light initiated radical reaction, is achieved. A series of random copolymers with the orthogonal crosslinker VBM, and LCST thermoresponsive monomers, methoxy ethyl vinyl ether (MOVE) or ethoxy ethyl vinyl ether (EOVE) or both, are synthesized. Introduction of VBM, even in small quantities, causes significant decreases in the observed phase transition temperatures for these thermoresponsive polymers and enables tuning of these temperatures. The hydrogels created from these polymers also exhibit clear LCST behavior with phase transition temperatures that are generally higher than for their corresponding polymers and over a wider temperature range. The use of this orthogonal reaction approach allows for control and design over both the polymer structure as well as that of the hydrogel.
    Keywords:  cationic polymerization; hydrogel; lower critical solution temperature; orthogonal crosslinking reaction; phase transition temperature; radical reaction; thermoresponsive
    DOI:  https://doi.org/10.1002/marc.202500797
  20. Adv Sci (Weinh). 2026 Jan 22. e17501
      Synthetic bioelectronics is rapidly advancing, propelled by breakthroughs in synthetic biology and bioelectronics. This convergence is key to next-generation wearable and implantable devices, enabling seamless integration with living systems. Here, we introduce an enzymatic hydrogel electrode (GelZymes) developed via a synthetic bioelectronic strategy to overcome the mechanical and interfacial limitations of conventional enzyme electrodes. GelZymes deliver two core advances: i) a monolithic and scalable 3D architecture that unifies the enzyme membrane and electrode, simplifying fabrication and eliminating interfacial instability; and ii) tissue-like viscoelasticity-combining stretchability and adhesiveness-rarely achievable with rigid enzyme membranes. GelZymes are synthesized through three steps: engineering a stretchable, mixed-conducting 3D hydrogel; implementing an enzyme-compatible, cascading crosslinking scheme to immobilize enzymes within the network; and balancing the trade-off between electronic/ionic conductivity and the density of redox-active enzyme sites to maximize bio-electrochemical performance. We further show that GelZymes enable a shift from invasive, tissue-interfaced biosensing to noninvasive, tissue-integrated biosensing, offering a practical pathway to bridge current biosensor technologies with living systems.
    Keywords:  continuous glucose monitor; enzyme membrane; hydrogel electrode; synthetic bioelectronics; wearable health
    DOI:  https://doi.org/10.1002/advs.202517501
  21. Lab Chip. 2026 Jan 21.
      3D printing is reshaping droplet microfluidics by converting digital designs into sealed, volumetric devices that integrate non-planar droplet generators and junctions, as well as embedded distributors. This Critical Review distills design rules that link geometry, key dimensionless groups (Ca, φ, λ), and wetting control to the robust production of single and multiple emulsions. We compare 3D printing modalities using criteria specific to droplet microfluidics, attainable feature size, optical clarity, chemical resistance, surface roughness, native wettability, and cleanability, and provide practical guidance on material-fluid compatibility, extractables, and long-run stability. We formalize scale-up via hydraulic balancing and unit-resistor strategies that preserve monodispersity across arrays, and outline selective surface treatments and multi-material printing approaches for achieving durable wettability patterns. Finally, we highlight AI/digital-twin workflows for predictive design and adaptive control, and map pathways toward standardized, manufacturable devices. These principles offer a conservative, application-oriented blueprint for 3D-printed droplet microfluidic devices.
    DOI:  https://doi.org/10.1039/d5lc01011j
  22. Mater Horiz. 2026 Jan 20.
      Developing materials that combine both softness and stiffness is crucial for meeting the demands of complex and versatile applications. The realization of multistability through elaborate units has been demonstrated, but the trade-off between performance and light weight across different states remains underdeveloped. In this work, we pioneer the application of the soft-stiff responsive strategy to lightweight cellular materials through architecturally nesting two materials with contrasting properties. The proposed cellular materials can be reconfigured and switched between soft and stiff states, as demonstrated experimentally, theoretically and numerically. The soft state represents high perturbation sensitivity and prominent vibration isolation properties. The stiff state exhibits a strong load-carrying capability due to multi-synergistic mechanisms, with a crushing modulus and strength 668.78 and 1037.55 times as high, respectively, as the soft state in the cases of soft materials embedded in metal materials. The manipulable mechanical properties can be tuned across a broad design space while maintaining robust switchability. These advantages of the proposed bistate cellular materials offer promising application prospects from adaptive protection to shock absorption and beyond.
    DOI:  https://doi.org/10.1039/d5mh01776a
  23. Adv Funct Mater. 2025 Dec 05. pii: e19601. [Epub ahead of print]
      Mechanical loading plays a critical role in heart development and function, with cardiac preload (tissue stretch during chamber filling) and afterload (resistance against which the heart works to eject blood) potentially playing distinct roles in postnatal cardiomyocyte maturation. To dissect the effects of various types of mechanical loading on postnatal cardiomyocytes, we developed a novel "crossbow" bioreactor system capable of independently and dynamically modulating preload and afterload under auxotonic conditions in 3D engineered cardiac tissues. The system employs tunable, curved polydimethylsiloxane (PDMS) cantilever arms that increase resistance to cardiac contractions as they are deflected and a ratcheted center beam to allow for control of preload via change in cardiac tissue length. Culture of cardiobundles made from neonatal rat cardiomyocytes embedded in a fibrin-based hydrogel on the crossbow system reveals physiological, rather than pathological, responses to loading. Progressively increased afterload over two weeks of culture enhances cardiomyocyte contractile force, while progressively increased preload promotes cardiomyocyte elongation and cycling. The crossbow system holds potential for refining our understanding of mechanosensing in cardiac developmental and pathological remodeling, making it a promising tool for in vitro studies of cardiac biology, disease modeling, and pharmaceutical testing.
    Keywords:  NRVM; bioreactor; heart tissue engineering; mechanobiology
    DOI:  https://doi.org/10.1002/adfm.202519601
  24. Adv Mater. 2026 Jan 19. e12404
      Stroke remains a leading cause of neurological disability worldwide. A major obstacle to brain tissue regeneration after stroke is the persistent local inflammation and the absence of extracellular matrix (ECM) support within the infarct cavity, which severely impedes the brain's endogenous repair. Inspired by the natural interactions between stromal and parenchymal cells, we developed an engineered living material to recreate a regenerative niche within the stroke cavity. This system integrates a programmable supramolecular DNA hydrogel with interleukin-10-secreting engineered-mesenchymal stem cells (eMSCs) and neural stem cells (NSCs). The hydrogel mimics the structural and mechanical properties of the native ECM, enhancing the retention and viability of transplanted cells. Meanwhile, eMSCs modulate the inflammatory environment, suppress glial scar formation, and promote vascular regeneration, thereby facilitating the neuronal differentiation of NSCs. In a rat model of ischemic stroke, these engineered living materials significantly promote neuronal regeneration, synaptic remodeling, and neovascularization, leading to improved motor and cognitive function. These findings highlight a modular strategy for repairing damaged neural tissues by re-establishing stromal-parenchymal interactions, offering a promising therapeutic avenue for post-stroke brain regeneration.
    Keywords:  DNA hydrogel; inflammation regulation; ischemic stroke; nerve regeneration; stem cells
    DOI:  https://doi.org/10.1002/adma.202512404
  25. Adv Sci (Weinh). 2026 Jan 21. e20529
      Soft robotics has gained significant attention for its potential to deliver safe, adaptable, and biocompatible machines, by embracing the mechanical compliance of soft materials. However, the manufacture of soft robotic devices and machines still largely relies on petroleum-based polymers. Furthermore, in light-induced 3D printing, a key technology for fabricating complex 3D monolithic soft robots, non-sustainable resins remain predominant. This work addresses this issue by developing a photocurable bio-based resin to monolithically fabricate soft robots. We formulate a resin using soybean oil as a renewable precursor and shape it via Digital Light Processing into an origami-inspired vacuum-actuated actuator. The bio-based material has a Young's modulus of 18.9 MPa and an elongation at break of 19.6%. The origami deformation, based on folding rather than stretching, enables actuator operation, despite the lower elongation range of our material compared to silicone elastomers. We report on the characterization of the bulk material properties and the mechanical performance of the actuator, which performs 2000 cycles without failure before testing ceased. Finally, we design and fabricate a monolithic soft robotic gripper with integrated origami actuation using our bio-based material. We show the functional operation of the gripper in grasping different objects, as well as in underwater settings.
    Keywords:  bio‐based materials; high resolution 3D printing; origami actuators; soft gripper; soft robotics; sustainable materials
    DOI:  https://doi.org/10.1002/advs.202520529
  26. Chem Sci. 2026 Jan 04.
      By coupling semiconductor nanomaterials with living microbes, nanomaterial-microorganism hybrid systems (NMHSs) create powerful biohybrids that unlock new routes for efficient and sustainable solar-to-chemical conversion. Central to the performance of this system is the biotic-abiotic interface, where photoelectrons must efficiently traverse from inorganic materials into complex cellular redox networks. This review highlights recent progress in understanding and engineering these interfaces across three dimensions: material architecture, microbial electron-handling machinery, and interfacial construction strategies. By dissecting how composition, size, and morphology of photosensitizers align with extracellular matrices, transmembrane conduits, and intracellular compounds, we reveal principles for minimizing interfacial resistance and maximizing charge transfer. We further classify interface communication modes into extracellular wiring, transmembrane bridging, and intracellular embedding, and evaluate corresponding construction approaches. By drawing connections between interfacial features and electron-transfer performance, we propose a multidimensional framework that integrates material engineering, microbial adaptation, and interface optimization. This perspective emphasizes the synergistic co-design of both abiotic and biotic components to achieve efficient and stable solar-to-chemical conversion, offering new opportunities for rational design of high-performance NMHSs.
    DOI:  https://doi.org/10.1039/d5sc07884a
  27. Small. 2026 Jan 20. e10157
      Flexible pressure sensors are critical components in next-generation wearable electronics and intelligent human-machine interface (HMI). However, conventional designs often suffer from limited sensitivity and uniaxial force detection, restricting their applicability in complex environments. Here, a bioinspired omnidirectional iontronic sensor (BOIS) is presented, engineered via triboelectric coupling and featuring a cross-scale architecture inspired by the spatial encoding properties of cochlear cilia. Through the integration of a 70° inclined macroscopic ciliary array based on Fibonacci helix optimization and 3D printing technology, the sensor achieves high-resolution detection of both normal and shear forces. The incorporation of iontronic effects further enhances sensitivity via synergistic charge modulation. The resulting flexible sensing platform demonstrates excellent mechanical compliance, multi-axis responsiveness, and high precision in monitoring dynamic joint motions such as wrist bending and finger flexion. This work offers a robust strategy for advancing omnidirectional tactile sensing, with promising applications in medical rehabilitation, soft robotics, and HMI.
    Keywords:  no‐contact sensing; omnidirectional iontronic sensors; pressure sensors; triboelectric nanogenerators
    DOI:  https://doi.org/10.1002/smll.202510157
  28. ACS Omega. 2026 Jan 13. 11(1): 2194-2205
      Gel viscoelasticity governs the mechanical identity of functional biomaterials. This paper presents the design and rheological characterization of hemoglobin (Hb)-based hydrogels, in which the network is maintained either by native Hb or by intramolecularly ββ-cross-linked Hb (XLHb). Native Hb has a α2β2 structure constructed via reversible, noncovalent interactions between αβ subunits, whereas in XLHb the tetrameric α2β2 structure is stabilized covalently. Conjugation of the β subunits of native Hb with four-armed 10 kDa polyethylene glycol (PEG) produces a physically cross-linked supramolecular gel exhibiting liquid-like viscoelasticity and self-healing behavior. By contrast, XLHb yields a chemically cross-linked gel exhibiting solid-like mechanical properties attributed to a permanent covalent network among PEG termini. Additionally, to explore intermediate states, we synthesized a hybrid gel by reacting a combination of Hb and XLHb with four-armed PEG. Rheological analysis revealed a critical transition from liquid-like to solid-like viscoelastic behavior between 80% and 90% XLHb ratios. These findings provide a mechanistic rationale for designing hybrid gel systems with precisely tunable viscoelastic properties through control of cross-linking modalities and through application of unified network backbone strategies.
    DOI:  https://doi.org/10.1021/acsomega.5c11304
  29. Nano Lett. 2026 Jan 20.
      Liquid materials with shape reconfigurability can open a pathway for fabricating smart all-liquid constructs with tremendous potential applications. Creating such materials usually relies on controllable jamming/assembly of nanoparticle surfactants at liquid/liquid interfaces. Here we show that lignin nanoparticles (LNPs), one kind of well-established green Pickering emulsifier, can act as a simplified alternative to nanoparticle surfactants for regulating liquid morphologies. Owing to their good dispersibility in water and inherent high binding energy and strong associations at the soybean oil/water interface, the LNPs can generate jammed, highly elastic interfacial films that enable them to lock both the oil and water droplets into largely distorted, nonequilibrium geometries at pH >4. They will undergo agglomeration and lose their liquid structuring capacity with their interfacial binding energy and mechanical strength strongly decreased at lower pH values, thus allowing reversibly reconfiguring liquid shapes via adjusting the pH of the aqueous phase.
    Keywords:  lignin nanoparticles; liquids; oil/water interface; reversible jamming; shape reconfiguration
    DOI:  https://doi.org/10.1021/acs.nanolett.5c05365
  30. ACS Appl Mater Interfaces. 2026 Jan 19.
      Polyacrylamide (PAM) hydrogels are extensively used as extracellular matrix mimics to study specific cell-material interactions. However, conventional biofunctionalization strategies lack chemo-selectivity and control over ligand density, compromising reproducibility and experimental reliability. In this work, we introduce firefly luciferin-inspired click ligation to enable efficient and tunable biofunctionalization of PAM hydrogels. A novel acrylamide-based comonomer containing cyanobenzothiazole (CBT) moieties is synthesized and incorporated into PAM hydrogels. CBT mediates biofunctionalization of PAM with N-Cys bearing biomolecules via luciferin click chemistry. Biofunctionalization occurs within only a few minutes, under mild conditions, with high efficiency, not requiring light exposure. Compared to the widely used sulfo-SANPAH (SS)-based approach, our method offers enhanced biofunctionalization efficiency, homogeneity, and control over biomolecule loading while preserving biochemical functionality. This translates into improved presentation of cell-adhesive cues, resulting in significantly increased cell attachment, spreading, and proliferation, as demonstrated by using label-free holotomography. The novel luciferin click ligation offers a robust, efficient, and reproducible alternative for PAM biofunctionalization, providing precise control over the ligand density while maintaining bioactivity. As PAM hydrogels continue to evolve into increasingly sophisticated mechanobiology tools, our approach may serve as a new standard for engineering the interfacial properties of these materials to achieve robust two-dimensional (2D) cell culture platforms for fundamental studies in cell-material interactions.
    Keywords:  bioconjugation; biofunctionalization; cell–material interactions; chemical selectivity; ligand loading; poly(acrylamide) hydrogels
    DOI:  https://doi.org/10.1021/acsami.5c20298
  31. ACS Synth Biol. 2026 Jan 22.
      Nitrogenase catalyzes the reduction of atmospheric nitrogen gas to ammonia, forming the foundation of biological nitrogen fixation in diazotrophic microbes. While functional nitrogenase can be assembled in non-native hosts, its activity is severely limited. This is partially due to the O2 sensitivity, which irreversibly inactivates the enzyme. Here, we aimed to address this challenge by compartmentalizing nitrogenase into carboxysomes-bacterial microcompartments that restrict O2 diffusion. We demonstrate that nitrogenase subunit NifH can be selectively localized to the carboxysomes of Nostoc punctiforme. Electron microscopy indicated normal assembly of these NifH-loaded carboxysomes, while growth experiments suggested minimal impact to the carboxysome function. Mass spectrometry confirmed accumulation of the fusion proteins in purified carboxysomes. These data set the stage for further development of nitroxysomes, exploring integration of fully active nitrogenase complexes into these carboxysomes. If successful, this approach will pave the way to engineer nitrogen fixation directly into crops, promoting sustainable agriculture to enhance global food security.
    Keywords:  Nitrogenase; bacterial microcompartment; biological nitrogen fixation; carboxysome; protein shell; synthetic biology
    DOI:  https://doi.org/10.1021/acssynbio.5c00568
  32. ACS Omega. 2026 Jan 13. 11(1): 1703-1716
      In continuous culture, a population of microorganisms is propagated in a stable environment over many generations. This is particularly relevant for experimental evolution and metabolic studies. However, continuous culture protocols are difficult to implement, so they are not commonly used in microbiology laboratories. Here, we present the ModuloStat, a modular, open-source framework that facilitates continuous culture in mini-bioreactors. The ModuloStat system is grounded on digital fabrication tools easily accessible in FabLabs and programmable electronics. Maintaining a culture is divided into tasks assigned to dedicated printed circuit boards with a microcontroller connected to a Wi-Fi network. According to Internet of Things principles, each board operates a set of sensors and actuators autonomously and can receive and send information. The boards are stacked to implement complex behaviors and can be modified to accommodate new features. A thermoregulated box holds the components and can be placed on a laboratory bench or transported under a sterile hood for inoculation. Sterility is ensured by autoclaving, after assembly, all components that will come into contact with the culture medium. In-situ optical density monitoring combined with modularity and computer control enables many cultivation modes. Additionally, we present the construction of the Bacillus subtilis strain ZB designed for bioreactor culture that exhibits a zero-biofilm phenotype. To demonstrate the system's versatility, we performed several experimental cultures with this model organism, including chemostat, turbidostat, medium swap, and a cascade of bioreactors.
    DOI:  https://doi.org/10.1021/acsomega.5c09710
  33. Nat Mater. 2026 Jan 19.
      Metastases arise from a multistep process during which tumour cells face several microenvironmental mechanical challenges, which influence metastatic success. However, how circulating tumour cells (CTCs) adapt their mechanics to such microenvironments is not fully understood. Here we report that the deformability of CTCs affects their haematogenous dissemination and identify mechanical phenotypes that favour metastatic extravasation. Combining intravital microscopy with CTC-mimicking elastic beads, mechanical tuning in tumour lines and profiling of tumour-patient-derived cells, we demonstrate that the inherent mechanical properties of circulating objects dictate their ability to enter constraining vessels. We identify cellular viscosity as a rheostat of CTC circulation and arrest, and show that cellular viscosity is crucial for efficient extravasation. Moreover, we find that mechanical properties that favour extravasation and subsequent metastatic outgrowth can be opposite. Altogether, our results establish CTC viscosity as a key biomechanical parameter that shapes several steps of metastasis.
    DOI:  https://doi.org/10.1038/s41563-025-02462-w
  34. Mater Today Bio. 2026 Feb;36 102705
      Implantable bioelectronic devices, such as brain-computer interfaces (BCIs), face persistent challenges in achieving stable, rapid, and reversible adhesion on wet tissues due to hydration layers and mechanical mismatch, which can cause interfacial failure and unstable signals. Here, we report a conductive hydrogel interface with tissue-adaptive, temperature-controllable adhesion. The material is synthesized via dynamic co-entanglement of poly(acrylic acid) and poly(lipoic acid) with LA-NHS, establishing a dual physico-chemical anchoring mechanism that enables efficient tissue integration in aqueous environments. The hydrogel penetrates tissue microstructures within 5 s, withstands burst pressures >213 mmHg, exhibits <10 % swelling, ∼2784 % extensibility, and a low modulus of 41 kPa, thereby conforming to soft, irregular surfaces and reducing interfacial mismatch. Its temperature-triggered adhesion allows safe detachment and repositioning without apparent tissue damage, supporting repeated applications. In vivo and ex vivo tests confirm rapid hemostasis in mouse liver and tail injury models, effective sealing of porcine gastric, bladder, and intestinal defects, and stable electrocorticography and electrocardiography recordings. Moreover, the hydrogel demonstrates high cytocompatibility (>90 %), <5 % hemolysis, reactive oxygen species scavenging, and ∼90 % antibacterial efficiency. By integrating rapid wet adhesion, mechanical compliance, electrical functionality, and bioprotective features, this hydrogel provides a versatile platform for next-generation bioelectronic interfaces and soft therapeutic devices.
    Keywords:  Hemostasis; Hydrogel; Implantable bioelectronics; Wet adhesion
    DOI:  https://doi.org/10.1016/j.mtbio.2025.102705
  35. J Cell Biol. 2026 Mar 02. pii: e202504025. [Epub ahead of print]225(3):
      Cell migration and cytoskeletal remodeling are energetically demanding processes. Reorganizing the cytoskeleton requires ATP to fuel the actomyosin complex, enabling cells to adhere to and migrate through a matrix. While it is known that energy is required for cell migration, the mechanism by which cell-extracellular matrix adhesion influences cell energetics is unclear. Here, we investigated the relationship between cell-extracellular matrix adhesion and cellular metabolic state with a focus on vinculin given its role in connecting the cytoskeleton to focal adhesions and extracellular space. Knocking out vinculin increases the metabolic activity in cells and results in fast, frequent Rho kinase activity-dependent changes in cell shape and protrusions. The cellular protrusion dynamics and bioenergetics are interrelated processes, as stimulating RhoA/Rho kinase activity increases dynamic blebbing protrusions and energy production, and inhibiting metabolism decreases the frequency of blebbing cell protrusions. This link between cell-extracellular matrix adhesion and bioenergetics provides a novel basis by which cellular metabolism and cell migration could be controlled.
    DOI:  https://doi.org/10.1083/jcb.202504025
  36. ACS Omega. 2026 Jan 13. 11(1): 1154-1163
      Zinc ions (Zn2+) play vital roles in living organisms, and Zn2+-deficient systems provide valuable platforms for studying zinc-dependent biological processes. Protein-functionalized materials offer advantages in constructing such systems by combining the physical removability of a solid-phase matrix with the high selectivity of zinc-binding proteins. Poly-(N-isopropylacrylamide) (PNIPAM) hydrogel serves as a promising matrix by enabling temperature-controlled reversible adsorption. The zinc-binding domain of the Zap1 protein (Zap1zf12) is well suited as the protein component owing to its Zn2+ specificity, dual binding sites, and PNIPAM-compatible structure. Here, we integrated Zap1zf12 into PNIPAM, generating a thermoresponsive hybrid hydrogel (PNIPAM-co-Zap1zf12) for selective Zn2+ removal. PNIPAM-co-Zap1zf12 was constructed through rational cross-linking sites design in Zap1zf12, optimized protein modification, and refined hydrogel synthesis. This material exhibited reversible adsorption in response to biocompatible temperature shifts (37 °C capture, 25 °C release), allowing regeneration without competitive chelators. It achieved a Zn2+ removal efficiency of 98.4 ± 7.3% (from 804.1 ± 41.9 nmol/L to 12.6 ± 5.8 nmol/L), and was successfully applied in various minimal culture media for selective Zn2+ depletion. Therefore, PNIPAM-co-Zap1zf12 extends the applicability of the hybrid hydrogels by integrating dual-site zinc-binding proteins and enabling selective Zn2+ adsorption. Moreover, it offers an effective approach for generating zinc-deficient conditions.
    DOI:  https://doi.org/10.1021/acsomega.5c08458
  37. Nat Commun. 2026 Jan 21.
      Plastic foams play a crucial role across various industries and building constructions, due to their lightweight structure, thermal insulation properties, and energy absorption capabilities. However, the escalating global demand for petrochemical-based foams is raising significant environmental concerns. Here, we report an all-cellulose molecular foam through an ethanol-induced cellulose molecular programmed assembly. This cellulose molecular foam features a honeycomb-like gradient porous structure, exhibits a high compressive modulus of 11.8 MPa, demonstrates a high thermal stability up to 264.1 °C, and maintains a low thermal conductivity of 0.047 W m-1 K-1. Additionally, it supports diverse shaping processes including casting, molding, and continuous manufacturing. Due to its molecular-level reversible design, all-cellulose foam is both recyclable and biodegradable, offering a potential substitute for conventional petrochemical foams in numerous building and industrial applications. Furthermore, a life cycle assessment reveals that all-cellulose foam significantly reduces carbon emissions, affirming its environmental benefits and positioning it as a promising, eco-friendly alternative.
    DOI:  https://doi.org/10.1038/s41467-026-68803-8
  38. Nature. 2026 Jan 19.
      The exponential growth of scientific literature presents an increasingly acute challenge across disciplines. Hundreds of thousands of new chemical reactions are reported annually, yet translating them into actionable experiments becomes an obstacle1,2. Recent applications of large language models (LLMs) have shown promise3,4,5,6, but systems that reliably work for diverse transformations across de novo compounds have remained elusive. Here we introduce MOSAIC (Multiple Optimized Specialists for AI-assisted Chemical Prediction), a computational framework that enables chemists to harness the collective knowledge of millions of reaction protocols. MOSAIC is built upon the Llama-3.1-8B-instruct architecture7, training 2,498 specialized chemical experts within Voronoi-clustered spaces. This approach delivers reproducible and executable experimental protocols with confidence metrics for complex syntheses. With an overall 71% success rate, experimental validation demonstrates the realizations of over 35 novel compounds, spanning pharmaceuticals, materials, agrochemicals, and cosmetics. Notably, MOSAIC also enables the discovery of new reaction methodologies that are absent from the expert's training, a cornerstone for advancing chemical synthesis. This scalable paradigm of partitioning vast domains into searchable expert regions enables a generalizable strategy for AI-assisted discovery wherever accelerating information growth outpaces efficient knowledge access and application.
    DOI:  https://doi.org/10.1038/s41586-026-10131-4