bims-enlima Biomed News
on Engineered living materials
Issue of 2026–03–15
34 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool



  1. Adv Compos Hybrid Mater. 2026 ;9(2): 126
      Many biological materials, such as bone, are organic-inorganic composites, made from a polymeric matrix that supports biomineralization under mild conditions. These materials are usually composed of a small set of abundant components like polysaccharides, proteins, and minerals, and exhibit a remarkable combination of density normalized stiffness, toughness, and functionality. Producing bio-inspired synthetic porous composites with a similar combination of properties through energy-efficient processes still presents an unmet challenge. Some aspects of this challenge can be addressed using living bacteria that induce biomineralization. However, living bacteria limit biomedical applications, especially in vivo, require careful handling, and are costly. To address these limitations, we introduce enzyme-containing granular precursors exclusively made from naturally sourced polymers. These precursors can be cast or direct ink written into cm-sized structures before they are mineralized under benign conditions to reach CaCO3 contents up to 92 wt% with a porosity of 56 vol%. The resulting mineralized scaffolds exhibit a compressive strength up to 4 MPa (specific: 5.2 MPa·cm3·g- 1) and a compressive modulus of 56 MPa (specific: 72 MPa·cm3·g- 1). Although measured in the dry state, these values fall within the range reported for human trabecular bone with similar porosities (50-90% (Morgan et al., Annu Rev Biomed Eng 20:119-43, 91; Tanoto et al., Extreme Mech Lett 73:102265, 92). The resulting biomineral-organic composites show low cytotoxicity. These findings highlight the potential of this approach to 3D print biocompatible CaCO3-based composites under mild conditions. We envisage this formulation to open up new possibilities for tissue engineering.
    Supplementary Information: The online version contains supplementary material available at 10.1007/s42114-026-01662-5.
    Keywords:  3D Printing; Biomineralization; Calcium Carbonate Scaffolds; Granular Hydrogels
    DOI:  https://doi.org/10.1007/s42114-026-01662-5
  2. BMC Methods. 2026 ;3(1): 8
       Background: Engineered vasculature is essential for the biofabrication of functional tissue mimics. To fabricate engineered vasculature, three-dimensional (3D) bioprinting has emerged as a promising approach due to its ability to form perfusable structures with customized geometries. Sacrificial ink extrusion, where sacrificial inks are printed into a crosslinkable hydrogel precursor support bath, is a versatile bioprinting modality for fabricating interconnected perfusable networks. However, the fabrication of self-supporting structures with a vessel-like shell remains challenging using conventional sacrificial ink extrusion approaches. To enable the fabrication of self-supporting, perfusable networks, we developed a 3D bioprinting approach termed Gelation of Uniform Interfacial Diffusant in Embedded 3D Printing (GUIDE-3DP). This approach leverages the diffusion of crosslinking initiators from a printed sacrificial ink into a gel precursor support bath to generate branched, perfusable networks with precise control over channel inner and outer diameters.
    Methods: Here, we present an end-to-end protocol for fabricating self-supporting vascular-like networks using the GUIDE-3DP method. We describe methods for freeform print path design, support bath and sacrificial ink preparation, 3D printing of perfusable structures, and seeding of printed structures with endothelial cells. Through this protocol, perfusable structures with complex branching geometries can be designed, fabricated, and endothelialized.
    Discussion: To highlight the ability of GUIDE-3DP to fabricate self-supporting, perfusable networks with complex geometries, we demonstrate the fabrication of three representative structures: (1) an interconnected retinal vasculature network, (2) a hierarchical branched vascular network, and (3) a dual-material capillary-like network. We further demonstrate the endothelialization of printed structures with one or two cell types via single- or dual-material printing. Beyond vascular-like networks, this protocol is readily adaptable to design and fabricate mimics of other perfusable structures in the human body.
    Clinical trial number: Not applicable.
    Supplementary Information: The online version contains supplementary material available at 10.1186/s44330-026-00059-6.
    Keywords:  Biofabrication; Bioprinting; Perfusable structures; Vascular mimics
    DOI:  https://doi.org/10.1186/s44330-026-00059-6
  3. Adv Sci (Weinh). 2026 Mar 13. e24320
      The practical application of engineered living materials (ELMs) is currently hindered by some critical challenges, such as streamlining fabrication processes and achieving long-term stability. Here, a semi-interpenetrating ELM was developed relying on thermosensitive self-assembly of hydroxybutyl chitosan (HBC) and spontaneous covalent protein interactions. This semi-interpenetrating network provided superior mechanical properties over HBC hydrogels. Furthermore, this material can be adapted for diverse scenarios based on engineered bacteria encapsulated, and its applications in biotherapy treatment and environmental remediation were validated. Compared to planktonic bacteria or enzymes, this ELM presented enhanced tolerance to harsh environments, including high temperatures, extreme pH values, high salinity, and digestive fluids, resulting in improved therapeutic efficacy with excellent biosafety in ulcerative colitis treatment and long-term degradation of the pollutant paraoxon. In summary, our material offers advantages including simple preparation, excellent mechanical properties, high stability, customizability, and biosafety, laying a foundation for the application of ELMs.
    Keywords:  SpyCatcher/SpyTag; bioremediation; engineered living materials; hydroxybutyl chitosan; ulcerative colitis treatment
    DOI:  https://doi.org/10.1002/advs.202524320
  4. Adv Sci (Weinh). 2026 Mar 08. e22500
      Soft robotic actuators enable lightweight and compliant motion, but their fabrication typically relies on silicone molding, 3D printing, or textile lamination-processes that require expensive materials, long production times, or complex fabrication protocols. We introduce a rapid manufacturing strategy using low-cost thermoplastic pouches that combines vacuum processing and laser cutting. By removing air gaps between layers, this method enables precise sealing and cutting, allowing complex inflatable geometries to be fabricated in under 10 min at a material cost below $0.10 per actuator. Compared to silicone elastomers, the reduced compliance of thermoplastics minimizes deformation losses and channels more energy into effective stiffening. The reliability of the method is verified through material testing and repeatable pressurization experiments, including response times of approximately 0.4s at operating pressure of 50-70kPa. We further use finite element modeling to predict bending behavior, derive geometric rules for programmable deformation, and construct a surrogate model for inverse design of homogeneous and heterogeneous bending actuators. Using this framework, target shapes such as alphabetic letters and spirals are achieved, and functional soft robotic prototypes, including crawlers, swimmers, and soft grippers, are demonstrated. These results position vacuum-laser processing as an accessible and scalable platform for rapid fabrication of adaptive soft robotic systems.
    Keywords:  bending actuators; laser cutting; plastic pouches; soft robotics; vacuum
    DOI:  https://doi.org/10.1002/advs.202522500
  5. Nat Commun. 2026 Mar 10.
      Gel-based soft materials are attractive for flexible electronics and biointerfaces but are often limited by insufficient mechanical robustness and constrained functional integration. Here, we introduce a geometry-programmed self-wrinkling strategy that enables the spontaneous formation of aligned wrinkle architectures during thermal-evaporative gelation of poly(vinyl alcohol)-based organo-hydrogels. Without external patterning or post-processing, this process produces materials with enhanced mechanical robustness and pronounced anisotropy in deformation, fracture, and ionic transport. By leveraging these intrinsic properties, we demonstrate multiple sensing and actuation functions, including directional strain sensing, multidirectional sliding detection, deformation-driven rolling sensors, and temperature-triggered alarms. These results highlight geometry-programmed self-wrinkling as a scalable route to integrate structural reinforcement and directional functionality into soft materials through a physically driven formation process.
    DOI:  https://doi.org/10.1038/s41467-026-70433-z
  6. Adv Mater. 2026 Mar 14. e19972
      This study presents a facile and versatile method to synthesize tailored, compartmentalized, polysaccharide-based microgels, with ultra-low crosslinked shells for the development of self-setting colloidal biomaterial inks. Compartmentalization is achieved by exploiting spatially controlled oxygen-inhibition of the crosslinking process in droplets obtained by droplet-based microfluidics, leading to physically distinct core and shell regions inside dextran microgels. The shell exhibits a markedly lower cross-linking density, resulting in reduced stiffness, tunable degradation, and higher macromolecular permeability than the core. The facile control of the core-to-shell ratio by varying the initiator concentration and oxygen availability represents a novel strategy to engineer microgel compartmentalization. This work establishes oxygen-controlled photopolymerization as a new design principle for structuring microgels in flow, offering precise spatial control over polymer network architecture without complex templating or multi-phase emulsions. Beyond dextran, this concept is broadly applicable to other acrylated and methacrylated hydrogel systems, opening new avenues for designing hierarchical soft materials. We demonstrate the applicability of these advanced microgels for the fabrication of millimeter-sized tissue constructs, via 3D printing by exploiting the fusion of ultra-low crosslinked shell compartments, thereby eliminating the need for additional chemical crosslinkers, initiators, or support baths to stabilize the final printed constructs.
    Keywords:  3D printing; bio‐based microgels; compartmentalized microgels; core–shell; dextran; microfluidics
    DOI:  https://doi.org/10.1002/adma.202519972
  7. ACS Appl Mater Interfaces. 2026 Mar 12.
      Accurate monitoring of the mechanical activity of muscle tissue is crucial for myocardial function assessment, human-machine interaction, and flexible electronics, yet it remains challenging to achieve mechanically compliant sensing with stable mechanical coupling to soft biological tissues. Here, we report a mechanically tunable and photocurable conductive hydrogel based on polyacrylamide/polyethylene glycol diacrylate/lithium phenyl-2,4,6-trimethylbenzoylphosphinate/silver nanowire (PAAm/PEGDA/LAP/AgNWs) composites. By rationally modulating the double-network structure and the AgNWs content, the material achieves a balanced integration of a Young's modulus (162 ± 9 kPa) matching that of muscle tissue, ultrahigh stretchability (>1200%), and stable electrical sensing, enabling effective force sensing under physiological deformation. Moreover, the photocurable nature of the hydrogel allows high-resolution fabrication via digital light processing (DLP) 3D printing, enabling in situ monolithic integration of sensing and encapsulation layers, which overcomes the manufacturability limitations of many previously reported conductive hydrogels. Two proof-of-concept devices were developed to demonstrate cross-type muscle sensing and cross-scale force detection, including long-term monitoring of contractile forces (15-30 μN) from in vitro cultured myocardial tissues using a microcantilever structure, and wearable facial muscle tension sensing in the range of 1-5 mN. This work demonstrates a scalable conductive hydrogel sensing platform that combines tissue-matched mechanics, advanced manufacturability, and broad biomechanical sensing capability, highlighting its potential for biomechanical research and human-machine interaction applications.
    Keywords:  DLP 3D printing; conductive hydrogel; facial expression recognition; flexible bioelectronics; myocardial force sensing; tissue-matched modulus
    DOI:  https://doi.org/10.1021/acsami.5c23060
  8. Nat Commun. 2026 Mar 07.
      Natural organisms often couple reversible shape reconfiguration and autonomous motion to adapt and respond to dynamic environments. However, synthetic soft materials rarely achieve both behaviors within a single platform due to fundamental trade-offs in structural anisotropy, solvent compatibility, and actuation reversibility. Here, we report a bicontinuous, uniaxially aligned liquid crystal elastomer-hydrogel composite (BALCEH) that allows both multi-stimuli shape reconfiguration and solvent-driven self-propulsion. The material integrates hydrophilic and hydrophobic networks, resulting in asymmetric solvent uptake and directional swelling across both aqueous and non-aqueous environments. This architecture supports reversible actuation under humidity, temperature, and organic solvents, governed by the interplay between anisotropic hydrogel expansion and LCE elasticity. BALCEH also achieves sustained Marangoni propulsion, with trajectory programmability through fuel composition and geometry. Additionally, spatial rearrangement of the dual networks imparts adaptive wettability, switching between superoleophobic and superhydrophobic states. By coupling deformation and motion in a single system, BALCEH offers a versatile platform for untethered soft robotics and intelligent, reconfigurable materials.
    DOI:  https://doi.org/10.1038/s41467-026-69432-x
  9. Microsyst Nanoeng. 2026 Mar 10. pii: 85. [Epub ahead of print]12(1):
      Spatial organization is fundamental to tissue physiology, as it governs how cells migrate, grow, differentiate, and interact within their native environments. In living tissues, cells are positioned within finely tuned microarchitectures defined by chemical gradients, boundaries, and mechanical cues - features that are essential for proper tissue function and homeostasis. Microphysiological systems (MPSs) aim to replicate key aspects of human tissue in vitro, yet without appropriate spatial control, they often fail to reproduce certain aspects of tissue-level organization and function. In this review, we categorize spatial patterning strategies into two main approaches: direct methods, which involve the physical placement of cells or compartments using techniques such as 3D bioprinting, microfluidic compartmentalization, and physical trapping; and indirect methods, which rely on cellular responses to engineered environmental cues, including extracellular matrix (ECM) composition, mechanical gradients, and soluble factor distributions. While direct methods offer precision and reproducibility, indirect strategies more closely reflect natural developmental and self-organizing processes. We discuss how these approaches are applied across diverse biological structures, from cellular interfaces and barrier tissues to dynamic host-microbe systems. Enhancing spatial fidelity in MPSs is essential for recapitulating tissue complexity, and will be key to advancing disease modeling, developmental biology, and drug screening applications.
    DOI:  https://doi.org/10.1038/s41378-025-01141-9
  10. Tissue Eng Part C Methods. 2026 Mar 11. 19373384261427525
      Biological research groups may face a high barrier to entry when constructing custom 3D cell culture devices to investigate multi-tissue interactions in vitro. Standard fabrication methods such as lithography, etching, or molding are expensive and require specialized equipment and expertise. To address this, we developed an accessible approach for producing polyethylene glycol (PEG)-based cell culture devices using stereolithography 3D printing with a polydimethylsiloxane intermediate mold. Both the intermediate molding steps and the sterilized final device show low cytotoxicity, and the final device swells to predictable dimensions and retains its shape for at least 10 days. We used this approach to develop a human pluripotent stem cell-derived neural spheroid outgrowth model that supports directed neurite extension over 14 days. Together, this method provides a highly customizable, affordable platform for rapid fabrication of PEG-based microphysiological systems for diverse tissue engineering applications.
    Keywords:  3D printing; casting; human pluripotent stem cells; hydrogel device fabrication; neurite extension
    DOI:  https://doi.org/10.1177/19373384261427525
  11. Mater Horiz. 2026 Mar 11.
      Hydrogels are emerging as a transformative class of materials for bridging the interface between electronics and biological systems. Their softness, high water content, and tunable ionic/electronic conductivity enable conformal, low-impedance, and biocompatible contact with tissues. This review surveys recent advances in hydrogel-integrated multimodal bioelectronic systems, with an emphasis on the stable signal acquisition, coupled sensing-actuation functions, and stimulus-responsive behaviors that support adaptive interfaces. We compare hydrogels with conventional biointerface materials and highlight key advantages such as stretchability, breathability, ionic conduction, and tissue compatibility. We then discuss representative system-level demonstrations in three domains: closed-loop brain monitoring with ultrasound neuromodulation, gastrointestinal (GI) retention and leakage detection, and cardiac monitoring, pacing, and repair. Finally, we summarize the remaining challenges including long-term stability, scalable manufacturing, and integration with microelectronics and outline opportunities for clinically deployable, autonomous, and personalized hydrogel-based bioelectronic systems.
    DOI:  https://doi.org/10.1039/d5mh01852h
  12. Nat Commun. 2026 Mar 11.
      The preparation of sustainable biophosphors exhibiting room-temperature phosphorescence (RTP) for additive manufacturing presents both significant scientific promise and substantial synthetic challenges. To address this technological gap, with this research, we engineer CX-Wood using rational molecular design by grafting carboxyl-functional groups onto native lignocellulosic matrices, enabling direct ink writing (DIW) using our RTP wood composite. Structural characterization reveals that carboxylation induces (i) partial crystal lattice distortion in the cellulose microfibrils and (ii) enhances the hydrogen-bonding network density, collectively establishing a rigid supramolecular architecture conducive to triplet-state stabilization. This structural modification improves room-temperature phosphorescent performance. Crucially, the introduced carboxyl moieties simultaneously optimize the rheological behavior to yield an aqueous-based phosphorescent ink with exceptional print fidelity. Leveraging this dual functionality, we prepare architecturally complex 3D phosphorescent constructs exhibiting afterglow emission. This biomass-derived platform establishes a green model for manufacturing smart luminescent materials with tailored properties.
    DOI:  https://doi.org/10.1038/s41467-026-70488-y
  13. Nat Commun. 2026 Mar 13. pii: 2446. [Epub ahead of print]17(1):
      The era of protein design has enabled the creation of hybrid protein-inorganic interfaces, leading to both surface-directed self-assembly of de novo protein architectures and protein-directed formation of inorganic materials. However, the resulting patterns of protein assembly are often unexpected, implying that essential interactions are not accounted for in current design platforms. Here, we use high-speed atomic force microscopy (AFM) analyzed through machine learning to follow the assembly of protein nanorods in aqueous electrolytes on two types of mica exhibiting disparate symmetry elements, which are imprinted on the overlying hydration structure. Using Monte Carlo simulations, we reproduce the observed phases and show that an observed smectic phase, previously thought to be unstable for non-interacting rods in two dimensions, emerges when crystal symmetry introduces a directional bias. The findings demonstrate the importance of incorporating solvent forces as modulated by the hydration structure inherent to interfacial systems when designing protein assemblies at liquid-crystal interfaces. Coupling physics-based simulations that can account for these factors to de novo protein design algorithms can lead to improved design platforms for bio-inspired, hybrid materials.
    DOI:  https://doi.org/10.1038/s41467-026-69170-0
  14. Langmuir. 2026 Mar 07.
      Nonspherical hydrogel particles offer unique anisotropic properties and functionalities that are inaccessible to conventional spherical hydrogels. However, achieving precise shape control without complex fabrication equipment or organic solvents remains a major challenge. Herein, we present a solvent-free and template-guided strategy for synthesizing nonspherical hydrogel particles using polyhedral liquid marbles (LMs) as reaction vessels. The polyhedral LMs were constructed by assembling millimeter-sized hydrophobic solid polymer plates around droplets of poly(ethylene glycol)-based vinyl monomers containing a photoinitiator. Upon UV irradiation, free radical polymerization proceeded efficiently inside the confined droplets, yielding gel particles whose shapes directly reflected the LM geometries, including cubic, tetrahedral, octahedral, dodecahedral, and icosahedral forms. Furthermore, the degree of swelling in water was finely tunable by varying the cross-linking density of the gel network, while the incorporation and removal of NaCl particles enabled the formation of a multihollow internal structure. As a proof of concept, cubic hydrogel particles exhibited a swelling-induced mechanical function, where water absorption was converted into macroscopic mechanical work capable of lifting an external object, demonstrating the mechanical advantage of shape-defined hydrogels. The LM-based method allows for geometrically defined, solvent-free synthesis of anisotropic hydrogel particles using simple procedures without specialized apparatus or organic solvents. The proposed approach provides a versatile platform for producing shape-programmable soft materials that may find applications in soft robotics, stimuli-responsive systems, and 3D hydrogel assemblies.
    DOI:  https://doi.org/10.1021/acs.langmuir.5c06259
  15. Nat Mater. 2026 Mar 11.
      Hydrogels are prevalent materials with applications ranging from drug delivery systems, contact lenses and tissue engineering scaffolds. However, they require considerable perturbation to observe their nanoscale, solution-phase structures necessary for predicting bulk properties. Although studies suggest that methylcellulose, a quintessential hydrogel material, can be described by a semiflexible biopolymer network model, there remain demonstrable inconsistencies in the predicted concentration dependence of rheological properties and in the observation of higher-order features. Here we image solvated hydrogels with high spatiotemporal resolution via liquid-phase transmission electron microscopy to avoid desolvation and shear artefacts. Corroborated by scattering and scanning electron microscopy, we observe that methylcellulose hydrogels form a network with high persistence length and micrometre-scale fibril bundles arranged in hierarchical assemblies, providing a more accurate prediction of bulk rheology. In addition, network structures are observed for hydroxypropyl methylcellulose and hydroxypropyl cellulose. These observations across multiple-length scales lead to a clearer understanding of how nanoscale structure impacts microscale structure and macroscopic behaviour, aiding the development of more accurate structure-property relationships for hydrogel materials.
    DOI:  https://doi.org/10.1038/s41563-026-02491-z
  16. Proc Natl Acad Sci U S A. 2026 Mar 17. 123(11): e2521560123
      In vitro biological neural networks (BNNs) provide well-defined model systems for constructively investigating how living cells interact with their environments to shape high-dimensional dynamics that can be used to generate coherent temporal outputs, such as those required for motor control. Here, we develop a real-time closed-loop BNN system that is capable of generating periodic and chaotic temporal signals by integrating cultured cortical neurons with microfluidic devices and high-density microelectrode arrays. We show that training a simple linear decoder with fixed feedback weights enables the system to learn and autonomously generate diverse temporal patterns. When feedback is switched on, the irregular activity in the BNNs is transformed into low-dimensional, structured dynamics, producing coherent trajectories that are characterized by stable transitions between different neural states. BNNs trained on various target frequencies-ranging from 4 to 30 s-can be trained to sustain oscillations at distinct frequencies, demonstrating their adaptability. Importantly, top-down control of the self-organized network formation with microfluidic devices is the key to suppressing excessive synchronization and increasing dynamic complexity in BNNs, facilitating the training process and the generation of robust outputs. This work offers a biologically inspired platform for understanding the physical basis of cortical computations and for advancing energy-efficient neuromorphic computing paradigms.
    Keywords:  biocomputing; cell engineering; in vitro neural network; microelectrode array; reservoir computing
    DOI:  https://doi.org/10.1073/pnas.2521560123
  17. Nat Mater. 2026 Mar 10.
      Complex and robust tissue self-organization requires defined initial conditions and dynamic boundaries-neighbouring tissues and extracellular matrix that actively evolve to guide morphogenesis. A major challenge in tissue engineering is identifying material properties that are compatible with controlling initial culture conditions while mimicking dynamic tissue boundaries. Here we describe a highly tunable granular biomaterial, MAGIC matrix, that supports both long-term bioprinting and gold-standard tissue self-organization. We identify that significant stress relaxation at the long timescales and large deformation magnitudes relevant to self-organization is required for optimal morphogenesis. We apply optimized MAGIC matrices toward precise extrusion bioprinting of saturated cell suspensions directly into three-dimensional culture. Carefully controlling initial conditions for tissue growth yields dramatic increases in organoid reproducibility and complexity across multiple tissue types, enabling high-throughput generation of organoid arrays and perfusable three-dimensional microphysiological systems. Our results identify key biomaterial parameters for optimal organoid morphogenesis and lay the foundation for fabricating more complex and reproducible self-organized tissues.
    DOI:  https://doi.org/10.1038/s41563-026-02519-4
  18. Sci Adv. 2026 Mar 13. 12(11): eaec0783
      Living microorganisms have evolved dedicated sensory machinery to detect environmental perturbations, processing these signals through biochemical networks to guide behavior. Replicating such capabilities in synthetic active matter remains a fundamental challenge. Here, we demonstrate that synthetic active particles can adapt to hidden hydrodynamic perturbations through physical embodiment alone, without explicit sensing mechanisms. Using reinforcement learning to control self-thermophoretic particles, we show that they learn navigation strategies to counteract unobserved flow fields by exploiting information encoded in their physical dynamics. Particles successfully navigate perturbations that are not included in their state inputs, revealing that embodied dynamics can serve as an implicit sensing mechanism. This discovery establishes physical embodiment as a computational resource for information processing in active matter, with implications for autonomous microrobotic systems and bioinspired computation.
    DOI:  https://doi.org/10.1126/sciadv.aec0783
  19. Nat Chem. 2026 Mar 13.
      Expanding the genetic code has revolutionized our ability to study and manipulate biological systems through site-specific incorporation of noncanonical amino acids (ncAAs). However, current methods are primarily limited to single-type ncAA incorporation in mammalian cells owing to translation inefficiency. Here we introduce a multi-type rare codon recoding strategy that addresses this limitation. By systematically evaluating and repurposing rare codons, alongside engineering mutually orthogonal aminoacyl-tRNA synthetase/tRNA pairs, we achieve the expression of proteins containing two or three distinct ncAAs at site-specific positions with recoding rates of up to 90% at wild-type protein expression levels in mammalian cells. This approach facilitates a broad range of applications, including dual bioorthogonal labelling and sequential protein activation. We further demonstrate the utility of this strategy by incorporating up to five distinct ncAAs into a single protein, revealing a redefinable nature of the genetic code and opening unprecedented avenues for future applications in biomedicine and synthetic biology.
    DOI:  https://doi.org/10.1038/s41557-026-02084-y
  20. Small. 2026 Mar 12. e13952
      Tissue engineering and regenerative medicine applications require the integration of multifunctional materials, offering tissue-specific mechanical cues and geometric guidance to support cell differentiation. In this context, supramolecular gel noodles formed by ionic cross-linking of pre-assembled micellar networks offer unique opportunities for creating anisotropic soft materials. However, controlling fibrillar alignment over extended lengths remains a challenge. Herein, a shear-induced method to fabricate 1D gel noodles with enhanced macroscopic alignment using dipeptide-based gelators is reported. By implementing a two-stage extrusion protocol, we generate a thin tail segment with a distinct flow history that exhibits higher retained alignment than the pump-driven segment. Polarized optical microscopy and small-angle neutron scattering confirm superior fibrillar orientation in the thin segment, and mechanical testing reveals up to ∼400-fold increase in nominal stress at failure. The method is effective across multiple gelators, demonstrating its broad applicability for tuning macroscopic alignment in gel noodles. Preliminary C2C12 culture on the thin segment demonstrates improved cell adhesion, elongation, and increased MyoD expression compared to the thick segment. These findings provide a scalable route to introduce anisotropy in supramolecular gel noodles through processing history, and we present cell culture data as proof of compatibility and contact guidance relevant to aligned tissue-mimetic scaffolds.
    Keywords:  2D SANS; anisotropic alignment; gel noodles; muscle cell alignment; tensile strength
    DOI:  https://doi.org/10.1002/smll.202513952
  21. Nat Rev Mater. 2025 Mar;10(3): 191-210
      The engineering of therapeutic living cells through genetic programming is poised to transform medicine. Diverse living medicines, including mammalian cells, fungi, bacteria, and viruses, are under development. However, for these medicines to progress in the clinic, new strategies are needed to successfully deliver them into the body. Unlike conventional small molecule and protein-based biologics, living medicines present distinct challenges for delivery, including the need to maintain viability, control replication, manage metabolism, and mitigate immunogenicity. This Review focuses on delivery strategies for living medicines, identifying key challenges and efforts to overcome them. We survey clinically adopted biomaterial strategies for delivering conventional drugs and explore how these approaches can be tailored for living medicines. Finally, we discuss remaining challenges and future directions towards next-generation living medicine delivery.
    DOI:  https://doi.org/10.1038/s41578-024-00766-y
  22. ACS Appl Mater Interfaces. 2026 Mar 10.
      Defective clearance of phagocytosed DNA contributes to inflammation, yet the molecular factors governing DNA degradation within phagosomes remain unclear. Here, we present a materials-based platform using engineered microparticles to dissect how DNA is processed inside macrophage phagosomes. Using microcontact printing, we fabricated two classes of DNA-containing microparticles: thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) microspheres encapsulating intercalator-labeled DNA and chromatin-mimetic particles composed of multilayered histone-DNA assemblies with tunable cross-linking. These structures provide precise control over DNA accessibility, protein association, and degradability. Upon phagocytosis by macrophages, DNA embedded within hydrated PNIPAM networks remained intact, indicating restricted diffusion of phagosomal enzymes. In contrast, DNA electrostatically complexed with histone was efficiently degraded but only after proteolytic removal of the histone barrier. When histone was chemically cross-linked, DNA degradation was inhibited. These results demonstrate that proteolysis of DNA-bound proteins is a critical prerequisite for DNase II-mediated cleavage in macrophage phagosomes. This modular microparticle platform offers a reductionist approach for probing the biochemical and physical determinants of DNA degradation within phagocytes and enables a systematic investigation of how protein-DNA interactions, cross-linking, or pathological stabilization of chromatin-like structures influences intracellular DNA persistence and inflammatory signaling.
    Keywords:  DNA; chromatin; degradation; macrophage; microparticle; phagocytosis
    DOI:  https://doi.org/10.1021/acsami.5c25569
  23. Cell Biomater. 2025 May 27. pii: 100052. [Epub ahead of print]1(4):
      Fibroblast activation drives fibrotic disease; however, the complex interplay of how tissue mechanics and macrophage signaling combine to influence fibroblast activation remains unclear. Using hyaluronic acid hydrogels to mimic lung stiffness and viscoelasticity, we investigated macrophage influence on fibroblast activation. Fibroblasts cultured on stiff (50 kPa) hydrogels mimicking fibrotic tissue exhibit increased activation, as measured by cell spreading and type I collagen and cadherin-11 expression, compared to fibroblasts cultured on soft (1 kPa) viscoelastic hydrogels mimicking normal lung. Macrophage-conditioned media did not alter these trends, however co-culture with M2 macrophages increased fibroblast activation independent of direct macrophage contact, even on soft viscoelastic hydrogels. Blocking interleukin 6 (IL6) signaling mitigated this pro-fibrotic effect but did not affect fibroblast-only cultures. These findings demonstrate that M2 macrophages override hydrogel viscoelasticity to promote fibroblast activation independent of direct contact in an IL6-dependent manner and highlight the utility of hydrogels in deconstructing complex tissue microenvironments.
    Keywords:  fibrosis; hydrogels; macrophages; mechanotransduction
    DOI:  https://doi.org/10.1016/j.celbio.2025.100052
  24. Soft Matter. 2026 Mar 11.
      Mechanical oscillations play fundamental roles in cellular processes such as motility, signalling, and structural regulation; however, the mechanisms by which artificial cytoskeletal networks can be engineered to reproduce such autonomous oscillatory behaviours remain poorly understood. In this study, we demonstrate that a chemically polyethylene glycol-crosslinked filamentous actin hydrogel exhibits autonomous, long-lasting, and synchronised mechanical oscillations during self-organised polymerisation. These oscillations arise from chemo-mechanical responses coupled with the treadmilling polymerisation-depolymerisation equilibrium of filamentous actin. We propose that the rigid and highly hierarchical structure of the chemically crosslinked network plays an important role in the emergence of such autonomous mechanical oscillations. Our results reveal how hierarchical crosslinking and chemo-mechanical coupling drive sustained oscillations in active polymer networks, providing new insight into the fundamental mechanisms underlying autonomous dynamics in soft materials.
    DOI:  https://doi.org/10.1039/d5sm01205h
  25. ACS Biomater Sci Eng. 2026 Mar 11.
      Adipocyte spheroids offer a promising three-dimensional (3D) cell culture model for obesity research, as they reproduce the structure and cell-cell interaction of adipose tissue more accurately compared to two-dimensional (2D) cultures. However, the mass production of uniform, small adipocyte spheroids remains challenging, limiting their use in large-scale analyses, such as drug screening. Here, we develop a method that combines simple microfluidics with templated emulsification to enable the large-scale production of small, uniform adipocyte spheroids. By encapsulating preadipocytes in hollow agarose microcapsules and incubating them for 2 days, we reproducibly generated more than 100,000 uniform spheroids with diameters of approximately 60 μm. These preadipocytes were subsequently differentiated into adipocyte spheroids through an 8-day induction period. This platform facilitates large-scale 3D analysis for obesity research and can be adapted to produce various other spheroid and organoid models, broadening its utility in biomedical research.
    Keywords:  3D cell culture; adipocyte spheroids; hydrogel capsule; microfluidics
    DOI:  https://doi.org/10.1021/acsbiomaterials.6c00142
  26. ACS Nano. 2026 Mar 11.
      To monitor neuronal activity with high fidelity, in vitro models must recapitulate not only the cellular composition but also the three-dimensional (3D) microenvironment of the brain. Here, we present an electronic brain biochip that integrates animal-derived decellularized extracellular matrix (dECM) hydrogels with flexible, multichannel electrodes to build a multilayer 3D neural network in which each layer can be independently monitored. Brain dECM hydrogels provide tissue-like biochemical and structural cues that accelerate neurite outgrowth and neural connectivity between layers, enabling the formation of functionally active 3D networks within 3 weeks. We use a low-cost, readily available dECM source from porcine brain tissue, upcycling biological waste into high-value neural scaffolds without compromising biocompatibility. The dECM hydrogels are compatible with both rat primary neurons and hiPSC-derived neurons. Flexible electrode interfaces support real-time, multichannel electrophysiological recording and controlled chemical stimulation. The combination of dECM scaffolding and flexible electrode interfaces supports signal capture throughout the 3D network volume. Functional assays under chemical stimulation reveal bursting and synchronized activity in which all layers participate. By coupling a dECM-based, 3D neural architecture to flexible, multichannel electronics, this work establishes a scalable "electronic organoid" platform for the study of neuronal dynamics and neuropharmacology. Collectively, these advances represent an important step toward artificial brain models that bridge the gap between engineered neural tissues and functional neurobiology.
    Keywords:  biochip; brain neurons; electrophysiological monitoring; extracellular matrix hydrogel; flexible bioelectronics; in vitro neural networks
    DOI:  https://doi.org/10.1021/acsnano.5c21848
  27. Nature. 2026 Mar 10.
      
    Keywords:  Cell biology; Computational biology and bioinformatics
    DOI:  https://doi.org/10.1038/d41586-026-00786-4
  28. Nano Lett. 2026 Mar 12.
      The mechanical properties of materials, e.g., elastic modulus and hardness, are important for many engineering applications. Here, we introduce a hierarchically ordered structure (HOS) polymer system that exhibits exceptionally large, reversible changes in mechanical behavior upon electrochemical lithiation and delithiation. Full lithiation of the HOS polymer induces a substantial mechanical transition from polymer-like to metal-like attributes, yielding a 10-fold increase in elastic modulus and a 3-fold increase in hardness, with values comparable to those of aluminum. Upon removal of Li+ ions, the elastic modulus and hardness return to nearly pristine polymer levels, and this transformation remains highly repeatable over many electrochemical cycles. Reversible transitions between polymer-like and metal-like mechanical behaviors offer a new pathway for engineering materials for applications that require tunable mechanical properties, such as soft robotics and stimuli-responsive systems.
    Keywords:  Energy Storage; Mechanical Property; Polymer
    DOI:  https://doi.org/10.1021/acs.nanolett.5c05837
  29. Mater Horiz. 2026 Mar 10.
      Tissue adhesives provide a minimally invasive alternative to sutures and staples, but achieving strong and durable adhesion on wet and dynamically deforming tissues remains a major challenge. Water disrupts interfacial bonding, and repeated deformation accelerates delamination, limiting the performance of existing synthetic and natural polymer systems. Here, we introduce a fully natural tissue adhesive based on a hybrid composite of bacterial cellulose (BC) and carboxymethyl cellulose (CMC) that integrates mechanical robustness with chemical reactivity. A three-dimensional BC nanofiber network provides wet-resistant structural stability and preserves its layered architecture after chemical processing, while CMC chains functionalized with N-hydroxysuccinimide (NHS) ester and citric acid crosslinks enable rapid covalent bonding with tissue surfaces. This combination yields fast wet adhesion (∼10 s), high shear strength on skin and heart tissues (∼25 kPa), and exceptional fatigue resistance, maintaining interfacial integrity over more than 300 deformation cycles. The BC/CMC tissue adhesive also supports long-term cell viability, confirming its cytocompatibility. Furthermore, kirigami-inspired laser-cut designs enable conformal, strain-accommodating adhesion on highly compliant tissues such as the lungs. Together, this natural polymer hybrid strategy provides a versatile and biocompatible platform for reliable sealing and repair on wet, dynamically moving biological surfaces.
    DOI:  https://doi.org/10.1039/d5mh02244d
  30. Small Methods. 2026 Mar 09. e02336
      Vat photopolymerization is a high-resolution and high-throughput technology used in many biomedical applications. However, achieving geometric precision in printed devices with features spanning orders of magnitude in length scale is non-trivial. Here, a new characterization tool combining fast, high-resolution optical coherence tomography imaging with a high-powered digital light processing projector enables real time measurements of photopolymer curing. The direct, quantitative measurement of hydrogel working curves (the relationship between cure depth and light exposure) shows that the critical energy for gelation (Ec) exhibits extreme size dependence, demanding a rethinking of gray-scaling light intensity for achieving predictable voxel formation at high resolutions. This in situ method also enables measurement of size-dependent working curves and dead zone thicknesses using oxygen permeable window materials, which is impossible via ex situ methods. Generally, size sensitivity is amplified at low irradiance, high dye-loading, and in the presence of oxygen permeable windows. Despite the extreme size sensitivity, calibrating the light exposure to the size dependent Ec allows a 3x improvement in layer-growth uniformity compared to a naïve approach. Overall, these results highlight the challenges in high-resolution printing of hydrogels and provide a framework to measure and account for size dependence.
    Keywords:  bioprinting; cure depth; dead zone; hydrogels; optical coherence tomography; oxygen inhibition; vat photopolymerization; working curve
    DOI:  https://doi.org/10.1002/smtd.202502336
  31. Small Methods. 2026 Mar 11. e01650
      Data-driven flexible motion sensors have drawn more attention recently. Compared with the current mainstream motion capture technologies, like the depth-of-field camera with the environmental limitations, silicon-based inertial devices with a mismatch in mechanical properties between their rigid morphology and the soft biological tissues in a microenvironment, etc., wearable motion sensing technology presents obvious advantages. Here, we demonstrated theoretically and experimentally a conductive/dielectric heterogeneous-interface (CDHI) regulated motion sensor inspired by biological sensory systems. This kind of device can recognize both the motion directions and parameters of external objects with the corresponding potential signals, and the function can be further extended to 3D space through a programmed interface pattern and machine learning assistance. Results show that this potential amplitude can be up to ∼ 102 ± 5 mV, motion height up to 30 cm, and frequency as low as 0.2 Hz, motion space of 0°∼360° in horizontal direction and up-down in vertical direction, respectively. The practical feasibility was further explored for human finger interactive electronics successfully, including virtual interactive control, the Sokoban game, and human-hand/manipulator follow-up control, respectively. The proposed wearable 3D tactile communicator provides a new sensing experience that the present array sensors via a touch mode cannot offer.
    Keywords:  data‐driven; flexible 3D motion sensor; heterogeneous interface; human finger electronics; wearable communicator
    DOI:  https://doi.org/10.1002/smtd.202501650
  32. ACS Appl Mater Interfaces. 2026 Mar 09.
      Rational control over polymer surface chemistry is central to designing nanocarriers with predictable stability and intracellular trafficking. Here, we report a modular materials strategy based on poly(succinimide) to elucidate how balanced cationic functionality governs nanocarrier assembly, colloidal robustness, and nanobio interfacial interactions. Amphiphilic polymer derivatives were prepared by sequential conjugation of oleyl chains and cationic headgroups to generate three nanocarrier variants containing guanidinium and choline, choline only, or guanidinium only. Systematic physicochemical characterization revealed that cooperative guanidinium-choline conjugation is essential for colloidal stability in physiological media. In contrast, guanidinium-only nanocarriers suffer from rapid aggregation. Cellular uptake studies demonstrated that guanidinium-choline surface chemistry dictates rapid, energy-independent membrane translocation and preferential nuclear localization, while others internalized via clathrin-mediated endocytosis and remain lysosomally sequestered. Leveraging this accelerated nuclear drug delivery enables amplified cancer cell apoptosis. The direct translocation capability further facilitated rapid penetration into three-dimensional (3D) tumor spheroids, highlighting the importance of surface charge balance for transport across multicellular barriers. Collectively, this study establishes cationic conjugation balance as a parameter that links polymer design to nanocarrier stability, cellular entry mechanism, and intracellular targeting capabilities.
    Keywords:  apoptosis; biopolymer; camptothecin; drug delivery; endosomal escape; guanidinium; methotrexate; nanoparticle; nuclear delivery; topotecan
    DOI:  https://doi.org/10.1021/acsami.5c25970
  33. Dis Model Mech. 2026 Feb 01. pii: dmm052620. [Epub ahead of print]19(2):
      Protein-based pharmaceuticals, such as engineered antibodies, form a major drug class of steadily increasing market share. However, these biologic medicines are costly to manufacture, are subject to strict supply chain and storage constraints, and often require invasive administration routes. Engineered microbes that secrete bioactive products directly within the microbiome milieu may mitigate these challenges. Here, we describe a cell microfactory platform based on the probiotic yeast Saccharomyces boulardii for the production of nanobody biologics in the gastrointestinal (GI) tract. High-level secretion of nanobodies by S. boulardii was achieved by optimizing promoters, secretion signals and antibody formats. In mice, oral gavage of S. boulardii allowed efficient and transient colonization of the colonic compartment, and in situ production of a therapeutic nanobody directed against tumor necrosis factor (TNF). In a mouse model of chemical-induced colitis, GI-delivery of anti-murine TNF nanobody via live S. boulardii improved both survival and disease severity without causing overt perturbation of microbiome composition. These results position S. boulardii as a synthetic biotic platform for the in situ production and delivery of protein-based therapeutics to the GI tract.
    Keywords:   Saccharomyces boulardii ; Inflammatory bowel disease; Synthetic biotic; TNF; VHH nanobody
    DOI:  https://doi.org/10.1242/dmm.052620