bims-enlima Biomed News
on Engineered living materials
Issue of 2025–11–16
thirty-six papers selected by
Rahul Kumar, Tallinna Tehnikaülikool



  1. Nat Commun. 2025 Nov 12. 16(1): 9931
      Cephalopods exhibit versatile control over their optical appearance, texture, and shape for adaptive camouflage and signaling. Achieving such multi-feature dynamic control in synthetic materials remains a significant challenge. Here, we introduce a halftone-encoded 4D printing method that enables simultaneous and programmable control over optical appearance, mechanical properties, surface texture, and shape transformation within a single smart hydrogel film in response to various external stimuli (e.g., temperature, solvents, and mechanical stress)-a capability beyond existing synthetic materials. By encoding halftone binary patterns composed of highly crosslinked ("1") and lightly crosslinked ("0") domains, we spatially regulate localized polymer-solvent interactions and microstructural heterogeneities. The interplay, arrangement, and integration of these binary domains collectively dictate macroscale multifunctionality within a single material system. This binary encoding approach offers a simple yet powerful platform for designing multifunctional synthetic materials with complex, reconfigurable behaviors, unlocking opportunities in soft robotics, adaptive surface engineering, and secure information storage.
    DOI:  https://doi.org/10.1038/s41467-025-65378-8
  2. FEMS Microbiol Rev. 2025 Nov 06. pii: fuaf055. [Epub ahead of print]
      In the innovative field of Engineered Living Materials (ELMs) microbiology and material sciences meet. These materials incorporate living organisms, such as bacteria, fungi, plants, or algae, to enable unique functions like self-assembly, actuation, and dynamic interaction. By utilizing (micro)biological systems in material design, ELMs promise to transform industries including healthcare, construction, and agriculture. In the early phase of ELM technology development, researchers implemented a single living strain in an already established user material. However, the complexity and potential of these materials is limited by the abilities of this single strain. Even though synthetic biology brings the opportunity to add a range of non-native bioactivities to these cells and thus the material, the increasing metabolic burden upon implementation of multiple non-native pathways limits the capacity of a single strain. Furthermore, higher organisms and non-standard hosts are often desired in material settings for their native physical or metabolic advantages. However these are not always straightforward to further engineer. Thus, the use of multiple, specialised strains broadens the functionalities and thus the applicability of ELMs. Multi-strain ELMs are a brand-new technology, with many promising applications.
    Keywords:  bio-ELM; division of labour; engineered living materials; microbial consortia; sustainable materials; synthetic biology
    DOI:  https://doi.org/10.1093/femsre/fuaf055
  3. Acta Biomater. 2025 Nov 11. pii: S1742-7061(25)00836-0. [Epub ahead of print]
      Natural tissue comprises fibrous proteins with complex fiber alignment patterns. Here, we develop a reproducible method to fabricate biomimetic scaffolds with patterned fiber alignment along two independent orientations. While extrusion-based approaches are commonly used to align fibrous polymers in a single orientation parallel to the direction of flow, we hypothesized that extrusion-based 3D printing could be utilized to achieve more complex patterns of fiber alignment. Specifically, we show that control of lateral spreading of a printed filament can induce fiber alignment that is either parallel or perpendicular to the flow direction. Theoretical prediction of the printing parameters that control fiber orientation was experimentally validated using a collagen biomaterial ink. The velocity ratio of the printhead movement relative to the ink extrusion rate was found to dictate collagen fiber alignment, allowing for the informed fabrication of collagen scaffolds with prescribed patterns of fiber alignment. For example, controlled variation of the ink extrusion rate during a single print resulted in scaffolds with specified regions of both parallel and perpendicular collagen fiber alignment. Human corneal mesenchymal stromal cells seeded onto the printed scaffolds adopted a spread morphology that aligned with the underlying collagen fiber patterns. This technique worked well for filaments either printed onto a printbed in air or extruded within a support bath using embedded 3D printing, enabling the fabrication of 3D structures with aligned collagen fibers. Taken together, this work demonstrates a theoretical and experimental framework to achieve the reproducible fabrication of 3D printed structures with controlled collagen fiber patterns that guide cellular alignment. Statement of Significance Natural tissues contain collagen fibers aligned in multiple directions, which are essential for guiding cell behavior; however, most existing fabrication methods can achieve only unidirectional fiber alignment. Here, we introduce an extrusion-based 3D printing strategy that enables precise control over collagen fiber orientation in both parallel and perpendicular directions. This allows multidirectional collagen fiber alignment patterned spatially within a single construct, thereby guiding corneal mesenchymal stromal cells to align multidirectionally. This approach works when printing in air or with embedded printing in a support bath. Thus, this strategy can enable the fabrication of complex 3D scaffolds that mimic the anisotropic architecture of native tissues.
    Keywords:  Cell alignment; Collagen inks; Extrusion-based 3D printing; Fiber orientation
    DOI:  https://doi.org/10.1016/j.actbio.2025.11.013
  4. Nat Chem. 2025 Nov 14.
      Customizing the toughness of polymer networks independently of their chemical composition and topology remains an unsolved challenge. Traditionally, polymer network toughening is achieved by using specialized monomers or solvents or adding secondary networks/fillers that substantially alter the composition and may limit applications. Here we report a class of force-responsive molecules-tetrafunctional cyclobutanes (TCBs)-that enable the synthesis of single-network end-linked gels with substantially decreased or increased toughness, including unusually high toughness for dilute end-linked gels, with no other changes to network composition. This behaviour arises from stress-selective force-coupled TCB reactivity when stress is imparted from multiple directions simultaneously, which traditional bifunctional mechanophores cannot access. This molecular-scale mechanoreactivity translates to bulk toughness through a topological descriptor, network strand continuity, that describes the effect of TCB reactivity on the consequent local network topology. TCB mechanophores and the corresponding concepts of stress-selective force-coupled reactivity and strand continuity offer design principles for tuning the toughness of simple yet commonly used single-network gels.
    DOI:  https://doi.org/10.1038/s41557-025-01984-9
  5. Adv Sci (Weinh). 2025 Nov 09. e12971
      Cell migration plays a crucial role in the dynamic processes that guide tissue development, regeneration, and repair; yet, developing cell culture platforms that allow control over cell migration in 3D space and time remains a challenge. Here, a strategy is presented using chemically-responsive granular hydrogels to enable dynamic control over 3D cell migration. Dynamic microgels are fabricated via hyaluronic acid crosslinked via reversible guest-host interactions between adamantane (guest) and β-cyclodextrin (host), which swell in the presence of a cytocompatible competitive guest molecule (adamantane carboxylic acid, Ad-COOH) and de-swell when Ad-COOH is removed. When formed into granular hydrogels, the addition of Ad-COOH results in a dynamic porous material with reduced microgel stiffness and increased pore size. Ad-COOH addition also results in the reduction of mesenchymal stromal cell (MSC) migration from embedded aggregates (spheroids); however, MSC migration returns when Ad-COOH is removed. Furthermore, suspension bioprinting of jammed spheroids into dynamic granular hydrogels results in 4D printed constructs with patterned cellular regions (e.g., lines, zigzags, spirals) where cellular egress is controlled over time through the presence of Ad-COOH to create distinct spatiotemporal cellular patterns. This platform offers precise, on-demand modulation of cell migration, enabling new opportunities to fabricate dynamic, complex engineered tissues.
    Keywords:  4D bioprinting; granular hydrogels; migration; suspension printing
    DOI:  https://doi.org/10.1002/advs.202512971
  6. APL Bioeng. 2025 Dec;9(4): 046111
      The organization of cells and extracellular matrix (ECM) informs tissue function. This structure/function relationship is especially evident in musculoskeletal (MSK) tissues in which a specific ECM organization (e.g., anisotropy) guides directional properties under load. Injury disrupts the ECM structure, and new methods are needed to recapitulate the organization of cells and ECM within MSK tissue constructs to improve tissue models as well as to fabricate implants for repair. To address this, we use digital light processing (DLP) to rapidly 3D print custom molds that support large (centimeter-scale) meniscal tissue construct formation from meniscal fibrochondrocytes embedded within collagen gels. Importantly, these hydrogel molds include multiple pillars designed to anchor the tissue constructs and provide biophysical cues to direct tissue organization. Here, the effect of pillar spacing aspect ratio, mold size, and mold curvature on tissue contraction and cellular organization is investigated both experimentally and in silico. Pillar placement results in either disorganized (1:1 pillar spacing) or anisotropic (1:2 or 1:4 pillar spacing) cell spreading, with anisotropy observed in molds ranging from 6 mm to 2.4 cm in length. The introduction of mold curvature does not impact final construct width but does increase cellular anisotropy relative to molds without curvature. Furthermore, culture in the presence of the contractility inhibitor Cytochalasin D reduces construct contraction. These observations of cell behavior and construct compaction based on mold design are supported by coarse-grain simulations. Overall, this work establishes an adaptable DLP-based platform to grow custom MSK constructs for tissue models or repair.
    DOI:  https://doi.org/10.1063/5.0289256
  7. Nature. 2025 Nov;647(8089): 383-389
      All polymers exhibit gas permeability through the free volume of entangled polymer chains1-3. By contrast, two-dimensional (2D) materials including graphene stack densely and can exhibit molecular impermeability4-6. Solution-synthesized 2D polymers that exhibit the latter by poly-condensation have been a longstanding goal. Herein, we demonstrate self-supporting, spin-coated 2D polyaramid nanofilms that exhibit nitrogen permeability below 3.1 × 10-9 Barrer, nearly four orders of magnitude lower than every class of existing polymer, and similar for other gases tested (helium, argon, oxygen, methane and sulfur hexafluoride). Optical interference during the pressurization of nanofilm-coated microwells allows measurement of mechanosensitive rim opening and sealing, creating gas-filled bulges that are stable exceeding three years. This discovery enables 2D polymer resonators with high resonance frequencies (about 8 MHz) and quality factors up to 537, similar to graphene. A 60-nm coating of air-sensitive perovskites reduces the lattice degradation rate 14-fold with an oxygen permeability of 3.3 × 10-8 Barrer. Molecularly impermeable polymers promise the next generation of barriers that are synthetically processable, chemically amenable and maximize molecular rejection with minimal material, ultimately advancing sustainability goals.
    DOI:  https://doi.org/10.1038/s41586-025-09674-9
  8. Adv Healthc Mater. 2025 Nov 10. e03989
      While three - dimensional (3D) printing enables fabrication of hollow geometries through precise ink deposition, its reliance on photo- or thermal-curing often compromises resolution and biocompatibility. Alternatively, aqueous-phase chemical reactions offer a novel pathway for direct conversion of polymer films into high-resolution hollow structures without requiring external energy inputs or templates, yielding superior mechanical integrity. Despite these advances, the incorporation of living cells during hollow hydrogel formation remains a critical challenge. This review provides a comprehensive analysis of two key fabrication strategies: 1) chemical reaction-driven assembly in aqueous media and 2) 3D printing technologies. The respective design principles are critically evaluated. A systematic comparison reveals distinct advantages-aqueous-phase chemical methods offer enhanced resolution and mechanical strength, whereas 3D printing enables the control of customized geometries. Beyond fabrication, how these hollow hydrogel architectures exhibit transformative applications in drug delivery, tissue engineering, and biosensing are explored. By identifying current limitations and future opportunities, this review outlines a roadmap for the rational design of hollow hydrogels that can bridge the gap between structural engineering and clinical translation.
    Keywords:  3D printing; aqueous‐phase chemical reactions; film‐to‐tube transformation; hollow hydrogels; medical catheters; tissue engineering
    DOI:  https://doi.org/10.1002/adhm.202503989
  9. ACS Biomater Sci Eng. 2025 Nov 15.
      The biophysical cues of natural and synthetic hydrogels, including stiffness and the rate of cell-mediated degradation, are often tuned to better understand how to form vessel networks in tissue constructs. Interpenetrating networks (IPN) combine the bioactivity and fibrillar architecture of naturally derived hydrogels and the tunability of synthetic hydrogels. We developed a poly(ethylene glycol) (PEG)-collagen (type I) IPN to investigate the interactive effects of stiffness, the rate of proteolytic degradation, and a fibrillar collagen network on the formation of microvascular networks and cell-mediated hydrogel remodeling. Endothelial cells and fibroblasts were encapsulated in the PEG-collagen IPN, wherein the initial stiffness and rate of degradation were controlled by matrix metalloproteinase-sensitive peptide cross-linker concentration and identity, respectively. We found increased vascular network assembly in PEG-collagen IPN hydrogels that were stiff and slowly degrading and decreased cell-mediated stiffening in hydrogels that were soft and more rapidly degrading compared to PEG hydrogels. Collagen in the IPN was rapidly remodeled by the cells. In both PEG-only and IPN conditions, we found that the cells made the hydrogels more viscoelastic over the course of the experiment. To test if these results were due to the bioactivity or fibrillar architecture of collagen, we evaluated materials where collagen was not fully cross-linked or was added as dry-spun fibers. Unlike the IPN, both materials were less supportive of vasculogenic assembly and did not lead to a reduction in cell-mediated stiffening, suggesting that collagen's fibrillar network is important for increasing vasculogenic potential. Taken together, these results highlight the important interactions of matrix stiffness, degradability, and fibrillar architecture in the design of hydrogels to support vascularization.
    Keywords:  collagen; interpenetrating networks; poly(ethylene glycol); vasculogenesis
    DOI:  https://doi.org/10.1021/acsbiomaterials.5c01285
  10. Science. 2025 Nov 13. 390(6774): eadx7604
      Although metagenomic sequencing has revealed a rich microbial biodiversity in the mammalian gut, methods to genetically alter specific species in the microbiome are highly limited. Here, we introduce Metagenomic Editing (MetaEdit) as a platform technology for microbiome engineering that uses optimized CRISPR-associated transposases delivered by a broadly conjugative vector to directly modify diverse native commensal bacteria from mice and humans with new pathways at single-nucleotide genomic resolution. Using MetaEdit, we achieved in vivo genetic capture of native murine Bacteroides by integrating a metabolic payload that enables tunable growth control in the mammalian gut with dietary inulin. We further show in vivo editing of segmented filamentous bacteria, an immunomodulatory small-intestinal microbial species recalcitrant to cultivation. Collectively, this work provides a paradigm to precisely manipulate individual bacteria in native communities across gigabases of their metagenomic repertoire.
    DOI:  https://doi.org/10.1126/science.adx7604
  11. Nat Commun. 2025 Nov 14. 16(1): 10006
      Materials that compute-or process stimuli to generate a result output-are important in applications ranging from soft robotics to therapeutics. Here, we report a NAND gate based on the interactions of three self-trapped beams in a photoresponsive hydrogel. The beams self-trap by triggering localised contraction and corresponding refractive index changes (Δn) and communicate with each other through the interconnected hydrogel network. Light-induced Δn in one region suppresses contraction (and Δn) elsewhere. This inhibits self-trapping and reduces the power of the central beam-which competes with two equidistant neighbours-compared to either peripheral beam, which competes with just one neighbour. The NAND gate exploits this geometry-dependent inhibition: the central beam's peak power-the output-exceeds a threshold value unless both neighbours-inputs-are on, i.e., an output = 0 is retrieved only with input [1, 1]. We then demonstrate two and, separately, twelve sequentially chained NAND operations, and propose a route to multiple, simultaneously linked operations in a single, internally mediated step. Here, the output from one operation is spontaneously directed to subsequent operations. Our findings open pathways to soft materials with autonomous computational functionality.
    DOI:  https://doi.org/10.1038/s41467-025-64960-4
  12. Proc Natl Acad Sci U S A. 2025 Nov 18. 122(46): e2517114122
      DNA computing circuits leverage molecular interactions to construct a highly parallel and biologically compatible information processing paradigm. However, their development has been constrained by a critical gap between intrinsic computational parallelism and the limited readout bandwidth. Multibit outputs from complex circuits often require multiple separate tests, limiting the integration and debugging efficiency. Here, we overcome this bottleneck by decoupling computation from readout via a DNA origami display-based interface by integrating strand displacement and unstable binding reactions. We convert multibit molecular outputs from DNA circuits into spatially resolved geometric bits, enabling direct visualization via superresolution microscopy for high-throughput readout. We experimentally demonstrated the direct readout of an 8-bit decoder circuit and simultaneous display of 16 parallel-running logic gates. This high-bandwidth platform unlocks capabilities in circuit debugging and multiplexed execution, paving the way for large-scale DNA computing and high-throughput biosensing.
    Keywords:  DNA computing; DNA origami; DNA-PAINT; high-throughput readout
    DOI:  https://doi.org/10.1073/pnas.2517114122
  13. ACS Nano. 2025 Nov 13.
      Biological skins integrate optical and electrical signaling for dynamic environmental interactions, inspiring the development of artificial photonic ionic skins. However, existing synthetic systems often lack mechanical robustness, fast response, and dual-mode sensing capabilities of their natural counterparts. Here, we present a bioinspired photonic ionic skin that synergistically combines cellulose nanocrystal (CNC)-based chiral nanostructures with an ionically conductive network to achieve high-performance mechano-optical-electrical coupling. The system features an interpenetrating double-network architecture comprising a rigid chiral CNC framework embedded within a flexible hydrogel matrix, endowing the material with exceptional mechanical robustness and resilience. The resulting composite ionogel exhibits significantly enhanced strength, modulus, and toughness that are 2.8-fold, 2.6-fold, and 7.4-fold greater than those of the pristine hydrogels, respectively, while maintaining near-zero hysteresis and excellent cyclic stability. Additionally, dual-mode sensing capabilities have also been realized in the ionogel system through stress-dependent modulation of both its photonic bandgap and ionic conductivity. Mechanical deformation induces dynamic shifts in structural coloration across the visible to near-infrared spectrum while simultaneously altering the electrical properties. Notably, the integration of mechanical robustness and ultralow hysteresis endows the ionogel sensor with an ultrafast response/recovery time of 0.3/1.4 ms (corresponding to 520 Hz) and stable signal output under high-frequency stimulation, outperforming conventional sensing materials. Capitalizing on its high-frequency detection capability, the ionogel sensor demonstrates efficient texture classification and recognition when integrated with a machine learning model. This work establishes a robust platform for the development of next-generation wearable sensors, soft robotics, and human-machine interfaces that require skin-like multifunctionality.
    Keywords:  chiral nanostructures; dual-mode sensing; high-frequency detection; photonic ionic skin; structural coloration
    DOI:  https://doi.org/10.1021/acsnano.5c13067
  14. ACS Appl Mater Interfaces. 2025 Nov 14.
      Rapid growth in health care and robotics demands that tactile sensors have integrated physical and biochemical sensing within the same materials system at a relatively low cost. To address this, we develop a direct ink writing (DIW) fabricated, multilayered sensor architecture featuring two distinct printed patterns: an interdigitated electrode (IDE) pattern for physical sensing and a three-electrode configuration for biochemical sensing. The IDE pattern enables proximity and pressure sensing through the conductive networks formed by the MXene-PVDF composite layer, while the three-electrode pattern is designed for biochemical sensing, specifically detecting the H1N1 virus by leveraging MXene's functionalized surface terminations. Both patterns share the same layered structure, consisting of a top MXene-PVDF composite layer, an intermediate pure PVDF layer for mechanical stability, and a silver paste base layer for robust electrical interfacing and optimized interlayer adhesion. Finally, by integrating the IDE and three-electrode patterns into a robotic arm, we create an automated detection system capable of simultaneous physical and biochemical sensing. This system demonstrates significant potential for real-world applications, such as customs security screening, where enhanced efficiency and accuracy are achieved through the seamless combination of physical and biochemical sensing.
    Keywords:  MXene; biochemical sensing; direct ink writing (DIW); flexible sensors; multifunctional material platform; pressure sensing; proximity sensing
    DOI:  https://doi.org/10.1021/acsami.5c18741
  15. Biotechnol Bioeng. 2025 Nov 11.
      Hydrogels are commonly used to immobilize mammalian cells, offering mechanical support in 3D cultures and acting as barriers for immunoprotection in transplantation, such as islet encapsulation for diabetes therapy. Cell immobilization restricts bulk fluid motion, resulting in diffusion-limited molecular transport and nutrient concentration gradients, particularly for oxygen consumed by immobilized cells. Oxygen mass transport models are essential for designing immobilization strategies but often rely on assumed diffusion coefficients due to a lack of experimental data. We propose a cost-effective, accessible system for experimentally measuring oxygen diffusion coefficients in cell-laden hydrogels, tested on alginate-immobilized pancreatic beta cells (MIN6). Compared to water, oxygen diffusivity was significantly lower in alginate gels and inversely correlated with the dynamic loss modulus. Diffusivity also decreased with increasing alginate concentration from 2% to 5%. Cell viability depended heavily on gel concentration and cell density, as predicted by Thiele modulus and effectiveness factor values calculated from the measured diffusion coefficients. This platform, combining a simple experimental setup with dimensionless numbers, offers a practical way to predict maximal diffusion distances in cell immobilization strategies. The proposed approach can support rational design of cell encapsulation, immobilized cell culture, and tissue engineering strategies.
    Keywords:  alginate; beta cells; cell immobilization; diabetes; hydrogel; oxygen diffusion
    DOI:  https://doi.org/10.1002/bit.70095
  16. Proc Natl Acad Sci U S A. 2025 Nov 18. 122(46): e2517985122
      Naturally evolved materials and structures inspire next-generation sustainable manufacturing workflows and the development of intelligent, multifunctional, high-performance materials. However, integrating compositional and structural elements from diverse natural sources into a unified, high-performance platform remains a significant challenge. Here, we present a scalable strategy for creating robust, tunable, multifunctional surfaces by seamlessly integrating sunflower (Helianthus annuus) pollen structures onto regenerated silk fibroin films from Bombyx mori. Through a dry process, pollen grains are transformed into continuous, homogeneous patterns over wafer-scale areas, which can be reconfigured via thermally induced capillary action. These geometrically controlled pollen textures are precisely transferred onto one or both sides of the silk films, producing biotextured biopolymer platforms. The hierarchical pollen architecture imparts exceptional surface properties that surpass those of existing natural or synthetic analogs, while preserving the intrinsic advantages of silk fibroin, including recyclability and biodegradability. This approach, decoupling and reintegrating fundamental natural elements at both compositional and structural levels, opens pathways for combining diverse bioresources to realize sustainable materials with enhanced versatility.
    Keywords:  bioinspiration; micro/nanotexturing; multifunctional film; pollen; silk fibroin
    DOI:  https://doi.org/10.1073/pnas.2517985122
  17. Proc Natl Acad Sci U S A. 2025 Nov 18. 122(46): e2515324122
      Metabolic rewiring helps to construct efficient microbial cell factories; however, these cells suffer from metabolic stress during long-term fed-batch fermentation. Thus, the construction of robust cells is vital for industrial application of microbial cell factories at the laboratory scale. Here, we systematically characterized longevity factors and pathways for biosynthesis of the diterpenoid sclareol and found that weakening nutrient-sensing pathways and enhancing mitophagy synergistically improved sclareol production by 70.3% (20.1 g/L with a yield of 0.046 g/g glucose). Further enhancing central metabolism improved sclareol production to 25.9 g/L with a yield of 0.051 g/g glucose, the highest production achieved in microbes. Omics data demonstrated that the extension of chronological lifespan by upregulating the expression of lifespan-related genes automatically remodeled the cellular metabolism and improved overall cellular robustness for efficient chemical biosynthesis. We also showed that our strategy significantly improved the biosynthesis of other products such as sesquiterpene β-elemene and phenolic acids. Therefore, this study may provide metabolic connections between cell aging and biosynthetic capacity.
    Keywords:  bioproduction; chronological lifespan; metabolic engineering; sclareol; yeast
    DOI:  https://doi.org/10.1073/pnas.2515324122
  18. Angew Chem Int Ed Engl. 2025 Nov 10. e19925
      Stimuli-responsive biomaterials hold great promise in controlled therapeutic delivery, tissue engineering, and biosensing applications. Recently, molecular assembly via autonomous compilation has been employed to create topologically specified protein cargos that can be site-specifically tethered to and conditionally released from biomaterials following user-programmable Boolean logic. Prior implementation has been confined to simple fluorescent protein outputs and model protease inputs. In this manuscript, we extend the applicability of this framework by assembling all 7 unique logical operations emanating from a YES/OR/AND 3-input operator set to deliver bioactive proteins spanning diverse categories: growth factors (epidermal growth factor), model enzymes (β-lactamase, NanoLuciferase, and thioredoxin A), therapeutic nanobodies (anti-human epidermal growth factor receptor 2), de novo-engineered cytokines (Neoleukin), and fluorescent proteins (mGreenLantern). In so doing, we demonstrate programmable biomacromolecule release from material anchors in response to precise combinations of three orthogonal protease actuators while maintaining native bioactivity. Through inclusion of a photocleavable protein motif, we further establish that visible light can be employed as an additional input in specifying logic-based protein release. We anticipate these methods will powerfully expand opportunities for targeted therapeutic delivery and beyond.
    Keywords:  Bioactive therapeutics; Boolean logic; Drug delivery; Protein engineering; Stimuli‐responsive
    DOI:  https://doi.org/10.1002/anie.202519925
  19. Nat Biotechnol. 2025 Nov 11.
      A standardized 'parts list' of sequences for genetic engineering of microbes has been indispensable to progress in synthetic biology, but few analogous parts exist for mammalian systems. Here we design libraries of extant, ancestral, mutagenized or miniaturized variants of polymerase III promoters and guide RNA (gRNA) scaffolds and quantify their abilities to mediate precise edits to the mammalian genome through multiplex prime editing. We identify thousands of parts for reproducible editing in human and mouse cell lines, including hundreds with greater activity than commonly used sequences. Saturation mutagenesis screens identify tolerated sequence variants that further enhance sequence diversity. In an application to molecular recording, we design a 'ten key' array that, in mammalian cells, achieves balanced activity of pegRNAs as predicted by the activity of the component parts. The data reported here will aid the design of synthetic loci encoding arrays of gRNAs exhibiting predictable, differentiated levels of activity for applications in multiplexed perturbation, biological recorders and complex genetic circuits.
    DOI:  https://doi.org/10.1038/s41587-025-02896-2
  20. Adv Sci (Weinh). 2025 Nov 14. e12037
      Programmable hydrogels are an emerging class of intelligent materials engineered to respond precisely to specific stimuli, offering tailored functionalities with significant potential for biomedical applications, including drug delivery, tissue engineering, and wound healing. This review comprehensively explores various programmable hydrogels responsive to diverse triggers, including temperature, gene expression, color, shape, and mechanical force. The design and fabrication methods underlying these systems are detailed, highlighting the roles of crosslinkers, adhesion groups, and photosensitive functional groups. Furthermore, the key physical, chemical, and biological properties that govern the performance and functionality of hydrogels are analyzed. The review further examines the mechanisms and recent advancements in self-executing hydrogels, such as self-activated, self-oxygenated, self-expandable, and self-powered systems, demonstrating how these innovative designs drive the development of next-generation programmable hydrogels. The main challenges in hydrogel design, including complexity, reproducibility, and clinical translation, are also addressed. Finally, a perspective on future research directions, highlighting the integration of the latest technologies to realize programmable hydrogels with dynamic closed-loop responsiveness, bionic synergy, and robust clinical applicability, is offered.
    Keywords:  adaptive hydrogels; programmable hydrogels; self‐adjustable hydrogels; self‐destructive hydrogels; smart hydrogels
    DOI:  https://doi.org/10.1002/advs.202512037
  21. Biomacromolecules. 2025 Nov 10.
      In this study, we present a novel approach to convert reversible polymer networks into stable, nonresponsive networks using bio-orthogonal Suzuki-Miyaura coupling (SMC). By leveraging boronic acids, which form reversible boronate esters with cis-diols for shear-thinning injectable gels and serve as SMC substrates to create stable C-C bonds, we achieve switching from responsive to nonresponsive behavior. We demonstrate the concept with a responsive precursor based on sodium alginate modified with phenyl boronic acid, cross-linked with three model iodide-functionalized (macro-)molecules that exhibit irreversible gelation under bio-orthogonal conditions. The resulting networks exhibit robust mechanical stability, minimal pH and temperature responsiveness, high degradation resistance and excellent hemocompatibility. The proposed approach underlines the potency of SMC as a robust synthetic strategy toward the synthesis and transformation of polymer networks for advanced biomedical applications.
    DOI:  https://doi.org/10.1021/acs.biomac.5c01053
  22. ACS Appl Mater Interfaces. 2025 Nov 12.
      Mechanical metamaterials have attracted significant interest for their ability to achieve extraordinary mechanical properties, and various control and programming strategies for active mechanical metamaterials have been extensively explored. Inspired by deformation mechanisms governed by mechanical instabilities and heterogeneous material distribution, we propose two fundamental building blocks featuring horizontally constrained inclined beam configurations but exhibiting opposite response behaviors. By strategically arranging liquid crystal elastomer-based active regions and tuning geometric parameters, the energy bifurcation points of these units can be programmatically modulated to achieve tailored functionalities under mechanical actuation and temperature variation. Integrating these units as encoding components, we demonstrate diverse structural configurations and assembly strategies that enable programmable response and deformation systems with binary information storage and mechanical logic computing capabilities. These systems showcase potential applications in untethered logic controllers and information encryption devices.
    Keywords:  bistable; liquid crystal elastomers; mechanical metamaterials; programmable; reconfigurable
    DOI:  https://doi.org/10.1021/acsami.5c18074
  23. Biomacromolecules. 2025 Nov 12.
      Leveraging recent advances in protein design, we explored de novo designed proteins as building blocks for hydrogels. Specifically, we investigated two homodimers, a highly stable β-barrel dimer and a helical dimer. By incorporating elastin-like polypeptide (ELP) segments, we developed a novel gelation mechanism that enables recombinant proteins to self-assemble into hydrogels in a temperature-dependent manner, exhibiting a sol-gel transition near body temperature. Our results demonstrate that the secondary structure of the protein building blocks plays a crucial role in determining the mechanical properties and microstructure of the resulting hydrogels. The β-barrel homodimer-based hydrogels exhibited superior mechanical strength at lower temperatures due to their stable hydrogen bonding networks. Additionally, these hydrogels displayed excellent drug encapsulation capabilities and fatigue resistance, underscoring their potential for biomedical applications. This work advances our understanding of protein architecture in guiding hydrogel behavior and offers a versatile platform for tailored biomedical materials.
    DOI:  https://doi.org/10.1021/acs.biomac.5c00691
  24. STAR Protoc. 2025 Nov 11. pii: S2666-1667(25)00595-7. [Epub ahead of print]6(4): 104189
      Mechanical properties of cells determine their ability to deform when subjected to force, which is crucial in many biological processes. Here, we present a protocol to quantify these properties on living cells by applying piconewton-range forces with optically trapped microspheres. We describe steps for sample preparation of both adherent and suspended cells, calibration of optical trap stiffness, and generation of force-deformation curves. We next detail how to quantify cellular mechanical properties from the resulting data. For complete details on the use and execution of this protocol, please refer to Rodenburg et al.1.
    Keywords:  Biophysics; Cell biology; Single cell; Single-molecule assays
    DOI:  https://doi.org/10.1016/j.xpro.2025.104189
  25. ACS Appl Bio Mater. 2025 Nov 13.
      The development of sustainable, soft, and recyclable materials for skin-integrated electronics is critical for advancing wearable health monitoring while minimizing electronic waste. Here, chitosan-agarose-based hydrogels integrated with poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) are fabricated as recyclable, biocompatible, and thermoresponsive materials for flexible temperature sensors. The hydrogels are synthesized using a green and easy process, forming interpenetrated dual networks that exhibit high water content, mechanical compliance, and enhanced electroconductivity. Morphological analysis reveals highly porous interconnected structures, while Fourier transform infrared spectroscopy confirms the successful incorporation of PEDOT:PSS. The hydrogels display high swelling capacity, tunable mechanical properties within the physiological range of human skin, and enhanced electrochemical performance. The temperature-sensing capability of the hydrogels demonstrates a negative temperature coefficient of resistance (TCR) of up to -1.5% °C-1, outperforming similar hydrogel-based sensors while maintaining stability over repeated thermal cycles. Importantly, the hydrogels can be disassembled, reprocessed, and reused for multiple sensing cycles without significant loss of performance, demonstrating true recyclability and supporting circular material use in soft electronics. The convergence of natural biopolymers with conducting polymers within these hydrogels provides a promising platform for developing eco-friendly, flexible bioelectronic devices, aligning with the requirements of sustainable materials science while addressing the need for high-performance, soft temperature sensors for wearable healthcare applications.
    Keywords:  PEDOT:PSS; agarose; chitosan; hydrogel; skin electronics; sustainable and recyclable temperature sensor
    DOI:  https://doi.org/10.1021/acsabm.5c01607
  26. Trends Biotechnol. 2025 Nov 12. pii: S0167-7799(25)00407-X. [Epub ahead of print]
      Due to health and pollution concerns, sustainable textile production is receiving increasing attention. Bacterial cellulose (BC) offers an environmentally friendly alternative to petroleum-based fabrics. However, the use of petroleum-based synthetic colorants and toxic reagents in dyeing processes impedes the fully sustainable production of colored BC. To address this issue, we developed a one-pot production system for colored BC biosynthesis, aiming to simplify and streamline the manufacturing process. A co-culture strategy using Escherichia coli for natural colorant synthesis and Komagataeibacter xylinus for BC synthesis was developed and optimized to achieve the one-pot production of multicolored BC, including proviolacein-BC (green), prodeoxyviolacein-BC (blue), violacein-BC (navy), deoxyviolacein-BC (purple), astaxanthin-BC (red), β-carotene-BC (orange), and zeaxanthin-BC (yellow). This study demonstrates the robust co-culture strategy and platform for efficient, scalable, and eco-friendly process biopolymer-based fabric production, offering a sustainable alternative for applications in the living materials industry.
    Keywords:  Escherichia coli; Komagataeibacter xylinus; bacterial cellulose; co-culture; metabolic engineering; natural colorants; one-pot production; sustainability
    DOI:  https://doi.org/10.1016/j.tibtech.2025.09.019
  27. ACS Synth Biol. 2025 Nov 11.
      Genetically encoded biosensors are powerful tools for linking metabolite production to fluorescent outputs, but stresses imposed by engineered pathways can confound their signals. In this study, we developed four fluorescence-based biosensors for inhibitors of protein tyrosine phosphatase 1B (PTP1B), a therapeutic target for cancer and diabetes, and compared their performance in the presence of heterologous terpenoid pathways, a promising source of new inhibitors. When expressed in Escherichia coli, all four could reliably detect an exogenously supplied PTP1B inhibitor, but only one remained functional alongside terpenoid pathways, where pathway-derived stress reduced overall fluorescence. This sensor, which links PTP1B inhibition to the assembly of a split T7 RNA polymerase, exhibited a high dynamic range with minimal toxicity, a common liability of T7-based circuits. Variants of this sensor with different sensitivities to inhibition and stress allowed us to separate the terpenoid pathways that made PTP1B inhibitors from those that did not. Our findings show how pathway-specific stresses (e.g., terpene synthase expression) can alter biosensor signals as strongly as their target analytes and provide a framework for disentangling these confounding effects in high-throughput screens.
    Keywords:  T7 RNA polymerase; bacterial two-hybrid; biosynthetic pathways; cellular burden; enzyme inhibitors; protein tyrosine phosphatases
    DOI:  https://doi.org/10.1021/acssynbio.5c00275
  28. Cell. 2025 Nov 12. pii: S0092-8674(25)01191-2. [Epub ahead of print]
      Intrinsically disordered regions (IDRs) of proteins are defined by molecular grammars. This refers to IDR-specific non-random amino acid compositions and non-random patterning of distinct pairs of amino acid types. Here, we introduce grammars inferred using NARDINI+ (GIN) as a resource that uncovers IDR-specific and IDRome-spanning grammars. Using GIN-enabled analyses, we find that specific IDR features and GIN clusters are associated with distinct biological processes, intra-cellular localization preferences, specialized molecular functions, and functionalization as assessed by cellular fitness correlations. IDRs with exceptional grammars, defined as sequences with high-scoring non-random features, are harbored in proteins and complexes that enable spatial and temporal sorting of biochemical activities within the nucleus. Overall, GIN can be used to extract sequence-function relationships of individual IDRs or clusters of IDRs, to redesign extant IDRs or design de novo IDRs, to perform evolutionary analyses through the lens of molecular grammars and GIN clusters, and to make sense of IDR-specific disease-associated mutations.
    Keywords:  RNA polymerase; biomolecular condensates; cancer; intrinsically disordered regions; molecular grammars; subcellular localization; transcriptional regulation
    DOI:  https://doi.org/10.1016/j.cell.2025.10.019
  29. Proc Natl Acad Sci U S A. 2025 Nov 18. 122(46): e2525453122
      
    DOI:  https://doi.org/10.1073/pnas.2525453122
  30. Small. 2025 Nov 14. e07990
      Hydrogel-based sorption atmospheric water harvesting (H-SAWH) offers a promising solution to water scarcity, particularly in arid regions. Hydrogels, with their three-dimensional (3D) polymer networks, exhibit excellent hygroscopicity, tunable structure, and chemical adaptability, making them strong candidates for next-generation water capture systems. This review introduces a purpose-driven polymer engineering approach that incorporates environmental and application-specific constraints into the molecular design of hydrogels, moving beyond the traditional focus on maximizing water uptake. Diverse H-SAWH applications, from portable devices to agricultural systems, are highlighted, and key material requirements, including responsive water release, mechanical durability, and climate resilience, are identified. Hydrogels are conceptualized as customizable water reservoirs, with tailored porosity, stimuli-responsive features, and hygroscopic additives designed to enhance vapor capture and release cycles. Advances in synthesis methods, including precision crosslinking and salt integration strategies, are reviewed for their role in improving system robustness and performance. Persistent challenges related to salt leakage, water purity, scalability, and environmental durability are critically assessed from a molecular perspective. Finally, the importance of field validation and techno-economic analysis is emphasized to ensure real-world deployment. This review frames the future of H-SAWH as a convergence of smart polymer design and sustainable water technology for decentralized, climate-resilient freshwater access.
    Keywords:  atmospheric water harvesting; hydrogel synthesis; purpose‐driven material design; sorption‐based atmospheric water harvesting; stimuli‐responsive hydrogels
    DOI:  https://doi.org/10.1002/smll.202507990
  31. Nature. 2025 Nov 12.
      
    Keywords:  Materials science; Technology
    DOI:  https://doi.org/10.1038/d41586-025-03708-y
  32. PNAS Nexus. 2025 Nov;4(11): pgaf046
      Humans are drawn to patterns and hierarchies in nature, mimicking them particularly in decoration and architecture. Natural patterns, however, are never purely esthetic and, since evolution works on a variety of factors simultaneously, natural structural systems are intrinsically multifunctional. In order to understand the roles that structural patterns play in biology (and therefore their potential capabilities and utilization in design, architecture and engineering), we need to catalog and encapsulate the diversity of examples and the materials involved. Here, we provide a first classification of biological "tilings," tessellated natural architectures that involve the repeated pattern of geometric, discrete elements bound by a joint material. By examining 100 examples across the Tree of Life, we reveal this natural structural motif is unexpectedly prevalent: we cover a huge taxonomic diversity, eight orders of magnitude in size scale, and myriad morphologies and functions ranging from optics to armor, allowing us to construct a hierarchical system of eight variables to classify form, function, and materiality in biological tilings. Using diverse means of data analysis (including multiple correspondence analysis), we show this database can be explored to reveal fundamental links among anatomical characteristics and functions as well as connections among and within taxonomic groups. Our resulting collection of "tessellated materials" and its companion website act therefore as a multidisciplinary meeting point (e.g. for biologists, designers, engineers, architects). In this way, our database offers windows for exploring selective pressures and trade-offs and a launchpad for future research and collaborative, cross-disciplinary, bioinspired projects.
    Keywords:  biological architecture; biomimetics; composite biomaterials; material design; multivariable classification
    DOI:  https://doi.org/10.1093/pnasnexus/pgaf046
  33. Nat Biotechnol. 2025 Nov;43(11): 1766
      
    DOI:  https://doi.org/10.1038/s41587-025-02893-5
  34. ACS Appl Bio Mater. 2025 Nov 12.
      Over the years, 3D printing has become a multidisciplinary research hotspot and state-of-the-art technology for developing bioinspired structures with intricate geometry, mechanical robustness and verified designs. However, the extrusion complexity of thermoplastic elastomeric filaments makes it challenging to design complex shapes in filament-based extrusion 3D printing. Herein, the paucity of low-modulus ethylene-co-vinyl acetate (EVA) polymer for the fabrication of bone tissue mimetic scaffolds was addressed by compounding with hydroxyapatite (HAP) and the effects of HAP incorporation on extrudability, printability, mechanical properties and osteoblast-material interactions were studied. The systematic optimization of printability and printing parameters enabled successful 3D printing of composite scaffolds with controlled deposition, pore geometry and architecture using a pellet-extrusion 3D printer. The die swell, unstable extrudate deposition and warpage of the EVA polymer melt subsided upon HAP addition. Confocal Raman microscopy and scanning electron microscopy (SEM) confirmed the uniform dispersion of HAP in EVA matrix, necessary to yield stable extrusion of the polymer melt. Dynamic mechanical analysis (DMA) revealed a 5-fold increase in storage modulus as well as a shift in Tg of the composites from -13°C to -9.8°C for 40 vol % HAP, confirming the possible polymer-HAP interactions. Biocompatibility studies demonstrated robust viability, proliferation and cellular integrity, especially in scaffolds with 40 vol % HAP. Moreover, F-actin staining of MG-63 cells revealed expanded cell pseudopods distributed evenly across the scaffold surface with a polygonal spreading pattern, confirming the cell adhesion and proliferation conducive for osteogenesis on the composite scaffolds. Osteogenic differentiation, as evidenced by ALP activity and Alizarin red S staining, indicated statistically higher levels of osteogenic-related factors and mineralization in composite scaffolds relative to neat EVA. These primary findings collectively support that the EVA-HAP composite, especially with 40 vol % HAP loading, provides a suitable microenvironment for osteoblast activities and is expected to promote bone tissue formation.
    Keywords:  composite; ethylene-co-vinyl acetate; extrudability; extrusion 3D printing; printability
    DOI:  https://doi.org/10.1021/acsabm.5c01291
  35. ACS Biomater Sci Eng. 2025 Nov 14.
      Rationale: Extrusion 3D bioprinting is an additive manufacturing tissue engineering technique that uses cell-laden viscous biomaterials known as bioinks. Manually mixing cell suspensions into viscous biomaterials can be challenging due to the high viscosity ratio between the two fluids. Static mixers are an attractive approach as they can quickly and reproducibly mix two fluids, including those with a high viscosity ratio. However, static mixers intended for viscous applications have not been comprehensively investigated for bioink preparation. This work evaluates the mixing performance, shear stress, and cell viability using four different types of static mixers intended for high viscosity mixing. Methods: Three static mixers intended for mixing viscous solutions were designed based on the Sulzer SMX, Ross ISG, and serpentine mixers and fabricated using resin 3D printing. CELLMIXER, a Kenics-style static mixer commercially available through CELLINK, was used as a comparator. Two biomaterial inks based on PEGDA and methacrylated gelatin were used to characterize each mixer's performance. Shear stress was estimated via fluid dynamics simulations using shear-thinning attributes measured experimentally through rheology. Mixing effectiveness was evaluated using fluorescent beads, from which the most effective design was chosen for live cell mixing experiments. Viability of cell lines (A549 and NIH-3T3) and primary human lung fibroblasts was evaluated postmixing. A demonstration of extrusion bioprinting was performed using the mixed bioinks. Results: The SMX-style mixer provided the most uniform mixing and yielded the lowest simulated shear stresses among the designs investigated. A549, NIH-3T3, and primary human lung fibroblasts maintained viabilities above 96% postmixing using the SMX-style mixer with a more homogeneous cell distribution compared to the CELLMIXER. The bioprinting demonstration validated our mixing system for producing viable tissue constructs with evenly distributed cells. Conclusions: We present a simple, reproducible, and flexible system for mixing cells into viscous biomaterial inks. Our approach facilitates standardized fabrication of cell-laden tissue constructs to ensure consistency in the growing field of extrusion 3D bioprinting.
    Keywords:  biomaterial ink; extrusion 3D bioprinting; gelatin methacrylate; poly(ethylene glycol) diacrylate; static mixer
    DOI:  https://doi.org/10.1021/acsbiomaterials.5c01334