bims-enlima Biomed News
on Engineered living materials
Issue of 2025–07–06
fifty-four papers selected by
Rahul Kumar, Tallinna Tehnikaülikool
  1. Genetically Encoded Interpenetrating Polymer Networks as Injectable Biomaterials for Controlled Therapeutic Protein Delivery.
  2. Ionic Crosslinking Improves the Stiffness and Toughness of Protein Hydrogels.
  3. Accelerated data-driven materials science with the Materials Project.
  4. Resolving hyperelasticity-adhesiveness conflict in polymer networks by in situ constructing mechanical heterogeneities.
  5. Drug-Inspired Design of Supramolecular Polymers for Enhanced Drug Loading and Sustained Therapeutic Release.
  6. Biohybrid microstructured hydrogels obtained via in situ extracellular matrix deposition and decellularization using supercritical CO2.
  7. Nanoscale electrostatic control in ferroelectric thin films through lattice chemistry.
  8. Nonliving dehydrated leaves-inspired surface anti-wrinkling.
  9. Molecularly Shielded, On-Demand, Ultrasound-Cured Polymer Networks.
  10. A biomimetic multi-component subunit vaccine via ratiometric loading of hierarchical hydrogels.
  11. Three-dimensional robotic structures fabricated and powered entirely with proteins.
  12. Hybrid epoxy-acrylate resins for wavelength-selective multimaterial 3D printing.
  13. A 3D printing UV-curing resin that enables continuous color change of elastomers.
  14. Xolography for Rapid Volumetric Production of Objects from the Nanoscopic to Macroscopic Length Scales.
  15. Biomaterials for organically generated habitats beyond Earth.
  16. 3D extrusion bioprinting: rational bioink design and advanced fabrication techniques.
  17. Allomelanin-Inspired Polyurethane Nanocomposites with Multi-Radiation Resistance and Enhanced Mechanical Properties.
  18. Photoactivated Nano-Compatibilized Two-Phase Polymer Blends: An Approach for Determining Mechanical Behavior.
  19. Janus particles stabilized asymmetric porous composites for thermal rectification.
  20. Roadmap for Animate Matter.
  21. Photo-triggered Hyaluronic Acid Hydrogel for 3D Culture and Cell Recovery.
  22. Flow-induced 2D nanomaterials intercalated aligned bacterial cellulose.
  23. 2D fracture-resistant high-entropy-oxide scaffold enabled multifunctional nanomembrane.
  24. Genetic Code Expansion to Enable Site-Specific Posttranslational Peptide Epitope Tagging of G Protein-Coupled Receptors in Live Cells.
  25. Accelerating cell culture media development using Bayesian optimization-based iterative experimental design.
  26. An mRNA lipid nanoparticle-incorporated nanofiber-hydrogel composite for cancer immunotherapy.
  27. Edge-activated graphene nanopores for thermally robust hydrogen membrane separations.
  28. N-alkylated polydithiocarbamates derived from thiocarbonyl fluoride as macro-photoiniferters for living 3D printing.
  29. "Grafting-to" Polymers of Xylan-g-allyl Glycidyl Ether Toughen PEG Hydrogel via Microphase Separation: Thermoresponsive and Photoreactive Molecular Assembly in DLP 3D Printing.
  30. Modular shape-changing tensegrity-blocks enable self-assembling robotic structures.
  31. Intraspecies warfare restricts strain coexistence in human skin microbiomes.
  32. The vaccine we all wear: Skin microbiota can be engineered into topical vaccines.
  33. Bioprinting of piezoresistive organohydrogel networks for advanced real-time mechanosensing in engineered tissue models.
  34. Deciphering the stability of two-dimensional III-V semiconductors: Building blocks and their versatile assembly.
  35. From in vitro to in vivo: Diverse applications of kirigami technology in medical devices.
  36. Porous Organic Cages as Building Blocks for Framework Materials.
  37. A generalized platform for artificial intelligence-powered autonomous enzyme engineering.
  38. 3D printing offers a way to study mimicry by insects.
  39. A Molecular Glue Approach to Control the Half-Life of CRISPR-Based Technologies.
  40. Engineered In Vitro Platforms for Mechanochemical Control of Cell Migration.
  41. Reversible Physical Gelation of Thermotropic Liquid Crystals Driven by Nanoplate Self-Assembly.
  42. Development of Smart Photocrosslinkable Epoxy-Based Inks for 4D Printing.
  43. Three-dimensional conductive conjugated polyelectrolyte gels facilitate interfacial electron transfer for improved biophotovoltaic performance.
  44. Mechanically Tunable Slide-ring Polymers via Photo-regulated Topological Control.
  45. Engineering polystyrene microtube-embedded composite hydrogels for tunable vascular morphogenesis.
  46. Scalable modulation of CRISPR‒Cas enzyme activity using photocleavable phosphorothioate DNA.
  47. Multicolor Digital Light Processing 3D Printing Enables Dissolvable Supports for Freestanding and Non-Assembly Structures.
  48. Synthetic Mucins as Glycan-Defined Prebiotics.
  49. Design Principles for Engineering Ionic Liquid-Gold Nanoparticles for Therapeutic Delivery to the Brain.
  50. Silk Fibroin-Based Matrices for the Guidance of Cell Interaction, Tissue Regeneration, and Crosstalk.
  51. Innovations and Applications of Composite Hydrogels: from Polymer-Based Systems to Metal-Ion-Doped and Functional Nanomaterial-Enhanced Architectures.
  52. Learning predictive signals within a local recurrent circuit.
  53. pH-Responsive Bilayer Hydrogel with Synergistic Antibacterial/Anti-inflammatory Effect for Infected Wound Healing.
  54. Predicting heteropolymer phase separation using two-chain contact maps.
  1. ACS Biomater Sci Eng. 2025 Jul 03.
    Genetically Encoded Interpenetrating Polymer Networks as Injectable Biomaterials for Controlled Therapeutic Protein Delivery.
    Murial L Ross, Shivani P Kottantharayil, Tina K Nguyen, Rashmi Ravichandran, Cole A DeForest.
      Though recombinant protein therapeutics hold great potential in treating many diseases, their intravenous delivery introduces challenges with off-target effects and short circulation half-lives. Injectable biomaterial depots have proven useful in confining therapeutic administration to specific bodily locations but have faced difficulties in simultaneously controlling drug release, network mechanics, and functionalization. Toward addressing these limitations, this work introduces the first recombinant protein-based interpenetrating polymer network (IPN), which we exploit for injectable therapeutic deposition. Each of the self-sorting telechelic biopolymer networks is comprised of an intrinsically disordered XTEN protein midblock differentially flanked with one of two orthogonally self-assembling coil domains that enable rapid shear-thinning and self-healing responsiveness in biomaterials with tunable viscoelasticity. Exploiting the orthogonal and genetically encoded click-like SpyLigation/SnoopLigation chemistries to independently tether proteins-of-interest to each underlying network, we demonstrate that fluorescent proteins and growth factors (rhIGF-1, rhEGF) can be released in a controlled fashion from materials with tunable viscoelasticity while retaining high bioactivity following network dissolution. Such recombinant IPN biomaterials offer exciting opportunities for next-generation biotherapeutic delivery.
    Keywords:  biomaterials; coiled-coils; drug delivery; injectable; recombinant proteins
    DOI:  https://doi.org/10.1021/acsbiomaterials.5c00813
  2. Polym Sci Technol. 2025 Jun 24. 1(4): 342-350
    Ionic Crosslinking Improves the Stiffness and Toughness of Protein Hydrogels.
    Linglan Fu, Hongbin Li.
      Protein-based hydrogels are promising materials for biomedical and materials science applications. However, engineering hydrogels with both high stiffness and high toughness, a key requirement for many applications, remains challenging. Recently, by using the denatured crosslinking method, we developed highly stiff and tough protein hydrogels based on the polyprotein (FL)8 via introducing chain entanglements into the hydrogel network, which allow for stiffening the hydrogel without sacrificing toughness. These hydrogels exhibited a Young's modulus of ∼0.7 MPa and breaking strain of ∼100% in tensile tests. To further enhance their stretchability and toughness, here we report the engineering of a protein/alginate hybrid hydrogel, in which the protein and alginate networks are covalently joined. Alginate was chemically modified with tyramine to introduce phenol groups, allowing the modified alginate to be photochemically crosslinked together with the polyprotein (FL)8 to form a hybrid network hydrogel. Using calcium-mediated ionic crosslinking, we demonstrated the feasibility to tune the Young's modulus and breaking strain of these hydrogels by controlling the degree of tyramine modification of alginate. Our results showed that incorporating noncovalent ionic crosslinking into the hydrogel network increased the hydrogel's stretchability from ∼100% to over 200% without compromising stiffness, significantly improving the hydrogel's toughness. This work expands the mechanical tunability of protein hydrogels and the repertoire of strategies for engineering hydrogels with a broad range of mechanical properties.
    Keywords:  alginate; chain entanglements; high toughness and stiffness; hybrid network hydrogel; ionic crosslinking; photocrosslinking; protein hydrogels
    DOI:  https://doi.org/10.1021/polymscitech.5c00024
  3. Nat Mater. 2025 Jul 03.
    Accelerated data-driven materials science with the Materials Project.
    Matthew K Horton, Patrick Huck, Ruo Xi Yang, Jason M Munro, Shyam Dwaraknath, Alex M Ganose, Ryan S Kingsbury, Mingjian Wen, Jimmy X Shen, Tyler S Mathis, Aaron D Kaplan, Karlo Berket, Janosh Riebesell, Janine George, Andrew S Rosen, Evan W C Spotte-Smith, Matthew J McDermott, Orion A Cohen, Alex Dunn, Matthew C Kuner, Gian-Marco Rignanese, Guido Petretto, David Waroquiers, Sinead M Griffin, Jeffrey B Neaton, Daryl C Chrzan, Mark Asta, Geoffroy Hautier, Shreyas Cholia, Gerbrand Ceder, Shyue Ping Ong, Anubhav Jain, Kristin A Persson.
      The Materials Project was launched formally in 2011 to drive materials discovery forwards through high-throughput computation and open data. More than a decade later, the Materials Project has become an indispensable tool used by more than 600,000 materials researchers around the world. This Perspective describes how the Materials Project, as a data platform and a software ecosystem, has helped to shape research in data-driven materials science. We cover how sustainable software and computational methods have accelerated materials design while becoming more open source and collaborative in nature. Next, we present cases where the Materials Project was used to understand and discover functional materials. We then describe our efforts to meet the needs of an expanding user base, through technical infrastructure updates ranging from data architecture and cloud resources to interactive web applications. Finally, we discuss opportunities to better aid the research community, with the vision that more accessible and easy-to-understand materials data will result in democratized materials knowledge and an increasingly collaborative community.
    DOI:  https://doi.org/10.1038/s41563-025-02272-0
  4. Nat Commun. 2025 Jul 02. 16(1): 6094
    Resolving hyperelasticity-adhesiveness conflict in polymer networks by in situ constructing mechanical heterogeneities.
    Ping Zhang, Haowei Ruan, Qingxian Li, Yunfeng He, Canhui Yang.
      Stretchable materials with low hysteresis and strong adhesion are needed in applications, but unifying the two contradictory mechanical properties is challenging. Herein, we propose the design principles of polymer networks that are hyperelastic yet adhesive by rationalizing mechanical heterogeneities. The heterogeneous networks comprise a viscoelastic adhesive surface and a hyperelastic non-adhesive bulk. The former has a stiffness much smaller than that of the latter. We synthesize the networks by harnessing the oxygen inhibition mechanism, construct a polymerization phase diagram by reconciling the kinetics of polymerization and radical quenching of oxygen, and establish a power law criterion for the transition from a viscoelastic adhesive network to a hyperelastic adhesive network. We illustrate the principle with heterogeneous poly(butyl acrylate-co-acrylic acid) networks, achieving hysteresis <5% and adhesion energy >300 J/m2. We show that the adhesion energy-thickness relation of hyperelastic adhesive polymer networks is nonlinear below a transition thickness. Hyperelastic and adhesive stretchable materials potentialize high-cycle and fatigue-resistant soft human-machine interfaces and beyond.
    DOI:  https://doi.org/10.1038/s41467-025-61450-5
  5. ACS Nano. 2025 Jun 30.
    Drug-Inspired Design of Supramolecular Polymers for Enhanced Drug Loading and Sustained Therapeutic Release.
    Boran Sun, Mi-Kyung Shin, Meng Qin, Caleb F Anderson, Tian Xu, Jiarui Yang, Claire Sklar, Vsevolod Y Polotsky, Honggang Cui.
      Supramolecular polymeric hydrogels have emerged as a dynamic, versatile platform for localized therapeutic delivery, leveraging reversible and tunable noncovalent interactions. Despite their potential, designing supramolecular polymers that combine high drug loading with sustained, controlled release remains a considerable challenge. Here, we introduce a series of drug-inspired, peptide-based monomers engineered as supramolecular hydrogelators to facilitate high-affinity coassembly with therapeutic agents. By strategically utilizing electrostatic complexation and π-π stacking interactions, these hydrogelators self-assemble into robust supramolecular polymer networks with well-defined nanostructures, achieving nearly 100% fingolimod loading efficiency and extremely high loading capacity (up to approximately 32% by mass). Our results demonstrate that these tailored supramolecular interactions not only enhance the fingolimod drug loading efficiency and capacity, but also modulate the self-assembly and dissociation process, enabling prolonged and predictable drug release both in vitro and in vivo. We believe this work advances the field of supramolecular polymers by integrating drug-inspired molecular design principles and contributes to the development of advanced drug delivery systems with broader biomedical applications.
    Keywords:  controlled release; drug delivery; fingolimod; hydrogels; hypertension; supramolecular polymers
    DOI:  https://doi.org/10.1021/acsnano.5c02462
  6. Biofabrication. 2025 Jul 03.
    Biohybrid microstructured hydrogels obtained via in situ extracellular matrix deposition and decellularization using supercritical CO2.
    Vanessa Morais Lima, Albane Carré, Emmanuelle Poque, Maria-Dimitra Chiotelli, Natan Wiele, Christelle Harscoat-Schiavo, Raphaëlle Savoire, Teresa Simon-Yarza.
      In recent decades, our understanding of biomaterials has shifted from seeing them simply as physical supports for cells or drug delivery platforms to recognizing their active and dynamic role in tissue repair, guided by their physicochemical, mechanical, and biological properties. Biologically derived materials such as the decellularized extracellular matrix (dECM) offer the advantage of replicating the biomolecular cellular environment and have been proposed for tissue regeneration. However, their use as scaffolds is hindered by poor mechanical properties and limited tunability of physical features. Herein, we fabricated a bioinspired hybrid hydrogel by integrating a chemically cross-linked microporous polysaccharide scaffold with native ECM directly secreted by cells. First, the scaffold synthesis and culture conditions were optimized to enhance ECM deposition by fibroblasts. To obtain an acellular scaffold, decellularization using supercritical CO2 was performed and compared to a conventional method, demonstrating its superiority in ensuring efficient decellularization while preserving an enriched ECM lining the surface of the pores and preventing scaffold damage. The biohybrid hydrogel was characterized by a very low amount of DNA (< 5 ng DNA /mg) and a network of highly interconnected pores covered by an abundant ECM including collagen I, collagen IV, fibronectin, elastin and laminin. This work presents a new versatile strategy that can be adapted to various tissues to engineer biomimetic microstructured materials overcoming the limitations associated with polymer-based and dECM-based strategies when used independently.
    Keywords:  Extracellular matrix; biohybrid material; decellularization; polysaccharide hydrogel; scaffold; supercritical CO2
    DOI:  https://doi.org/10.1088/1758-5090/adebb4
  7. Nat Commun. 2025 Jul 03. 16(1): 6131
    Nanoscale electrostatic control in ferroelectric thin films through lattice chemistry.
    Ipek Efe, Alexander Vogel, William S Huxter, Elzbieta Gradauskaite, Iaroslav Gaponenko, Patrycja Paruch, Christian L Degen, Marta D Rossell, Manfred Fiebig, Morgan Trassin.
      Nanoscale electrostatic control of oxide interfaces enables physical phenomena and exotic functionalities beyond the realm of the bulk material. In technologically-relevant ferroelectric thin films, the interface-mediated polarization control is usually exerted by engineering the depolarizing field. Here, in contrast, we introduce polarizing surfaces and lattice chemistry engineering as an alternative strategy. Specifically, we engineer the electric-dipole ordering in ferroelectric oxide heterostructures by exploiting the charged sheets of the layered Aurivillius model system. By tracking in-situ the formation of the Aurivillius charged Bi2O2 sheets, we reveal their polarizing effect leading to the characteristic Aurivillius out-of-plane antipolar ordering. Next, we use the polarizing Bi2O2 stacking as a versatile electrostatic environment to create new electric dipole configurations. We insert multiferroic BiFeO3 into the Aurivillius framework to stabilize a ferrielectric-like non-collinear electric-dipole order in the final heterostructure while maintaining the antiferromagnetic order of BiFeO3. We thus demonstrate that engineering the lattice chemistry stabilizes unconventional ferroic orderings at the nanoscale, a strategy that may be expanded beyond the realm of electrically ordered materials.
    DOI:  https://doi.org/10.1038/s41467-025-60176-8
  8. Sci Adv. 2025 Jul 04. 11(27): eadx7398
    Nonliving dehydrated leaves-inspired surface anti-wrinkling.
    Xin-Lu Deng, Kai-Ming Hu, Wen-Qiang Yuan, Zhi-Qi Dong, Heng Zou, Fan Yang, Xue-Song Jiang, Guang Meng, Wen-Ming Zhang.
      "Living" organisms in nature exhibit robust and biologically intelligent surface anti-wrinkling. Nonetheless, the complexities of self-regulating stress or structural characteristics through growth or gene expression render the anti-wrinkling of "nonliving" artificial surfaces using bionic principles a pressing yet formidable challenge. Here, inspired by nonliving dehydrated leaves, we propose an on-demand customizable, material invariant, parametric surface anti-wrinkling strategy using leaf vein-imitated boundary curvature-coupled constraints. This strategy allows for an exact surface customization with enhanced anti-wrinkling capability, tailored to specific anti-wrinkling demands while maintaining the original cross-section materials. The defined parameters, anti-wrinkling width and concave radius, are customized by the anti-wrinkling design criteria via the dimensionless dual-correction stiffness model, which are simple linear or quadratic functions of anti-wrinkling demands and cross-section properties. Experiments at different scales and materials validate the correctness of the design criteria. The strategy in this study is effective on diverse wrinkle-prone surfaces at multiple scales and can inform real engineering design of the nonliving artificial surfaces.
    DOI:  https://doi.org/10.1126/sciadv.adx7398
  9. Macromolecules. 2024 Jul 23. 57(14): 6465-6473
    Molecularly Shielded, On-Demand, Ultrasound-Cured Polymer Networks.
    Adrian A Lorenzana, Hsu Shwe Yee Naing, Jichao Song, Jessica D Schiffman, John Klier, Shelly R Peyton.
      Networks formed from polymers can range from soft hydrogels to ultrahard protective coatings, making them useful for a wide range of applications from cell culture to highly bonded adhesives. Polymer networks are commonly crosslinked via heat or high energy light, and recently mechanical force has also been used to induce the formation of crosslinks in pre-existing networks. Here, we demonstrate a new strategy to use mechanical deformation and ultrasound to induce liquid-to-solid crosslinking. We synthesized graft copolymers with large poly(ethylene glycol) (PEG) side-chains acting as molecular shielding groups to protect otherwise highly reactive epoxide group. Solutions of highly shielded polymers could remain as a liquid solution when left undisturbed, and we could initiate gelation of these solutions with ultrasound in 20 seconds. These ultrasound-sensitive polymers are particularly useful in light and heat sensitive applications, and where precise control over the gelation time is required.
    Keywords:  Epoxide; methacrylates; poly(ethylene glycol)
    DOI:  https://doi.org/10.1021/acs.macromol.4c00315
  10. Nat Commun. 2025 Jul 01. 16(1): 5443
    A biomimetic multi-component subunit vaccine via ratiometric loading of hierarchical hydrogels.
    Fanfan Du, Simseok A Yuk, Yuan Qian, El Hadji Arona Mbaye, Michael P Vincent, Sharan Bobbala, Tirzah M Abbott, Hyeohn Kim, Yang Li, Haoyu Li, Sijia Yi, Baofu Qiao, Evan A Scott.
      The development of subunit vaccines that mimic the molecular complexity of attenuated vaccines has been limited by the difficulty of intracellular co-delivery of multiple chemically diverse payloads at controllable concentrations. We report on hierarchical hydrogel depots employing simple poly(propylene sulfone) homopolymers to enable ratiometric loading of a protein antigen and four physicochemically distinct adjuvants in a hierarchical manner. The optimized vaccine consisted of immunostimulants either adsorbed to or encapsulated within nanogels, which were capable of noncovalent anchoring to subcutaneous tissues. In female BALB/c and C57BL/6 mice, these 5-component nanogel vaccines demonstrated enhanced humoral and cell-mediated immune responses compared to formulations with standard single adjuvant and antigen pairing. The use of a single simple homopolymer capable of rapid and stable loading and intracellular delivery of diverse molecular cargoes holds promise for facile development and optimization of scalable subunit vaccines and complex therapeutic formulations for a wide range of biomedical applications.
    DOI:  https://doi.org/10.1038/s41467-025-60416-x
  11. Nat Protoc. 2025 Jul 02.
    Three-dimensional robotic structures fabricated and powered entirely with proteins.
    Haiyang Jia, Huan Sun, Johannes Flommersfeld, Wentao Shi, Frank Siedler, Petra Schwille.
      Assembling and upscaling biomolecular activity to perform work in man-made devices is a challenge in synthetic biology. Here we report the step-by-step process to construct fully protein-based micro-three-dimensional (3D) printed robotic structures, which are coated with and actuated by a minimal actomyosin cortex. This approach can be used to program self-powered soft robots assembled from multiple biomolecular modules, devising biophysical assays to quantify active forces produced in 3D and engineering smart 3D microchips for synthetic cell assembly. The procedure covers the establishment of 3D printing microstructures from protein materials, the assembly of actomyosin-based active coatings and the robotic structure design and characterization. The detailed step-by-step instructions will guide scientists in replicating the preparation procedures, facilitating the adoption of biomolecular microrobots and the development of 3D protein-based robotic technology and their applications. The procedure is suited for users with expertise in biomaterials and requires 15 d to complete.
    DOI:  https://doi.org/10.1038/s41596-025-01186-0
  12. Nat Mater. 2025 Jul;24(7): 1116-1125
    Hybrid epoxy-acrylate resins for wavelength-selective multimaterial 3D printing.
    Ji-Won Kim, Marshall J Allen, Elizabeth A Recker, Lynn M Stevens, Henry L Cater, Ain Uddin, Ang Gao, Wyatt Eckstrom, Anthony J Arrowood, Gabriel E Sanoja, Michael A Cullinan, Benny D Freeman, Zachariah A Page.
      Structures in nature combine hard and soft materials in precise three-dimensional (3D) arrangements, imbuing bulk properties and functionalities that remain elusive to mimic synthetically. However, the potential for biomimetic analogues to seamlessly interface hard materials with soft interfaces has driven the demand for innovative chemistries and manufacturing approaches. Here, we report a liquid resin for rapid, high-resolution digital light processing (DLP) 3D printing of multimaterial objects with an unprecedented combination of strength, elasticity and resistance to ageing. A covalently bound hybrid epoxy-acrylate monomer precludes plasticization of soft domains, while a wavelength-selective photosensitizer accelerates cationic curing of hard domains. Using dual projection for multicolour DLP 3D printing, bioinspired metamaterial structures are fabricated, including hard springs embedded in a soft cylinder to adjust compressive behaviour and a detailed knee joint featuring 'bones' and 'ligaments' for smooth motion. Finally, a proof-of-concept device demonstrates selective stretching for electronics.
    DOI:  https://doi.org/10.1038/s41563-025-02249-z
  13. iScience. 2025 Jul 18. 28(7): 112867
    A 3D printing UV-curing resin that enables continuous color change of elastomers.
    Yiyang Gao, Qihao Jiang, Yanming Liu.
      This study introduces a UV-curing resin leveraging the Christiansen effect to achieve dynamic color modulation in phase-separated elastomers (PSE) through solvent composition and temperature control. By matching refractive indices between solvent (dimethyl phthalate/tributyl citrate) and polymer phases, PSE selectively transmits-specific wavelengths, enabling continuous color shifts from red to purple. The elastomers exhibit robust mechanical properties (>600% elongation, >300 kPa modulus) and function across a broad temperature range (-25°C-130°C). Compatible with 3D printing, the resin enables real-time solvent adjustments during fabrication, supporting spatially continuous color transitions without parameter modifications. This approach advances applications in adaptive optical devices, temperature-responsive displays, and multi-material 3D printing, offering a dye-free strategy for structural coloration in smart materials.
    Keywords:  Chemistry; Materials science; Physics
    DOI:  https://doi.org/10.1016/j.isci.2025.112867
  14. Adv Mater. 2025 Jun 29. e2503245
    Xolography for Rapid Volumetric Production of Objects from the Nanoscopic to Macroscopic Length Scales.
    Xichuan Li, Yuan Xiu, Kenny Lee, Jin Zhang, Nathaniel Corrigan, Cyrille Boyer.
      Light-mediated 3D printing has revolutionized additive manufacturing, progressing from pointwise stereolithography, to layer-by-layer digital light processing, and most recently to volumetric 3D printing. Xolography, a novel light-sheet-based volumetric 3D printing approach, offers high-speed and high-precision fabrication of complex geometries unattainable with traditional methods. However, achieving nanoscale control (<100 nm) within these 3D printing systems remains unexplored. This work leverages polymerization-induced microphase separation (PIMS) within the xolography process to prepare network polymer materials with simultaneous control over feature sizes at the nano-, micro-, and macro-scale. By controlling the chain length and mass fraction of macromolecular chain transfer agents used in the PIMS process, precise manipulation of nanodomain size within 3D printed materials is demonstrated, while optimization of the other resin components enables the fabrication of rigid materials with feature sizes of 80 µm. Critically, the rapid one-step fabrication of complex and multi-component structures such as a functional waterwheel with interlocking parts, at high volume-building rates is showcased. This combined approach expands the design space for functional nanomaterials, opening new avenues for applications in diverse fields such as polymer electrolyte membranes, biomedical delivery systems, and semi-permeable microcapsules.
    Keywords:  auxiliary‐free fabrication; high resolution; nanostructure; polymerization‐induced microphase separation; self‐assembly; volumetric 3D printing; xolography
    DOI:  https://doi.org/10.1002/adma.202503245
  15. Sci Adv. 2025 Jul 04. 11(27): eadp4985
    Biomaterials for organically generated habitats beyond Earth.
    Robin Wordsworth, Rafid Quayum, Elida Kocharian, Ann Pearson, Xavier Portillo, Madeleine Yang, Charles S Cockell, Shannon Nangle, George Church.
      Sustaining life beyond Earth requires the creation of habitats, which is typically assumed to require costly transport of high-mass components from Earth. Here, we investigate an alternative approach based on in situ fabrication using biologically generated materials. We show that several common biomaterials are capable of blocking UV radiation, transmitting visible light, and maintaining pressure differences sufficient to permanently stabilize liquid H2O in a vacuum or low-pressure environment. As a proof of concept, we then demonstrate growth of eukaryotic green alga in a 3D printed PLA bioplastic habitat under Mars-relevant conditions of a 600 Pa CO2 background atmosphere. Our results demonstrate that products of biology itself can be used to create habitats in extraterrestrial environments. This approach is scalable, sustainable, and plausibly could be extended to construction of human habitats in the future.
    DOI:  https://doi.org/10.1126/sciadv.adp4985
  16. Trends Biotechnol. 2025 Jun 27. pii: S0167-7799(25)00223-9. [Epub ahead of print]
    3D extrusion bioprinting: rational bioink design and advanced fabrication techniques.
    Maximilian Jergitsch, Miguel Angel Mateos-Timoneda.
      The field of 3D extrusion bioprinting has rapidly evolved, presenting significant advancements in tissue engineering applications. Traditionally, the development of printable hydrogel formulations has relied more on empirical approaches rather than rational design principles. However, to better mimic the dynamic and spatiotemporal nature of the extracellular matrix (ECM), novel bioinks with tunable properties and synthetic flexibility are being developed. Simultaneously, variations of extrusion bioprinting methods have been developed to improve the fabrication of sophisticated tissue patterns to emulate their in vivo counterparts. This review will provide a focused overview of recent advancements in bioink design and extrusion bioprinting technologies. By addressing the latest developments in these strategies, this review aims to offer insights into the future direction of extrusion bioprinting.
    Keywords:  3D bioprinting; bioink; extracellular matrix (ECM); hydrogel; viscoelasticity
    DOI:  https://doi.org/10.1016/j.tibtech.2025.06.008
  17. ACS Appl Mater Interfaces. 2025 Jun 29.
    Allomelanin-Inspired Polyurethane Nanocomposites with Multi-Radiation Resistance and Enhanced Mechanical Properties.
    Lauren M Irie, Broderick Lewis, Ashley K Nensel, Elisabeth I Latawiec, Anni J Kuningas, Michael R Wasielewski, Zheng Wang, Kenneth R Shull, Nathan C Gianneschi.
      Approaches for protecting polymeric materials against ionizing radiation are of importance for applications including in space, in aseptic medical devices, and in the nuclear industry. Allomelanin is a specific subclass of nitrogen-free melanin found to play a key role in the protection of fungal species in extreme environments. Herein, we prepared allomelanin-inspired nanomaterials by oxidatively polymerizing dihydroxynapthalene (DHN) isomers 1,7-DHN and 2,3-DHN. We demonstrate that these materials can be easily dispersed into a polyurethane (PU) elastomer, yielding products with tunable mechanical properties and optical transparency. We show that at loadings as low as 0.25 wt %, this approach provides UVB protection to the PU matrix maintaining mechanical properties despite exposure, preservation of composite surface chemistry, and suppression of crack formation. Furthermore, we show that these composites maintain their mechanical properties after exposure to gamma irradiation, demonstrating the multiradiation protective effect of these allomelanin-inspired nanomaterials.
    Keywords:  allomelanin; composites; dihydroxynapthalene; polyurethane elastomer; radiation resistant; synthetic melanin; ultraviolet radiation; γ radiation
    DOI:  https://doi.org/10.1021/acsami.5c05674
  18. J Phys Chem B. 2025 Jun 28.
    Photoactivated Nano-Compatibilized Two-Phase Polymer Blends: An Approach for Determining Mechanical Behavior.
    Surbhi Khewle, Pratyush Dayal.
      Light-activated polymers (LAPs) are shape-shifting materials capable of transforming their shapes in response to photoinduced chemical reactions, such as cis-trans isomerization and dimerization. Owing to the underlying photochemical reaction, these materials often exhibit behavior analogous to multicomponent/phase polymer blends. In this work, we present a free-energy-based theoretical framework to predict the mechanical behavior of nanoparticle-compatibilized elastic LAP blends that exhibit phase separation. In particular, we incorporate the impact of domain sizes and interfacial areas and establish a criterion for the materials' susceptibility to mechanical failure under various loading conditions, namely uniaxial and biaxial stretching. Our framework can also be adapted to high-entropy polymers and thermoresponsive or light-activated systems, with potential applications in soft robotics, biomedical devices, micromechanics, 4D printing, and material origami. Additionally, by integrating our model with physics-informed neural networks, we facilitate efficient analysis of complex domain geometries and enable comprehensive parametric studies.
    DOI:  https://doi.org/10.1021/acs.jpcb.5c02717
  19. Nat Commun. 2025 Jul 01. 16(1): 5650
    Janus particles stabilized asymmetric porous composites for thermal rectification.
    Chao Jiang, Xiao Yang, Xingmei He, Chunyang Wang, Haisheng Chen, Xinghua Zheng, Fuxin Liang.
      Thermal rectification is a noteworthy phenomenon of asymmetric material, which enables the directional transfer of thermal energy. But the design and construction of such asymmetric thermal conductive materials with complex structures are full of challenges. Here, an additive manufacturing method is proposed to fabricate asymmetric porous composites from layer-by-layer cast emulsions, stabilized with Janus particles (JPs), for thermal rectification. The emulsions are remarkably stable, allowing each layer to be manipulated independently without interference, resulting in a porous structure with significant asymmetry. The thermal rectification of JPs-stabilized asymmetric porous composites (JAPCs) is investigated through both experiments and simulations. It is found that their thermal rectification ratios can be adjusted by altering the contrast between the two layers of the asymmetric porous composites, with a maximum value of 38%. This emulsion casting additive manufacturing method is suitable for large-scale production. A simple model demonstrates the potential of JAPCs to regulate thermal energy in ambient conditions with fluctuating temperatures. It is explored to achieve multilayer alternating porous composites, which cannot be achieved with gradient asymmetric approaches. This method provides a practical way to design and fabricate complicated porous structures with potential applications in additive manufacturing.
    DOI:  https://doi.org/10.1038/s41467-025-60792-4
  20. J Phys Condens Matter. 2025 Jul 03.
    Roadmap for Animate Matter.
    Giorgio Volpe, Nuno A M Araujo, Maria Guix, Mark Miodownik, Nicolas Martin, Laura Alvarez, Juliane Simmchen, Roberto di Leonardo, Nicola Pellicciotta, Quentin Martinet, Jérémie Palacci, Wai Kit Ng, Dhruv Saxena, Riccardo Sapienza, Sara Nadine, João Mano, Reza Mahdavi, Caroline Beck Adiels, Joe Forth, Christian Santangelo, Stefano Palagi, Ji Min Seok, Victoria A Webster-Wood, Shuhong Wang, Lining Yao, Amirreza Aghakhani, Thomas Barois, Hamid Kellay, Corentin Coulais, Martin van Hecke, Christopher J Pierce, Tianyu Wang, Baxi Chong, Daniel I Goldman, Andreagiovanni Reina, Vito Trianni, Giovanni Volpe, Richard Beckett, Sean P Nair, Rachel Armstrong.
      Humanity has long sought inspiration from nature to innovate materials and devices. As science advances, nature-inspired materials are becoming part of our lives. Animate materials, characterized by their activity, adaptability, and autonomy, emulate properties of living systems. While only biological materials fully embody these principles, artificial versions are advancing rapidly, promising transformative impacts in the circular economy, health and climate resilience within a generation. This roadmap presents authoritative perspectives on animate materials across different disciplines and scales, highlighting their interdisciplinary nature and potential applications in diverse fields including nanotechnology, robotics and the built environment. It underscores the need for concerted efforts to address shared challenges such as complexity management, scalability, evolvability, interdisciplinary collaboration, and ethical and environmental considerations. The framework defined by classifying materials based on their level of animacy can guide this emerging field to encourage cooperation and responsible development. By unravelling the mysteries of living matter and leveraging its principles, we can design materials and systems that will transform our world in a more sustainable manner.&#xD.
    Keywords:  active matter; animate materials; animate matter; roadmap
    DOI:  https://doi.org/10.1088/1361-648X/adebd3
  21. Chembiochem. 2025 Jul 02. e202500310
    Photo-triggered Hyaluronic Acid Hydrogel for 3D Culture and Cell Recovery.
    Francesco Palmieri, Marième Gueye, Lucía Vicario Del Rio, Saskia Bunschuh, Pradeep Chopra, Silvia Mihăilă, Tina Vermonden, Riccardo Levato, Geert-Jan Boons.
      Properties of semi-synthetic hydrogels can be fine-tuned making these attractive for various applications in regenerative medicine. Here, we describe a hydrogel platform based on hyaluronic acid (HA) modified by (1R,8S,9S)-bicycle[6.1.0]non-4-yn-9-ylmethanol (BCN) and a cross-linker composed of light sensitive o-nitrobenzyl and polyethylene glycol (PEG) chains terminating in azides. The two components can undergo strain-promoted azide-alkyne cycloaddition (SPAAC) resulting in rapid gel formation. First, we incorporated adipose-derived mesenchymal stromal cells (aMSCs) in the hydrogel and demonstrated that the cells can be easily retrieved by UV light mediated degradation maintaining viability and retaining spindle-like shape when the cells were replated. Next, we provided a proof-of-concept of inducing light-mediated softening of the hydrogel to modulate the morphology of the encapsulated cells. A co-culture of endothelial cells (cord blood-derived endothelial colony forming cells (ECFCs) and bone marrow derived mesenchymal stromal cells (bmMSCs), which are commonly studied for their ability to form capillary-like vascular networks, were cultured in the regular and light induced softened hydrogels. Non-photoexposed hydrogels showed cells with a prevalently rounded morphology, whereas stretched cells connecting into a primitive capillary network were observed in the light-softened hydrogels. Photo-induced softening offers potential to locally control cell shape and self-organization capacity.
    Keywords:  hyaluronic acid; hydrogels; photosensitivity; polymeric biomaterials; synthetic methods
    DOI:  https://doi.org/10.1002/cbic.202500310
  22. Nat Commun. 2025 Jul 01. 16(1): 5825
    Flow-induced 2D nanomaterials intercalated aligned bacterial cellulose.
    M A S R Saadi, Yufei Cui, Shyam P Bhakta, Sakib Hassan, Vijay Harikrishnan, Ivan R Siqueira, Matteo Pasquali, Matthew Bennett, Pulickel M Ajayan, Muhammad M Rahman.
      Bacterial cellulose is a promising biodegradable alternative to synthetic polymers due to the robust mechanical properties of its  nano-fibrillar building blocks. However, its full potential of mechanical properties remains unrealized, primarily due to the challenge of aligning nanofibrils at the macroscale. Additionally, the limited diffusion of other nano-fillers within the three-dimensional nanofibrillar network impedes the development of multifunctional bacterial cellulose-based nanosheets. Here, we report a simple, single-step, and scalable bottom-up strategy to biosynthesize robust bacterial cellulose sheets with aligned nanofibrils and bacterial cellulose-based multifunctional hybrid nanosheets using shear forces from fluid flow in a rotational culture device. The resulting bacterial cellulose sheets display high tensile strength (up to ~ 436 MPa), flexibility, foldability, optical transparency, and long-term mechanical stability. By incorporating boron nitride nanosheets into the liquid nutrient media, we fabricate bacterial cellulose-boron nitride hybrid nanosheets with even better mechanical properties (tensile strength up to ~ 553 MPa) and thermal properties (three times faster rate of heat dissipation compared to control samples). This biofabrication approach yielding aligned, strong, and multifunctional bacterial cellulose sheets would pave the way towards applications in structural materials, thermal management, packaging, textiles, green electronics, and energy storage.
    DOI:  https://doi.org/10.1038/s41467-025-60242-1
  23. Nat Commun. 2025 Jul 04. 16(1): 6176
    2D fracture-resistant high-entropy-oxide scaffold enabled multifunctional nanomembrane.
    Chuanzheng Li, Wenqing Zhu, Quanfeng He, Hang Wang, Yushan Geng, Zhibo Zhang, Yun Teng, Jilai Wang, Zhutian Xu, Linfa Peng, Yong Yang.
      In flexible electronics, the need for ultrathin encapsulation offering a blend of features is crucial. While metal-oxide films are often considered promising candidates, their inherent brittleness has limited their practical utility. Here, we have engineered freestanding fracture-resistant high-entropy-oxide (HEO) nanomembranes by creating an in-situ nano-oxide scaffold within hydrogels. The HEO nanomembranes exhibit ductility nearing 90% and toughness exceeding 300 MJ/m3, surpassing traditional metal and metal-oxide films, as well as many advanced 2D materials. These mechanical properties are a result of the dual-phase nanostructure, where the HEO scaffold intertwined with decomposed hydrogel chains provides hierarchical toughening mechanisms that effectively impede and deflect crack propagation. Furthermore, our nanomembranes demonstrate strong adhesion to diverse substrates and impressive optical characteristics, boasting a visible transmittance of 83.2%. Even under high-temperature and humid conditions with a ~ 5% bending strain, the nanomembrane proves effective in preventing oxidation of copper circuits.
    DOI:  https://doi.org/10.1038/s41467-025-61446-1
  24. Methods Mol Biol. 2025 ;2937 217-227
    Genetic Code Expansion to Enable Site-Specific Posttranslational Peptide Epitope Tagging of G Protein-Coupled Receptors in Live Cells.
    Jordan M Mattheisen, Thomas Huber, Thomas P Sakmar.
      Genetically encoded monoclonal antibody (mAb) epitope tags are often engineered into heterologously expressed proteins to allow for detection or purification. The most common method for epitope tagging is to introduce the nucleotide sequence encoding a known mAb peptide epitope into the gene of interest to create a fusion protein. This strategy can be used to introduce one or more epitope tags co-translationally into the expressed protein of interest. We describe here a method to introduce mAb epitope tags posttranslationally into expressed proteins that harbor a noncanonical amino acid (ncAA) with a reactive side chain. Genetic code expansion using amber codon suppression facilitates the site-specific introduction of the ncAA, which can then be covalently linked to an activated peptide epitope using a bioorthogonal coupling reaction. The coupling reactions described can be used for in vitro applications or in live cells in culture. We describe a specific example of posttranslational epitope tagging of the extracellular surface of a G protein-coupled receptor in live cells.
    Keywords:  Amber codon suppression; Bioorthogonal reaction; Epitope; G protein-coupled receptor; Genetic code expansion; Posttranslational
    DOI:  https://doi.org/10.1007/978-1-0716-4591-8_13
  25. Nat Commun. 2025 Jul 01. 16(1): 6055
    Accelerating cell culture media development using Bayesian optimization-based iterative experimental design.
    Harini Narayanan, Joshua A Hinckley, Rachel Barry, Brendan Dang, Lenna A Wolffe, Adel Atari, Yuen-Yi Tseng, J Christopher Love.
      Optimizing operational conditions for complex biological systems used in life sciences research and biotechnology is an arduous task. Here, we apply a Bayesian Optimization-based iterative framework for experimental design to accelerate cell culture media development for two applications. First, we show that this approach yields new compositions of media with cytokine supplementation to maintain the viability and distribution of human peripheral blood mononuclear cells in the culture. Second, we apply this framework to optimize the production of three recombinant proteins in cultivations of K.phaffii. We identified conditions with improved outcomes for both applications compared to the initial standard media using 3-30 times fewer experiments than that estimated for other methods such as the standard Design of Experiments. Subsequently, we also demonstrated the extensibility of our approach to efficiently account for additional design factors through transfer learning. These examples demonstrate how coupling data collection, modeling, and optimization in this iterative paradigm, while using an exploration-exploitation trade-off in each iteration, can reduce the time and resources for complex optimization tasks such as the one demonstrated here.
    DOI:  https://doi.org/10.1038/s41467-025-61113-5
  26. Nat Commun. 2025 Jul 01. 16(1): 5707
    An mRNA lipid nanoparticle-incorporated nanofiber-hydrogel composite for cancer immunotherapy.
    Yining Zhu, Zhi-Cheng Yao, Shuyi Li, Jingyao Ma, Christine Wei, Di Yu, Jessica L Stelzel, Bobby Y X Ni, Yang Miao, Kyra Van Batavia, Xiaoya Lu, Jinghan Lin, Yifan Dai, Jiayuan Kong, Ruochen Shen, Kailei D Goodier, Xiang Liu, Leonardo Cheng, Ivan Vuong, Gregory P Howard, Natalie K Livingston, Joseph Choy, Jonathan P Schneck, Joshua C Doloff, Sashank K Reddy, John W Hickey, Hai-Quan Mao.
      Hydrogel materials have emerged as versatile platforms for various biomedical applications. Notably, the engineered nanofiber-hydrogel composite (NHC) has proven effective in mimicking the soft tissue extracellular matrix, facilitating substantial recruitment of host immune cells and the formation of a local immunostimulatory microenvironment. Leveraging this feature, here we report an mRNA lipid nanoparticle (LNP)-incorporated NHC microgel matrix, termed LiNx, by incorporating LNPs loaded with mRNA encoding tumour antigens. Harnessing the high transfection efficiency of LNPs in antigen-presenting cells, LiNx demonstrates substantial levels of immune cell recruitment, antigen expression and presentation, and cellular interaction. These attributes collectively create an immunostimulating microenvironment and yield a potent immune response with a single dose at a level comparable to the conventional three-dose LNP immunization protocol. Further investigation reveals that the LiNx generates not only high levels of Th1 and Th2 responses, but also a distinct Type 17 T helper cell response critical for bolstering antitumour efficacy. Our findings elucidate the mechanism underlying LiNx's role in potentiating antigen-specific immune responses, presenting a strategy for cancer immunotherapy.
    DOI:  https://doi.org/10.1038/s41467-025-61299-8
  27. Nat Commun. 2025 Jul 01. 16(1): 6052
    Edge-activated graphene nanopores for thermally robust hydrogen membrane separations.
    Chi Cheng, Lohyun Kim, Aaron H Persad, Chun Man Chow, Rohit Karnik.
      Temperature-dependent, selective molecular diffusion through porous materials is crucial for membrane separations and is typically modeled as an Arrhenius-type activated process. Although this dependence can be described phenomenologically by an activation energy, tracing its molecular origins is often difficult, hindering robust membrane design for practical applications. Here, we investigate gas transport across monolayer nanoporous graphene membranes and observe significant, reversible, temperature-robust, and gas species-selective activated transport, with increased selectivity at rising temperatures, unlike many conventional membranes. Combined experiment and modelling trace this behavior to graphene nanopore edge functional groups, whose thermal fluctuations modulate effective pore size. This activated transport remains stable with aging over 1 year and shows selectivity exceeding 70 for hydrogen/hydrocarbon mixture separation at 220 °C, representative of dehydrogenation reactor temperatures. Our results demonstrate the thermal and long-term robustness of nanoporous graphene membranes, suggesting potential for precise engineering of nanopore surface chemistries in membranes for challenging molecular separations.
    DOI:  https://doi.org/10.1038/s41467-025-61110-8
  28. Nat Commun. 2025 Jul 01. 16(1): 5813
    N-alkylated polydithiocarbamates derived from thiocarbonyl fluoride as macro-photoiniferters for living 3D printing.
    Pengfei Ruan, Haonan Xiang, Wenbin Yi, Jieping Wang.
      Polydithiocarbamates represent a unique class of sulfur-containing polymers possessing advanced functionalities. However, their structural and functional exploration has been limited by significant synthetic challenges. Existing methods primarily yield polydithiocarbamates incorporating secondary amides within the polymer backbone. Herein, we report a versatile synthetic strategy enabling access to previously inaccessible N-alkylated polydithiocarbamates. Utilizing secondary diamines, dithiols, and thiocarbonyl fluoride, we efficiently synthesize these polymers with diverse structures. Notably, these materials function as superior macro-photoiniferters for fully open-to-air 3D printing, exhibiting enhanced resolution and outperforming small-molecule analogues. Critically, the dormant dithiocarbamate functionalities within the 3D-printed structures can be reactivated for iterative modifications, demonstrating the potential for living 3D printing. More interestingly, the unique capability of the macro-photoiniferter (P1) to eliminate stair-stepping layer patterns without requiring printer modifications or additional pre- or post-processing steps represents a simple yet powerful approach that could substantially enhance the flexibility and output quality of DLP 3D printing. We demonstrate that thiocarbonyl fluoride is a key reagent for the controlled synthesis of sulfur-containing polymers. We anticipate that our polydithiocarbamate-based macro-photoiniferters will drive advancements in diverse fields, including biomedicine, energy, and materials science.
    DOI:  https://doi.org/10.1038/s41467-025-60955-3
  29. Small. 2025 Jul 01. e2502129
    "Grafting-to" Polymers of Xylan-g-allyl Glycidyl Ether Toughen PEG Hydrogel via Microphase Separation: Thermoresponsive and Photoreactive Molecular Assembly in DLP 3D Printing.
    Yidong Zhang, Qingbo Wang, Wangfang Deng, Silva Hazer, Axel Luukkonen, Andrey Pranovich, Outi M H Salo-Ahen, Ronald Österbacka, Chunlin Xu, Xiaoju Wang.
      Utilizing naturally derived biopolymers in the macromolecular design of thermoresponsive polymers offers sustainable and biodegradable smart building blocks to functional materials. Here, a novel graft polymer of xylan-g-allyl glycidyl ether (xylan-g-AGE) that is thermoresponsive to self-assemble and photoreactive in photopolymerization is reported. This research highlights an innovative use of the debranched wood xylan, a chemically engineered linear polysaccharide of β-1,4-linked xylose, as the backbone in grafting polymer, which allows a greater degree of spatial coordination for sidechains than the analogous cellulose. Induced by the reformation of H-bonds and hydrophobic effect, xylan-g-AGE transits from solvated coil chain to self-assembled mesoglobules upon the temperature change above its lower critical solution temperature (LCST). When xylan-g-AGE is used in photoresins to fabricate hydrogels with good geometric fidelity via DLP 3D printing, solvated xylan-g-AGE stiffens the polyethylene glycol (PEG) hydrogel strongly, due to higher crosslink density of available AGE moiety and faster crosslinking rate, while self-assembled xylan-g-AGE toughens the PEG hydrogel better, attributed to the strategy of "dual chemically independent domains" that smartly combines tough domain of PEG and soft domain of self-assembled xylan-g-AGE. Conductive hydrogel is fabricated by incorporating 2D MXene sheets into this hydrogel matrix in DLP printing, which demonstrates superior performance as wearable strain sensors.
    Keywords:  DLP printing; conductive hydrogel; photopolymerization; thermoresponsive polymer; xylan
    DOI:  https://doi.org/10.1002/smll.202502129
  30. Nat Commun. 2025 Jul 01. 16(1): 5888
    Modular shape-changing tensegrity-blocks enable self-assembling robotic structures.
    Luyang Zhao, Yitao Jiang, Muhao Chen, Kostas Bekris, Devin Balkcom.
      Modular robots are currently designed to perform a variety of tasks, primarily focusing on locomotion or manipulation through the reconfiguration of rigid modules. However, the potential to integrate multiple functions, such as making each robot deployable and capable of building lattice structures for self-construction and infrastructure creation, remains largely unexplored. To advance the field, we hypothesize that combining tensegrity principles with modular robotics can create lightweight, deformable units capable of integrating three critical functions within a single design: navigating varied terrains, manipulating arbitrary shape objects, and assembling weight-sustainable, active large infrastructures. Here, we designed untethered modular robots that are deformable, lightweight, deployable, outdoor-scale, capable of bearing loads, and capable of 3D attachment and detachment. With these characteristics, the system can form various 3D structures using different assembly methods, such as walking into position or being transported by rotorcraft. The deformability and lightweight nature of each block enable the assembled structures to dynamically change shape, providing capabilities such as added compliance during locomotion and manipulation and the ability to interact with the environment in tasks like tent and bridge assemblies. In summary, we suggest that integrating lightweight and deformable properties into modular robot design offers potential improvements in their adaptability and multi-functionality.
    DOI:  https://doi.org/10.1038/s41467-025-60982-0
  31. Nat Microbiol. 2025 Jul;10(7): 1581-1592
    Intraspecies warfare restricts strain coexistence in human skin microbiomes.
    Christopher P Mancuso, Jacob S Baker, Evan B Qu, A Delphine Tripp, Ishaq O Balogun, Tami D Lieberman.
      Determining why only a fraction of encountered or applied strains engraft in a given person's microbiome is crucial for understanding and engineering these communities. Previous work has established that metabolic competition between bacteria can restrict colonization success in vivo, but other mechanisms may also prevent successful engraftment. Here we combine genomic analysis and high-throughput agar competition assays to demonstrate that intraspecies warfare presents a significant barrier to strain coexistence in the human skin microbiome by profiling 14,884 pairwise interactions between Staphylococcus epidermidis isolates cultured from 18 people from 6 families. We find that intraspecies antagonisms are abundant, mechanistically diverse, independent of strain relatedness and consistent with rapid evolution via horizontal gene transfer. Critically, these antagonisms are significantly depleted among strains residing on the same person relative to random assemblages, indicating a significant in vivo role. Wide variation in antimicrobial production and resistance suggests trade-offs between these factors and other fitness determinants. Together, our results emphasize that accounting for intraspecies warfare may be essential to the design of long-lasting probiotic therapeutics.
    DOI:  https://doi.org/10.1038/s41564-025-02041-4
  32. Science. 2025 Jul 03. 389(6755): 37-38
    The vaccine we all wear: Skin microbiota can be engineered into topical vaccines.
    Djenet Bousbaine.
      Skin microbiota can be engineered into topical vaccines.
    DOI:  https://doi.org/10.1126/science.adz0485
  33. Trends Biotechnol. 2025 Jul 01. pii: S0167-7799(25)00212-4. [Epub ahead of print]
    Bioprinting of piezoresistive organohydrogel networks for advanced real-time mechanosensing in engineered tissue models.
    Miriam Filippi, Asia Badolato, Antonia Georgopoulou, Diana Mock, Jakob Schreiner, Mike Y Michelis, Esther Amstad, Robert K Katzschmann.
      Understanding biomechanics in 3D cell culture is key to advancing tissue engineering, yet integrating real-time sensing into soft tissues remains a challenge. We developed a stretchable, piezoresistive hydrogel by combining PEDOT:PSS with a polyvinyl alcohol-sodium alginate matrix, optimized for detecting mechanical stimuli. This conductive organohydrogel exhibited a linear strain response. It was co-printed with a muscle cell-laden bioink to fabricate complex tissue architectures, maintaining structural stability and supporting tissue maturation. The embedded conductive hydrogel functioned as a flexible strain sensor, capable of detecting both bulk and localized mechanical inputs, with high sensitivity (0.054 per unit strain) and a strain detection limit of approximately 3%. Sensor data enabled spatial mapping of mechanical forces, offering a new strategy for real-time mechanosensing in engineered tissues. This approach provides a novel solution for integrating soft, biocompatible sensors into living tissues for applications in biomechanics and regenerative medicine.
    Keywords:  PEDOT:PSS; biomechanics; bioprinting; hydrogels; sensors; stretchable electronics; tissue engineering
    DOI:  https://doi.org/10.1016/j.tibtech.2025.05.026
  34. Sci Adv. 2025 Jul 04. 11(27): eadu5294
    Deciphering the stability of two-dimensional III-V semiconductors: Building blocks and their versatile assembly.
    Yuan Yan, Kaiyun Chen, Minglei Sun, Yinchang Ma, Peiyao Wang, Junkai Deng, Xixiang Zhang, Jefferson Zhe Liu.
      Two-dimensionalization unlocks the unique and superior physical properties of materials, but extending it to nonlayered crystals is challenging. Using density functional theory and machine learning, we unveil a universal rule for creating stable two-dimensional counterparts of traditional high-performance III-V semiconductors, i.e., the versatile assembly of building blocks originating from orbital hybridization and electron transfers adhering to the electron counting rule. Akin to LEGO construction, the various building blocks are arranged in different configurations, introducing diverse two-dimensional structures with higher energetic stability than previous structures. Regression analysis reveals the energies of these structures as a linear superposition of the energies of their building blocks, further confirming the LEGO concept. Notably, the predicted two-dimensional GaSb exhibits a hole mobility (~108 square centimeters per volt per second) that far surpasses that of graphene (2 × 105 square centimeters per volt per second). This study highlights the expansion of nonlayered materials into two dimensions and the potential of two-dimensional confinement in traditional materials.
    DOI:  https://doi.org/10.1126/sciadv.adu5294
  35. Mater Today Bio. 2025 Aug;33 101961
    From in vitro to in vivo: Diverse applications of kirigami technology in medical devices.
    Fengqin Li, Yang Zhou, Yuxue Hu, Xiaoming Feng, Guizhong Tian.
      Kirigami, as a paper-cutting art, has developed into an innovative design and manufacture strategy with the support of material diversity and modern manufacturing technology. Combining the mechanical, electrical, and magnetic properties of materials, carefully designed geometric shapes can significantly improve mechanical flexibility, two-dimensional and three-dimensional reconfiguration, and functionality. This paper focuses on medical devices, and reviews the pattern design, deformation characteristics, function realization and diversified applications of advanced kirigami technology in this field. And the design influencing factors, basic deformation mechanism and various fabrication methods of kirigami are also discussed. Medical devices are mainly classified by in vitro and in vivo applications, with different functions such as monitoring, power supply, and treatment as sub-categories. At the same time, the application potential of kirigami-based smart devices in medical applications and the auxiliary role of simulation technology in design are discussed. On this basis, the challenges and prospects of the research and development in the field of medical health inspired by kirigami are summarized and prospected.
    Keywords:  In vitro and in vivo medical devices; Kirigami; Smart technology
    DOI:  https://doi.org/10.1016/j.mtbio.2025.101961
  36. Angew Chem Int Ed Engl. 2025 Jun 30. e202509618
    Porous Organic Cages as Building Blocks for Framework Materials.
    Marcos Martínez-Fernández, Yannic Hartmann, Bernd M Schmidt.
      Confined nanospaces play a fundamental role in nature, inspiring synthetic analogues that emulate biological precision and efficiency. Among these, porous crystalline materials such as covalent organic frameworks (COFs), metal-organic frameworks (MOFs), and molecular cage compounds have emerged as powerful platforms for catalysis, separation, and energy storage. Recent developments highlight the potential of porous organic cages (POCs) as modular building blocks for the construction of advanced materials. In this Minireview, their integration into extended frameworks, such as Cage-COFs and Cage-MOFs, is described, as they allow precise control over porosity and enhance chemical robustness. These hybrids merge the structural regularity of COFs with the discrete functionality of cages, enabling the design of lightweight, hierarchically organised materials. In addition, polymer-containing Cage-POPs and supramolecular frameworks are discussed. Collectively, these developments position POCs as versatile synthons for next-generation porous materials, unlocking pathways toward functional, adaptive, and recyclable architectures.
    Keywords:  Covalent organic frameworks; Porous materials; Self-assembly; metal-organic frameworks; porous organic cages
    DOI:  https://doi.org/10.1002/anie.202509618
  37. Nat Commun. 2025 Jul 01. 16(1): 5648
    A generalized platform for artificial intelligence-powered autonomous enzyme engineering.
    Nilmani Singh, Stephan Lane, Tianhao Yu, Jingxia Lu, Adrianna Ramos, Haiyang Cui, Huimin Zhao.
      Proteins are the molecular machines of life with numerous applications in energy, health, and sustainability. However, engineering proteins with desired functions for practical applications remains slow, expensive, and specialist-dependent. Here we report a generally applicable platform for autonomous enzyme engineering that integrates machine learning and large language models with biofoundry automation to eliminate the need for human intervention, judgement, and domain expertise. Requiring only an input protein sequence and a quantifiable way to measure fitness, this automated platform can be applied to engineer a wide array of proteins. As a proof of concept, we engineer Arabidopsis thaliana halide methyltransferase (AtHMT) for a 90-fold improvement in substrate preference and 16-fold improvement in ethyltransferase activity, along with developing a Yersinia mollaretii phytase (YmPhytase) variant with 26-fold improvement in activity at neutral pH. This is accomplished in four rounds over 4 weeks, while requiring construction and characterization of fewer than 500 variants for each enzyme. This platform for autonomous experimentation paves the way for rapid advancements across diverse industries, from medicine and biotechnology to renewable energy and sustainable chemistry.
    DOI:  https://doi.org/10.1038/s41467-025-61209-y
  38. Nature. 2025 Jul 02.
    3D printing offers a way to study mimicry by insects.
    Thomas N Sherratt, Karl Loeffler-Henry.
      
    Keywords:  Animal behaviour; Evolution
    DOI:  https://doi.org/10.1038/d41586-025-01766-w
  39. J Am Chem Soc. 2025 Jun 30.
    A Molecular Glue Approach to Control the Half-Life of CRISPR-Based Technologies.
    Vedagopuram Sreekanth, Max Jan, Kevin T Zhao, Donghyun Lim, Surached Siriwongsup, Jessie R Davis, Marie McConkey, Veronica Kovalcik, Sam Barkal, Benjamin K Law, James Fife, N Tian, Michael E Vinyard, Basheer Becerra, Martin Kampmann, Richard I Sherwood, Luca Pinello, David R Liu, Benjamin L Ebert, Amit Choudhary.
      Cas9 is a programmable nuclease that has furnished transformative technologies, including base editors and transcription modulators (e.g., CRISPRi/a), but several applications of these technologies, including therapeutics, mandatorily require precision control of their half-life. For example, such control can help avert any potential immunological and adverse events in clinical trials. Current genome editing technologies to control the half-life of Cas9 are slow, have lower activity, involve fusion of large response elements (>230 amino acids), utilize expensive controllers with poor pharmacological attributes, and cannot be implemented in vivo on several CRISPR-based technologies. We report a general platform for half-life control using the molecular glue, pomalidomide, that binds to a ubiquitin ligase complex and a response-element bearing CRISPR-based technology, thereby causing the latter's rapid ubiquitination and degradation. Using pomalidomide, we were able to control the half-life of large CRISPR-based technologies (e.g., base editors and CRISPRi) and small anti-CRISPRs that inhibit such technologies, allowing us to build the first examples of on-switch for base editors. The ability to switch on, fine-tune, and switch-off CRISPR-based technologies with pomalidomide allowed complete control over their activity, specificity, and genome editing outcome. Importantly, the miniature size of the response element and favorable pharmacological attributes of the drug pomalidomide allowed control of activity of base editor in vivo using AAV as the delivery vehicle. These studies provide methods and reagents to precisely control the dosage and half-life of CRISPR-based technologies, propelling their therapeutic development.
    DOI:  https://doi.org/10.1021/jacs.5c06230
  40. Cold Spring Harb Perspect Biol. 2025 Jun 30. pii: a041795. [Epub ahead of print]
    Engineered In Vitro Platforms for Mechanochemical Control of Cell Migration.
    Bishwa Ranjan Si, Qinling Yuan, Sanjiban Nath, Bhawana Agarwal, Alice Amitrano, Debanik Choudhury, Konstantinos Konstantopoulos.
      Cell migration in confined environments follows distinct mechanisms compared to conventional 2D migration. By using in vitro models and incorporating extracellular cues from the tissue microenvironment, we can gain deeper insights into the complexities of cell migration. In this work, we explore various engineered in vitro models to study cell migration. We delve into biophysical tools, such as traction force microscopy, to understand how cells generate forces in response to their surroundings. We highlight the use of novel optogenetic tools for precise, spatiotemporal control of protein expression at the cellular level. Lastly, we examine emerging therapeutic strategies designed to target abnormal cell migration.
    DOI:  https://doi.org/10.1101/cshperspect.a041795
  41. ACS Nano. 2025 Jul 02.
    Reversible Physical Gelation of Thermotropic Liquid Crystals Driven by Nanoplate Self-Assembly.
    Yifan Ning, Dai-Bei Yang, Zhe Liu, Shengsong Yang, Yugang Zhang, Chinedum O Osuji, Jeffery G Saven, Christopher B Murray.
      Physically gelled soft materials, driven by the self-assembly of low-molecular-mass gelators (LMGs), have emerged as a platform for designing advanced gels that exhibit reversible gelation and property tunability. Liquid crystal (LC) gels are of great interest due to their supramolecular orderings as gel hosts and their enhanced electro-optical properties. In this study, we demonstrate the physical gelation of a nematic LC driven by nanoplate self-assembly, expanding the concept of gelators from small molecules to nanoparticles. These nanoplates are functionalized with promesogenic ligands and form a fibrillar network in LCs with face-to-face interplate stacking, resembling LMGs. The critical gelation volume fraction in the tilt test is only 0.14 v %, comparable to values reported for LMGs. Rheological analyses confirm viscoelastic properties characteristic of gelation. In situ small-angle X-ray scattering (SAXS) characterizes the formation of nanoplate networks in the LC with decreasing temperature, wherein LC mesogens become trapped in pores. Molecular dynamics (MD) simulations reveal that the interaction between ligand-coated nanoplates and LC-forming mesogens induces a multidomain LC structure, increasing friction between LC domains and stabilizing the gel. This study establishes direct relationships among molecular interactions, nanostructures, and mechanical properties in physically gelled LCs. The findings inspire the future gelator design of both LMGs and nanoplates, with potential applicability in bioscaffold engineering and liquid crystalline nanocomposites.
    Keywords:  coarse-grained simulation; in situ X-ray scattering; liquid crystal; nanoplate; reversible gelation; self-assembly
    DOI:  https://doi.org/10.1021/acsnano.5c06675
  42. Adv Healthc Mater. 2025 Jul 01. e2501574
    Development of Smart Photocrosslinkable Epoxy-Based Inks for 4D Printing.
    Tarun Agarwal, Shengbo Guo, Shuaiqi Song, Yin-Lin Shen, Lijie Grace Zhang.
      4D printing technology enables the fabrication of constructs capable of shape transformation when exposed to external stimuli. Epoxy-based shape memory polymers (SMPs) have shown great potential for various 4D printing applications. However, due to their thermocurable nature, the fabrication of 4D constructs using epoxy-based materials is often limited to a mold casting strategy, limiting design flexibility and often yielding flat structures. In this work, photocurable smart 4D inks are developed by integrating polyethylene glycol diacrylate (PD) into epoxy-based materials. These inks undergo a two-step crosslinking process: i) photocuring of the PD network, and ii) thermocuring of the SMP, resulting in an interpenetrating polymer network (IPN). The inclusion of PD in the 4D inks not only enables the formation of complex shapes via the restructuring step but also allows for fine-tuning of mechanical properties and thermal responsiveness. Additionally, these inks offered greater versatility in employable fabrication techniques, including mold casting, photolithography, and stereolithography (SLA).
    Keywords:  4D printing; epoxy‐based resin; interpenetrating polymer network; polyethylene glycol diacrylate; shape memory polymers
    DOI:  https://doi.org/10.1002/adhm.202501574
  43. Nat Commun. 2025 Jul 01. 16(1): 5955
    Three-dimensional conductive conjugated polyelectrolyte gels facilitate interfacial electron transfer for improved biophotovoltaic performance.
    Zhongxin Chen, Samantha R McCuskey, Weidong Zhang, Benjamin Rui Peng Yip, Glenn Quek, Yan Jiang, David Ohayon, Shujian Ong, Binu Kundukad, Xianwen Mao, Guillermo C Bazan.
      Living biophotovoltaics represent a potentially green and sustainable method to generate bio-electricity by harnessing photosynthetic microorganisms. However, barriers to electron transfer across the abiotic/biotic interface hinder solar-to-electricity conversion efficiencies. Herein, we report on a facile method to improve interfacial electron transfer by combining the photosynthetic cyanobacterium Synechococcus elongatus PCC 7942 (S. elongatus) with a conjugated polyelectrolyte (CPE) atop indium tin oxide (ITO) charge-collecting electrodes. By self-assembly of the CPE with S. elongatus, soft and semitransparent S. elongatus/CPE biocomposites are formed with three-dimensional (3D) conductive networks that exhibit mixed ionic-electronic conduction. This specific architecture enhances both the natural and mediated exoelectrogenic pathway from cells to electrodes, enabling improved photocurrent output compared to bacteria alone. Electrochemical studies confirm the improved electron transfer at the biotic-abiotic interface through the CPE. Furthermore, microscopic photocurrent mapping of the biocomposites down to the single-cell level reveals a ~ 0.2 nanoampere output per cell, which translates to a 10-fold improvement relative to that of bare S. elongatus, corroborating efficient electron transport from S. elongatus to the electrode. This synergistic combination of biotic and abiotic materials underpins the improved performance of biophotovoltaic devices, offering broader insights into the electron transfer mechanisms relevant to photosynthesis and bioelectronic systems.
    DOI:  https://doi.org/10.1038/s41467-025-61086-5
  44. Angew Chem Int Ed Engl. 2025 Jul 02. e202511493
    Mechanically Tunable Slide-ring Polymers via Photo-regulated Topological Control.
    Xiaoqing Wang, Chenjuan Yu, Maolin Wang, Shiyu Zhao, Qimo Mao, Yuping Wang.
      Post-synthetic dynamic control of polymer topology to modulate material properties on demand remains a grand challenge in polymer science. Here, we demonstrate a light-responsive slide-ring polymer network whose mechanical properties can be reversibly tuned through photoisomerization of incorporated azobenzene units. In the trans-state, azobenzene enables unhindered sliding of macrocycles along the polymer backbone, yielding a softer, more ductile material. UV-induced switching to the sterically demanding cis-configuration restricts ring mobility, thereby increasing the Young's modulus by two-fold while reducing toughness. Control experiments with non-interlocked analogs revealed the opposite mechanical response-light-induced softening-highlighting the pivotal role of topology in property regulation. Furthermore, the azobenzene linkage confers controlled degradability under mild conditions. This work establishes a versatile strategy for post-synthetic topological control via molecular photoswitches, enabling the design of adaptive polymers with stimuli-responsive mechanical properties for applications in smart materials.
    Keywords:  slide-ring polymers, photo-responsive, azobenzene, topological regulation
    DOI:  https://doi.org/10.1002/anie.202511493
  45. Biomed Mater. 2025 Jul 03.
    Engineering polystyrene microtube-embedded composite hydrogels for tunable vascular morphogenesis.
    Xianyang Li, Sadia Khan, Liyuan Wang, Yan Chen, Xiang Fang, Yingge Zhou, Ying Wang.
      Establishing functional vascular systems within 3D tissue constructs is crucial for their successful use in disease modeling, drug testing, and regenerative medicine. Current methods face challenges in creating small- to medium-sized microvessels and precisely controlling key vascular features, such as vascular density, vessel diameter, and network connectivity, to generate hierarchical, multiscale vascular systems that mimic natural functionality. In this study, we developed a composite hydrogel incorporating polystyrene microtubes (PS-MTs) to improve control over microvessel morphogenesis and functionality. PS-MTs were fabricated via core-sheath electrospinning, fragmented by ultrasonication, and incorporated into fibrin gels. Scanning electron microscopy revealed both micro- and nano-topographic features of the embedded PS-MT fragments. Endothelial cells and fibroblasts were cocultured in this composite hydrogel under interstitial flow conditions for 7 days. The PS-MTs exhibited excellent biocompatibility, and the composite hydrogel showed no adverse effects on the cell viability of EC-fibroblast cocultures on chip. Fluorescence and confocal microscopy revealed a 40% increase in vascular area fraction and more than a twofold increase in average vessel diameter in the high PS-MT density group (> 4%) compared to controls. Perfusion assays using a fluorescent microbead suspension demonstrated a 71% increase in the field-average speed of microbead flow, indicating enhanced perfusability, consistent with the observed morphological changes. Additionally, permeability assays showed a 66% decrease in dextran permeability, suggesting improved vascular barrier integrity. In conclusion, incorporating PS-MTs into fibrin hydrogels effectively modulated the structural organization and functional maturation of microvascular networks in a dose-dependent manner. This strategy holds promise for advancing the biofabrication of functional, multiscale vascular networks for engineered tissues. By tuning PS-MT density within the composite hydrogel, this approach enables local modulation of vessel morphogenesis, offering a flexible strategy for engineering application-specific vascular architectures.
    Keywords:  3D Tissue Constructs; Endothelial Cells; Hydrogel; Interstitial flow; Microvascular Network Formation; Microvessel Morphogenesis; Topography
    DOI:  https://doi.org/10.1088/1748-605X/adebd0
  46. Nat Commun. 2025 Jul 01. 16(1): 5939
    Scalable modulation of CRISPR‒Cas enzyme activity using photocleavable phosphorothioate DNA.
    Menglu Hu, Bingni Zhang, Yuanyue Shan, Feng Cao, Yihui Wang, Weiwei Qi, Xue Wang, Yuting Shen, Xinyi Guo, Mengmeng Zhang, Tian Tian, Wei Xie, Mingfeng Zhang, Fang Liang, Duanqing Pei, Xiaoming Zhou.
      The regulation of CRISPR‒Cas activity is critical for developing advanced biotechnologies. Optical control of CRISPR‒Cas system activity can be achieved by modulation of Cas proteins or guide RNA (gRNA), but these approaches either require complex protein engineering modifications or customization of the optically modulated gRNAs according to the target. Here, we present a method, termed photocleavable phosphorothioate DNA (PC&PS DNA)-mediated regulation of CRISPR‒Cas activity (DNACas), that is versatile and overcomes the limitations of conventional methods. In DNACas, CRISPR‒Cas activity is silenced by the affinity binding of PC&PS DNA and restored through light-triggered chemical bond breakage of PC&PS DNA. The universality of DNACas is demonstrated by adopting the PC&PS DNA to regulate various CRISPR‒Cas enzymes, achieving robust light-switching performance. DNACas is further adopted to develop a light-controlled one-pot LAMP-BrCas12b detection method and a spatiotemporal gene editing strategy. We anticipate that DNACas could be employed to drive various biotechnological advances.
    DOI:  https://doi.org/10.1038/s41467-025-61094-5
  47. ACS Cent Sci. 2025 Jun 25. 11(6): 975-982
    Multicolor Digital Light Processing 3D Printing Enables Dissolvable Supports for Freestanding and Non-Assembly Structures.
    Keldy S Mason, Ji-Won Kim, Elizabeth A Recker, Jenna M Nymick, Mingyu Shi, Franz A Stolpen, Jaechul Ju, Zachariah A Page.
      The limited diversity in photocurable resin chemistries has precluded access to certain geometries using digital light processing (DLP) 3D printing, a rapid, precise, economical, and low-waste manufacturing technology. Specifically, freestanding structures with floating overhangs (e.g., hooks) and mobile nonassembly structures that cannot be physically separated (e.g., joints) represent two such geometries that are difficult or impossible to access with contemporary DLP 3D printing. Herein, we disclose novel resins that selectively react with different colors of light to form soluble thermoplastics and insoluble thermosets. Systematic characterization of the acrylate- and epoxy-based resins and corresponding polymers from simultaneous UV and visible (violet or blue) light exposure revealed a rapid multimaterial 3D printing process (∼0.75 mm/min) capable of providing supports that dissolve in ethyl acetate, a "green" solvent, within 10 min at room temperature. Relative to manual support removal, the present process provides comparable or improved surface finishes and higher throughput. Finally, several proof-of-concept structures requiring dissolvable supports were 3D printed, including hooks, chains, and joints, which were scanned using computed tomography to showcase the process's geometric versatility and high fidelity. This work provides fundamental design principles for multimaterial resin chemistry and lays a foundation for automating next generation additive manufacturing.
    DOI:  https://doi.org/10.1021/acscentsci.5c00289
  48. ACS Cent Sci. 2025 Jun 25. 11(6): 918-926
    Synthetic Mucins as Glycan-Defined Prebiotics.
    Jill W Alty, Carolyn E Barnes, Agnese M Nicoli, Bradley S Turner, Ekua A Beneman, Amanda E Dugan, Spencer D Brucks, Austin G Kruger, Richard R Schrock, Katharina Ribbeck, Laura L Kiessling.
      The human microbiome contains at least as many bacterial cells as human cells. Some bacteria offer benefits, like improving gut barrier function, suppressing pathobiont growth, and modulating immunity. These benefits have popularized probiotics, but probiotic retention is often hindered by low colonization efficiency in the mucosal layer that lines all epithelial cells. Mucins, the primary components of mucus, are essential for the organization and regulation of microbial populations. The molecular mechanisms of mucin-probiotic interactions remain understudied due, in part, to the inability to incisively manipulate native mucin sequences or their glycans. Here, we used synthetic mucins with defined glycan presentations to interrogate glycan-dependent interactions between mucus and three probiotic lactobacilli species. The nutrient conditions under which bacteria were cultured influenced glycan binding preferences, suggesting mucin-probiotic interactions change with nutrient availability. The addition of synthetic mucins to native mucin increased Limosilactobacillus fermentum adherence. Additionally, an increase in glycosidase activity indicated that native and synthetic mucins function as prebiotics, as probiotic bacteria can cleave the displayed O-glycans. Thus, synthetic mucins can cultivate target probiotic bacteria and increase adhesion as binding sites, highlighting their value as tools for elucidating native mucin functions and as promising agents for promoting human health.
    DOI:  https://doi.org/10.1021/acscentsci.5c00317
  49. ACS Nano. 2025 Jul 03.
    Design Principles for Engineering Ionic Liquid-Gold Nanoparticles for Therapeutic Delivery to the Brain.
    Talia A Shmool, Laura K Martin, Andreas Jirkas, Sophie V Morse, Claudia Contini, Yuval Elani, Jason P Hallett.
      Ionic liquid (IL) nanotechnology holds significant promise for designing nanoscale materials with tunable viscosity, polarity, and thermal stability for advanced therapeutic applications. However, the field currently lacks comprehensive guidelines for integrating ILs into complex therapeutic formulations. Herein, we propose the key design considerations for engineering immunoglobulin G (IgG) conjugated to gold nanoparticles (AuNPs) in the presence of choline-based ILs. By judicious IL cation and anion selection, we fine-tune the supramolecular assemblies and leverage the unique physicochemical properties of ILs to impart AuNPs with advantageous characteristics including enhanced structural, thermal, and thermodynamic stabilities, highly tunable morphologies, and markedly reduced aggregation propensities. Through systematic circular dichroism measurements, the thermodynamic parameters of the complex formulations were determined, offering insight into the IgG conformational changes and design parameters for systems of enhanced IgG conjugation to AuNP surfaces. In demonstrating the power of our design approach, the complex formulation of IgG-choline chloride-AuNPs, also including trehalose, histidine, and arginine, was delivered via focused ultrasound and microbubbles across the blood-brain barrier and showed a 7.6-fold increase in delivery in vivo compared to the traditional formulation. We demonstrate that IgG-IL-AuNPs can be easily and precisely manipulated at the nanometer scale, enabling the formation of versatile structural configurations. Holistically, we believe the rational design approach developed will advance the engineering of tailored IL-nanocarriers for targeted therapeutic delivery and broaden the scope of IL applications in biomedicine.
    Keywords:  amino acids; blood−brain barrier; focused ultrasound; gold nanoparticles; ionic liquids; therapeutic delivery
    DOI:  https://doi.org/10.1021/acsnano.5c02375
  50. Macromol Biosci. 2025 Jun 29. e00629
    Silk Fibroin-Based Matrices for the Guidance of Cell Interaction, Tissue Regeneration, and Crosstalk.
    Behnaz Sadat Eftekhari, Behnaz Ashtari, Mozhgan Jahani, Elham Afjeh-Dana, Paul A Janmey, Sara Simorgh, Mazaher Gholipourmalekabadi.
      The interactions between cells and the extracellular matrix are essential regulators of cell behaviors such as adhesion, proliferation, migration, differentiation, and function. From the perspective of tissue regeneration, some physicochemical characteristics of the material, including hydrophilicity, topology, and charge of the material surface, can significantly affect cell adhesion, proliferation, and differentiation. Many biomaterials are introduced for tissue engineering scaffolds, biomimicking natural tissues. Among the biomaterials, silk proteins (fibroin and sericin) have many excellent characteristics, making them ideal candidates for regenerative medicine. Several studies have tuned silk fibroin characteristics to specify cell adhesion, proliferation, and stem cell differentiation by combining fibroin with other materials, coating, modification, and biofunctionalization. In the current review article, the essential properties of silk fibroin-based scaffolds (presence of cell adhesion motifs, wettability, charge, elasticity) and their influences on cell adhesion, proliferation, and migration, as well as their biodegradation and the body's immune response are discussed. In addition, the crosstalk between silk fibroin and various cells is discussed, as well as different methods for blending or biofunctionalization of silk fibroin with the aim of engineering a silk-based scaffold with a specifically tuned response to biological systems and subsequently affecting the behavior of the cells.
    Keywords:  cell signaling; cell‐matrix cross‐talk; silk fibroin
    DOI:  https://doi.org/10.1002/mabi.202400629
  51. Small. 2025 Jun 29. e2503147
    Innovations and Applications of Composite Hydrogels: from Polymer-Based Systems to Metal-Ion-Doped and Functional Nanomaterial-Enhanced Architectures.
    Ligang Zou, Yixin Li, Shuaiyang Feng, Zhenyu Wang, Hui Xiao, Sixun Chen, Yingqi Wang, Liangcan He, Xiang Mao.
      Hydrogels are 3D polymer networks cross-linked by physical interactions or covalent bonds. Been considered as versatile fabrication platforms for biomaterials due to their excellent biocompatibility and water-solubility. Particularly, the single-component hydrogels exhibit similar properties as above, but have obvious restrictions such as poor mechanical properties, rapid swelling, and unexpected instability. It can limit applications in biomedicine, mechanical proceeding, and electrochemical engineering. To address these limitations, researchers have investigated composite hydrogels' construction, properties, and expanded applications. It mainly focuses on the fabrication of composite hydrogels with integrations of different materials, expanded mechanical properties, varied performances, functionalities, and obvious advantages. This review expounds on the developments in hydrogel-based polymer materials, especially the progress made in the preparation methods, the mechanism of action, and technology development. The review also explores the positive impact of the introduction of innovative elements such as metal ions, nanomaterials, and bioactive molecules on the performance of hydrogels and their pioneering works, providing new perspectives for the design and optimization of hydrogels under specific application requirements. Finally, it looks forward to the challenges and future development potential of composite hydrogels, emphasizing the continuous improvement in design, functional integration, and application suitability, and reveals further prospects in this field.
    Keywords:  bio‐compatible polymers; composites hydrogels; functional hydrogels; metallic materials; nanomaterials
    DOI:  https://doi.org/10.1002/smll.202503147
  52. Proc Natl Acad Sci U S A. 2025 Jul 08. 122(27): e2414674122
    Learning predictive signals within a local recurrent circuit.
    Toshitake Asabuki, Colleen J Gillon, Claudia Clopath.
      The predictive coding hypothesis proposes that top-down predictions are compared with incoming bottom-up sensory information, with prediction errors signaling the discrepancies between these inputs. While this hypothesis explains the presence of prediction errors, recent experimental studies suggest that prediction error signals can emerge within a local circuit, that is, from bottom-up sensory input alone. In this paper, we test whether local circuits alone can generate predictive signals by training a recurrent spiking network using local plasticity rules. Our network model replicates experimentally observed features of prediction errors, such as biphasic neural activity patterns and context dependency. Our findings shed light on how synaptic plasticity can shape prediction errors and enable the acquisition and updating of an internal model of sensory input within a recurrent neural network.
    Keywords:  prediction error signal; predictive coding; recurrent spiking network; synaptic plasticity
    DOI:  https://doi.org/10.1073/pnas.2414674122
  53. ACS Appl Mater Interfaces. 2025 Jul 03.
    pH-Responsive Bilayer Hydrogel with Synergistic Antibacterial/Anti-inflammatory Effect for Infected Wound Healing.
    Mengxin Huangfu, Yuankun Ren, Wei Yang, Yu Liu, Xiyu Li.
      Hydrogels are promising candidates for wound dressings owing to their good biocompatibility, high-water retention, and extracellular matrix-mimicking structure. However, conventional single-layer hydrogels are hard to cope with given the dynamic pH fluctuations (pH 6-8.9) of infected wounds, which exacerbate bacterial colonization and oxidative stress. Here, we engineered a multifunctional bilayer hydrogel (named PPTC) comprising a hydrophobic polydimethylsiloxane (PDMS) top layer and a polyacrylamide (PAM)-based bottom layer integrated with tannic acid (TA) and curcumin-loaded alginate microspheres (Alg@Cur). The PDMS top layer was adopted to prevent external contamination and moisture loss, while the adhesive PAM-TA-Alg@Cur (PTC) bottom layer was designed to achieve a pH-responsive therapeutic synergy. In vitro studies showed that TA exhibited a rapid release (76.66% within 12 h) to suppress bacterial proliferation and inflammation, while Alg@Cur could slowly release curcumin in a pH-dependent manner (90.32% at pH 8.5 vs 38.06% at pH 6, cumulatively), targeting alkaline microenvironments to mitigate oxidative stress. Their synergy demonstrated potent antibacterial activity (≥99.90% inhibition against Staphylococcus aureus and Escherichia coli) and reactive oxygen species scavenging ability (93.89% DPPH elimination). In a rat-infected wound model, the PPTC bilayer hydrogel synergistically accelerated infected wound healing by reducing inflammation, enhancing collagen deposition, and promoting angiogenesis. This work pioneers a pH-driven therapeutic platform for advancing smart dressings for infected wound management.
    Keywords:  antibacterial; antioxidant; infected wound healing; multifunctional bilayer hydrogel; pH-responsive
    DOI:  https://doi.org/10.1021/acsami.5c08728
  54. J Chem Phys. 2025 Jul 07. pii: 014102. [Epub ahead of print]163(1):
    Predicting heteropolymer phase separation using two-chain contact maps.
    Jessica Jin, Wesley Oliver, Michael A Webb, William M Jacobs.
      Phase separation in polymer solutions often correlates with single-chain and two-chain properties, such as the single-chain radius of gyration, Rg, and the pairwise second virial coefficient, B22. However, recent studies have shown that these metrics can fail to distinguish phase-separating from non-phase-separating heteropolymers, including intrinsically disordered proteins (IDPs). Here, we introduce an approach to predict heteropolymer phase separation from two-chain simulations by analyzing contact maps, which capture how often specific monomers from the two chains are in physical proximity. While B22 summarizes the overall attraction between two chains, contact maps preserve spatial information about their interactions. To compare these metrics, we train phase-separation classifiers for both a minimal heteropolymer model and a chemically specific, residue-level IDP model. Remarkably, simple statistical properties of two-chain contact maps predict phase separation with high accuracy, vastly outperforming classifiers based on Rg and B22 alone. Our results thus establish a transferable and computationally efficient method to uncover key driving forces of IDP phase behavior based on their physical interactions in dilute solution.
    DOI:  https://doi.org/10.1063/5.0269504
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