bims-enlima Biomed News
on Engineered living materials
Issue of 2026–03–08
35 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool
  1. Tough hydrogels enabled by transient entanglements.
  2. The Intersecting Physical Mechanisms That Regulate Cell Viability in 3D Synthetic Hydrogels.
  3. Mechanical performance of hybrid polymer-lipid vesicles with leaflet asymmetry engineered using microfluidics.
  4. Engineering sensor-based antithetic integral controllers for enhanced dynamic performance and noise attenuation.
  5. Scalable Production of DNA-Probe-Functionalized Heteromeric MspA Nanopores for Biosensing.
  6. Assembling a True "Olympic Gel" From over 16 000 Combinatorial DNA Rings.
  7. Heterogeneity by design.
  8. In Situ Characterisation of Hydrogels via Dynamic Interface Printing.
  9. Controlling the Physical Properties in Hybrid Hydrogel Networks via Tunable Supramolecular Interactions.
  10. Advancing Genetic Code Expansion in Live Cells Through Metabolic Engineering.
  11. Harnessing Phase Separation for the Development of High-Performance Hydrogels.
  12. Design-driven optimization of low-cost reagent formulations for reproducible and high-yielding cell-free gene expression.
  13. Phase-Change Silicone Elastomers for Tough, Soft Actuators.
  14. Fabrication and Characterization of Tetra-PEG-Derived Hydrogels of Controlled Softness.
  15. Mechanistic Origins of Yielding in Hybrid Double-Network Hydrogels.
  16. Advances in extrusion-based bioprinting enabled by advanced printhead and nozzle designs.
  17. Preserving Microstructure Enhances Cohesion and Mechanical Performance in Spirulina-Based 3D-Printed Biomaterials.
  18. Leveraging bond dissociation kinetics to tune shear-thickening behavior in dynamic covalent tetra-PEG hydrogels.
  19. Polycaprolactone-Itaconic Acid Resins for Additive Manufacturing of Environmentally Degradable 3D and 4D Materials by Thiol-ene Photopolymerization.
  20. Bioinspired nanofluidic iontronic device with integrated photoreceptor and photosynaptic functions.
  21. Ultrahigh-Molecular-Weight Polymer Gels in Aqueous Media Using Cucurbit[8]uril-Assisted Radical Polymerization.
  22. Enhancing the Spinnability of Cellulose-Based Textile Waste by Doping with High Molecular Weight Bacterial Cellulose.
  23. A Modular Toolkit for Nanoscale Interrogation of Multiprotein Assemblies Inside Living Cells.
  24. Nonlinear elasticity and transition to macroscopic irreversibility in composite hydrogels.
  25. Repurposing bacterial secretion systems for the design of living therapeutics.
  26. Genome modelling and design across all domains of life with Evo 2.
  27. Genetically encoded assembly recorder temporally resolves cellular history.
  28. NEO-PGA: Nonvolatile electro-optically programmable gate array.
  29. Small-Molecule Activation of mRNA Translation by Click-to-Release Reaction in Cells.
  30. Mesoscale Modeling of Hydrogels Under Frictional Shear Stress.
  31. Localized Thermomechanical Measurements of Polymers and Blends with AFM-IR.
  32. 3D-Printed Dual Photo- and Thermally Responsive Materials for Smart Adaptability.
  33. Tuning Mechanical and Self-Healing Properties Using Multivalent Crosslinking.
  34. Targeted metabolic glycoengineering using multivalent mannosyl metal-organic frameworks (MOFs).
  35. Directed Evolution of Enzymes for Bioorthogonal Chemistry Using Acid Chloride Proximity Labeling.
  1. Nat Commun. 2026 Mar 05.
    Tough hydrogels enabled by transient entanglements.
    Zhaoyang Yuan, Zhenxing Cao, Hao Wang, Haitao Wu, Jing Zheng, Rongchun Zhang, Jinrong Wu.
      Achieving high toughness and strength simultaneously in single-covalent-network hydrogels remains a longstanding challenge. Herein, we report a simple yet effective strategy to resolve this strength-toughness conflict by constructing polyacrylamide (PAAm) networks with abundant dangling chains that form transient entanglements. Unlike permanently trapped entanglements, these transient entanglements can slip and fully disentangle upon loading, enabling highly efficient energy dissipation and stress redistribution over a broad range of strains. Besides, these networks exhibit superior homogeneity compared to other structures, effectively mitigating stress concentration. As a result, our single-covalent-network hydrogels exhibit good mechanical properties, including a fracture strain of 5071%, a fracture strength of 1.06 MPa, a fatigue threshold of 1968 J·m⁻², and a fracture energy of approximately 60,000 J·m⁻². Moreover, these hydrogels feature low friction and high wear-resistance. Such a simple yet robust design paradigm effectively overcomes the longstanding strength-toughness trade-off without the complexity of multi-network architectures, opening avenues for next-generation hydrogels in biomedicine, wearable electronics, and other demanding environments.
    DOI:  https://doi.org/10.1038/s41467-026-70194-9
  2. Adv Mater. 2026 Mar 05. e21245
    The Intersecting Physical Mechanisms That Regulate Cell Viability in 3D Synthetic Hydrogels.
    Nathan R Richbourg, Akaansha Rampal, Adrian Lorenzana, Juan F Flechas-Beltran, Shelly R Peyton.
      Hydrogels restrict protein transport to different extents, with nanoporous synthetic polymer networks providing far less protein permeability compared to microporous biopolymer networks. To evaluate whether reduced permeability was a driving factor in reduced cell viability in synthetic hydrogels, we compared poly(ethylene glycol) vinyl sulfone (PEG-VS) hydrogels with Matrigel to quantify the influences of modulus, transport, and confinement on encapsulated cells. We observed extensive reductions in cell viability when encapsulated in PEG-VS gels compared to Matrigel. In transwell experiments that decouple hydrogel-restricted serum from cell-gel adhesion, serum restriction reduced cell viability, matching the cell viability observed in 3D cultures. Our unique combination of 2D and 3D hydrogel-based cell cultures provides a framework for investigating the intersecting effects of the cell microenvironment's properties on cell viability. This work demonstrates that biomaterial-restricted protein transport is a critical design consideration when using synthetic 3D cell culture hydrogels.
    Keywords:  confinement; extracellular matrix; hydrogel design; poly(ethylene glycol); transport
    DOI:  https://doi.org/10.1002/adma.202521245
  3. Proc Natl Acad Sci U S A. 2026 Mar 10. 123(10): e2516407123
    Mechanical performance of hybrid polymer-lipid vesicles with leaflet asymmetry engineered using microfluidics.
    Yuting Huang, Arash Manafirad, Simon Matoori, Laura R Arriaga, Sijie Sun, Anqi Chen, Xin Yang, Anthony D Dinsmore, David J Mooney, David A Weitz.
      Lipid vesicles consist of aqueous cores surrounded by a bilayer of phospholipids. Hybrid polymer-lipid vesicles incorporate both polymers and lipids, offering promising properties for developing pharmaceuticals, biosensors, and artificial cells. The hybrid vesicles can be symmetric, with two leaflets of identical compositions, or asymmetric, in with leaflets of dissimilar compositions, which can lead to dramatically altered properties. However, existing methods for producing symmetric and asymmetric hybrid vesicles often result in heterogenous compositions and sizes, making it challenging to quantify the effect of asymmetry and limiting applications. Here, we use a microfluidic approach to produce hybrid vesicles with either symmetric or asymmetric leaflets and precisely engineered compositions. We find that the vesicles with asymmetric leaflets are significantly stiffer and tougher than those with symmetric leaflets; moreover, the lateral diffusivity of lipids is greatly decreased. The structure for improved toughness consists of a stretchable lipid inner leaflet and a fully continuous polymer outer leaflet. This approach to precisely engineer asymmetric structures can be applied to hybrid vesicles composed of block copolymers and phospholipids soluble in chloroform and hexane, further expanding their applications.
    Keywords:  microfluidics; polymer/lipid; vesicles
    DOI:  https://doi.org/10.1073/pnas.2516407123
  4. Cell Syst. 2026 Feb 27. pii: S2405-4712(25)00345-X. [Epub ahead of print] 101512
    Engineering sensor-based antithetic integral controllers for enhanced dynamic performance and noise attenuation.
    Maurice Filo, Stephanie K Aoki, Mucun Hou, Stanislav Anastassov, Mustafa Khammash.
      Effective cellular regulation relies on feedback control mechanisms to maintain homeostasis and mitigate environmental fluctuations. We develop and analyze a sensor-based antithetic integral feedback (sAIF) controller that achieves this by embedding proportional and integral actions within a minimal genetic architecture. Arising from a single modification to the classical antithetic control motif, this sAIF architecture intrinsically incorporates proportional feedback without requiring additional circuitry. Control-theoretic and stochastic analyses show that this proportional action speeds up the system's dynamic response and counteracts the noise amplification typical of pure integral feedback, enabling both improved speed and reduced cellular variability. Using intein-mediated splicing, we implement sAIF in E. coli and demonstrate robust perfect adaptation, strong disturbance rejection, and favorable noise properties. These findings establish a generalizable design principle for engineering high-performance biological controllers, with broad implications for synthetic biology, metabolic engineering, and cell-based therapies. A record of this paper's transparent peer review process is included in the supplemental information.
    Keywords:  chemical reaction networks; cybergenetics; genetic circuits; homeostasis; integral feedback control; inteins; noise; robust perfect adaptation
    DOI:  https://doi.org/10.1016/j.cels.2025.101512
  5. ACS Appl Mater Interfaces. 2026 Mar 04.
    Scalable Production of DNA-Probe-Functionalized Heteromeric MspA Nanopores for Biosensing.
    Xialin Zhang, Parker Hitt, Meni Wanunu, Jørgen Kjems.
      Biological nanopores enable single-molecule sensing but often lack specificity when analytes produce similar current signatures. Covalent tethering of recognition elements improves selectivity, yet site-specific functionalization of symmetric, multimeric pores like Mycobacterium smegmatis porin A (MspA) remains challenging. Existing gel-based strategies for isolating heteromeric pores are labor-intensive and low-throughput and can compromise protein functionality. Here, we report a modular strategy for producing hetero-octameric MspA nanopores with a single site-specific modification. By coexpressing MspA and a D56C MspA mutant bearing a C-terminal D16 tag in Escherichia coli (E. coli), we directed the assembly of asymmetric pores with defined subunit composition. To isolate the modified pores, we developed a rapid, nondenaturing purification method that integrates magnetic bead capture with toehold-mediated DNA strand displacement, demonstrating selective enrichment of functionalized pores in under 3.5 h while preserving structural integrity. Using this platform, we generated MspA nanopores functionalized with single DNA probes targeting dopamine, microRNA, and thrombin. Single-channel recordings demonstrated distinct current signatures upon target recognition, enabling label-free and selective detection. This approach offers a robust and scalable framework for engineering functionalized nanopores for diverse molecular sensing.
    Keywords:  hetero-octameric assembly; nanopore engineering; rapid selective enrichment; single-molecule sensing; site-specific functionalization
    DOI:  https://doi.org/10.1021/acsami.5c21011
  6. Adv Mater. 2026 Mar 06. e20549
    Assembling a True "Olympic Gel" From over 16 000 Combinatorial DNA Rings.
    Sarah K Speed, Yu-Hsuan Peng, Azra Atabay, Krishna Gupta, Toni Müller, Carolin Fischer, Ilka M Hermes, Jens-Uwe Sommer, Michael Lang, Elisha Krieg.
      Olympic gels are an elusive form of soft matter, comprising a 3D network of mechanically interlocked cyclic molecules. In the absence of defined network junctions, the high conformational freedom of the molecules was previously theorized to confer unique mechanical properties to Olympic gels, such as non-linear elasticity and unconventional swelling characteristics. However, the synthesis of an Olympic gel exhibiting these intriguing features is challenging, since unintended crosslinking and polymerization processes are often favored over cyclization. Here, we report the successful assembly of a true Olympic gel from a library of DNA rings comprising more than 16 000 distinct molecules. Each of these rings contains a unique sequence domain that can be enzymatically activated to produce reactive termini that favor intramolecular cyclization. We characterized the genetic, mechanical, and structural characteristics of the material by next-generation sequencing, oscillatory rheology, large-scale computational simulations, atomic force microscopy, and cryogenic electron microscopy. Our results confirm the formation of a stable Olympic gel, which exhibits unique swelling behavior and an elastic response that is exclusively determined by entanglements, yet persists on long time scales. By combining concepts from polymer physics, synthetic biology, and DNA nanotechnology, this new material class provides a flexible experimental platform for future studies into the effects of network topology on macroscopic material properties and its function as a carrier of genetic information in biological and biomimetic systems. This work moreover demonstrates that exotic material properties can emerge in systems with a high compositional complexity that is more reminiscent of biological than synthetic matter.
    Keywords:  DNA nanotechnology; Olympic gels; programmable materials; simulations; soft matter engineering; supramolecular chemistry
    DOI:  https://doi.org/10.1002/adma.202520549
  7. Nat Mater. 2026 Mar;25(3): 335
    Heterogeneity by design.
      
    DOI:  https://doi.org/10.1038/s41563-026-02545-2
  8. Adv Sci (Weinh). 2026 Mar 07. e15106
    In Situ Characterisation of Hydrogels via Dynamic Interface Printing.
    Callum Vidler, Michael Halwes, David J Collins.
      Hydrogels have become pivotal materials for tissue engineering, robotics, biomedical devices, and sensing applications due to their diverse material compositions and tunable mechanical properties. While significant effort has focused on developing novel manufacturing approaches such as extrusion bioprinting and light-based fabrication methods, there has been limited work in real-time characterisation of manufactured parts, which often requires tedious parameter optimization to achieve the desired structural resolution and material properties. Here, we demonstrate a high-throughput approach based on Dynamic Interface Printing (DIP) that enables simultaneous in situ fabrication, mechanical characterisation, and volumetric quantification of centimeter-scale hydrogel scaffolds within seconds. We establish automated stiffness-seeking capabilities through a characterisation-in-the-loop framework employing zero-order optimization algorithms, achieving target elastic moduli within 3%-5% accuracy across diverse material formulations without prior knowledge of material properties or structural information. We further introduce a three-dimensional nodal framework for volumetric grayscale lithography that generates spatially heterogeneous mechanical properties, demonstrating engineered nonlinear stress-strain relationships through crosslinking density modulation. In addition, we implement orthogonal light-sheet illumination coupled with machine learning segmentation algorithms, enabling real-time layer-wise structural reconstruction with >85% accuracy. This integrated methodology eliminates manual handling, automating part design and significantly shortening optimization timelines by providing real-time quantitative feedback on morphology and mechanical properties.
    Keywords:  bioprinting; dynamic interface printing; hydrogel; light‐sheet; mechanical characterization
    DOI:  https://doi.org/10.1002/advs.202515106
  9. Macromolecules. 2025 Jun 24. 58(12): 6077-6087
    Controlling the Physical Properties in Hybrid Hydrogel Networks via Tunable Supramolecular Interactions.
    Martin G T A Rutten, Chiara Raffaelli, Maxime O Grillaud, Riccardo Bellan, Wouter G Ellenbroek, Patricia Y W Dankers.
      The complex interplay of covalent and noncovalent interactions is intrinsically connected to the formation of biological macromolecules, including proteins and carbohydrates. The design of synthetic materials that exhibit a similar interplay of such complex interactions is challenging. Most synthetic networks use purely covalent polymers in different concentrations to capture the bulk stiffness. Here, we combine covalent and dynamic network interactions in fully synthetic systems. In a systematic approach, permanent covalent cross-links are replaced by dynamic cross-links. Via this approach, network mechanics can be tuned over several orders of magnitude, i.e., from 10 to over 1000 Pa. This large tunability is achieved by changes in the molecular design of the dynamic cross-links, all while the fundamental design and concentration of the components are kept constant. Furthermore, where experiments showed a clear relationship between the design of the dynamic cross-links and the mechanical strength, coarse-grained molecular dynamics simulations showed a similar trend between networks mechanics and cross-link interaction strength. Overall, we show a new approach for the design of networks in which components and concentrations are kept similar, but a wide range of physical properties can be captured by tuning the molecular design of the cross-links. In this way, synthetic materials are brought closer to the design and tunability of biological matter.
    DOI:  https://doi.org/10.1021/acs.macromol.5c00226
  10. Annu Rev Chem Biomol Eng. 2026 Mar 02.
    Advancing Genetic Code Expansion in Live Cells Through Metabolic Engineering.
    D'Jana R Wyllis, Saloni P Gupta, Shelby R Anderson, Aditya M Kunjapur.
      Genetic code expansion (GCE) is the ability to encode polypeptide building blocks beyond the standard 20 the ribosome uses for protein translation, known as nonstandard amino acids (nsAAs). The broadening of chemical functionalities in proteins produced by live cells has generated substantial value across fundamental and applied research settings. However, a common limitation of GCE approaches is their reliance on the supplementation of chemically synthesized nsAAs to cell culture media. To overcome this limitation of nsAA sourcing, efforts have engineered systems for nsAA biosynthesis, often in the same host that performs GCE. In recent years, these works have reported new chemical targets obtained through biosynthesis, as well as additional rationale for combining metabolic engineering and GCE, particularly for synthetic biology applications. Here, we review this rapidly advancing field and provide our perspectives on technical and conceptual innovations.
    DOI:  https://doi.org/10.1146/annurev-chembioeng-100724-081506
  11. Adv Sci (Weinh). 2026 Mar 02. e00032
    Harnessing Phase Separation for the Development of High-Performance Hydrogels.
    Yue Shao, Yiming Ma, Baihao Shao, Molly M Stevens.
      Hydrogels are indispensable for the development of next-generation bioelectronics, soft robotics, and biomedical devices, where their mechanical properties determine performance and reliability. Among strategies to enhance hydrogel mechanics, phase separation enables controlled heterogeneity resulting in gel networks that are reinforced by more than just covalent bonds and polymer entanglements. By regulating the demixing of polymer-rich and solvent-rich domains, phase separation leads to architectures that couple strength, elasticity, and dynamic responsiveness. This article reviews the recent advances in designing high-performance phase-separated hydrogels by linking phase separation behavior within polymer networks to emergent properties such as toughness, fatigue resistance, adhesion, and stimuli-responsiveness. We highlight how mesoscale organization governs multifunctional performance and demonstrate how these principles help resolve the key trade-offs in critical applications, such as high-pressure hemostatic sealants, low-impedance bioelectronics, perfusable tissue engineering scaffolds, and adaptive soft robotics. Finally, we discuss critical challenges, including in situ characterization and scalability, and future opportunities like machine-learning-guided design, which are essential to translate phase separation from a materials heuristic into design rules for reliable, high-performance hydrogel materials.
    Keywords:  hydrogel; phase separation; polymer; soft robotics; wearable sensors
    DOI:  https://doi.org/10.1002/advs.202600032
  12. Nat Commun. 2026 Mar 05.
    Design-driven optimization of low-cost reagent formulations for reproducible and high-yielding cell-free gene expression.
    Meagan L Olsen, Caroline E Copeland, Chad A Sundberg, Rochelle Aw, Zachary M Shaver, Govind Rao, James R Swartz, Ashty S Karim, Michael C Jewett.
      Access to recombinant proteins is vital in basic science and biotechnology research. Cell-free gene expression systems provide one approach to address this need, but widespread utilization remains limited by the cost, complexity, and inconsistency of current platforms. To address these limitations, we carry out a multi-dimensional definitive screening design to reduce the number of reagent components and remove costly secondary energy substrates. From 1,231 different reagent formulations, we discover a simple and reproducible system based on 12 components. The optimized reagent formulation can produce 2.4 ± 0.3 g/L of protein product at the 15-µL scale (~$60/gprotein) and 3.7 ± 0.2 g/L (~$39/gprotein) at the 4-mL scale with oxygen supplementation. This provides an average 95% reduction in cost over previous cell-free reagent formulations. We further show that the optimized reagent formulation can produce nucleoside triphosphates from nitrogenous bases and ribose and that it is robust to failure across batches of cell lysates, users/locations, and in the synthesis of more than 20 different proteins. For example, we demonstrate the production of fifteen therapeutically relevant products, including full-length aglycosylated monoclonal antibodies. We anticipate that our optimized reagent formulation will democratize the use of cell-free systems for protein manufacturing and synthetic biology applications.
    DOI:  https://doi.org/10.1038/s41467-026-69605-8
  13. Macromolecules. 2025 Aug 12. 58(15): 8067-8078
    Phase-Change Silicone Elastomers for Tough, Soft Actuators.
    Yoo Jin Lee, Asaf Dana, Sasha M George, Manivannan Sivaperuman Kalairaj, Yeh-Chia Tseng, Brandon M Nitschke, Jared A Gibson, Melissa A Grunlan, Taylor H Ware.
      Soft materials capable of controlled shape changes near ambient temperature are of interest for active devices that interact with living organisms. In this study, we achieve such functionalities by synthesizing responsive elastomers based on polydiethylsiloxane (PDES). Unlike conventional silicones, PDES elastomers are mesomorphic. Without any reinforcing additives, the mesophase improves the toughness of PDES to 8 times that of neat polydimethylsiloxane (PDMS) elastomers and 4 times that of Sylgard 184. Uniaxially stretched mesomorphic PDES elastomers undergo reversible shape changes under a bias load in response to temperature, generating 14% contractile strain on heating from 0 to 40 °C. The utility of PDES elastomers as actuators is enhanced by fabricating them into twisting actuators and describing strategies to minimize hysteresis during shape change cycles. The combination of toughness, actuation near ambient temperature, and environmental stability suggests that PDES could be attractive for biomedical devices where soft actuators interface with living organisms.
    DOI:  https://doi.org/10.1021/acs.macromol.5c01221
  14. Macromolecules. 2025 Jul 08. 58(13): 6916-6928
    Fabrication and Characterization of Tetra-PEG-Derived Hydrogels of Controlled Softness.
    Robert F Schmidt, Olga Matsarskaia, Takamasa Sakai, Michael Gradzielski.
      Tetra-PEG hydrogels are known for their exceptionally homogeneous network structure and high mechanical stability. In this study, we demonstrate how the tetra-PEG framework can be adapted to create hydrogels of widely variable softness, with elastic moduli as low as 1-10 Pa. This is achieved by systematically tuning the ratio of tetra-functional and linear PEG macromers, producing networks with long, linear polymer segments that are intermittently cross-linked. The resulting hydrogels may serve as simple model systems for more complex biological hydrogels. Using small-angle neutron scattering (SANS), dynamic light scattering (DLS), rheometry, and microrheology, we reveal how the ratio of linear and tetra-functional precursor macromers influences the network structure and mechanical properties. These hydrogels, with precisely controllable rheological and structural characteristics, offer a versatile platform for studying the structure-property relationship in hydrogels mimicking the properties of biological systems such as mucus. The introduced principles are general and provide a foundation for designing new hydrogel materials with tailored properties for biomedical applications.
    DOI:  https://doi.org/10.1021/acs.macromol.5c00695
  15. Macromolecules. 2025 Aug 26. 58(16): 8610-8621
    Mechanistic Origins of Yielding in Hybrid Double-Network Hydrogels.
    Vinay Kopnar, Adam O'Connell, Natasha Shirshova, Anders Aufderhorst-Roberts.
      Hybrid double-network hydrogels comprise transiently and permanently cross-linked polymer networks and exhibit enhanced toughness, arising from a local yielding transition. Here, we examine the precise nature of this yielding transition by constructing a series of hydrogel designs from alginate and polyacrylamide (PAAm) networks, systematically controlling their cross-linking chemistry. Using large amplitude oscillatory shear (LAOS) rheology (LAOS), we show the presence of a hitherto unobserved two-step yielding process. Analysis of individual oscillatory cycles and the use of chaotropic/kosmotropic reagents shows that the first step of yielding is determined by the hydrogen bonding between the two polymer networks. These interactions also influence the second step of yielding, which we show is governed by the ionic interactions within the alginate network. This work demonstrates that interactions between are as crucial as interactions within the polymer networks and thereby provides insights into how the yielding in soft composite materials can be identified, adjusted, and controlled.
    DOI:  https://doi.org/10.1021/acs.macromol.4c02431
  16. Mater Today Bio. 2026 Apr;37 102941
    Advances in extrusion-based bioprinting enabled by advanced printhead and nozzle designs.
    Jianfeng Li, Peer Fischer.
      3D printing is a rapidly evolving technology that enables new applications in biomedical engineering. In particular, its role in the fabrication of complex living tissues and multimaterial structures that support living cells opens new possibilities for biomaterial processing as well as potential clinical applications. Among the various 3D printing modalities developed over recent decades, extrusion-based printing shows particular promise for bioprinting and a number of successful examples are highlighted in this review. However, despite its widespread adoption, extrusion-based 3D printing is constrained by the limited range of viscoelasticities that can be processed, certain inefficiencies in multi-material printing, restricted spatial resolution and fundamental trade-offs between printing speed and cell viability in bioprinting applications. Here, we present a comprehensive review of existing printhead designs for extrusion-based 3D printing, with a specific focus on biomedical applications. We highlight recent technological breakthroughs, identify persistent bottlenecks and propose strategic directions for next-generation printhead development aimed at overcoming current limitations. Our goal is to catalyze innovation in printhead engineering for biomedical applications to enable the fabrication of structures that are still unattainable with current extrusion-based 3D printing systems.
    Keywords:  3D bio-printing; Acoustic field; Extrusion printing; Magnetic field; Multi-material printing; Nozzle; Printhead; Tissue engineering
    DOI:  https://doi.org/10.1016/j.mtbio.2026.102941
  17. ACS Appl Eng Mater. 2026 Feb 27. 4(2): 963-971
    Preserving Microstructure Enhances Cohesion and Mechanical Performance in Spirulina-Based 3D-Printed Biomaterials.
    Amelia Burns, Israel Kellersztein, Chiara Daraio.
      Spirulina platensis is a promising bioresource for developing structural materials, offering a renewable alternative to conventional polymers due to its rapid growth and characteristic helical microstructure. While its biochemical properties have been widely studied, the role of cellular morphology in determining macroscale mechanical performance remains underexplored. In this work, we examine how maintaining versus disrupting Spirulina's native trichome structure and cell walls impacts the cohesion, rheology, and mechanical behavior of 3D-printed biomaterials. Using hydroxyethyl cellulose (HEC) as a binder, we developed two classes of bioinks: trichome biocomposites, based on freeze-dried Spirulina trichomes, and lysed biocomposites, formed from thermally lysed Spirulina cells. Differential scanning calorimetry revealed stronger molecular interactions between lysed cells and HEC, while trichomes contributed instead via physical interlocking and structural integrity of the cell wall. Despite weaker molecular interactions, trichome-based biocomposite bioinks exhibited higher viscosity, improved printability, and higher rheological yield stress by up to 499%. Upon dehydration, trichome biocomposites showed lower shrinkage and higher mechanical performance under compression, with normalized compressive modulus and yield strength significantly exceeding that of lysed biocomposites (by up to 107% and 108%, respectively). These effects are attributed to mechanical interlocking and enhanced stress transfer through intact cell walls. Our findings demonstrate that preserving biological microstructure may enable improved material cohesion and function, offering design principles for scalable, sustainable biofabrication of algae-based structural materials.
    Keywords:  3D printing; Spirulina; biocomposites; microalgae; microstructure; processing; sustainable materials
    DOI:  https://doi.org/10.1021/acsaenm.5c01105
  18. Sci Adv. 2026 Mar 06. 12(10): eadz9563
    Leveraging bond dissociation kinetics to tune shear-thickening behavior in dynamic covalent tetra-PEG hydrogels.
    Anne D Crowell, Jiho Kang, Diana L Conrad, Thomas M FitzSimons, Eric V Anslyn, Delia J Milliron, Adrianne M Rosales.
      Dynamic covalent cross-links impart hydrogels with viscoelastic and self-healing properties, motivating applications as biomimetic cell scaffolds and injectable materials. The long bond lifetime results in complex rheological behavior including shear thickening. We hypothesized that this behavior applies broadly across dynamic covalent hydrogels and can be engineered through reaction rate constants. Thus, we synthesized multiarm poly(ethylene glycol) (PEG) hydrogels with conjugate addition, boronate ester, or terpyridine-zinc cross-links, which tune bond dissociation kinetics and hydrogel relaxation times over four orders of magnitude. All formulations exhibited shear thickening, with the onset dictated by the relaxation time. Although multiple mechanisms may underlie this behavior, chain stretching is hypothesized to contribute to shear thickening, as the cross-linking concentration remained constant under shear and networks with more defects correlated with increased shear thickening. These molecular and structural drivers of shear thickening apply across dilute dynamic covalent tetra-PEG hydrogels, clarifying their suitability for applications under shear.
    DOI:  https://doi.org/10.1126/sciadv.adz9563
  19. Macromolecules. 2025 Aug 26. 58(16): 8887-8897
    Polycaprolactone-Itaconic Acid Resins for Additive Manufacturing of Environmentally Degradable 3D and 4D Materials by Thiol-ene Photopolymerization.
    Bo Li, Gianluca Bartolini Torres, Baptiste Martin, Nicholas Taylor, Eugen Barbu, Annette Christie, Andreas Heise.
      Digital light processing (DLP) has emerged as a powerful tool for advanced manufacturing, enabling the fabrication of intricate 3D polymer structures and, more recently, responsive 4D architectures that adapt to environmental stimuli. However, current DLP technologies rely heavily on acrylate-based photocurable resins, which pose significant sustainability challenges from resin synthesis to end-of-life disposal. To address these issues, we present a novel solvent-free approach to functionalizing polycaprolactone (PCL) using biomass-derived itaconic acid (IA). The unsaturated moiety of IA enables efficient photopolymerization via thiol-ene chemistry in both dioxane and the sustainable solvent γ-valerolactone, affording excellent printability. In the resulting cross-linked networks, IA end-groups serve not only as photocurable sites but also as functional handles that confer environmental responsiveness, as demonstrated by pH-triggered 4D transformations and dye uptake. To simulate end-of-life conditions, we demonstrated hydrolysis and microbial degradation of the cross-linked materials in a sewage-derived inoculum, supporting the potential for biomass regeneration in a circular materials framework. This strategy provides a sustainable route to producing functional, mechanically robust resins for 3D and 4D printing, offering a reduced environmental impact without compromising performance.
    DOI:  https://doi.org/10.1021/acs.macromol.5c01310
  20. Nat Commun. 2026 Mar 05.
    Bioinspired nanofluidic iontronic device with integrated photoreceptor and photosynaptic functions.
    Wenchao Liu, Lian Duan, Xiangyu Zhang, Xinyi Zhu, Yongxin Ge, Guoheng Xu, Zhixiao Si, Jiqing Dai, Wenbo Chang, Miliang Zhang, Ronghua Lan, Zhijun Hu, Ruotian Chen, Kowit Hengphasatporn, Yasuteru Shigeta, Kai Xiao.
      Biological vision acquires external information through light-induced transmembrane ion transport, generating electrical impulses. Emulating the dual visual functions of photoreceptors and photosynapses through light-modulated ion transport presents a significant challenge. Herein, we present a bioinspired light-regulated nanofluidic iontronic device that can mimic biological visual functionalities, realized through an engineered carbon nanotube and molybdenum disulfide (CNT/MoS2) heterostructure. This bioinspired device combines two key functionalities of photoreceptor-like optical sensing and photosynaptic signal processing with dynamically adjustable polarity-switching behavior, achieved via bias voltage-modulated transient photoresponse speeds. Both theoretical and experimental results prove that light-modulated ion transport originates from the heterointerface-induced asymmetric photovoltage generation across CNT/MoS2 nanotube. Furthermore, we demonstrate its implementation for both accurate orientation recognition and reliable fingerprint detection under varying incident light angles. The device's bidirectional photoresponsiveness highlights its unique advantages for adaptive visual simulation systems.
    DOI:  https://doi.org/10.1038/s41467-026-70337-y
  21. Macromolecules. 2025 Aug 12. 58(15): 8197-8204
    Ultrahigh-Molecular-Weight Polymer Gels in Aqueous Media Using Cucurbit[8]uril-Assisted Radical Polymerization.
    Élise Ansart, Rebekka Hosch, Mark W Tibbitt, Stefan Mommer.
      Ultrahigh-molecular-weight (UHMW) polymer materials show enhanced material properties due to entanglements and reduced polymer dynamics that occur at extreme degrees of polymerization. While various living controlled polymerizations have been explored for the synthesis of UHMW polymers, free-radical polymerization (FRP) remains limited for this application, given low initiation efficiencies and poor reproducibility. In this work, we exploit host-guest interactions between Cucurbit[8]-uril and the thermoinitiator VA-044 to down-regulate the number of active radicals during the radical polymerization of acrylamide (AAm). This approach produces UHMW polymers (up to 5.5 MDa) that form hydrogels in situ. We investigate various reaction parameters (e.g., the concentration of CB[8] and ratio of CB[8] to VA-044) and apply this strategy to other water-soluble monomers. Additionally, detailed rheological analyses of the materials show how upon exceeding a molecular weight of M n = 3 MDa, the stiffness of the hydrogels increases and becomes frequency-independent. Due to the simplicity of this method, UHMW polymers and hydrogels in aqueous media can be easily accessed by using minimal amounts of the CB[8] macrocycle as an additive to an otherwise standard FRP procedure.
    DOI:  https://doi.org/10.1021/acs.macromol.5c00801
  22. Biomacromolecules. 2026 Mar 06.
    Enhancing the Spinnability of Cellulose-Based Textile Waste by Doping with High Molecular Weight Bacterial Cellulose.
    Kaniz Moriam, Crystal E Owens, Laurel Kroo, William Ghann, Jamal Uddin, Leena Pitkänen, Michael Hummel, Gareth H McKinley.
      Man-made cellulose fibers from well-managed forestry provide an eco-friendly alternative to polyester and cotton. The Ioncell process converts cellulose-based raw materials into high-quality textiles and offers strong potential for upcycling cellulose-based textile waste. Recycling discarded textiles is challenging because washing and abrasion degrade synthetic and natural fibers, reducing molecular weight and processability. Here, we demonstrate that adding a very small fraction of ultrahigh molecular weight bacterial cellulose enhances the spinnability of textile waste streams dominated by short-chain cellulose. This high molecular weight dopant systematically increases solution extensibility, stabilizing the extension-dominated fiber-spinning process. Viscoelastic stresses in a stable spinline scale with steady extensional viscosity at high strain rates and depend sensitively on chain extensibility. We quantify the enhanced tensile stress differences using capillarity-driven extensional rheometry combined with transient exponential shear rheometry to develop a spinnability metric for cellulose/ionic liquid solutions. These findings advance strategies for efficient recycling of postconsumer cellulose textiles.
    DOI:  https://doi.org/10.1021/acs.biomac.5c02370
  23. ACS Nano. 2026 Mar 06.
    A Modular Toolkit for Nanoscale Interrogation of Multiprotein Assemblies Inside Living Cells.
    Arthur Felker, Michael Philippi, Michael Holtmannspötter, Christoph Drees, Evelin Schäfer, Martin Steinhart, Rainer Kurre, Changjiang You, Jacob Piehler.
      Quantitative analysis of protein interactions and the formation of higher-order assemblies in living cells remain major challenges. Here, we introduce a versatile nanopatterning toolbox that employs capillary nanostamping of functionalized polymers to generate high-contrast biofunctionalized nanodot arrays (bNDAs) with diameters below 500 nm. By leveraging orthogonal adaptor designs, we achieve robust immobilization of diverse fluorescent protein fusions, enabling simultaneous and selective spatially controlled enrichment of cytosolic proteins into high-density cytosolic nanodot arrays (cNDAs). Focusing on the assembly of the multimeric myddosome complex, we demonstrate density-dependent recruitment and colocalization of the core components MyD88, IRAK4, IRAK1, and TRAF6 within cNDAs. Super-resolution microscopy revealed the distinct nanoscale clustering of MyD88 and IRAK4 and uncovered the ultrastructural architecture of IRAK4 oligomers. These analyses highlight the spatial organization and hierarchical assembly of the myddosome at the nanoscale in the native cellular context. Collectively, our findings establish cNDAs as a powerful platform for reconstituting and analyzing intricate multiprotein assemblies in live cells, offering exciting opportunities for elucidating the mechanistic principles underlying complex protein networks.
    Keywords:  capillary nanostamping; myddosome assembly; nanodot array; protein interaction analysis; super-resolution microscopy; surface biofunctionalization
    DOI:  https://doi.org/10.1021/acsnano.5c14657
  24. Soft Matter. 2026 Mar 03.
    Nonlinear elasticity and transition to macroscopic irreversibility in composite hydrogels.
    Ippolyti Dellatolas, Thibaut Divoux, Emanuela Del Gado, Irmgard Bischofberger.
      Filler-hydrogel composites combine enhanced mechanical properties with functionalities conferred by the nanofillers. When the nanofillers interact attractively with the hydrogel matrix, even low nanofiller volume fractions can lead to a strong increase in the linear viscoelastic moduli. Here, we build on our understanding of the microscopic phenomena at play in these systems to explore their nonlinear response, using attractive nanofillers embedded in a gelatin matrix. We identify a critical deformation beyond which the material no longer recovers its macroscopic viscoelastic properties, marking the onset of macroscopic irreversibility. Increasing nanofiller volume fraction leads to nanofiller-induced stiffening of the polymer matrix, yet the overall viscoelastic response of the composites remains qualitatively similar to that of pure hydrogels: under increasing strain amplitude, their elastic and viscous moduli, G' and G″, exhibit a pronounced overshoot followed by a crossover associated with yielding. A transition occurs in the composite at the strain amplitude where G' reaches its maximum, characterized by a marked change in the stress relaxation dynamics. Beyond , the composites no longer recover their initial viscoelastic properties in repeated strain amplitude sweeps, indicating that the material has sustained macroscopically irreversible changes and a permanent loss of elasticity. We thus identify three distinct regimes in the strain-stiffening materials: nonlinear elasticity, macroscopic irreversibility, and yielding. We further suggest that the plasticity underpinning macroscopic irreversibility is due to the breaking of bonds that contribute most to the composite's strain stiffening response in the hydrogel matrix.
    DOI:  https://doi.org/10.1039/d5sm00990a
  25. Curr Opin Microbiol. 2026 Mar 03. pii: S1369-5274(26)00020-2. [Epub ahead of print]91 102726
    Repurposing bacterial secretion systems for the design of living therapeutics.
    Stevens Robertin, Cammie F Lesser.
      The targeted delivery of therapeutics to sites of disease remains a major challenge. Almost all drugs, whether administered orally or intravenously, can cause systemic side effects. To circumvent these issues, synthetic biology-based approaches are being used to engineer bacteria to secrete therapeutic protein payloads directly at sites of disease. In the case of Gram-positive bacteria, the most straightforward approach has been to expand the repertoire of proteins recognized by their native protein secretion systems, which enable secretion across their cell membrane. However, for Gram-negative bacteria, these same secretion systems deposit proteins into the periplasm, the space between the two lipid bilayers of their complex outer envelope. Here, we review the ways that commensal and probiotic Escherichia coli are being engineered with additional secretion systems, including some originating from pathogens, outfitted to secrete desired therapeutic protein payloads. We discuss the potential advantages and limitations of each secretion system and potential areas for further investigation. Using examples of variants developed for the treatment of inflammatory bowel diseases, we provide a case study focused on the secretion systems, payloads, and transcriptional regulatory pathways that have been introduced. These studies demonstrate how advances in understanding bacterial secretion systems and synthetic biology are addressing therapeutic payload delivery challenges.
    DOI:  https://doi.org/10.1016/j.mib.2026.102726
  26. Nature. 2026 Mar 04.
    Genome modelling and design across all domains of life with Evo 2.
    Garyk Brixi, Matthew G Durrant, Jerome Ku, Mohsen Naghipourfar, Michael Poli, Gwanggyu Sun, Greg Brockman, Daniel Chang, Alison Fanton, Gabriel A Gonzalez, Samuel H King, David B Li, Aditi T Merchant, Eric Nguyen, Chiara Ricci-Tam, David W Romero, Jonathan C Schmok, Ali Taghibakhshi, Anton Vorontsov, Brandon Yang, Myra Deng, Liv Gorton, Nam Nguyen, Nicholas K Wang, Michael T Pearce, Elana Simon, Etowah Adams, Zachary J Amador, Euan A Ashley, Stephen A Baccus, Haoyu Dai, Steven Dillmann, Stefano Ermon, Daniel Guo, Michael H Herschl, Rajesh Ilango, Ken Janik, Amy X Lu, Reshma Mehta, Mohammad R K Mofrad, Madelena Y Ng, Jaspreet Pannu, Christopher Ré, John St John, Jeremy Sullivan, Joseph Tey, Ben Viggiano, Kevin Zhu, Greg Zynda, Daniel Balsam, Patrick Collison, Anthony B Costa, Tina Hernandez-Boussard, Eric Ho, Ming-Yu Liu, Thomas McGrath, Kimberly Powell, Sudarshan Pinglay, Dave P Burke, Hani Goodarzi, Patrick D Hsu, Brian L Hie.
      All of life encodes information with DNA. Although tools for genome sequencing, synthesis and editing have transformed biological research, we still lack sufficient understanding of the immense complexity encoded by genomes to predict the effects of many classes of genomic changes or to intelligently compose new biological systems. Artificial intelligence models that learn information from genomic sequences across diverse organisms have increasingly advanced prediction and design capabilities1,2. Here we introduce Evo 2, a biological foundation model trained on 9 trillion DNA base pairs from a highly curated genomic atlas spanning all domains of life to have a 1 million token context window with single-nucleotide resolution. Evo 2 learns to accurately predict the functional impacts of genetic variation-from noncoding pathogenic mutations to clinically significant BRCA1 variants-without task-specific fine-tuning. Mechanistic interpretability analyses reveal that Evo 2 learns representations associated with biological features, including exon-intron boundaries, transcription factor binding sites, protein structural elements and prophage genomic regions. The generative abilities of Evo 2 produce mitochondrial, prokaryotic and eukaryotic sequences at genome scale with greater naturalness and coherence than previous methods. Evo 2 also generates experimentally validated chromatin accessibility patterns when guided by predictive models3,4 and inference-time search. We have made Evo 2 fully open, including model parameters, training code5, inference code and the OpenGenome2 dataset, to accelerate the exploration and design of biological complexity.
    DOI:  https://doi.org/10.1038/s41586-026-10176-5
  27. Nature. 2026 Mar 03.
    Genetically encoded assembly recorder temporally resolves cellular history.
    Yuqing Yan, Jiaxi Lu, Zhe Li, Zuohan Zhao, Timothy F Shay, Shunzhi Wang, Yaping Lei, Yimei Wang, Wei Chen, Patrick Parker, Hongru Yang, Aileen Qi, Yongzhi Sun, Dwight E Bergles, David Baker, Dingchang Lin.
      Cells constantly change their molecular state in response to internal and external cues1. Mapping cellular activity in tissues with spatiotemporal precision is essential for understanding organ physiology, pathology, and regenerative processes. Current cell-sensing modalities primarily rely on either endpoint analysis that takes static snapshots, or real-time sensing that monitors a small subset of cells3,4. Here, we introduce Granularly Expanding Memory for Intracellular Narrative Integration (GEMINI), an in cellulo recording platform that leverages a computationally designed protein assembly as an intracellular memory device to record the history of individual cells. GEMINI grows predictably within live cells, capturing cellular events as tree-ring-like fluorescent patterns for imaging-based retrospective readout. Absolute chronological information of activity histories is attainable with hour-level accuracy. GEMINI effectively maps differential NFκB-mediated transcriptional changes, resolving fast dynamics of 15 minutes and providing quantifiable signal amplitudes. In a xenograft model, GEMINI records inflammation-induced signaling dynamics across tissue, revealing spatial heterogeneity linked to vascular density. When expressed in the mouse brain, GEMINI minimally impacts neuronal functions and can resolve both transcriptional changes and activity patterns of neurons. Together, GEMINI provides a robust and generalizable means for spatiotemporal mapping of cell dynamics underlying physiological and pathological processes in both culture and intact tissues.
    DOI:  https://doi.org/10.1038/s41586-026-10323-y
  28. Sci Adv. 2026 Mar 06. 12(10): eaea9383
    NEO-PGA: Nonvolatile electro-optically programmable gate array.
    Rui Chen, Andrew Tang, Jayita Dutta, Virat Tara, Julian Ye, Zhuoran Fang, Arka Majumdar.
      Programmable photonic integrated circuits promise reconfigurable, multifunctional photonic systems, analogous to electronic field programmable gate arrays. However, their scalability is constrained by reliance on volatile thermo-optic tuning, which incurs high power consumption, large footprints, and thermal cross-talk. Chalcogenide phase-change materials (PCMs) offer a superior alternative because of their nonvolatility and substantial optical contrast, yet challenges such as optical loss and bit precision have severely hindered their large-scale adoption. Here, we demonstrate low-loss, multibit control of the PCM Sb2Se3 using a closed-loop "program-and-verify" approach. We integrate electrically reconfigurable PCM gates into 300-millimeter silicon photonic platforms, implementing both circulating and forward Mach-Zehnder interferometer meshes. The circulating mesh enables broadband switching fabrics and high-Q coupled resonators with unprecedented local control of coupling rates, while the forward mesh supports spatial mode sorting. These results establish a scalable, nonvolatile photonic programmable gate array enabled by PCMs, opening pathways to general-purpose, on-chip programmable photonic systems.
    DOI:  https://doi.org/10.1126/sciadv.aea9383
  29. Angew Chem Int Ed Engl. 2026 Mar 01. e24223
    Small-Molecule Activation of mRNA Translation by Click-to-Release Reaction in Cells.
    Tess Vosman, Friedrich Burba, Martin Sumser, Milan Vrabel, Hannes Mikula, Andrea Rentmeister.
      mRNA is an emerging medical modality, however, approaches to control its activity lack behind other biologics. Bioorthogonal click-to-release reactions enable breaking chemical bonds at high reaction rates even in living cells to release a functionally active biomolecule ("uncaging"). We developed a 5' cap modified with a trans-cyclooctene (TCO-cap) that reacts with hydroxyaryl-tetrazines to efficiently release the native cap 0. This strategy is compatible with in vitro transcription and facilitates HPLC-based purification of the resulting TCO-capped mRNA, circumventing the need to digest uncapped mRNA produced in the process. Using eGFP- and luciferase-mRNAs in mammalian cells, we show that TCO-capped mRNAs are translationally muted and can be activated for translation by addition of cell-permeable, non-toxic sulfonamide-modified hydroxyphenyl-tetrazines. This work presents a new approach for small-molecule-induced translation in eukaryotes with potential to be applicable to any mRNA.
    Keywords:  5′ cap; click chemistry; mRNA; tetrazines; translation
    DOI:  https://doi.org/10.1002/anie.202524223
  30. Macromolecules. 2025 Dec 09. 58(23): 12440-12447
    Mesoscale Modeling of Hydrogels Under Frictional Shear Stress.
    Mehdi Karimi, Amir Poorghani, Angela A Pitenis, Alexander Alexeev.
      Hydrogels are three-dimensional networks of hydrophilic polymers often used as a simplified model of hydrated biological materials, from cartilaginous joints to the ocular tear film. However, the lubrication mechanisms of hydrogels remain poorly understood, partly due to their complex polymeric structure, which creates blurred interfaces during sliding that are challenging to study experimentally. In this study, we employ dissipative particle dynamics (DPD) to investigate the frictional behavior of a polymeric hydrogel network sliding against a solid wall in an explicit viscous solvent. This computational approach enables us to model hydrodynamic interactions and mesoscale polymer dynamics, capturing key aspects of hydrogel friction. Our simulations reveal that hydrogel friction is governed by the interplay between polymer relaxation and viscous shear, characterized by the Weissenberg number (Wi). At low Wi, friction coefficient remain nearly constant, dominated by polymer relaxation. However, at higher Wi, friction is dominated by viscous drag within a near-wall solvent layer, leading to a linear increase in friction coefficient with Wi. Furthermore, our results demonstrate an inverse relationship between the friction coefficient and the applied normal load, consistent with experimental observations. This work provides new insights into the fundamental tribological properties of hydrogels, shedding light on the micromechanics of hydrogel friction. Improving our understanding of hydrogel structure and dynamics under friction advances our knowledge of the mechanisms regulating biological lubrication in health and disease.
    DOI:  https://doi.org/10.1021/acs.macromol.5c01748
  31. Small. 2026 Mar 03. e14518
    Localized Thermomechanical Measurements of Polymers and Blends with AFM-IR.
    Carina Yi Jing Lim, Zhenan Bao, Lukas Michalek.
      Understanding the thermomechanical behavior of heterogeneous polymer systems is crucial for material design. Herein, we introduce a novel technique that couples chemistry-selective infrared (IR) heating with atomic force microscopy (AFM) nanomechanical measurements. We demonstrate that surface heating of the sample on the AFM-IR can be varied with the IR repetition rate, evidenced by melting poly(ethylene glycol) (PEG) films over a range of molecular weight-dependent melting points. Chemical-selective heating was demonstrated, where heating is dependent on the characteristic IR absorption bands of the material. Coupling of IR laser heating with nanomechanical measurements enables the qualitative detection of its glass transition temperature in thickness-confined semi-crystalline poly(lactic acid) (PLA) films, where an ultra-thin PLA film demonstrated a decrease in modulus to half its initial value with a significantly lower IR repetition rate relative to the IR repetition rate required to induce the same change in a thick PLA film. We further apply this technique to a polymer blend of PLA and uncrosslinked nitrile butadiene rubber to demonstrate phase-specific thermal characterization. This technique minimizes thermal drift, allows for rapid heating with concurrent AFM measurements and circumvents bulk material changes, paving a possible alternative avenue for the probing of thermomechanical properties of heterogenous films.
    Keywords:  atomic force microscope; infrared; nanomechanics; polymer thin films; thermomechanical measurements
    DOI:  https://doi.org/10.1002/smll.202514518
  32. Macromolecules. 2025 Aug 12. 58(15): 8249-8259
    3D-Printed Dual Photo- and Thermally Responsive Materials for Smart Adaptability.
    Tao Zhang, Gianni Pacella, Kunlin Chen, Ting Ye, Giuseppe Portale, Vincent S D Voet, Rudy Folkersma, Katja Loos.
      The development of intelligent 3D printing materials with photo- and thermally responsive properties remains a challenge, particularly for sustainable applications requiring reprocessability, multifunctionality, and precise control over dynamic behaviors. Herein, we report a solvent-free photoprintable ink featuring dual dynamic covalent bonds (DCBs), designed for photo- and thermally responsive 3D printing. The resin combines dynamic disulfides and β-hydroxy esters, further enhanced with photoswitchable spiropyran additives, enabling tunable photochromic and thermochromic properties. This material also exhibits shape memory functionality, allowing simultaneous shape and color transitions under heat. Printed prototypes demonstrate exceptional thermal stability and multifunctionality, supporting applications in anticounterfeiting, imaging, and sensing. These results provide a sustainable and innovative solution for intelligent 3D printing materials, bridging the gap between multifunctionality and reprocessability. By advancing the capabilities of responsive materials, this work paves the way for transformative progress in adaptive manufacturing and practical applications in next-generation functional devices.
    DOI:  https://doi.org/10.1021/acs.macromol.5c00567
  33. Macromolecules. 2026 Jan 27. 59(2): 663-670
    Tuning Mechanical and Self-Healing Properties Using Multivalent Crosslinking.
    Sreecharan Ajjagola, Alexis K Smith, Dominik Konkolewicz, Mehdi B Zanjani.
      Dynamic crosslinking in polymer networks has played a major role in contributing to various material properties, including toughness, tensile resistance, and self-healing. Dynamic covalent crosslinking, which connects two points on the polymer backbone using divalent crosslinkers, has been studied to date. Here, we systematically investigate the impact of using multivalent crosslinkers on the mechanical and self-healing properties of polymer materials. We used the thiol-Michael "click" chemistry to crosslink thiol-maleimide functional groups, which are well known for their thermoresponsive dynamic properties. Di-, tri-, tetra-, and hexathiols were used as crosslinkers to increase the complexity of the crosslinked polymer network. The results indicated that the mechanical and self-healing properties can be tuned by using multivalent networks, potentially paving the way for the development of better self-healing elastomers and opening opportunities for new chemistries to be explored.
    DOI:  https://doi.org/10.1021/acs.macromol.5c02522
  34. Mater Horiz. 2026 Mar 03.
    Targeted metabolic glycoengineering using multivalent mannosyl metal-organic frameworks (MOFs).
    Pei-Hong Tong, Chen Guo, Xi-Le Hu, Tony D James, Jia Li, Xiao-Peng He.
      Cell-type selective metabolic labeling of glycans in complicated biological environments remains a big challenge. Herein, we develop a glycan labeling tool by encapsulating a non-natural azido sugar (ManNAz) into a mannosyl ligand-modified metal-organic framework (MOF) (MIL-101-Man). The mannosyl ligands multivalently displayed on the surface of the MOFs bind specifically to mannose receptors (MRs) expressed on the surface of a target cell to mediate targeted delivery of the unnatural sugar. Upon endocytosis, exposure of the MOFs to the acidic environment of the endosomes and lysosomes resulted in the release of ManNAz to subsequently undergo metabolic incorporation into cellular glycans. A series of biological experiments followed by fluorescence-based biorthogonal cell labelling demonstrated the receptor-dependent uptake of MIL-101-Man, and an assay involving the co-culture of two cell lines in one cellular medium confirmed the target specificity of the MOFs for the glycoengineering of target cells that overly express MRs over adjacent control cells with minimal MR expression. This study offers an effective tool for the metabolic glycoengineering of cells in a receptor-targeting manner.
    DOI:  https://doi.org/10.1039/d5mh01986a
  35. ACS Cent Sci. 2026 Feb 25. 12(2): 185-196
    Directed Evolution of Enzymes for Bioorthogonal Chemistry Using Acid Chloride Proximity Labeling.
    Ashley N Ogorek, Shubhashree Pani, Eli J Mertick-Sykes, Jelena Momirov, Yichong Lao, Fernando Banales Mejia, Rachel S T Chan, Xuhui Huang, Bryan C Dickinson, Jeffrey D Martell.
      Combining bioorthogonal protecting groups with localized catalysts that can unmask them is a powerful approach to spatially and temporally modulate molecular activity. Enzymes are appealing catalysts in this context because they are genetically targetable, but enzymes are not always available to unmask a protecting group of interest. Here, we report a platform for ultrahigh-throughput enzyme evolution by combining yeast surface display with masked acylating probes, which selectively label yeast cells based on target biocatalytic activity. We introduce the phenylcyclopropyl (pCP) ester protecting group, which has improved bioorthogonality compared to existing ester protecting groups, and use our platform to evolve BS2 esterase for enhanced pCP unmasking. Evolved BS2 mutants are up to 232-fold more active toward the pCP group. Taking advantage of the enhanced bioorthogonality of the pCP group, we applied a pCP probe together with evolved BS2 to perform spatially resolved RNA tagging with high spatial specificity, including in mammalian cell lines with high endogenous esterase activity. Overall, this work delivers a new bioorthogonal protecting group and engineered enzymes capable of unmasking it, and more broadly, it provides a platform to rapidly engineer enzymes for protecting group removal, opening opportunities in imaging, proximity tagging, induced cell signaling, and therapeutics.
    DOI:  https://doi.org/10.1021/acscentsci.5c01746
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