bims-enlima 2025-12-07 papers

bims-enlima

Biomed News

on Engineered living materials

Issue of 2025–12–07
35 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool

Design principles for adaptive and evolving engineered living materials.
Thermo-reversible gelation of self-assembled conducting polymer colloids.
Stimuli-Responsive Chemical Systems That Mimic Biological Dynamics.
Modulating RNA condensates to control cell fate.
Optogenetic Control the Activity of Pyruvate Decarboxylase in Saccharomyces cerevisiae for Tunable Ethanol Production.
Atom-level enzyme active site scaffolding using RFdiffusion2.
Extensile Active Hydrogels Driven by Living FtsZ Polymers.
Polymerizable inverse HIPEs-based inks towards 3D printing of highly tailorable polymeric materials.
Genetically encoded green-light-responsive photocaged lysine for sequential control of protein function.
Unraveling positive deformation rate-elongation relationships in tough and highly stretchable ionogels under rapid deformation.
Hierarchical crack-resistant, tissue-mimetic hydrogels enabled by progressive nanocrystallization of anisotropic polymer networks.
Advancing aerogel recyclability through polyhexahydrotriazine reactivity.
Tailoring composite hydrogel performance via controlled integration of norbornene-functionalised Pluronic micelles.
Compression-Tension-Asymmetry and Stiffness Nonlinearity of Collagen-Matrigel Composite Hydrogels.
Synthesis of Conductive Polymers in Living Plants Using an Enzyme-Assisted Polymerization Strategy for Sensing and Energy Storage.
3D bioprinting of cell-laden constructs: Technologies, bioink design, and biomedical applications.
Seeking Precise Protein-like Functions from Random Heteropolymer Ensemble and through Dimensionality Reduction.
3D-Printed Gradient-Porous MXene@mRGO@SiO2 Microspheres/SiC Hybrid Elastomer for Broadband Electromagnetic Wave Absorption.
One-Pot and Closed-Loop Recycling of Biomass-Derived Soft Electronics Toward Zero e-waste.
Generating tolerance through in situ recruitment of regulatory T cells for allogeneic cell transplantation in a bioengineered lymphoid platform.
3D Printable Hydrogel with a Controlled Hierarchical Network through Aqueous PhotoATRP Using a Well-Defined Telechelic Bromide Macroinitiator.
In Situ Assembly of Bilayer Hydrogels by Templated Enzymatic Polymerization for Ultrahigh UV Absorption and Photothermal Transdermal Therapy.
Mechanism for a molecular assembler of sequence-controlled polymers using parallel DNA and a DNA polymerase.
Biohybrid Tendons Enhance the Power-to-Weight Ratio and Modularity of Muscle-Powered Robots.
Scale-Specific Viscoelastic Characterization of Hydrogels: Integrated AFM and Finite Element Modeling.
Biocompatible Ink Optimization Enables Functional Volumetric Bioprinting With Xolography.
Synthetic cells by the numbers.
Expanding the Usage of Lignin in DLP 3D Printing by Optimized Synthesis and Processing Parameters.
Control of encounter kinetics by chemically active droplets.
Towards tunable mechanical properties of in situ gelling chitosan hydrogels: impact of macromolecular structure including pattern of acetylation.
Conservation of mRNA operon formation in control of the heat shock response in mammalian cells.
All 3D Printed Soft Integrated Conductors.
Thermal Switching of Polymer Topology Enables Programmable Mechanical Properties in Soft Materials.
Design of a flexible cellulose framework via supramolecular structure modulation and its application in hydrogel sensors.
Engineering the Size of Bicontinuous Nanospheres via Multi-Inlet Vortex Mixing.

Curr Opin Biotechnol. 2025 Dec 03. pii: S0958-1669(25)00141-7. [Epub ahead of print]97 103397

Design principles for adaptive and evolving engineered living materials.

Yifan Cui, Mark W Tibbitt, Timothy K Lu, Tzu-Chieh Tang.

Engineered living materials (ELMs) combine living cells, typically microorganisms, such as bacteria, yeasts, or filamentous fungi, with structural carrier matrices to form systems capable of sensing, growth, and self-repair. Most current designs emphasize programming the microbes to render otherwise static materials functional. A less explored dimension is leveraging reciprocal microbial-material interactions themselves to engineer adaptive and evolving living materials as integrated systems. Achieving such dynamic behavior requires understanding how support matrices influence microbial behavior and how cells, in turn, reshape material properties over time. This review outlines key modes of cell-material interactions as a framework for expanding the functional toolbox of ELMs and for creating sustainable and programmable materials that respond to their environments and evolve.

DOI: https://doi.org/10.1016/j.copbio.2025.103397
Nat Commun. 2025 Dec 05. 16(1): 10879

Thermo-reversible gelation of self-assembled conducting polymer colloids.

Vidhika S Damani, Xinran Xie, Rachel E Daso, Khushboo Suman, Masoud Ghasemi, Weiran Xie, Ruiheng Wu, Yuhang Wu, Calvin L Chao, Julian E Alberto, Casey M Lorch, Ai-Nin Yang, Dan My Nguyen, Tulaja Shrestha, Kayla Otero, Chun-Yuan Lo, Darrin J Pochan, Enrique D Gomez, Jonathan Rivnay, Laure V Kayser.

Electrically conductive hydrogels based on conducting polymers have found increased use in bioelectronics due to their low moduli that mimic biological tissues, their ability to transport both ionic and electronic charges, and their ease of processing in various form factors via printing or injection. Current approaches towards conductive hydrogels, however, rely on covalent and therefore irreversible crosslinking mechanisms. Here, we report a thermo-responsive conducting polymer (TR-CP) that undergoes a fully reversible non-covalent crosslinking at 35 °C within less than a minute to form conductive hydrogels. The TR-CP is based on a block polyelectrolyte complex, that self-assembles into well-defined colloidal particles in water which undergo an isovolumetric sol-gel transition just below physiological temperature. The hydrogels have tunable mechanical properties in the 20 to 200 Pa range, are stable at various pH and salt conditions, self-healing, injectable, and biocompatible in vitro and in vivo. We demonstrate that the TR-CPs can be used to fabricate sensitive, conformal and reusable electrodes for surface electromyography. This thermo-responsive material provides exciting opportunities for stimuli-responsive and adaptive bioelectronics.

DOI: https://doi.org/10.1038/s41467-025-66034-x
Chemistry. 2025 Nov 29. e02993

Stimuli-Responsive Chemical Systems That Mimic Biological Dynamics.

Antonio Aguanell, Álvaro Sarabia-Vallejo, Marc Hennebelle, Ruth Pérez-Fernández.

  Living systems achieve adaptability, motion, and self-regulation through chemical networks operating out of equilibrium. Reproducing these dynamics synthetically demands precise control over kinetics, thermodynamics, and molecular design to convert energy inputs into time-programmed function. Recent advances in stimuli-responsive and chemically powered systems show how life-like behaviors such as oscillations, autonomous motion, adaptive responses, and compartmentalization can be encoded using fuel-driven cycles and stimulus-gated switches powered by chemical, photonic, or enzymatic inputs. This mini-review highlights molecular assemblies that sustain transient states, molecular machines powered by specific chemical inputs, responsive materials that reconfigure in response to environmental triggers, nucleic acid-based networks for sensing and regulation, and artificial cells that exhibit compartmentalization and signaling. Together, these developments bridge systems chemistry and biomimicry, expanding the chemical toolkit for engineering matter that can adapt and respond. Beyond mimicking biology, such systems deepen our understanding of the molecular foundations of living matter and open new routes to technology. Self-powered systems, molecular motors, smart materials, and artificial cells now form a rapidly growing toolbox with the potential to impact drug discovery, biosensing, energy, food production, and materials science. The field's future lies in integrating multiple life-essential functions into a single construct, ultimately enabling synthetic systems that replicate the complex network behaviors of living organisms and inspire next-generation innovation.

Keywords:  artificial cells; non‐equilibrium systems; smart materials; supramolecular chemistry; synthetic biology

DOI:  https://doi.org/10.1002/chem.202502993
Nat Biotechnol. 2025 Dec 02.

Modulating RNA condensates to control cell fate.

Kasey S Love, Kate E Galloway.

DOI: https://doi.org/10.1038/s41587-025-02936-x
ACS Synth Biol. 2025 Dec 03.

Optogenetic Control the Activity of Pyruvate Decarboxylase in Saccharomyces cerevisiae for Tunable Ethanol Production.

Meizi Liu, Yunhong Chen, Junjun Yan, Qi Xiao, Guoping Zhao, Yanfei Zhang.

  Saccharomyces cerevisiae is a widely used chassis in metabolic engineering. Due to the Crabtree effect, it preferentially produces ethanol under high-glucose conditions, limiting the synthesis of other valuable metabolites. Conventional metabolic engineering approaches typically rely on irreversible genetic modifications, making it insufficient for dynamic metabolic control. In contrast, optogenetics offers a reversible and tunable method for regulating cellular metabolism with high temporal precision. In this study, we engineered the pyruvate decarboxylase isozyme 1 (Pdc1) by inserting the photosensory modules (AsLOV2 and cpLOV2 domains) into rationally selected positions within the enzyme. Through a growth phenotype-based screening system, we identified two blue light-responsive variants, OptoPdc1D1 and OptoPdc1D2, which enable light-dependent control of enzymatic activity. Leveraging these OptoPdc1 variants, we developed opto-S. cerevisiae strains, MLy-9 and MLy-10, which demonstrated high efficiency in modulating both cell growth and ethanol production. These strains allow reliable regulation of ethanol biosynthesis in response to blue light, achieving a dynamic control range of approximately 20- to 120-fold. The opto-S. cerevisiae strains exhibited dose-dependent production in response to blue light intensity and pulse patterns, confirming their potential for precise metabolic control. This work establishes a novel protein-level strategy for regulating metabolic pathways in S. cerevisiae and introduces an effective method for controlling ethanol metabolism via optogenetic regulation.

Keywords:  AsLOV2 domain; Saccharomyces cerevisiae; dynamic regulation; optogenetics; pyruvate decarboxylase

DOI:  https://doi.org/10.1021/acssynbio.5c00411
Nat Methods. 2025 Dec 03.

Atom-level enzyme active site scaffolding using RFdiffusion2.

Woody Ahern, Jason Yim, Doug Tischer, Saman Salike, Seth M Woodbury, Donghyo Kim, Indrek Kalvet, Yakov Kipnis, Brian Coventry, Han Raut Altae-Tran, Magnus S Bauer, Regina Barzilay, Tommi S Jaakkola, Rohith Krishna, David Baker.

Designing new enzymes typically begins with idealized arrangements of catalytic functional groups around a reaction transition state, then attempts to generate protein structures that precisely position these groups. Current AI-based methods can create active enzymes but require predefined residue positions and rely on reverse-building residue backbones from side-chain placements, which limits design flexibility. Here we show that a new deep generative model, RoseTTAFold diffusion 2 (RFdiffusion2), overcomes these constraints by designing enzymes directly from functional group geometries without specifying residue order or performing inverse rotamer generation. RFdiffusion2 successfully generates scaffolds for all 41 active sites in a diverse benchmark, compared to 16 using previous methods. We further design enzymes for three distinct catalytic mechanisms and identify active candidates after experimentally testing fewer than 96 sequences in each case. These results highlight the potential of atomic-level generative modeling to create de novo enzymes directly from reaction mechanisms.

DOI: https://doi.org/10.1038/s41592-025-02975-x
Small. 2025 Dec 05. e10218

Extensile Active Hydrogels Driven by Living FtsZ Polymers.

Mikheil Kharbedia, Diego Herráez-Aguilar, Macarena Calero, Horacio López-Menendez, Clara Luque-Rioja, Lara H Moleiro, Cruz Santos, Pilar Lillo, Francisco Monroy.

  Embedding living polymers that consume chemical energy into synthetic gels offers a route to soft materials that self-regulate their mechanical state. Here, The bacterial cytokinetic protein FtsZ is integrated within a polyacrylamide network to create an active extensile hydrogel. Upon post-gelation activation with Mg2⁺ and GTP, FtsZ filaments treadmill and exert internal stresses that drive isotropic swelling and mechanical softening. These responses is described using a Flory-Rehner swelling framework, where activity-induced volume expansion lowers the polymer volume fraction and, consequently, the elastic modulus. Normalizing the measured moduli to the FR baseline isolates an additional, rate-dependent softening that arises from living FtsZ polymer dynamics. Rheological analysis reveals that biochemical energy input modulates the elastic state of a pre-formed network through active swelling and strain-dependent fluidization, establishing a minimal model for living-polymer-driven soft materials.

Keywords:  active matter; cytokinetic filaments; hydrogel; living polymers; soft robotics

DOI:  https://doi.org/10.1002/smll.202510218
J Colloid Interface Sci. 2025 Nov 25. pii: S0021-9797(25)02963-7. [Epub ahead of print]706 139571

Polymerizable inverse HIPEs-based inks towards 3D printing of highly tailorable polymeric materials.

Vanessa Rosciardi, Federico Serpe, Simone De Panfilis, Andrea Barbetta, Roberta Angelini.

  Due to its processing requirements, extrusion 3D printing of plastics is limited to a rather narrow range of thermoplastic polymers. Here we present a strategy to formulate 3D printing polymerizable inks with rheological features compatible with extrusion-based approaches and applicable to hardly processable polymers, surpassing their thermal limitations. To do so, we formulate inverse oil-in-water high internal phase emulsions (i-HIPEs) with dispersed phase consisting of polymeric precursors and reaching 90 % volume fraction. As opposed to their water-in-oil counterparts, inverse-HIPEs polymerization, after 3D deposition, yields dense plastic rather than macroporous structures, mimicking the deposition of a fused thermoplastic filament. To demonstrate the validity of the approach, we formulate highly tailorable inks for room-temperature 3D printing of polystyrene (PS) and polymethyl methacrylate (PMMA), which are notoriously difficult to process via conventional thermal strategies. Despite their potential, inverse-HIPEs are far less characterized than classical ones. Here we provide a comprehensive rheological characterization, showing that these emulsions behave as Herschel-Bulkley fluids, exhibiting controllable yield stress, elasticity, and shear-thinning behavior, which are modulated by droplet packing, phase hydrophobicity, and continuous phase viscosity. The resulting inks display shear recovery and good printing potential. Preliminary curing tests demonstrate that methacrylate-based HIPEs undergo rapid UV polymerization, whereas styrene-based systems are thermally polymerized but require alternative strategies for efficient photopolymerization. This work provides a robust framework for the design of broadly applicable, monomer-in-water inks that unlock new possibilities in additive manufacturing with chemically diverse polymer targets.

Keywords:  3D printing inks; HIPEs; Polymethylmethacrylate; Polystyrene; Rheology

DOI:  https://doi.org/10.1016/j.jcis.2025.139571
Chem Sci. 2025 Nov 25.

Genetically encoded green-light-responsive photocaged lysine for sequential control of protein function.

Manjia Li, Minghao Lu, Lijun Wang, Yuqing Zhang, Long Yan, Shushu Wang, Tao Peng.

Site-specific incorporation of photo-responsive unnatural amino acids (UAAs) into proteins via genetic code expansion offers a powerful approach to control and study protein function in biological systems. However, existing UAAs are all sensitive to UV or near-UV light, and no visible-light-responsive UAAs have been reported, limiting our ability to regulate multiple proteins simultaneously. Here, we present the genetic encoding of a green-light-activatable lysine derivative, SCouK, for sequential photocontrol of protein activities in live cells. SCouK, containing a photolabile thiocoumarin moiety at the N ε-amino group of lysine, can be genetically encoded into proteins in bacterial and mammalian cells. We show that site-specifically incorporated SCouK can be photoactivated across a broad wavelength range, from UV to green light, to restore the functions of EGFP and luciferase. Notably, SCouK is highly efficiently photodecaged by green light centered at 520 nm within 30 seconds, marking it as the first visible-light-responsive lysine derivative with the longest single-photon activation wavelength among genetically encoded photolabile UAAs. Additionally, we showcase the general capability of SCouK for the optical control of different kinases and temporal control and interrogation of the cGAS-STING pathway in live cells. Moreover, by combing SCouK with a UV-light-activatable tyrosine derivative, we achieve, for the first time, sequential photoactivation of two distinct UAA-modified proteins within a single live-cell sample. Overall, the unique features of SCouK, including site-specific incorporation, green-light-responsiveness, orthogonal activation wavelengths, high decaging efficiency, and general applicability, demonstrate its great potential to non-invasively and precisely manipulate proteins in complex living systems for functional studies and therapeutic applications.

DOI: https://doi.org/10.1039/d5sc08317f
Nat Commun. 2025 Dec 04.

Unraveling positive deformation rate-elongation relationships in tough and highly stretchable ionogels under rapid deformation.

Yueyin Guo, Yifan Liu, Caili Yuan, Neil R Champness, Jianchuan Wang, Lixu Yang.

Polymer ionogels are conductive materials with broad applications, however, the toughening and deformation mechanisms of ionogels under rapid deformation remain largely unexplored. Traditional toughening mechanisms based on sacrificial bonds between polymer chains suffer from the deformation rate-elongation trade-off. Here, we present a transparent, strong (26 MPa), tough (152 MJ m-3), stretchable (elongation 1028 %), and conductive ionogel that exhibits a positive correlation between deformation rate and elongation. The mechanical properties under different deformation rates and spectra results reveal that the enhanced mechanical properties with increasing deformation rate are attributed to the synergistic slide-ring effect and solvent/anion interactions, which effectively enhance molecular mobility and facilitate deformation delocalization. The generality of this strategy is further corroborated by the analogous mechanical properties exhibited by ionogels with diverse anions. This work offers a promising strategy to design materials and deepen understanding of toughening mechanisms under rapid deformation.

DOI: https://doi.org/10.1038/s41467-025-67045-4
Nat Commun. 2025 Dec 04. 16(1): 10890

Hierarchical crack-resistant, tissue-mimetic hydrogels enabled by progressive nanocrystallization of anisotropic polymer networks.

Huamin Li, Haidi Wu, Cheng Guan, Wenjie Hu, Wenwen Su, Dingdong Chen, Jiefeng Gao.

Addressing the persistent challenge of reconciling extreme mechanical robustness with tissue-mimetic functionality in hydrogels, we present a phase-transition-guided hierarchical engineering strategy that progressively architectures anisotropic polyvinyl alcohol networks through sequential mechanical training, wet-annealing, and salting-out. This triphasic processing induces programmable structural evolution: (1) mechanical training aligns polymer chains, (2) wet-annealing relaxes the stress while stabilizes oriented crystallites through solvent-plasticized rearrangement, and (3) salting-out densifies the network via chain aggregation and hydrogen-bond proliferation. The resultant hierarchical architecture achieves high fatigue resistance (threshold: 2083 J·m-2) through multi-scale energy dissipation: sacrificial hydrogen bonds consume energy, while aligned crystalline domains pin the crack and deflect crack propagation via anisotropic stress redistribution. Demonstrating tissue-surpassing mechanics (tensile strength: 61 ± 3 MPa, toughness: 106 ± 27 MJ·m-3, fracture energy: 85 ± 9 kJ m-2) coupled with biological functionality, the hydrogel directs cell alignment through contact guidance while resisting swelling-induced dimensional instability (<1.2% volume change in physiological saline). This biomimetic engineering strategy establishes a universal route to design synthetic extracellular matrices that concurrently emulate the anisotropic mechanics of tendons and crack-blunting resilience of cartilage, critical for load-bearing tissue regeneration.

DOI: https://doi.org/10.1038/s41467-025-65917-3
Nat Commun. 2025 Dec 05.

Advancing aerogel recyclability through polyhexahydrotriazine reactivity.

Chang-Lin Wang, Yi-Ru Chen, Brahim Mezari, Fabian Eisenreich, Željko Tomović.

Organic aerogels have emerged as promising materials for advanced thermal insulation. However, their chemically robust covalent networks pose a major barrier for effective recycling. Introducing specific chemical bonds into the aerogel scaffold that enable on-demand reversibility offers a viable pathway to enhance recyclability and promote the sustainable use of these materials. In this work, we demonstrate that hexahydrotriazine (HT) units undergo nucleophilic attack by amines and engage in metathesis reactions, fundamentally redefining their reactive behaviors. Based on this, we introduce a waste-minimized, closed-loop chemical recycling process for highly porous, thermally superinsulating organic aerogels. These materials are partially depolymerized into soluble oligomers upon exposure to primary amines and can be reassembled into fresh polymer networks on demand. Additionally, by varying the amine feedstocks during depolymerization, we tailor key aerogel properties, such as thermal conductivity and flame resistance, beyond their initial synthesis. Under heat and pressure, HT bond exchange enables aerogels to transform into high-performance thermoset-like films, which can subsequently revert to aerogels. This breakthrough in HT chemistry sets a benchmark for atom-efficient recycling, reprogramming, and reprocessing of HT-based materials, providing a transformative foundation for a circular materials platform with broad impact.

DOI: https://doi.org/10.1038/s41467-025-67059-y
Biomater Sci. 2025 Dec 04.

Tailoring composite hydrogel performance via controlled integration of norbornene-functionalised Pluronic micelles.

Nicola Contessi Negrini, Hongning Sun, Adam D Celiz.

Incorporating micelles into polymeric hydrogels offers a powerful route to combine the tuneable mechanical and structural properties of hydrogels with the precise drug-loading and release capabilities of nanocarriers. However, the method of micelle incorporation and its influence on hydrogel performance have yet to be studied in detail. Here, we present a modular strategy to tailor gelatin-norbornene hydrogels by integrating Pluronic® F127 micelles either physically or via covalent incorporation using norbornene-functionalised Pluronic (Pl_Nb). Pl_Nb was synthesised via Steglich esterification with >95% terminal functionalisation, forming stable, thermo-responsive micelles (2.5-15% w/v) with doxorubicin encapsulation efficiency of ∼80%, comparable to unmodified Pluronic. Micelles were either physically entrapped or chemically integrated into gelatin-norbornene networks via bioorthogonal thiol-ene crosslinking. The incorporation route dictated network mechanics and dynamics: chemical crosslinking conferred temperature-dependent behaviour and enhanced stress relaxation compared to physical crosslinking, whereas both incorporation routes reduced stiffness relative to neat hydrogels and slowed drug release compared to direct loading. All hydrogels were cytocompatible, and the released doxorubicin retained its bioactivity, reducing cancer cell viability. These findings establish micelle-hydrogel coupling as a versatile design approach for engineering biomaterials with potential in controlled therapeutic delivery and regenerative medicine.

DOI: https://doi.org/10.1039/d5bm01434d
Adv Healthc Mater. 2025 Dec 05. e03052

Compression-Tension-Asymmetry and Stiffness Nonlinearity of Collagen-Matrigel Composite Hydrogels.

David Böhringer, Jan Hinrichsen, Radik Gataulin, Sandra Wiedenmann, Marina Spörrer, Selda Sherifova, Paul Steinmann, Gerhard A Holzapfel, Ben Fabry, Silvia Budday.

  Collagen type I hydrogels, which self-assemble into 3D fiber networks, are commonly used for cell culture and tissue engineering applications. Collagen hydrogels replicate the nonlinear stress-strain relationship of collagenous tissue under extension. However, they buckle and soften under compression, whereas natural tissue exhibits significant stiffening due to the presence of cells and other matrix components. To more closely mimic the mechanical properties of natural tissue, varying concentrations of the basement membrane extract Matrigel are added to collagen. The stress-strain relationship of the resulting composite hydrogels is then analyzed under compression, tension, and shear. It is found that the addition of Matrigel increases the stiffness and reduces the compression-tension asymmetry. This can be explained by a reduced degree of freedom for collagen fiber buckling due to the constraints imposed by the surrounding fine-meshed Matrigel network. Consistent with this explanation, it is found that the collapse of composite hydrogels under uniaxial strain decreases with increasing concentration of Matrigel and other filler materials, such as alginate. Taken together, by adjusting the ratio of Matrigel to collagen, the mechanical compression-tension asymmetry and nonlinearity of composite hydrogels can be tuned to more closely mimic natural tissue and tailor cell behavior.

Keywords:  biopolymer; finite element method; mechanical testing; ogden model; parameter identification

DOI:  https://doi.org/10.1002/adhm.202503052
ACS Appl Mater Interfaces. 2025 Dec 02.

Synthesis of Conductive Polymers in Living Plants Using an Enzyme-Assisted Polymerization Strategy for Sensing and Energy Storage.

Miaomiao Zhang, Shengpeng Xia, Rui Li, Yiming Huang, Fengting Lv, Haotian Bai, Shu Wang.

  Living plants provide sustainable and adaptive systems, and enabling them with in vivo electroactivity could open promising avenues for green sensing and energy technologies. However, integrating conductive polymers into living tissues without harming the viability remains challenging. Here, we develop a living rose-based biohybrid system using an enzyme-assisted in vivo polymerization strategy to endow plants with electroactive functions. In the system, pyrrole monomers are transported throughout the plant and polymerized in situ on tissue surfaces, producing electroactive Rose/PPy stems that combine the properties of conductive polymers with living tissues. The system enables sensitive detection of plant hormones, including indole-3-acetic acid (IAA, 1.5 μM-100 μM) and salicylic acid (SA, 0.05 μM-3 μM), via differential pulse voltammetry. Rose/PPy also functions as a supercapacitor electrode, exhibiting a maximum capacitance of 1035 μF at 3 μA with 81% retention over 10,000 cycles, and a symmetric two-electrode device shows 49.7 μF at 3.5 μA with 85% retention over 5500 cycles. These results demonstrate the potential of Rose/PPy for both biosensing and energy storage. This work establishes a general strategy for constructing electroactive plant-based biohybrids, expands the applications of natural biomass in multifunctional materials, and provides insights into the seamless integration of electronics with living systems.

Keywords:  biosensing; conducting polymer; conductive plants; in vivo polymerization; supercapacitor

DOI:  https://doi.org/10.1021/acsami.5c19757
Biomed Mater. 2025 Dec 02.

3D bioprinting of cell-laden constructs: Technologies, bioink design, and biomedical applications.

Qinzhe Xing, Yufeng Liu, Jordan Lee Thomas, Wei Zhang, Muhammad Riaz, Michael Mak, Yibing Qyang.

  Three-dimensional (3D) cell printing is rapidly redefining how we engineer tissues by enabling the precise delivery of living cells within bio-inks to build complex, cell-laden structures. Unlike traditional approaches that seed cells onto inert scaffolds, this technique allows direct integration of cells into the construct, promoting enhanced cell infiltration, extracellular matrix (ECM) remodeling, and tissue-like functionality. Despite the explosion of interest, the field remains fragmented, with limited efforts to unify emerging data across platforms and applications. Our review addresses this gap by synthesizing recent advances in 3D cell printing in terms of key printing factors and parameters and adaptive bioprinting, presenting consensus and translative information such as printing parameters, identifying current established applications, and proposing future research directions based on the current in vivo or clinical results. We map current trends across biomaterial choices-including gelatin, decellularized ECM, alginate, collagen I, and fibrin-and explore how diverse cell types, from primary human cells to engineered stem cell derivatives, are shaping the future of tissue fabrication. These innovations are already influencing in vivo research in skin regeneration, cartilage repair, and vascular grafts, while the high-resolution capabilities of 3D printing are powering next-generation organ-on-chip models. We conclude with key translational challenges and propose future research priorities to move from bench to bedside.

Keywords:  3D Bio-printing; Bio-ink; Cell-containing Printing; Organ-on-chips; Skin patch; Vascular Graft

DOI:  https://doi.org/10.1088/1748-605X/ae2725
ACS Cent Sci. 2025 Nov 26. 11(11): 2053-2062

Seeking Precise Protein-like Functions from Random Heteropolymer Ensemble and through Dimensionality Reduction.

Guangqi Wu, Tianyi Jin, Haisen Zhou, Connor W Coley, Alfredo Alexander-Katz, Hua Lu.

Proteins achieve diverse biological functions through precise sequence-structure relationships, yet they can also function through statistical ensembles rather than as individual, static entities. Inspired by this paradigm, recent work has explored random heteropolymers (RHPs) as synthetic, scalable, and versatile protein mimetics. RHPs have been found to function as polymer ensembles capable of folding, binding, catalyzing, and stabilizing biomolecules with control over the monomer sequence. In this Outlook, we highlight recent advances in the discovery and mechanistic understanding of functional RHPs, emphasizing their emergent behaviors and utility across sustainability, human health, and pharmaceuticals. We discuss how autonomous experimentation, machine learning, and multiscale modeling are converging to accelerate design and discovery in this vast chemical space. By embracing statistical design principles, we propose a new framework for creating functional polymers that mirror biological systems.

DOI: https://doi.org/10.1021/acscentsci.5c01382
Small Methods. 2025 Dec 03. e01581

3D-Printed Gradient-Porous MXene@mRGO@SiO2 Microspheres/SiC Hybrid Elastomer for Broadband Electromagnetic Wave Absorption.

Mingwei Yang, Junrui Tan, Eun-Seong Kim, Longfei Tan, Qiong Wu, Guizhi Zhu, Changhui Fu, Nam-Young Kim, Xiangling Ren, Xianwei Meng.

  3D printing via direct ink writing (DIW) enables the precise fabrication of macroscale architectures for high-performance electromagnetic wave absorption elastomers (EMWAEs). However, achieving inks that combine excellent printability with superior electromagnetic and mechanical properties remains challenging. Here, a scalable fabrication strategy employing MXene@modified-RGO@SiO2 microspheres synthesized through continuous spheroidization is presented. The incorporation of SiO2 nanoparticles on the microsphere surface preserves the spherical morphology, enhances dispersion within the silicone elastomer matrix, and optimizes rheological behavior for stable DIW extrusion. Guided by electromagnetic simulations, three-layer gradient-porous structures is designed and printed that maximize interfacial polarization and multiple scattering effects. The resulting elastomers exhibit a minimum reflection loss (RLmin) of -44 dB and a maximum effective absorption bandwidth of 7.2 GHz at a thickness of only 3 mm. In addition to their outstanding electromagnetic performance, the printed materials demonstrate improved thermal conductivity and tensile strength, offering a multifunctional platform suitable for flexible and wearable electronic devices. This approach provides a simple, effective, and customizable route for integrating advanced fillers into 3D-printable elastomers, paving the way for next-generation EMWAEs with tunable architectures, broad bandwidth absorption, and mechanical robustness.

Keywords:  continuous spheroidization; direct ink 3D printing; electromagnetic wave absorption; gradient‐porous structures; silicone elastomers

DOI:  https://doi.org/10.1002/smtd.202501581
Small. 2025 Dec 03. e11832

One-Pot and Closed-Loop Recycling of Biomass-Derived Soft Electronics Toward Zero e-waste.

Keon-Woo Kim, Seongmin Lee, Jin Kon Kim, Chungryong Choi.

  The rapidly expanding soft electronics market has raised critical sustainability concerns. Most petrochemical-based polymers used in soft electronics incur considerable CO2 emissions during their production, and the complex architecture of these devices further hinders recycling. To address these challenges, the development of bio-based and efficiently recyclable materials is essential for reducing the carbon footprint and enabling closed-loop recovery. This study proposes a sustainable design strategy for scalable chemical recycling via a one-pot separation process. Bio-based materials, including a lipoic acid-derived elastomer as the deformable substrate and a gelatin-based hydrogel as the ionic conductor, are employed along with liquid metal and MXene to construct soft electronic devices. At the end of life (EoL), these devices can be fully disassembled through simple immersion in a recovery solution, taking advantage of the preservation of the intrinsic chemical and physical characteristics of each component to enable efficient one-pot recovery of raw materials, as well as allowing solvent reuse. Materials recovered from discarded soft electronics devices are reused to fabricate identical or other types of devices with performance comparable to that of their pristine counterparts. This strategy offers conceptual insights for the practical recycling of multi-component products, highlighting sustainable design principles.

Keywords:  closed‐loop; e‐waste; one‐pot recycling; soft electronics; sustainability

DOI:  https://doi.org/10.1002/smll.202511832
Mater Today Bio. 2025 Dec;35 102469

Generating tolerance through in situ recruitment of regulatory T cells for allogeneic cell transplantation in a bioengineered lymphoid platform.

Nikitha Kota, Danilo Settis, Martina Concato, Noemi Risso, Robin Vander Pol, Casey Lewis, Yongbin Liu, Yafet Arefeayne, Federica Banche-Niclot, Laura Segatori, Francesca Taraballi, Junhua Mai, Alessandro Grattoni, Corrine Ying Xuan Chua.

  Cellular therapies aim to treat or manage disease by introducing living cells that integrate into the host and restore or eliminate dysfunctional tissues. Despite their promise for clinical success, the host immune response to cellular treatments remains a challenge since traditional approaches for abrogating immune rejection involve systemic immunosuppression, which results in severe off-target toxicity. One alternate strategy for restraining immune responses involves harnessing the natural immunomodulatory capabilities of regulatory T cells (Tregs), a specialized subset of T cells that suppress inflammatory immune responses and can promote induction and maintenance of transplant tolerance. Here we propose using the NanoLymph platform, an implantable subcutaneous device for continuous localized recruitment of Tregs, to achieve immunological tolerance free of systemic immunosuppression. The NanoLymph features a dual-reservoir system for the sustained release of immunomodulatory agents through a nanoporous membrane and a vascularized compartment that supports cell homing and allograft integration with the host. This work demonstrates robust vascularization of the NanoLymph by four weeks post-implantation, along with sustained in vivo elution of immunomodulatory agents for up to one month that selectively recruit and expand Tregs. Finally, we demonstrate that NanoLymph prolongs cell persistence in a bioluminescent allogeneic transplant model. Overall, the NanoLymph represents a versatile platform to generate a safe and localized tolerogenic microenvironment relevant for cell transplant therapies.

Keywords:  Endocrine cell engraftment; Local immunomodulation; Lymphoid tissue; Treg promoting therapy

DOI:  https://doi.org/10.1016/j.mtbio.2025.102469
ACS Macro Lett. 2025 Dec 05. 1874-1880

3D Printable Hydrogel with a Controlled Hierarchical Network through Aqueous PhotoATRP Using a Well-Defined Telechelic Bromide Macroinitiator.

Xiaoguang Qiao, Xuzheng Guo, Menghan Si, Mengjie Zhou, Wenjie Zhang, Ge Shi, Yanjie He, Weihua Fan, Xinchang Pang.

It is known that reversible-deactivation radical polymerization (RDRP) offers distinct advantages in preparing homogeneous gel network microstructures. However, flexibly regulating hydrogel network microstructures via RDRP remains a significant challenge. Herein, we fully leveraged the advantages of atom transfer radical polymerization (ATRP) in preparing well-defined polymers and uniform hydrogel networks and proposed a strategy to construct hydrogel structures with a controlled hierarchical network. This approach employs a presynthesized, well-defined telechelic bromide macroinitiator (via ATRP) to initiate the photoATRP of vinyl monomers and divinyl cross-linkers. A primary polymer network was first formed by the telechelic macroinitiator. Subsequently, the active chain-end sites initiated ATRP of small-molecule cross-linkers, thereby grafting a covalently linked secondary cross-linked network. In other words, we have embedded larger, uniformly sized pores within a smaller, homogeneous network structure. The size of these "macropores" can be tuned by adjusting the molecular weight of the macroinitiator. This hierarchical architecture endows the hydrogel with significantly altered swelling behavior and mechanical properties. Furthermore, by using carbon-dot-catalyzed aqueous photoATRP, this type of hydrogel with a controllable hierarchical structure can be fabricated via digital light processing (DLP) 3D printing technology. This work provides new insights into the regulation of the microstructure and macroscopic properties of hydrogel materials.

DOI: https://doi.org/10.1021/acsmacrolett.5c00665
Small. 2025 Dec 02. e10083

In Situ Assembly of Bilayer Hydrogels by Templated Enzymatic Polymerization for Ultrahigh UV Absorption and Photothermal Transdermal Therapy.

Bingqian Jiao, Yinghui Shang, Dingze Zhou, Xia Wang, Qigang Wang.

  Ultraviolet radiation from sunlight is a principal cause of skin photodamage, leading to sunburn, photoaging, and skin cancers. Although numerous sunscreen materials have been developed, their performance remains limited by insufficient ultraviolet protection, low biosafety due to skin penetration of ultraviolet filters, poor skin adhesion, and a lack of therapeutic capacity for damaged tissues. Here a polyvinyl alcohol (PVA)-based bilayer hydrogel fabricated by in situ assembly is reported. During gelation, interpenetration and cross-linking of PVA chains at the interface fuse the two layers into an integrated structure. The resulting hydrogel exhibits exceptional ultraviolet absorption (SPF 1997.6 PA++++)-twentyfold greater than previously reported values-robust skin adhesion (317 J m-2), photothermally controlled transdermal drug delivery (over 12 h), and excellent biocompatibility. The top layer employs template-directed enzymatic polymerization of dopamine to produce polydopamine (PDA) nanoparticles that are firmly anchored within the PVA network. Extensive hydrogen bonding between PVA and PDA reduces the bandgap of PDA and enhances electron delocalization, markedly enhancing ultraviolet absorption. The bottom layer incorporates polysaccharides that confer robust skin adhesion and regulate drug release. This layered design enables the integration of skin protection and therapy, providing a generalizable approach for engineering complex soft materials.

Keywords:  bilayer hydrogels; in situ assembly; templated enzymatic polymerization; transdermal therapy; ultraviolet shielding

DOI:  https://doi.org/10.1002/smll.202510083
Nanoscale Horiz. 2025 Dec 05.

Mechanism for a molecular assembler of sequence-controlled polymers using parallel DNA and a DNA polymerase.

Jonathan Bath, Andrew J Turberfield.

Construction of a molecular assembler from DNA that executes a programmed sequence of chemical reactions is a formidable challenge but worthwhile because it would allow assembly and evolution of functional polymers. We present a mechanism using parallel DNA and a DNA polymerase to address two challenges that currently block progress.

DOI: https://doi.org/10.1039/d5nh00505a
Adv Sci (Weinh). 2025 Nov 30. e12680

Biohybrid Tendons Enhance the Power-to-Weight Ratio and Modularity of Muscle-Powered Robots.

Nicolas Castro, Ronald Heisser, Maheera Bawa, Bastien Aymon, Sarah Wu, Annika Marschner, Sonika Kohli, Angel Bu, Laura Rosado, Martin Culpepper, Xuanhe Zhao, Ritu Raman.

  Biohybrid robots powered by tissue engineered skeletal muscle have historically relied on architectures in which muscle actuators are placed directly on skeletons, thus limiting the accessible design space for such machines. By contrast, native musculoskeletal architecture relies on tendons to bridge the interface between muscles and skeletons, enabling precise, space-efficient, and energy-efficient force transmission. In this study, a mathematical model of the muscle-tendon-skeleton interface is used to design a biohybrid muscle-tendon unit composed of tissue engineered muscle coupled to adhesive tough hydrogel tendons. It is demonstrated that tuning tendon stiffness and pre-tension optimizes actuator performance, and tuning skeleton stiffness modulates force transmission from muscles to skeletons, with fatigue characteristics measured over > 7000 cycles. Furthermore, an ≈11X improvement in power-to-weight ratio of muscle-tendon units is demonstrated compared to previous demonstrations of robots powered by muscles alone. This work validates a robust approach for designing, manufacturing, and deploying muscle-tendon actuators that promises to enhance the modularity and efficiency of biohybrid robots.

Keywords:  bioactuator; biohybrid robotics; skeletal muscle; soft robotics; tissue engineering

DOI:  https://doi.org/10.1002/advs.202512680
Small. 2025 Dec 03. e07835

Scale-Specific Viscoelastic Characterization of Hydrogels: Integrated AFM and Finite Element Modeling.

Nicole Fertala, Klemens Uhlmann, Evgeny Grigoryev, Prannoy Seth, Jens Friedrichs, Julian Thiele, Carsten Werner, Daniel Balzani.

  Viscoelastic hydrogels mimic the dynamic mechanical properties of native extracellular matrices, making them essential for biomedical applications. However, characterizing their scale-dependent mechanical properties remains challenging, despite their critical influence on cell-material interactions and biomaterial performance. Here, an integrated experimental-computational approach is presented to quantify and model the viscoelastic behavior of interpenetrating polymer network hydrogels across micro- and macro-scales. Atomic force microscopy-based stress relaxation tests revealed that microgels exhibit rapid, localized relaxation, while macroscopic bulk gels displayed prolonged relaxation dominated by poroelastic effects. Finite element simulations accurately replicated experimental conditions, enabling the extraction of key parameters: fully relaxed elastic modulus, relaxation modulus, and relaxation time constant. A novel analytical model is further developed to predict viscoelastic parameters from experimental data with minimal error (<6%), significantly streamlining characterization. The findings highlight the necessity of scale-specific mechanical analysis and provide a robust platform for designing biomaterials with tailored viscoelasticity for tissue engineering and regenerative medicine.

Keywords:  atomic force microscopy; finite element modeling; interpenetrating polymer networks; scale‐dependent mechanics; viscoelastic hydrogels

DOI:  https://doi.org/10.1002/smll.202507835
Adv Mater. 2025 Nov 29. e12058

Biocompatible Ink Optimization Enables Functional Volumetric Bioprinting With Xolography.

Erik Brauer, Aiste Balciunaite, Matthias R Kollert, Julian Weihs, Raphael S Knecht, Rose Behncke, Susanna Quach, Niklas Felix König, Asia Badolato, Stella Monestier, Simone Bersini, Matteo Moretti, Miriam Filippi, René Hägerling, Milad Rezvani, Stefan Hecht, Ansgar Petersen, Robert K Katzschmann.

  Xolography is a novel linear volumetric manufacturing technique that offers unparalleled precision and speed. Yet, its application to bioprinting remains limited due to insufficient understanding of biocompatibility constraints. Here, this work establishes fundamental design principles for cell-compatible Xolography bioinks by dissecting the effects of extracellular pH, osmolality, and lysosomotropic stress on cell viability and function. By systematically studying the tolerances for these parameters, this work defines a framework for bioink formulations that enables fast, support-free fabrication of complex designs with maintained cell viability and function as validated in different murine and human cell lines, primary human cells and induced pluripotent stem cell (iPSC)-derived cells. These results show that, unlike triethanolamine, BisTris indeed can function as a fully biocompatible co-initiator enabling cell viability beyond 90% as well as uncompromised metabolic activity and differentiation performance when used in a tightly controlled formulation, contrasting previous reports. This work showcases the biomedical potential of the formulation by achieving fibroblast-driven extracellular matrix (ECM) formation, endothelial sprouting from pre-vascularized spheroids, and maintenance of an iPSC-derived hepatocyte differentiation phenotype within Xolography-printed constructs. These advancements transform Xolography into a powerful and foremost reliable bioprinting platform for fabrication of complex, cell-laden structures for versatile applications in tissue engineering, organ-on-a-chip models, and regenerative medicine.

Keywords:  3D printing; Xolography; biohybrid robotics; bioprinting; tissue engineering

DOI:  https://doi.org/10.1002/adma.202512058
iScience. 2025 Nov 21. 28(11): 113849

Synthetic cells by the numbers.

Chana G Sokolik, Maya Bar-Dolev, Ron Milo, Katarzyna P Adamala, Michael Levy.

  Can we build a living cell from non-living molecular components? This foundational question drives the field of synthetic cell engineering, having already reconstituted key cellular processes within synthetic environments, and now advancing toward their integration into systems of increasing complexity. At this stage of gradual complexification, it is essential to construct a general quantitative picture of synthetic cells that can clarify the capabilities and limitations of current systems and help guide future design efforts. Here, we adopt the "by the numbers" approach to provide a quantitative and intuitive overview of synthetic cell properties. Focusing on liposome-based systems, we compile and contextualize numerical estimates from the literature and use them to reason about the structural, biochemical, and functional characteristics of these synthetic constructs. Through this quantitative lens, we aim to highlight both the current performance achieved and the key challenges that remain in the path toward building autonomous synthetic cells.

Keywords:  experimental models in systems biology; mathematical biosciences; synthetic biology

DOI:  https://doi.org/10.1016/j.isci.2025.113849
ACS Appl Polym Mater. 2025 Nov 28. 7(22): 15255-15267

Expanding the Usage of Lignin in DLP 3D Printing by Optimized Synthesis and Processing Parameters.

Michelle Vigogne, Anika Kaufmann, Evgeny Grigoryev, Cosima Aeschbach, Henri Lila, Michael Schwidder, Julian Thiele.

  Digital light processing (DLP) has gained substantial interest in recent years as a versatile additive manufacturing technique across different disciplines. However, many materials used in DLP 3D printing are from non-sustainable sources. The use of renewable resources like lignin, a complex aromatic polymer derived from plant biomass and an industrial byproduct produced in ton-scale, in resins promotes the development of sustainable and environmentally friendly additive manufacturing processes and applications. Therefore, we first present a cost-effective and reproducible acrylation synthesis route that enables the modification of lignin using acryloyl chloride as a functionalization reagent. Further, we systematically investigate the effects of different contents of unmodified lignin up to 20 wt % and modified lignin with acrylate groups up to 30 wt % in resins using a time-efficient, self-developed step test to achieve optimal printing parameters with the smallest possible feature size. These parameters are used for high-resolution DLP 3D printing of microneedles for potential medical applications, which is why the cytotoxicity of the lignin resins is determined as well. The addition of lignin to resins influences their rheological properties and printability remarkably as well as the mechanical performance of the corresponding 3D-printed objects. Notably, higher lignin concentrations are found to enhance the mechanical strength of 3D-printed parts. Furthermore, we assess the effects of lignin acrylation in photopolymer formulations leading to improved solubility, substantial change in rheological properties from thixotropic to non-thixotropic behavior, and an enhanced E-modulus of 3D-printed materials. As a result, we showcase the feasibility to 3D-print with up to 30 wt % of modified lignin and present a 3D-printed material with 15 wt % of modified lignin, which is classified as non-cytotoxic according to EN ISO 10993-5. However, further increasing lignin content generally adversely affects the printability due to increased resin viscosity as well as light scattering and pronounced UV light absorption.

Keywords:  DLP 3D printing; high-resolution 3D printing; lignin-based resins; photopolymers; renewable materials

DOI:  https://doi.org/10.1021/acsapm.5c02394
Proc Natl Acad Sci U S A. 2025 Dec 09. 122(49): e2511670122

Control of encounter kinetics by chemically active droplets.

Jacques D Fries, Roxanne Berthin, Marie Jardat, Pierre Illien, Vincent Dahirel.

  Biomolecular condensates play a crucial role in the spatial organization of living matter. These membrane-less organelles, resulting from liquid-liquid phase separation, operate far from thermodynamic equilibrium, with their size and stability influenced by nonequilibrium chemical reactions. While condensates are frequently considered optimized nanoreactors that enhance molecular encounters, their actual impact on reaction kinetics remains unclear due to competing effects such as diffusion hindrance, and random trapping in nonspecific condensates. In this study, we develop a microscopic, stochastic model for chemically active droplets, incorporating reaction-driven modulation of protein interactions. Using Brownian dynamics simulations, we investigate how protein interactions and active coupling to a free energy reservoir influence phase separation, molecular transport, and reaction kinetics. We demonstrate that the intensity of the chemical drive governs surface dynamics, generating fluxes that modulate bimolecular reaction rates. Comparing active emulsions to homogeneous systems, we reveal that condensates can either accelerate or decelerate molecular encounters. Our findings provide key insights into the role of biomolecular condensates as potential regulators of intracellular reaction kinetics.

Keywords:  active matter; biophysics; phase separation; reaction kinetics

DOI:  https://doi.org/10.1073/pnas.2511670122
Carbohydr Polym. 2026 Feb 01. pii: S0144-8617(25)01463-8. [Epub ahead of print]373 124679

Towards tunable mechanical properties of in situ gelling chitosan hydrogels: impact of macromolecular structure including pattern of acetylation.

Inès Hamouda, Maïlys Da Rocha Moreau, Lisa Basso, Stéphane Trombotto, Alexandra Montembault, Laurent David, Sophie Lerouge.

  Injectable in situ gelling physically crosslinked chitosan (CH) hydrogels allowing cell encapsulation are appealing for biomedical applications. However, the variability of the CH source is one of the major difficulties in ensuring their reproducibility. We investigated here the effect of the CH degree and pattern of acetylation (DA and PA) on its final physicochemical properties. Hydrogels made from re-acetylated CH presenting statistical repartition of repeat units along the chains, with DA of 35, 10 and 1 %, were compared to a commercial CH with DA of 10 % differing by their PA. WAXS analysis showed different crystalline signatures depending on the PA of CH samples. Rheometry revealed faster gelation kinetics, but lower final modulus for hydrogels made of commercial versus statistical CH of same DA. Both also differed in terms of porosity and stability in solution. Hydrogel stiffness from 60 to 0.3 kPa were obtained by varying DA and PA. Hydrogels with the lowest DA were the most stable in solutions. Encapsulated L929 fibroblasts presented similar increasing metabolic activity over 7 days of culture within all hydrogels. This work demonstrates the relevance of controlling chitosan DA and PA for the generation of reproducible hydrogels with tunable final mechanical properties for targeted bio-applications. STATEMENT HYPOTHESIS: Not only the degree of acetylation (DA, i.e., the molar fraction of N-acetyl D-glucosamine units), but also the pattern of acetylation (PA; the repartition of the acetylated/deacetylated residue sequences along the chain), can influence the mechanical properties, the porosity, and the stability of physical in situ gelling CH hydrogels, therefore the behavior of encapsulated cells. Indeed, when the gel is formed using weak bases (here a combination of β-glycerophosphate and sodium hydrogen carbonate), the physical crosslinking density between CH chains can be influenced by the DA and the PA due to the resulting variation of NH2 moieties repartition. We expect that for CH presenting a higher DA, weak gels will be generated due to reduced physical interactions established between protonated NH3+ groups and the weak base. Also, we expect to generate more stable constructs with CH presenting lower DA. Furthermore, for the same DA, the chemical process used for obtaining CH (i.e., from the reacetylation of low DA CH or deacetylation of chitin under heterogeneous or homogenous conditions) yields CHs with different PA, which we presume to significantly affect final structural and mechanical properties of the obtained hydrogels. Understanding the impact of the CH macromolecular structure on its injectable in situ gelling hydrogel form is fundamental for the generation of suitable and reproducible CH-based hydrogel materials in biomedical applications.

Keywords:  Chitosan; Tissue engineering; acetylation degree; macrostructure; pattern of acetylation; thermosensitive hydrogel

DOI:  https://doi.org/10.1016/j.carbpol.2025.124679
Sci Adv. 2025 Dec 05. 11(49): eadu0315

Conservation of mRNA operon formation in control of the heat shock response in mammalian cells.

Emese Pataki, Jeffrey E Gerst.

Prokaryotes use polycistronic transcription (operons) to express multiple messenger RNAs (mRNAs) from a single promoter to coexpress functionally related genes. However, how do eukaryotes, which express monocistronic messages, achieve the same regulation? Previously, we demonstrated that yeast uses RNA operons, i.e., mRNAs assembled in trans (transperons), to control multiple cellular pathways such as the heat shock response (HSR). As the HSR is conserved from yeast to mammals, we used single-molecule RNA labeling and pulldown techniques to demonstrate that mammalian heat shock protein (HSP) mRNAs also form operons upon transcription during heat stress. HSP RNA operon formation is dependent on the heat shock factor 1 transcription factor and intra- and interchromosomal interactions between the HSP genes. Work in yeast identified a conserved RNA sequence motif and histone H4 functions that act downstream thereof to regulate transperon assembly. Our work highlights the evolutionarily conserved regulation of the HSR and for RNA operons in eukaryotic gene regulation.

DOI: https://doi.org/10.1126/sciadv.adu0315
ACS Appl Mater Interfaces. 2025 Dec 02.

All 3D Printed Soft Integrated Conductors.

Peiru Liu, Ligang Yao, Wei Liu, Zhen Lyu, Longhui Chen, Jianmin Yang, Fanan Wei.

  Soft integrated circuits, which possess mechanical properties similar to skin, hold significant potential in human-machine interface sensing and biomedical devices. The complex manufacturing techniques required for their multilayer circuit structures impose limitations on the application and innovation of flexible integrated circuits. This paper introduces a composite ink developed from the conductive polymer PEDOT:PSS (3,4-ethylenedioxythiophene/styrenesulfonate) and the hydrated matrix polymer PAAm (polyacrylamide). This ink demonstrates remarkable printability and is well-suited for high-resolution direct ink writing (DIW) 3D printing. A simple cross-linking process enables the transformation of the ink into a high-performance conductive hydrogel. Following post-treatment, the 3D-printed hydrogel exhibits a conductivity of 62 S/m in its gel state and 311 S/m in its dry gel state, along with a strain capacity of 210%. Furthermore, it maintains high stability in water, allowing for sustained performance over extended periods. Multifunctional integration of miniature 3D circuits is facilitated through printing, which enables the wireless transmission of electrical signals. Due to its outstanding biocompatibility, this material presents significant prospects for applications in implantable electronic engineering.

Keywords:  3D printing; PEDOT:PSS; conductive polymer; flexible inductor; soft integrated circuits

DOI:  https://doi.org/10.1021/acsami.5c17141
Adv Mater. 2025 Dec 06. e18403

Thermal Switching of Polymer Topology Enables Programmable Mechanical Properties in Soft Materials.

Hongyan Yang, Jiaqi Li, Shenglin Yao, Zhiwei Fan, Xiaolin Jin, Shuming Cui, Panchao Yin, Wei Zhang, Liqun Tang, Jiuling Wang, Taolin Sun.

  Soft materials with on-demand mechanical tunability remain challenging to realize, particularly those capable of large, reversible, and programmable changes within a single material system. In this work, a synthetic elastomer is designed that undergoes thermally reversible topological network reconfiguration, switching between brush- and linear-like architectures, thereby enabling a reversible transition from soft to stiff mechanical states. This reconfiguration is achieved by grafting crystallizable side chains onto a polymer backbone via Diels-Alder (DA) adducts at low annealing temperatures to form brush-like networks, while retro-DA reactions at higher temperatures release the side chains, yielding a linear topology. The brush architecture suppresses crystallization, whereas the linear form facilitates crystallinity to form an additional crystalline framework, leading to a reversible rubbery-to-glassy transition. As a result, the elastomers undergoing annealing cycles between 60 and 130 °C exhibit reversible enhancements in stiffness and strength by up to 286-fold and 25-fold, respectively. Coarse-grained molecular dynamics (CGMD) simulations reveal that the significantly improved stiffness and strength originate from the formation of a crystalline framework that effectively bears mechanical load and impedes crack propagation. This thermally programmable strategy enables dynamic control of mechanical behavior, offering a novel paradigm for designing intelligent materials with tailored and on-demand performance.

Keywords:  brush‐like architecture; crystallization; dynamic bond; tunable stiffness

DOI:  https://doi.org/10.1002/adma.202518403
Carbohydr Polym. 2026 Feb 01. pii: S0144-8617(25)01375-X. [Epub ahead of print]373 124591

Design of a flexible cellulose framework via supramolecular structure modulation and its application in hydrogel sensors.

Yantao Song, Minghui Yang, Tianhao Liu, Ce Sun, Min Jin, Haiyan Tan, Dingyuan Zheng, Yanhua Zhang.

  Cellulose framework derived from wood has been widely used as reinforcement for high performance hydrogel sensors fabrication. However, due to the native brittleness of wood, the cellulose framework-reinforced hydrogels present mechanical rigidity, limiting their applications as wearable electronics. Herein, we report a time-dependent alkaline treatment strategy to modulate the supramolecular structure of cellulose frameworks. The effect of NaOH treatment duration was systematically investigated to identify an optimal cellulose framework (designated ADW4) that synergistically combines flexibility and mechanical strength. The optimized ADW4 exhibited a highly crystalline structure with superior mechanical properties, demonstrating a 17.1 % increase in tensile strength and a 140.1 % improvement in toughness over natural wood. Employing the obtained optimal cellulose framework as the reinforcement yielded a conductive hydrogel (PADW4-Li), which demonstrated dramatically improved mechanical strength (a 35,700 % increase compared to pure polyacrylamide (PAM)) and excellent ionic conductivity (3 mS cm-1). The PADW4-Li hydrogel exhibits high utility, proving capable of not only monitoring physiological signals but also sensitively detecting minute deformations. The regulation of the supramolecular structure of the cellulose framework mediated by this alkali treatment endows it with both flexibility and mechanical strength, providing a new path for its use as the reinforcing phase of composite materials.

Keywords:  Alkaline treatment; Cellulose framework; Flexible sensor; Hydrogel; Mechanical reinforcement; Supramolecular structure modulation

DOI:  https://doi.org/10.1016/j.carbpol.2025.124591
Nano Lett. 2025 Dec 04.

Engineering the Size of Bicontinuous Nanospheres via Multi-Inlet Vortex Mixing.

Sultan Almunif, Simseok A Yuk, El Hadji Arona Mbaye, Swagat Sharma, Michael D Purdy, Sandeep Kumar, Natalie R Klug, Evan A Scott.

  Bicontinuous nanospheres (BCNs) are self-assembled nanostructures with interconnected aqueous channels that enable the coloading of hydrophilic and hydrophobic cargo; however, their size has been difficult to control. Here, we present a scalable approach to tune the size distribution of poly(ethylene glycol)-b-poly(propylene sulfide) BCNs using a multi-inlet vortex mixer. Higher mixing times and polymer concentrations produced larger BCNs, while shorter mixing times and lower concentrations yielded spherical micelles. Small-angle X-ray scattering and cryogenic transmission electron microscopy confirmed the BCN bicontinuous morphology, which persisted at smaller sizes. The porous BCN structure resulted in increased surface roughness compared to polymersomes (PSs). In vitro, BCNs and PSs of comparable sizes recruited distinct protein coronas early, but their profiles showed convergence by 24 h. In vivo, organ biodistribution was determined primarily by the nanocarrier size rather than the morphology. These findings establish a robust approach to BCN fabrication while revealing dynamic biological interactions that inform nanocarrier design.

Keywords:  bicontinuous nanospheres; flash nanoprecipitation; multi-inlet vortex mixer; nanoparticles; protein corona; self-assembly

DOI:  https://doi.org/10.1021/acs.nanolett.5c04791