bims-enlima 2026-01-04 papers

bims-enlima

Biomed News

on Engineered living materials

Issue of 2026–01–04
39 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool

Direct-Write Printing of Multifunctional Iontronic Composites That Sense, Rectify, and Actuate.
Random heteropolymers as enzyme mimics.
A Modular Route toward Macromer-Based Dynamic Gels via Prebonded Boronic Ester Cross-Links.
Rotational Multimaterial 3D Printing of Soft Robotic Matter With Embedded Asymmetrical Pneumatics.
Wetting-Mediated Remodeling of the Cytoskeletal Cortex by Phase-Separated Condensates in Cell-Free Reactions.
3D Printed Flexible Piezoelectric Sensors for Integrated Hybrid Electronics.
3D-printing of hierarchical porous monoliths using emulsion gels stabilized by lignin-containing cellulose nanofibrils for thermal insulation.
Design of a Mechanically Tough and Robust Lubricating Hydrogel via an Interpenetrating Hydrophilic-Hydrophobic Polymer Network.
Heart-On-a-Chip with Integrated Ultrasoft Mechanosensors for Continuous Measurement of Cell- and Tissue-Scale Contractile Stresses.
In situ mechanostimulation of biohybrid millirobots for enhanced cell functionality and delivery.
Liquid Supplied One Droplet Continuous 3D Printing.
DIW Printing of PEDOT:PSS on Living Plants for Biohybrid Systems.
Supramolecularly gated enzymes: On-demand activity switching via host-guest competition for precision tumor therapy.
Autonomous biogenesis of all thirty proteins of the Escherichia coli translation machinery.
An automated platform for accelerating and focusing adaptive laboratory evolution.
BARCODE: high throughput screening and analysis of soft active materials.
Flexible Conductive Paper-Based Sensors for On-Skin Electrophysiological Monitoring and Wearable Applications.
Bottom-up Strategies for Generating Polymer Protocells That Mimic Cellular Communication.
Soft Gel-Based Transformative Structured Engineering Design.
Ultrathin, Flexible, and Multifunctional Silk Fibroin-Ag Functional Engineered Membranes for Integrated Separation, Treatment, and Detection of Water Pollutants.
Toward the Nobel Prize: Dissecting Fundamental Principles and Applications of MOF and COF Materials.
Combination of Extrusion and Drop-on-Demand Bioprinting in One Process Enables the Local Placement of Cells or Signaling Factors Into (Bio) Printed Hydrogel Structures.
Biocompatible, Ion-Conductive Hydrogel-Filled Nerve Conduit for Peripheral Nerve Regeneration.
Printable polymer nanocomposites for scalable and architected radiative cooling.
Improving adenine base editor precision with directed evolution and extended guide RNAs.
Leveraging Viscosity to Unlock the Osteogenic Potential of BMP-2 Mimetic DWIVA.
4D Printing in Healthcare: Innovations, Challenges, and Future Directions.
Dynamic Reversible Full-Color Phosphorescence Afterglows from Stimuli-Responsive Carboxymethyl Chitosan Based Materials.
A technique to create hydrogels with tethered concentration gradients of molecules in vitro.
De novo design of small molecule-regulated protein oligomers.
Open-source cell culture automation system with integrated cell counting for passaging microplate cultures.
Self-Assembled Hydrogel from Pyrene-Modified Peptide as 3D Matrices for Neuronal Cell.
Hydrogel Embedding of Mesenchymal Stem Cells Supports Extracellular Vesicle Production.
Templating Methods for Materials Fabrication Across Scales.
Architected Redox-Active Colloids for Tunable Charge Transport in Aqueous Systems.
Self-supervised AI for decoding and designing disordered metamaterials.
Artificial intelligence-driven approaches for materials design and discovery.
Facile and robust integration of functional hydrogels into micropillar-structured elastomer platforms for stable cardiac bioelectronics.
Design and applications of synthetic biomolecular condensates.

ACS Nano. 2026 Jan 03.

Direct-Write Printing of Multifunctional Iontronic Composites That Sense, Rectify, and Actuate.

EunBi Oh, Eric Yang, Taekyoung Kim, Alexander Q Kane, Ryan L Truby.

  The development of advanced materials capable of performing multiple functions is a key step toward adaptive, autonomous systems for emerging technologies. However, multifunctional material systems designed to integrate sensory, computational, and actuation capabilities are challenging to realize due to manufacturing and materials limitations. Here, we present electrically controllable, multifunctional iontronic composites (MICs) that demonstrate ionic sensing, current regulation, and ionomotive bending actuation capabilities within a single architecture. Our MICs are fabricated using a multimaterial direct-write printing process, in which a poly(ionic liquid) (pIL) structural electrolyte is sandwiched between two Ti3C2Tx MXene-based electrodes. The printing process enables seamless integration of concentrated MXene electrode inks with pIL electrolytes with printable layer thicknesses down to 25 and 200 μm, respectively. When used as a sensor, MICs exhibit capacitance changes up to 4% under compressive loads of 45 N. When printed with electrodes of asymmetric thickness, MICs can also function as ionic diodes, achieving rectification ratios up to 14. Finally, the composites demonstrate ionomotive actuation with a maximum bending strain of 0.21%. Our key innovation lies in achieving all three functionalities through additive manufacturing, which reduces the number of fabrication steps required to integrate all MIC materials together. Our MICs represent a significant advance in electrically controlled, multifunctional composites and motivate new directions toward next-generation autonomous and responsive material systems for soft robotics, electronics, and adaptive structures.

Keywords:  3D printing; ionic diodes; multifunctional composites; multimaterial; soft actuators; soft sensors

DOI:  https://doi.org/10.1021/acsnano.5c17160
Nature. 2026 Jan;649(8095): 83-90

Random heteropolymers as enzyme mimics.

Hao Yu, Marco Eres, Shayna L Hilburg, Philjun Kang, Tianyi Jin, Alexandra Grigoropoulos, Zhixia Li, Daniel M Loh, Ivan Jayapurna, Zhiyuan Ruan, Wen Fu, Feipeng Yang, Priya Ganesh, Kali Toste, Shuni Li, Jinghua Guo, Haiyan Huang, F Dean Toste, R David Britt, Y Z, Alfredo Alexander-Katz, Ting Xu.

Despite successes in replicating the primary-secondary-tertiary structure hierarchy of protein, it remains elusive to synthetically materialize protein functions that are deeply rooted in their chemical, structural and dynamic heterogeneities1-12. We propose that for polymers with backbone chemistries different from that of proteins, programming spatial and temporal projections of sidechains at the segmental level can be effective in replicating protein behaviours13,14; and leveraging the rotational freedom of polymer can mitigate deficiencies in monomeric sequence specificity and achieve behaviour uniformity at the ensemble level2,3,15-20. Here, guided by the active site analysis of about 1,300 metalloproteins, we design random heteropolymers (RHPs) as enzyme mimics based on one-pot synthesis. We introduce key monomers as the equivalents of the functional residues of protein and statistically modulate the chemical characteristics of key monomer-containing segments, such as segmental hydrophobicity21. The resultant RHPs form pseudo-active sites that provide key monomers with protein-like microenvironments, co-localize substrates with catalytic or cofactor-binding sidechains and catalyse reactions such as oxidation and cyclization of citronellal with isopulegol/menthoglycol selectivity. This RHP design led to enzyme-like materials that can retain catalytic activity under non-biological conditions, are compatible with scalable processing and have expanded substrate scope, including environmentally long-lasting antibiotic tetracycline22.

DOI: https://doi.org/10.1038/s41586-025-09860-9
ACS Macro Lett. 2025 Dec 30.

A Modular Route toward Macromer-Based Dynamic Gels via Prebonded Boronic Ester Cross-Links.

Owen A Lee, Alexander D Claiborne, Atlas Quaine, Megan S Rothenberg, Sirilak Mekcham, Megan R Hill.

Reversible polymer gels are attractive materials as their dynamic cross-links impart properties such as self-healing, stress relaxation, and stimuli-responsiveness. A wide variety of chemistries have been explored to access such networks, among which boronic ester bonds stand out for their biocompatibility, selectivity, and tunable dynamics. Macromer functionalization is a well-established strategy for introducing boronic esters into networks, as the defined architecture of the macromer provides predictable network topologies with a direct link between dynamic cross-link chemistry and bulk properties, traits difficult to design into conventional polymeric materials. However, altering macromer chemistry can be time- and cost-intensive. Here we describe an alternative, modular strategy in which boronic esters are prebonded and coupled to commercial thiol-terminated poly(ethylene glycol) macromers via UV-initiated "click" chemistry. This route enables straightforward network synthesis and characterization, proceeds in high yield under modest UV light intensities, and avoids byproducts that complicate gel mechanics. The modular nature of this approach allows access to macromer-based networks with tunable mechanical and dynamic properties, without the need to synthesize new macromers. The resulting materials display hallmark dynamic mechanical properties and new capabilities, such as spatiotemporal control over macromer-based gel formation, highlighting prebonded cross-linkers as a versatile platform for constructing macromer-based dynamic networks.

DOI: https://doi.org/10.1021/acsmacrolett.5c00741
Adv Mater. 2025 Dec 30. e10141

Rotational Multimaterial 3D Printing of Soft Robotic Matter With Embedded Asymmetrical Pneumatics.

Jackson K Wilt, Natalie M Larson, Jennifer A Lewis.

  The rapid design and fabrication of soft robotic matter is of growing interest for shape morphing, actuation, and wearable devices. Here, we report a facile fabrication method for creating soft robotic materials with embedded pneumatics that exhibit programmable shape morphing behavior. Using rotational multimaterial 3D printing, asymmetrical core-shell filaments composed of elastomeric shells and fugitive channels are patterned in 1D, 2D, and 2.5D motifs. By precisely controlling the nozzle design, rotation rate, extrusion rate, and print path, one can control the local orientation, shape, and cross-sectional area of the patterned fugitive channel along each printed filament. Once the elastomeric matrix is cured, the fugitive ink is removed, leaving behind embedded channels that facilitate pneumatic actuation. Using a connected Fermat spiral pathing approach, one can automatically generate desired print paths required for more complex soft robots, such as hand-inspired grippers. Our integrated design and printing approach enables one to rapidly build soft robotic matter that exhibits myriad shape morphing transitions on demand.

Keywords:  3D printing; elastomers; pneumatics; soft robots

DOI:  https://doi.org/10.1002/adma.202510141
Biomacromolecules. 2025 Dec 29.

Wetting-Mediated Remodeling of the Cytoskeletal Cortex by Phase-Separated Condensates in Cell-Free Reactions.

Shuzo Kato, Archit Negi, Vincent Noireaux, Yusuke T Maeda.

Living cells dynamically coordinate gene expression with the spatial organization of their membranes and cytoskeletons. Unraveling how membrane-less organelles arise and interact with cytoskeletal networks remains a fundamental challenge in cell biology, biophysics, and bioengineering. Here, we present a synthetic biology platform that integrates cell-free transcription-translation (TXTL) reactions with phase-separated protein condensates, enabling precise investigation of their interplay with cytoskeletal elements. We show that the bacterial actin homologue MreB forms a scaffold that promotes the wetting of protein condensates in crowded solutions, triggering capillary-driven contraction of the cytoskeletal network. Remarkably, MreB filaments self-assemble into a cortical layer at water-oil droplet interfaces, where their contractile activity leads to wrinkling and global deformation of the synthetic compartment. Our results provide physical insights into how biomolecular condensates and cytoskeletal filaments cooperate to remodel cell-like structures, and establish a minimal model for studying wetting-mediated cytoskeletal dynamics at synthetic membranes.

DOI: https://doi.org/10.1021/acs.biomac.5c01410
Small. 2025 Dec 31. e11146

3D Printed Flexible Piezoelectric Sensors for Integrated Hybrid Electronics.

Daniel Wai Hou Ng, Hassene Ben Atitallah, Ghazaleh Haghiashtiani, Jinsheng Fan, Hyunjun Kim, Guebum Han, Riyan Mendonsa, Razman Zambri, Michael C McAlpine.

  The ability to 3D print high performance smart materials and multifunctional devices, all seamlessly integrated via a common manufacturing platform, can yield advances in soft robotics, wearable electronics, and human-machine interfaces. One of the most important smart materials in this context is piezoelectrics, due to their dual capabilities in sensing and actuating, which are critical for creating intelligent, responsive systems. In this study, we develop a direct-ink-writing (DIW) 3D printing approach for creating flexible and wearable piezoelectric devices using solution-processed poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE) as the functional ink. Ferroelectric and actuation-based characterizations are conducted to guide systematic optimization of the electrical poling conditions, yielding high performance 3D printed PVDF-TrFE transducers with d31 coefficient of 12.70 ± 0.71 pC·N-1. Three proof-of-concept smart devices were then fabricated: (1) a touch-based wearable human-machine interface for interactive gaming, (2) a tactile-sensing "electronic skin," and (3) a multifunctional hybrid electronic system combining piezoelectric sensors and quantum dot light-emitting diodes, all fully 3D printed. This work comprehensively demonstrates the ability for 3D printing to generate high performance materials and devices, the use of 3D printing for wearable piezoelectric sensor fabrication, and the versatility of 3D printing for the seamless multifunctional integration of hybrid electronic systems.

Keywords:  3d printing; human‐machine interfaces; light‐emitting diodes; piezoelectric polymers; wearable electronics

DOI:  https://doi.org/10.1002/smll.202511146
Carbohydr Polym. 2026 Mar 01. pii: S0144-8617(25)01571-1. [Epub ahead of print]375 124787

3D-printing of hierarchical porous monoliths using emulsion gels stabilized by lignin-containing cellulose nanofibrils for thermal insulation.

Chuhang Liu, Xiaojie Shi, Bo Lin, Zekun Song, Feng Jiang, Mei-Chun Li, Chaozheng Liu, Changtong Mei.

  3D printing of cellulose-based porous materials with tailored architecture is of significant interest for advanced thermal insulation applications. However, most existing approaches lack internal hierarchical porosity, thereby limiting their insulation efficiency. Here, we propose an emulsion gel ink strategy based on high internal phase Pickering emulsions (HIPPEs) stabilized by lignin-containing cellulose nanofibrils (LCNFs) and reinforced with sodium alginate (SA). This approach integrates emulsion templating with direct ink writing (DIW), enabling simultaneous control of macroscopic geometry and microscopic pore structure. LCNFs with tunable lignin content and surface charge effectively stabilize oil-water interfaces, while SA provides a viscoelastic matrix, ensuring high printability. After freeze-drying, the printed porous monoliths exhibit low density (~17.7 mg·cm-3), high porosity (> 98 %), and hierarchical pores templated by emulsified droplets and LCNF-SA network. The resulting structures combine excellent mechanical resilience and low thermal conductivity (~0.031 W·m-1·K-1). This work provides a scalable route to bio-based 3D-printed porous materials with programmable porosity and multifunctional performance.

Keywords:  3D-printing; Emulsion gel ink; Lignin-containing cellulose nanofibrils; Porous monoliths

DOI:  https://doi.org/10.1016/j.carbpol.2025.124787
Biomacromolecules. 2026 Jan 02.

Design of a Mechanically Tough and Robust Lubricating Hydrogel via an Interpenetrating Hydrophilic-Hydrophobic Polymer Network.

Lei Tang, Yiling Shen, Ruixue Huang, Yue Chen, Hailan Zhou, Shuyao Liu, Hongwu Chu, Guiyin Zhou.

Hydrogels show great potential for mimicking human weight-bearing tissues due to their extremely high water content and desirable behavior, including softness and elasticity. However, developing joint cartilage-mimicking hydrogels with both superior mechanical properties and stable lubrication remains challenging. This study presents a self-assembled heterostructure hydrogel approach. A mechanically robust hydrogel with sustained lubrication properties is achieved by incorporating a hydrophilic network into a hydrophobic polyethyl acrylate (PEA) matrix. Two polymer networks interweave at the microstructural level, generating water-rich and water-poor phases. Outstanding load-bearing capacity is achieved by the flexible hydrophilic polymer network efficiently dispersing impact stress into the rigid hydrophobic network. Meanwhile, a hydrated lubricating layer forms on the hydrophilic network's surface, ensuring sustained lubrication. Moreover, the hydrophobic PEA network incorporation limits swelling in the hydrophilic network, imparting exceptionally stable antiswelling properties to the hydrogel. This study demonstrates that the heterostructure hydrogel maintains stable mechanical properties in aqueous solutions while providing lubricity, offering a novel approach to developing biomimetic materials with mechanical robustness and sustained lubricity.

DOI: https://doi.org/10.1021/acs.biomac.5c02455
Small. 2025 Dec 31. e04493

Heart-On-a-Chip with Integrated Ultrasoft Mechanosensors for Continuous Measurement of Cell- and Tissue-Scale Contractile Stresses.

Ali Mousavi, Christina-Marie Boghdady, Shihao Cui, Sabra Rostami, Amid Shakeri, Naimeh Rafatian, Mark Aurousseau, Gregor Andelfinger, Milica Radisic, Christopher Moraes, Houman Savoji.

  Heart-on-a-chip platforms aim to recapitulate cardiac tissue structure and function in vitro. Traditionally, microfabricated pillars are used to estimate contractile forces based on pillar deflection. However, this approach measures only global forces at the pillar interface and lacks the spatial resolution needed to capture local mechanical stresses. In this study, we present a non-destructive optical method for continuous, multi-scale stress mapping using ultrasoft edge-labeled micro-spherical stress gauges (eMSGs). These embedded mechanosensors visibly deform in response to cellular and extracellular matrix (ECM)-generated stresses, enabling real-time measurements at cell and tissue scales. Our platform features dual cell-seeding chambers with flexible polydimethylsiloxane pillars, into which neonatal rat cardiomyocytes are seeded within a fibrin/Geltrex hydrogel containing eMSGs. Over time, tissues compacted, aligned, and exhibited spontaneous contractions and calcium transients. By modulating ECM composition, we found that reduced fibrin concentration enhanced contractile frequency, regularity, and force generation. Analysis of eMSG deformation enabled calculation of lateral and longitudinal stresses, revealing the impact of compaction and contraction on local mechanics. Finally, drug testing was performed using norepinephrine, which enhanced contractile force, and blebbistatin, which inhibited contraction, demonstrating robust pharmacological responsiveness. This platform provides a powerful tool for real-time biomechanical analysis and drug testing in engineered cardiac tissues.

Keywords:  cell‐generated stresses; contractility; drug screening; heart‐on‐a‐chip; ultrasoft mechanosensors

DOI:  https://doi.org/10.1002/smll.202504493
Sci Adv. 2026 Jan 02. 12(1): eadx9616

In situ mechanostimulation of biohybrid millirobots for enhanced cell functionality and delivery.

Jianhua Zhang, Xianqiang Bao, Zhou Zhu, Rongjing Zhang, Chunxiang Wang, Mingtong Li, Kaichen Xu, Yong He, Dietmar W Hutmacher, Ziyu Ren, Metin Sitti.

This study proposes a perforated, soft millirobot with dual functions: in situ mechanostimulation to enhance cell functionality and local cell delivery. Following protein modification and silica coating, the soft millirobots exhibit excellent biocompatibility, promoting cell adhesion and tissue ingrowth within their perforated architectures under both in vitro and in vivo conditions. They can apply in situ mechanostimulation to various cellular morphologies, including two-dimensional (2D) cell sheets, 3D cell-laden hydrogels, and ex vivo tissue models. The mechanical stimulation improves the functionality of muscle cells by enhancing cellular orientation, myotube contraction, and myocyte differentiation. In parallel, we develop an integrated robotic platform combining magnetic actuation with ultrasound imaging. It demonstrates the proof of principle that delivers 2D cell-sheet and 3D cell-laden biohybrid millirobots to narrow regions in an ex vivo pig liver model. This work expands the potential applications of soft millirobots in mechanobiology studies and future cell-based therapies.

DOI: https://doi.org/10.1126/sciadv.adx9616
Small Methods. 2025 Dec 28. e01906

Liquid Supplied One Droplet Continuous 3D Printing.

Jiawei Sun, Wangjun Xiong, Lidian Zhang, Ming Yang, Haihua Zhou, Yanlin Song, Lei Wu.

  Digital light processing (DLP) 3D printing is widely regarded as a highly sustainable additive manufacturing technique, prized for its rapid production capabilities and high resolution across diverse applications. Recent research has centered on optimizing curing surfaces and resin formulation to achieve continuous printing. Nevertheless, as printing continuity improves, issues such as excessive heat buildup from the exothermic curing process and constraints in printing volume persist or intensify. To address these challenges, we introduce a liquid-supplied one-droplet 3D printing approach, which incorporates a controlled liquid supply mechanism into a drop-on-demand one 3D printing system. This design enables consistent in situ curing within the droplet reservoir alongside real-time resin replenishment, effectively removing limitations on printing volume. Furthermore, the continuous infusion of ambient liquid promotes internal thermal circulation within the droplet, facilitating heat dissipation and mitigating systemic heat accumulation during prolonged UV curing. As a result, this method supports high-speed continuous printing with thermally independent operation, improved printing accuracy, enhanced stability, and mechanical performance-compatible with polyacrylate, ceramic, and flexible resins. This thermally regulatable strategy for fabricating intricate 3D architectures holds considerable promise for on-demand, continuous 3D manufacturing.

Keywords:  enhance long‐term mechanical property; on‐demand resin supply; reduce heat accumulation; resin versatility; unlimited printing volume

DOI:  https://doi.org/10.1002/smtd.202501906
ACS Omega. 2025 Dec 23. 10(50): 61867-61876

DIW Printing of PEDOT:PSS on Living Plants for Biohybrid Systems.

Erica Hild, Rachel Blau, Debika Datta, Milena Zeru, Steven Schara, Patrick Joseph O Smith, Ivonne González-Gamboa, Darren J Lipomi, Nicole F Steinmetz, Jonathan K Pokorski.

Global agriculture faces mounting stressors including drought, flooding, and pathogen infection, yet methods to noninvasively monitor plant health remain limited. Plant biohybrids aim to address this by merging soft, flexible conductive materials with living systems. However, achieving stable, biocompatible interfaces on dynamic, nonplanar leaf surfaces remains a challenge. This paper hypothesizes that in situ printing of conductive polymers on a leaf surface will broaden the scope of plant biohybrids and compares a commercial PEDOT:PSS versus a softer and stretchable PEDOT, where PSS is replaced with a soft block polymer. To test this, shear-thinning conductive polymer inks (∼103 Pa·s) were formulated for both polymers and printed directly onto leaves with direct ink writing (DIW). Biocompatibility and tissue integrity were evaluated through reactive oxygen species (ROS) assays, chlorophyll measurements, and SEM imaging, confirming minimal stress and preservation of microstructures such as trichomes. Importantly, the prints remained intact for over 28 days with relatively low drops in conductivity over 2 weeks. This noninvasive approach expands opportunities in plant-based biosensing, environmental monitoring, and biohybrid technologies.

DOI: https://doi.org/10.1021/acsomega.5c08520
Mater Today Bio. 2026 Feb;36 102649

Supramolecularly gated enzymes: On-demand activity switching via host-guest competition for precision tumor therapy.

Huijuan Yang, Xiangrui Shi, Ziyi Li, Lan Yang, Xinlei Gao, Hui Chen, Qinghua Zhang, Fengting Lv, Xuli Feng.

  Dynamic control over enzyme function has been of great interest in the field of enzyme engineering and disease treatment, however, achieving on-demand regulation of native enzymes in living systems remains challenging due to the complexity of cellular environments and the lack of selective interactions. Here, we introduce a novel enzyme activity regulation system based on supramolecular host-guest recognition that enables reversible and on-demand regulation of native enzyme activity in living cells without covalent modification. This system utilizes the high-affinity interaction between cucurbit[7]uril (CB[7]) and amantadine (Ad) to precisely control enzyme function. CB[7] binds to key residues on the enzyme surface, blocking the active site and switching off enzyme activity. Upon intracellular administration of Ad, CB[7] is competitively removed, restoring enzyme activity and allowing for dynamic regulation of cellular functions. This strategy was successfully validated with model enzymes, including catalase (CAT) and β-galactosidase (β-Gal), demonstrating its broad applicability. Furthermore, we extended this approach to enzyme/prodrug therapy, achieving localized prodrug activation and targeted cell death while minimizing off-target effects and systemic toxicity. Thus, this non-covalent, reversible regulation of enzyme activity represents a significant advancement over traditional methods, offering a versatile and biocompatible tool for studying protein function and developing targeted therapeutic strategies.

Keywords:  Cellular enzyme regulation; Non-covalent modification; Prodrug activation; Reversible control; Supramolecular recognition

DOI:  https://doi.org/10.1016/j.mtbio.2025.102649
Nat Commun. 2025 Dec 30.

Autonomous biogenesis of all thirty proteins of the Escherichia coli translation machinery.

Matthaeus Schwarz-Schilling, Ilan Cohen, Aurore Dupin, Noa Avidan, Yoav Barak, Yoshihiro Shimizu, Shirley S Daube, Roy H Bar-Ziv.

The cell-free biogenesis of the protein translation machinery is essential for the creation of a self-regenerating synthetic cell. Here, we demonstrate the autonomous and simultaneous biogenesis of all thirty proteins of the translation machinery of E. coli in a reconstituted transcription-translation system. We first establish self-regeneration of every translation protein by determining the threshold concentration required for its own synthesis from a synthetic gene coding for the protein, thereby demonstrating the functionality of all nascent proteins, separately. Simultaneous biogenesis of multiple translation proteins at their threshold results in delayed synthesis below detection levels. To achieve self-regeneration of multiple translation proteins, we induce boundary-free compartmentalization of the reaction by immobilizing the genes on a surface at high density. The co-localization of genes, molecular machinery, messenger RNA and nascent proteins at the surface create sufficient conditions to catalyze the simultaneous self-regeneration of sub-groups up to all thirty translation proteins, as measured by total internal reflection fluorescence on the surface. Our approach provides mechanistic insight and presents a general methodology for the biogenesis of cellular machines toward autonomous synthetic systems.

DOI: https://doi.org/10.1038/s41467-025-67772-8
Metab Eng. 2025 Dec 25. pii: S1096-7176(25)00197-1. [Epub ahead of print]

An automated platform for accelerating and focusing adaptive laboratory evolution.

Peter Ruppen, Maximilian Ole Bahls, Michael Sebastian Gerlt, Martin Peter Edelmann, Tania Michelle Roberts, Philippe Marlière, Sven Panke.

  The rate of change in adaptive laboratory evolution (ALE), in which a population of microorganisms is continuously cultivated under a specific selective pressure, is controlled by the cellular mutagenesis rate and the randomness of where in the genetic material mutations are introduced. The constant selection pressure makes it a crucial, yet slow, method in developing microorganisms with novel phenotypes for which a rational engineering pathway is either too complex or unknown. A variety of targeted genome editing methods to accelerate evolution and facilitate the engineering of complex novel traits are available. However, these protocols require (nearly) as many successive transformation steps as loci they target, leaving the actual engineering process quite labor-intense, cumbersome, and at odds with the continuous nature of ALE. Here, we provide a fully integrated microfluidic platform that automates and accelerates bacterial transformation by electroporation to the mere push of a button. We demonstrate the functionality and effect by using oligonucleotide-directed mutagenesis in an ALE experiment to accelerate the engineering of riboflavin prototrophy into Escherichia coli.

Keywords:  Automation; E. coli; Electroporation; Genome editing; Medium Exchange; Microfluidics; Transformation

DOI:  https://doi.org/10.1016/j.ymben.2025.12.007
Nat Commun. 2025 Dec 31.

BARCODE: high throughput screening and analysis of soft active materials.

Qiaopeng Chen, Aditya Sriram, Ayan Das, Katarina Matic, Maya Hendija, Keegan Tonry, Jennifer L Ross, Moumita Das, Ryan J McGorty, Rae M Robertson-Anderson, Megan T Valentine.

Active, responsive, non-equilibrium materials-at the forefront of materials engineering-offer dynamical restructuring, mobility and other complex life-like properties. Yet, this enhanced functionality comes with significant amplification of the size and complexity of the datasets needed to characterize their properties, thereby challenging conventional approaches to analysis. To meet this need, we present BARCODE: Biomaterial Activity Readouts to Categorize, Optimize, Design and Engineer, an open-access software that automates high throughput screening of microscopy video data to enable non-equilibrium material optimization and discovery. BARCODE produces a unique fingerprint or 'barcode' of performance metrics that visually and quantitatively encodes dynamic material properties with minimal file size. Using three complementary material-agnostic analysis branches, BARCODE significantly reduces data dimensionality and size, while providing rich, multiparametric outputs and rapid tractable characterization of activity and structure. We analyze a series of datasets of cytoskeleton networks and cell monolayers to demonstrate BARCODE's abilities to accelerate and streamline screening and analysis, reveal unexpected correlations and emergence, and enable broad non-expert data access, comparison, and sharing.

DOI: https://doi.org/10.1038/s41467-025-67963-3
ACS Appl Mater Interfaces. 2025 Dec 31.

Flexible Conductive Paper-Based Sensors for On-Skin Electrophysiological Monitoring and Wearable Applications.

George Al Boustani, Lukas Bichlmaier, Tetsuhiko F Teshima, Oleksandr Berezin, Lennart Jk Weiß, Koji Sakai, Kenji Kondo, Lukas Hiendlmeier, Defne Tüzün, Beatrice De Chiara, Marta Nikić, Gil G Westmeyer, Shigeyoshi Inoue, Markus Becherer, Bernhard Wolfrum.

  Flexible, skin-conformable electrodes require materials that combine mechanical robustness, environmental stability, high electrical performance, and biocompatibility. Here, we present a flexible conductive composite film composed of poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS), cellulose nanofibers (CNF), and the ionic liquid 1-ethyl-3-methylimidazolium ethyl sulfate (EMIM ES). The composite is fabricated via a simple aqueous blending and filtration process, yielding a free-standing film with a robust fibrous microstructure. ATR-FTIR analysis confirms the successful integration of all components, while SEM imaging reveals a percolated nanofibrillar architecture that enhances interfacial adhesion and structural integrity. Mechanical testing reveals a tensile strength of up to 335 MPa, accompanied by a strain of 21%, attributed to the increasing CNF content. Composite films with low CNF content exhibit excellent electrical stability across humidity levels between 10% and 90% and temperatures of 15-55 °C, and maintain electrochemical performance after 100,000 cycles of mechanical fatigue testing. On-skin electrophysiological recordings from a rodent model demonstrate stable signal acquisition without skin irritation, establishing the hybrid films as a promising platform for soft, wearable bioelectronic interfaces.

Keywords:  PEDOT:PSS; cellulose nanofibers (CNF); conductive composites; flexible electrodes; ionic liquids; wearables

DOI:  https://doi.org/10.1021/acsami.5c22432
Chemistry. 2025 Dec 29. e03397

Bottom-up Strategies for Generating Polymer Protocells That Mimic Cellular Communication.

Gloria Saorin, Xinan Huang, Voichita Mihali, Cornelia G Palivan.

  In the last decade, the design of artificial organelles and cells has emerged as an area with far-reaching implications due to the potential that such systems have for both understanding bioprocesses in a simple and controlled manner, and for developing advanced solutions for medical applications. Significant efforts have been devoted to developing artificial organelles and cells as single compartments or compartments-in-compartments to enable the study of internal reactions. However, a major challenge in approaching natural processes is to be able to mimic complex signaling and communication pathways. In this review, we present bottom-up strategies that introduce polymer-based protocells for studying intra- and intercellular communication. Whereas intracellular communication involves in situ reactions that are triggered by an external stimulus, intercellular communication is achieved by exchange of chemical signals between two different types of protocell, the "sender" and "receiver." By spatially segregating different molecules and nano-assemblies that serve as artificial organelles in sender and receiver protocells, respectively, various reactions have been studied, including single and cascade enzymatic reactions. Such interconnected systems, which facilitate exchange and flow of information in a close-to-nature manner, increase our insight into complex natural signaling pathways and hold promise for creation of programmable artificial cell- and tissue-like systems for tomorrow's medicine.

Keywords:  artificial organelles; intercellular communication; intracellular communication; polymers; protocells

DOI:  https://doi.org/10.1002/chem.202503397
Acc Mater Res. 2025 Dec 26. 6(12): 1422-1434

Soft Gel-Based Transformative Structured Engineering Design.

Kaixin Jiang, Xue Chen, Chunyan Dai, Ben Bin Xu.

Soft gels, a category of soft materials, consist of polymer networks with small molecules, such as water or other solvents. They possess mechanical flexibility and softness along with tunable physical and chemical functionalities. These gels are capable of responding to external stimuli, such as temperature, pH, light, and electric and magnetic fields, making them highly suitable for applications in drug delivery, tissue engineering, sensors, and soft robotics. As many advantages as soft gels have, there are many more mechanisms to be understood to bridge clear structure-function relationships. There is also a continuous need to facilitate these new functionalities into the device or product technologies. In this Account, we aim to provide an overview of recent progress in functional soft gels with a focus on structural design and innovative fabrication techniques. We start with exploring how structural design can impart diverse functionalities to soft gels. This is followed by a discussion of mechanics with an emphasis on elastic instabilities that are deliberately introduced and controlled to achieve shape morphing. The multilength scale instabilities will be linked with local to global surface deformation and/or macroscopic deformation of gel objects. We then examine how chemical modificationsespecially cross-linking and network formationcontribute to the architecture and functionality of soft gels. These chemical modifications have been harnessed to enrich the designability of the gel to enable extra function or provide dedicated controllability. Manufacturing techniques also play a vital role in establishing structural varieties that enable programmable responses to external stimuli for specific applications. We offer a quick scan on the frontier technologies on fabricating soft gel-based devices with an alignment to the advanced manufacturing trend with novelty structural design. Finally, the applications of functional soft gels were selectively scoped in areas such as sensing, energy and sustainable materials, and biomedical devices. They are well-suited for both diagnostic and therapeutic functions. All the above applications will be enabled by the novel structural design with realization of unique structure-property relationships. Designed structures can be programmed to exhibit specific mechanical behaviors, which, in turn, enable responsive and functional soft gels. Importantly, when a stimulus activates the designated trigger points, the engineered structure responds in the manner that we designed. This interplay within the gel ultimately manifests as a controllable response, highlighting how transformative structural engineering serves as the foundation for achieving multifunctionality. We conclude by highlighting the current challenges and future directions in the development of high-performance functional soft gels through structure-based design.

DOI: https://doi.org/10.1021/accountsmr.4c00348
ACS Appl Mater Interfaces. 2026 Jan 02.

Ultrathin, Flexible, and Multifunctional Silk Fibroin-Ag Functional Engineered Membranes for Integrated Separation, Treatment, and Detection of Water Pollutants.

Mindi Ming, Xiehe Wang, Yi Liu, Jing Ren, Jinrong Yao, Xin Chen, Zhengzhong Shao, Shengjie Ling.

  Multifunctional membranes integrating pollutant separation, treatment, and detection are highly desirable but challenging to create. Here, we report a coordination-adsorption-reduction strategy to fabricate ultrathin, flexible, self-supporting silk fibroin-Ag (SAFE) membranes at the air-water interface. Mechanistic studies reveal that silver(Ι) center coordination guides silk fibroin aggregation, which templates uniform AgNP growth. The resulting membranes achieve exceptional electrical conductivity (up to 1.9 × 107 S m-1) and mechanical robustness. Functionally, they provide high-flux separation and superior pollutant adsorption, while the embedded AgNPs offer multifaceted treatment via antimicrobial, catalytic, and electrochemical activities and enable sensitive SERS detection of trace contaminants. This integrated "separation-treatment-detection" approach establishes SAFE membranes as a promising platform for intelligent and sustainable water purification.

Keywords:  air−water interfacial assembly; high-flux separation; multifunctional water purification; silk fibroin materials; silver nanoparticles; ultrathin film

DOI:  https://doi.org/10.1021/acsami.5c22309
Adv Mater. 2025 Dec;37(52): e71859

Toward the Nobel Prize: Dissecting Fundamental Principles and Applications of MOF and COF Materials.

Stefan Wuttke.

DOI: https://doi.org/10.1002/adma.71859
Eng Life Sci. 2025 Dec;25(12): e70062

Combination of Extrusion and Drop-on-Demand Bioprinting in One Process Enables the Local Placement of Cells or Signaling Factors Into (Bio) Printed Hydrogel Structures.

Finn Dani, Nieves Cubo-Matteo, Leonie Schlicht, Michael Gelinsky, Anja Lode.

  Combining the volumetric fabrication of hydrogel constructs using extrusion bioprinting with highly precise drop-on-demand (DoD) bioprinting offers exciting opportunities in biofabrication. This technical report presents a technique in which a solenoid micro-pipette is operated as an additional tool in an extrusion (bio)printing system to deposit small volumes of bioinks into extrusion-printed hydrogel constructs. Using three exemplary approaches, we show that this enables the patterned placement of cells or growth factors within 3D constructs and thus influences developmental processes. Human cells within low-viscosity bioinks, deposited into extrusion-printed hydrogel constructs by filling inter-strand cavities or by injection into the hydrogel strands, maintained their viability and functionality up to 28 days. As demonstrated for salivary gland cells, the properties of the hydrogel matrix can influence the fate of the injected cells: In a stiff alginate (Alg)-based hydrogel, they formed aggregates, which is beneficial for organoid formation, and in softer hydrogels, they migrated to neighboring cell clusters. Locally injected signaling factors such as vascular endothelial growth factor (VEGF) attracted endothelial cells and fibroblasts, which migrated into previously cell-free hydrogel areas. The combination of extrusion and DoD bioprinting opens new approaches to integrate different cell types and functionalizations in one construct, facilitating the creation of more complex and dynamic models.

Keywords:  bioprinting; cell migration; cell placement; drop‐on‐demand; organoid

DOI:  https://doi.org/10.1002/elsc.70062
ACS Appl Mater Interfaces. 2026 Jan 02.

Biocompatible, Ion-Conductive Hydrogel-Filled Nerve Conduit for Peripheral Nerve Regeneration.

Joyce Huang, Jing Tian, Tzu Chun Chung, Sam Denton, Youchao Teng, Kun-Wei Yeh, Stephanie K Seidlits, Nasim Annabi, Song Li.

  Peripheral nerve injury can result in a loss of sensation and muscle control. Native axon regeneration rates are insufficient to bridge a large gap due to severe damage, leading to a permanent loss of function. Contemporary use of autografts as a treatment, while effective, is limited by donor-site morbidity. Conductive nerve guides can provide mechanical support for regenerating axons, while electrical conductivity provides bioelectrical cues. However, conventional materials used to provide electrical conductivity to hydrogels are not biodegradable and can induce inflammation, which can further impede regeneration. To address these issues, a biodegradable conductive hydrogel containing choline-based bioionic liquid (BioIL) was designed to bridge large nerve gaps and support native axon regeneration. Choline, a small molecule precursor of various biomolecules, combined with a gelatin-based hydrogel, creates a biodegradable and resorbable hydrogel. Conjugation of BioIL to a gelatin methacrylol (GelMA) hydrogel, followed by saline submersion, imparted an ionic conductivity to the hydrogel. Ion-conductive GelMA/BioIL hydrogels supported the myelination function of Schwann cells and the axon outgrowth from dorsal root ganglia in vitro. Implantation of GelMA/BioIL-filled poly(l-lactide-co-caprolactone) nerve conduit in a rat model of peripheral nerve injury improved the recovery of motor and sensory function. The engineered GelMA/BioIL hydrogel increased the number of regenerated axons, improved the myelination of regenerated axons, and reduced the atrophy of downstream muscle. These results support the use of a BioIL-functionalized hydrogel in creating effective, biocompatible nerve conduits for peripheral nerve regeneration.

Keywords:  biomaterials; hydrogel; ion-conduction; ionic liquids; nerve regeneration; peripheral nerve injury

DOI:  https://doi.org/10.1021/acsami.5c19623
Nat Commun. 2025 Dec 27.

Printable polymer nanocomposites for scalable and architected radiative cooling.

Kai Zhou, Songtao Tang, Pranto Karua, Fukang Wu, Sungmin Hong, Diya Patel, Gwendolyn M Reeser, Donald M Cropek, Paul V Braun, Lili Cai.

Space cooling and lighting together consume 25% of global electricity, yet existing daytime radiative coolers are mostly limited to porous planar coatings that block visible light and lack durability. Here, we introduce rheology-optics coupling as a design principle that links polymer viscoelasticity to particle dispersion and optical scattering. Guided by this principle, we develop printable polydimethylsiloxane-zirconium oxide composites that achieve solar reflectance ( ~ 97.3%) and mid-infrared emissivity ( ~ 96.9%) comparable to the best reported values, despite a low filler loading of only ~4.5 vol.%. These scalable coatings provide up to 7.4 oC sub-ambient cooling and cut electricity use by 37% versus commercial paint in pilot-scale testing, while withstanding mechanical, thermal, and environmental stresses. Beyond planar coatings, the rheology-tunable polydimethylsiloxane-zirconium oxide ink enables direct ink writing of daylight-regulating architectures that deliver sub-ambient radiative cooling while admitting diffuse daylight for illumination, reducing both cooling and lighting demand. This work provides a practical and versatile platform for radiative cooling.

DOI: https://doi.org/10.1038/s41467-025-67831-0
Nat Biotechnol. 2026 Jan 02.

Improving adenine base editor precision with directed evolution and extended guide RNAs.

DOI: https://doi.org/10.1038/s41587-025-02977-2
Small. 2025 Dec 30. e08366

Leveraging Viscosity to Unlock the Osteogenic Potential of BMP-2 Mimetic DWIVA.

Finlay Cunniffe, Ziyuan Luo, Eva Barcelona-Estaje, Eva Forrest, Manuel Salmeron-Sanchez, Marco Cantini.

  Growth factor mimetics offer great potential for osteogenic biomaterials; yet, their use remains limited, likely due to an incomplete understanding of the effects of the microenvironment on their activity. The extracellular matrices (ECMs) where growth factors are presented in vivo are viscoelastic environments, where dynamic receptor-ligand interactions drive cellular responses. Here, supported lipid bilayers of varying viscosity are used as 2D dynamic ECM models, where the bone morphogenetic 2 (BMP-2) mimetic DWIVA is presented to mesenchymal stem cells alongside the adhesive peptide RGD. DWIVA is demonstrated to have no impact on mechanotransductive processes, including actin organisation, focal adhesion formation and YAP localisation, which are exclusively controlled by viscosity via RGD. Interestingly, DWIVA promotes osteogenic markers' expression only on a viscous bilayer, through a process that involves non-canonical BMP-2 pathways; on a mobile bilayer or on a static control, it lacks osteogenic activity. Crucially, osteogenesis is accompanied by a translocation of BMP receptor 1a to the cell edge, where it colocalises with focal adhesions. Our ECM models hence reveal that both a viscosity-enabled threshold of cell-generated forces and a dynamic environment are necessary to harness the osteogenic potential of DWIVA, uncovering key microenvironment properties for the design of DWIVA-based biomaterials.

Keywords:  BMP‐2; DWIVA; mesenchymal stem cell; osteogenesis; viscosity

DOI:  https://doi.org/10.1002/smll.202508366
ACS Appl Bio Mater. 2025 Dec 31.

4D Printing in Healthcare: Innovations, Challenges, and Future Directions.

Kunal Agam Kanaujia, Vimal Kumar Yadav, Satendra Singh Yadav, Mohd Talha, Shubhini A Saraf, Shailendra Kumar.

  4D printing, an advancement of traditional 3D printing through the integration of smart stimuli-responsive materials, is revolutionizing biomedical applications by enabling dynamic and adaptive medical constructs. In contrast to conventional additive manufacturing that produces static structures, 4D printing introduces time-dependent transformations in response to environmental or physiological cues, thereby opening avenues for precision and personalized medicine. This review advances the central hypothesis that 4D printing serves as a paradigm shift in biomedical engineering by uniting personalized fabrication with responsive functionality, thereby bridging the gap between static medical devices and adaptive, patient-specific therapeutics. This article first outlines the principles and mechanisms of 4D printing, with emphasis on shape-morphing strategies and responsive biomaterials such as hydrogels, shape-memory polymers, and bioderived polymers. The review then examines the biomedical applications of these materials in drug delivery, regenerative medicine, and personalized healthcare, highlighting innovations such as spatiotemporally controlled implants, on-demand release systems, and adaptive scaffolds for tissue regeneration. Furthermore, the integration of AI-driven design optimization, gene-editing vectors, and next-generation biomaterials is discussed as an emerging frontier that could significantly enhance therapeutic precision and responsiveness. Finally, key translational challenges, including scalability, material limitations, and regulatory considerations, are critically analyzed in this review. By consolidating these perspectives, this review positions 4D printing not only as an extension of 3D printing but also as a disruptive enabler of intelligent and adaptive healthcare solutions.

Keywords:  4D printing; personalized medicines; regenerative medicine; scaffolds; tissue engineering

DOI:  https://doi.org/10.1021/acsabm.5c01165
Adv Mater. 2025 Dec 28. e18820

Dynamic Reversible Full-Color Phosphorescence Afterglows from Stimuli-Responsive Carboxymethyl Chitosan Based Materials.

Yu Song Cai, Zhengshuo Wang, Yijing Cui, Xiang Chen, Guangxin Yang, Hanlin Ou, Hua Yuan, Wang Zhang Yuan.

  Pure organic stimuli-responsive persistent room-temperature phosphorescence (p-RTP) materials hold significant promise for encryption, bioimaging, sensing, and wearable optoelectronics. However, developing highly efficient smart p-RTP systems featuring full-color tunability and multi-dimensional reversible responsiveness remains a long-standing challenge, especially for nonconventional luminophores lacking significant conjugation. Herein, it is found that marine-derived carboxymethyl chitosan (CMCS) exhibits intrinsic excitation-tunable panchromatic (400-610 nm) photoluminescence (PL) and a record-high p-RTP quantum yield of 10.1% amongst nonconventional polymeric luminophores. Leveraging its outstanding PL, rigid conformation, and, moreover, inherent amino/carboxyl groups, we further construct a pyrenedicarboxylic acid salt-doped phosphorescence system that demonstrates efficient (8.8%), prolonged (515.1 ms), and dynamically tunable (495-710 nm) p-RTP with cyclable control via pH, delay time (td), and excitation wavelength (λex). Moving beyond conventional aromatic structural modification strategies, this work achieves multimode stimuli-responsive and efficient p-RTP through the synergy between nonaromatic CMCS and aromatic chromophores, and the effective control of their intra/intermolecular interactions, chain conformation, and consequent dye aggregation, enabling versatile applications across anti-counterfeiting, encryption, information storage, and phosphorescent textiles.

Keywords:  carboxymethyl chitosan; full‐color phosphorescence afterglows; luminescent fibers; stimuli‐responsive luminescent materials

DOI:  https://doi.org/10.1002/adma.202518820
Soft Matter. 2026 Jan 02.

A technique to create hydrogels with tethered concentration gradients of molecules in vitro.

Thomas C O'Shea, Ahmad Salem, Kelly M Schultz.

This work develops a technique to create and quantify tethered molecular concentration gradients in a hydrogel using a flow chamber. This device is designed to enable isotropic scaffold swelling, nutrient diffusion and real-time microrheological measurements. A hydrogel is first photopolymerized in the flow chamber ensuring that the mechanical properties of the hydrogel across samples are the same prior to molecular concentration gradient creation. Then molecules are passively diffused into the scaffold and a second photopolymerization tethers the concentration gradient into the material. This technique creates in vitro mimics of aspects of biological environments, such as the environment around a hydrogel implanted in the body for cell delivery. We use a well-defined synthetic scaffold with a poly(ethylene glycol) (PEG)-norbornene backbone cross-linked with a matrix metalloproteinase (MMP)-degradable peptide, a standard material for cell encapsulation. The method to tether molecular concentration gradients is validated using a fluorescent PEG-thiol (FITC-PEG-SH), an ideal polymer. We first create a calibration curve by measuring the fluorescence intensity of hydrogels with known uniform concentrations of the tethered fluorescent molecule. The calibration curve is used to calculate spatial concentration from measured fluorescence intensity in hydrogels with polymer or protein concentration gradients. FITC-PEG-SH is diffused through our hydrogel in a flow chamber for 6, 24 and 48 hours. We make consistent gradients and quantify the concentration of the fluorescent molecule every 25 µm along the material. Next, we make tethered concentration gradients of tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine found in the wound environment, after 24 hours of diffusion. These gradients are consistent when normalized by the concentration at the edge of the hydrogel, which varies due to pore clogging. From both molecular concentration gradients, we calculate an effective diffusion coefficient that is the same order of magnitude as the value calculated using the multiscale diffusion model. Significant advances made with this technique include limited confinement of the material, which enables isotropic swelling and facile nutrient diffusion, the ability to image through the device and the same hydrogel rheological properties across samples. This technique can be used in future work to characterize cell-laden hydrogels which present the same physical cues to cells and tethered concentration gradients of chemical cues using microrheology.

DOI: https://doi.org/10.1039/d5sm01194a
Science. 2026 Jan;391(6780): eady6017

De novo design of small molecule-regulated protein oligomers.

Qihan Jin, Yukai Wang, Dachuan Chen, Jinyang Liao, Zhanyuan Cui, Yuxuan Fan, Anping Zeng, Mingqi Xie, Longxing Cao.

Small molecule-regulated protein oligomerization provides a powerful mechanism for manipulating biological processes by controlling protein proximity with high temporal precision. However, such systems only rarely exist in nature and remain a substantial challenge for de novo design. In this work, we describe a computational method for designing protein homooligomers whose assembly is regulated by small-molecule ligands with matching symmetry. We designed protein homotrimers regulated by the Food and Drug Administration (FDA)-approved drug amantadine and further designed amantadine-responsive heterodimers and heterotrimers. Biophysical characterization confirmed their amantadine-dependent assembly, and their crystal structures closely matched the design models. We demonstrated their broad applicability in controlling protein localization, membraneless condensate formation, and gene expression. Our approach opens new avenues for designing small molecule-responsive proteins and expands the chemogenetic toolkit for manipulating complex biological processes.

DOI: https://doi.org/10.1126/science.ady6017
PNAS Nexus. 2025 Dec;4(12): pgaf385

Open-source cell culture automation system with integrated cell counting for passaging microplate cultures.

Greg Courville, Shivanshi Vaid, Alexis Toruño, Paul Lebel, Joana P Cabrera, Preethi Raghavan, Axel Jacobsen, George R R Bell, Manuel D Leonetti, Rafael Gómez-Sjöberg.

Tissue culture in 96-well microplates is conventionally a tedious, highly manual process sensitive to individual technique and experimenter error. Here, we describe the Automated Cell Culture Splitter, a system for passaging plates of adherent or suspension cells, for routine culture maintenance or specialized applications such as seeding plates for microscopy. The system is built around the Opentrons OT-2 liquid handling robot and incorporates a novel on-deck imaging-based cell counter which allows it to compensate for density disparities across a source plate and control the number of cells seeded on a per-well basis. We find this solution can cut hands-on time by 61% and the results compare favorably to our existing manual cell culture processes in terms of both seeding density precision and biological outcomes, achieving a control of seeding density with a well-to-well coefficient of variation under 11%. The system is designed to be adaptable and an accessible entry point into automation for high-throughput cell culture; to that end, all of the source code and hardware designs are released under open source licenses.

DOI: https://doi.org/10.1093/pnasnexus/pgaf385
ACS Appl Bio Mater. 2025 Dec 30.

Self-Assembled Hydrogel from Pyrene-Modified Peptide as 3D Matrices for Neuronal Cell.

Devi Wahyuningtyas, Yoyo Cheng-Ting Yu, Chin-Yun Hsieh, Yung-An Huang, Ruei-Yu He, Tzu-Hung Teng, Bryan Po-Wen Chen, Jung-Ren Huang, David T Wu, Joseph Jen-Tse Huang.

  Self-assembled hydrogels offer biomimetic platforms for three-dimensional (3D) cell culture; yet, achieving stability and functionality under physiological conditions remains a challenge. Here, we report a series of pyrene (Py)-modified peptides designed to form hydrogels with tunable physical and biological properties. Among them, Py-L3K3 uniquely formed stable, fluorescent hydrogels at both neutral and basic pH, in contrast to Py-K6 and Py-A3K3, which gelled only at basic pH. Molecular dynamics simulations revealed pH-dependent clustering as a key mechanism driving hydrogel formation. Structural analysis showed that Py-L3K3 forms nanofibrillar networks with granular surface morphologies and β-sheet-rich conformations. Rheological studies demonstrated its solid-like viscoelastic behavior and self-healing capability, as determined by oscillatory shear measurements. Importantly, Py-L3K3 supported neuronal cell viability, attachment, and growth under physiological conditions, highlighting its potential as a 3D culture scaffold. These findings present Py-L3K3 as a promising candidate for applications in neuronal engineering and injectable regenerative biomaterials.

Keywords:  3D cell culture; biomaterial; nanofibrils; peptide hydrogel; pyrene

DOI:  https://doi.org/10.1021/acsabm.5c01646
Biotechnol Bioeng. 2026 Jan 02.

Hydrogel Embedding of Mesenchymal Stem Cells Supports Extracellular Vesicle Production.

Rachel K Moen, Gabriella Faircloth, Nicole T Marguerite, Mariachiara Conti, Ethan S Lippmann, Jamey D Young.

  Extracellular vesicles (EVs) derived from adherent cells are promising therapeutics for a wide variety of diseases. Previous studies have shown that mesenchymal stem cell (MSC)-derived EVs have many applications in wound healing and regenerative medicine. Specifically, MSC-derived EVs are safer than cell-based therapies because EV treatments do not involve the administration of live cells to patients. However, a lack of scalable workflows for producing EVs from 2D adherent sources is a major current limitation of the field. One proposed method for culture scale-up is to encapsulate MSCs in a gelatin methacryloyl (GelMA) hydrogel, which provides a 3D matrix that better mimics the in vivo microenvironment of human cells and can be shaped into spherical beads or thin films to support the growth of shear-sensitive cells inside bioreactors. To establish proof of concept, we embedded MSCs in a layer of GelMA hydrogel to assess the production rate, molecular properties, and functional characteristics of EVs collected from 3D cultures. Hydrogel-encapsulated MSCs yielded a greater number of EVs per volume of culture compared to traditionally grown unencapsulated MSCs, and 3D cultures produced EVs with improved functionality in a scratch assay relative to vehicle treatment. These findings support the hypothesis that GelMA can be used to support scalable manufacturing of bioactive EVs from adherent cell sources.

Keywords:  3D cell culture; GelMA; extracellular vesicles; hydrogel; mesenchymal stem cells

DOI:  https://doi.org/10.1002/bit.70149
Chem Rev. 2025 Dec 29.

Templating Methods for Materials Fabrication Across Scales.

Zuyang Ye, Chen Chen, Yucong Su, Ji Feng, Yadong Yin.

Templating methods have emerged as a powerful toolbox for the rational design and scalable fabrication of nanostructured and hierarchical materials with controlled morphology, dimensionality, and spatial organization. By leveraging predefined scaffolds across molecular, colloidal, and macroscopic length scales, templated synthesis and template-assisted self-assembly enable the bottom-up construction of materials with tailored structural and functional properties. This review provides a comprehensive overview of templating strategies categorized by operational scale and templating modality. We first discuss nanoscale and microscale templating approaches based on colloidal, molecular, and other noncolloidal templates. We then examine template-assisted self-assembly strategies guided by nanoscale and macroscale templates that facilitate the organization of building blocks into ordered architectures. Next, multiscale integration strategies that bridge bottom-up and top-down fabrication are reviewed, including physical-field-directed assembly and 3D-printed templates. Finally, representative applications in photonics, energy conversion and storage, and biomedicine are presented, followed by an outlook on future opportunities and challenges in the fabrication of hierarchical materials via templating.

DOI: https://doi.org/10.1021/acs.chemrev.5c00709
Small. 2025 Dec 28. e10692

Architected Redox-Active Colloids for Tunable Charge Transport in Aqueous Systems.

Sinae Lee, Jeongwon Kim, Eunsung Kim, Sanghyuk Park, Won-Jang Cho, Gi-Ra Yi, Hee Jung Park, Dong Ha Kim, Hyerim Hwang.

  Colloids, a foundational class of soft matter, are increasingly explored as programmable frameworks for electrochemical function. Traditionally regarded as passive carriers, colloids can be architected to form internal pathways for ion and electron transport. Their dispersibility, processability, and compatibility with aqueous media make them promising candidates for safe and sustainable redox systems, yet aqueous electrolytes remain limited by narrow potential windows, poor stability of redox sites, and sluggish charge transport. Architected redox-active colloids (RACs) composed of polystyrene (PS) spheres embedded with ethyl viologen (EV) address these limitations. Fabricated through a swelling-mediated loading process, RACs allow independent control of particle size, redox-site density, and internal EV organization. This design enables direct control over redox capacity and reversibility, surpassing what is accessible in dissolved redox molecules or simple colloidal dispersions. Colloids with densely organized and spatially continuous EV domains exhibit enhanced charge transport and stability, demonstrating that internal architecture, rather than total redox content alone, governs electrochemical performance. These findings establish RACs as a robust and flow-compatible platform for aqueous electrochemical systems and provide a generalizable strategy for designing soft colloidal materials with integrated charge transport functionality.

Keywords:  internal architecture control; redox‐active colloids; swelling‐mediated loading

DOI:  https://doi.org/10.1002/smll.202510692
Sci Adv. 2026 Jan 02. 12(1): eadx7389

Self-supervised AI for decoding and designing disordered metamaterials.

Min Shen, Ke Liu, Sheng Mao, Chiara Daraio.

Disordered microstructures are key to the distinct multifunctional properties of many natural materials. However, understanding the relationship between their microstructures and physical functions remains formidable, hindering engineering applications. Here, we introduce a physics-guided, self-supervised artificial intelligence (AI) framework called generative networks for disordered metamaterials (GNDM), trained on a progressively expanding dataset starting from a few initial samples. We integrate a formula writing module in the training process of neural networks to enforce the identification of the most selective set of hidden geometric invariants that dictate bulk properties. By inversely solving the formulae, GNDM manipulate disordered geometric features to extrapolate property space and design previously unknown structures via its generator module, validated by experiments. GNDM offers an all-in-one AI framework that closes the loop of feature extraction, property prediction, formula writing, and inverse design, unraveling the regulative role of disorder, a critical challenge in the study of metamaterials with complex microstructures.

DOI: https://doi.org/10.1126/sciadv.adx7389
Nat Mater. 2026 Jan 02.

Artificial intelligence-driven approaches for materials design and discovery.

Mouyang Cheng, Chu-Liang Fu, Ryotaro Okabe, Abhijatmedhi Chotrattanapituk, Artittaya Boonkird, Nguyen Tuan Hung, Mingda Li.

Materials design is an important component of modern science and technology, yet traditional approaches rely heavily on trial and error and can be inefficient. Computational techniques, enhanced by modern artificial intelligence, have reshaped the landscape of designing new materials. Among these approaches, inverse design has shown great promise in designing materials that meet specific property requirements. In this Review, we present key computational advances in materials design over the past few decades. We follow the evolution of relevant materials design techniques, from high-throughput forward machine learning methods and evolutionary algorithms, to advanced artificial intelligence strategies such as reinforcement learning and deep generative models. We highlight the paradigm shift from conventional screening approaches to inverse generation driven by deep generative models. Finally, we discuss current challenges and future perspectives of materials inverse design. This Review may serve as a brief guide to the approaches, progress and outlook of designing future functional materials with technological relevance.

DOI: https://doi.org/10.1038/s41563-025-02403-7
Sci Adv. 2026 Jan 02. 12(1): eaeb9059

Facile and robust integration of functional hydrogels into micropillar-structured elastomer platforms for stable cardiac bioelectronics.

Hyun Su Lee, Eunyoung Jeong, Heewon Choi, Jeong-Uk Kim, Nathaniel S Hwang, Donghee Son, Yoonsoo Shin, Dae-Hyeong Kim.

Establishing stable electrical communication between living tissues and bioelectronic devices requires soft, conductive, and conformable interfaces. Conductive hydrogels are attractive for this role because their hydrated polymer networks and mixed ionic/electronic conductivity reduce impedance and enhance charge transfer. Yet, challenges remain in integrating hydrogels with device components and achieving reliable tissue adhesion. Here, we present a materials and structural design strategy that enables electrically and mechanically robust devices through sequential formation of elastomer-metal-hydrogel multilayers and single-step laser patterning. The device consists of a micropillar-structured waterborne polyurethane substrate with a Au layer strongly bonded to the pillars, showing <2% resistance change under 28% strain. Functional hydrogels provide low interfacial impedance (~36.2 ohms at 1 kilohertz), effective insulation (~51,536 ohms at 1 kilohertz), and strong adhesion (~226 newtons per meter on cardiac tissue). Without elastomer-hydrogel decoupling, performance remains stable under dynamic aqueous conditions. Applied to rodent cardiac tissue, the integrated interface enables real-time electrocardiography monitoring and feedback-controlled electrical stimulation.

DOI: https://doi.org/10.1126/sciadv.aeb9059
Nat Nanotechnol. 2025 Dec 30.

Design and applications of synthetic biomolecular condensates.

Avigail Baruch Leshem, Dor Gaash, Ayala Lampel.

Designed biomolecular condensates are emerging condensed-phase assemblies, initially conceived to mimic cellular biomolecular condensates for use in biology-inspired applications such as delivery and storage of biomolecules. In recent years, rational design approaches informed by supramolecular chemistry and biomolecular nanotechnology, including the use of peptide and DNA nanotechnology for building-block minimalization and site-specific interactions, have evolved rapidly, going beyond the molecular basis of cellular condensates in terms of both composition and functionality. Thus, synthetic condensates are designed from diverse molecular building blocks, including single- or multicomponent polypeptides, peptides, RNA, DNA or biopolymers; moreover, their applications are continuously evolving to encompass new nanotechnology-relevant functions including biosensing and bioadhesion, where condensates offer advantages such as responsiveness, programmability and molecular compartmentalization. In this Review, we show the main concepts behind the molecular design of synthetic condensates, from biological mimicry to purely synthetic approaches. We discuss the mechanisms that allow control and regulation of condensate properties and the remaining challenges in analysing these properties. Finally, we discuss the applications of synthetic condensates thus far, the potential in leveraging condensates as platforms for nanotechnological applications, and the remaining hurdles towards realizing this promise. We also provide an overview of the patent landscape, highlighting trends in commercial development across areas such as delivery systems, microreactors and sensing technologies.

DOI: https://doi.org/10.1038/s41565-025-02053-5