bims-enlima 2025-12-14 papers

bims-enlima

Biomed News

on Engineered living materials

Issue of 2025–12–14
forty-two papers selected by
Rahul Kumar, Tallinna Tehnikaülikool

Multimaterials by Patterning Microphase Separation of a Single Copolymer.
Self-Healing Electrogenic Living Hydrogels for Durable Bioelectronics.
Up-and-down transformable embedded ink writing strategy for soft 3D architectures.
Protein-Based Nanostructures: Column-free Biosynthesis of Bundlemer Peptides with Programmable, Orthogonally Reactive Handles for Nanomaterial Construction.
Influence of mechanical properties of agarose hydrogels on bacterial growth and secretory activity.
Selective infusion of spatially controlled domains via vat photopolymerization 3D-printing for chemically diverse multimaterial parts.
Hierarchical core-shell DNA condensates enable programmable information storage and encryption.
A Hydration-Entropy Lubrication Coupling Strategy for Superhydrophilicity and Ultralow Friction of Hydrogel Coatings.
Double-Network Polysaccharide-Collagen Hybrid Bioink.
Biomaterial-minimalistic photoactivated bioprinting of cell-dense tissues.
Programmable Assembly of Multistranded Helices in Water.
pH-Triggered Coassembly of Cello-oligosaccharides and Hyaluronic Acid into Hydrogels.
Self-assembly of hybrid 3D cultures by integrating living and synthetic cells.
Optimization of the genetic code expansion technology for intracellular labelling and single-molecule tracking of proteins in genomically re-coded E. coli.
Local and sustainable production of biomaterials.
Bioinspired Color-Changing Polymeric Hydrogel Actuators/Robots.
Advanced Encapsulation Technologies for Extracellular Vesicles: From Single Units to Macroscale Packaging.
Polydimethylsiloxane gel thickness and stiffness affect the initial adhesion of Escherichia coli and Staphylococcus aureus.
Genetic control of morphological transitions in a coacervating protein template.
In-Material Computation: A Computational Metamaterial for Data-Efficient Tactile Interfaces.
Brush-like Polymer Surface on Silk Fibroin Films for Controlled Release of Local Anesthetics.
Loop closure grasping: Topological transformations enable strong, gentle, and versatile grasps.
Functionalizing Nucleic Acids: Synthesis and Purification Strategies for Bioconjugates as Biomaterials.
Modular programming of interaction and geometric specificity enables assembly of complex DNA origami nanostructures.
Thermally Switchable Photoactivity in Azobenzene-Functionalized DNA Condensates.
Bioinspired Out-of-Equilibrium Conductive Hydrogels: Unlocking Fuel and Light-Responsive Transient Conducting Properties.
Promoting probiotic delivery and colonization through controllable polymer surface display.
Mesoporous optically clear heat insulators for sustainable building envelopes.
3D-Printed Multifunctional Hydrogel for Integrated Electromagnetic Interference Shielding, Infrared Stealth, and Wearable Sensing.
Microscopic robots that sense, think, act, and compute.
Programmable self-destruction of artificial cells with death signaling.
Engineering the auxin-inducible degron system for tunable in vivo control of organismal physiology.
Chemically gated artificial nanochannels for programmable subcellular signal modulated transport regulation.
Injectable Nanocomposite Biomaterial for 3D Printing of Personalized Matrices and Their Use in Bioreactors for Bioengineering Advanced Cell Culture Models.
Evaporation-driven generic, high-throughput and roll-to-roll printing of nanomaterials.
Photoredox-controlled alternating copolymerization enables highly crystalline structures and block copolymers from thermoplastic to elastomer.
Bioactive Artificial Cells as Autonomous Metabolic Actuators Enable Bidirectional Communication with Tumor Cells.
Talin force coupling underlies eukaryotic cell-substrate adhesion.
Mass spectrometry-based profiling of single-cell histone post-translational modifications to dissect chromatin heterogeneity.
Negative Pressure Actuated Microfluidic Droplet Generation Enables High-Throughput and Robust Synthesis of Cell-Laden Alginate Microgels.
Percolation transition in entangled granular networks.
Materials for Yeast Immobilization in Alcoholic Fermentation: Bridging Conventional Techniques and 3D Bioprinting.

Adv Mater. 2025 Dec 12. e17801

Multimaterials by Patterning Microphase Separation of a Single Copolymer.

Congqi Qi, Bohan Liu, Zheqi Chen, Yingwu Luo.

  Living systems achieve robustness by integrating soft and rigid components into seamless architectures, yet synthetic emulation of this strategy remains limited. Here, we present a strategy to generate multimaterials from a single copolymer by patterning phase separation. Specifically, we design a block copolymer of metastable nanostructure, and then spatially program photocrosslinking to locally arrest phase separation at different levels during annealing, thereby producing patterns that span moduli from regimes of rubbers to plastics. The resulting multimaterial exhibits spatially distinct mechanical properties, but is chemically identical, and is seamlessly integrated through a shared polymer network topology. This approach inherently eliminates interfacial incompatibility of dissimilar materials, enhances structural integrity of the multimaterial, and establishes a versatile platform for programmable, multiscale rigid-soft integrated devices.

Keywords:  fracture; multimaterials; phase separation; soft materials

DOI:  https://doi.org/10.1002/adma.202517801
ACS Appl Mater Interfaces. 2025 Dec 09.

Self-Healing Electrogenic Living Hydrogels for Durable Bioelectronics.

Ruohan Zhang, Yang Gao, Seokheun Choi.

  Living conductive hydrogels that unite biological activity with robust electrogenic performance are emerging as transformative platforms for adaptive bioelectronics, yet most lose electrical functionality after mechanical damage or extended use. Here, we introduce an electrogenic living hydrogel embedding Bacillus subtilis spores─metabolically dormant, environmentally resilient, and capable of germinating into electrogenic bacteria─within a dual self-healing framework. The primary mechanism exploits hydrogen-bonded poly(3,4-ethylenedioxythiophene):polystyrenesulfonate-poly(vinyl alcohol) (PEDOT:PSS-PVA) networks to restore mechanical integrity, while a secondary, conductivity-specific mechanism is activated by rupture of carbon nanotube (CNT)-loaded cellulose acetate microcapsules at the fracture interface, re-establishing percolation pathways. Germination triggers extracellular electron transfer (EET) by B. subtilis, synergistically boosting conductivity beyond the undamaged state and reducing internal resistances. As a proof-of-concept, the hydrogel served as the anode in a paper-based microbial fuel cell (MFC), achieving a maximum power density of 1.5 μW cm-2 and an open-circuit voltage of 0.38 V─comparable to state-of-the-art paper MFCs. By integrating mechanically resilient matrices, microcapsule-mediated conductivity restoration, and biologically triggered electroactivity, this platform establishes a paradigm for self-repairing, high-performance living electronics with broad potential in biosensing, energy harvesting, and soft bioelectronic systems.

Keywords:  Bacterial endospores; Electrogenic bacteria; Electrogenic hydrogels; Living Electronics; Self-healing

DOI:  https://doi.org/10.1021/acsami.5c20049
Nat Commun. 2025 Dec 12.

Up-and-down transformable embedded ink writing strategy for soft 3D architectures.

Yaxin Zhang, Tianqi Pang, Zixun Sun, Xinying Li, Jianping Wang, Xiang Lin, Fengxian Gao, Min Gong, Dongrui Wang, Liang Zhang.

The fabrication of 3D soft material architectures is essential for advancing fields such as soft robotics, wearable technologies, and biological engineering. However, conventional embedded 3D printing is constrained by rheological complexity and nozzle-dependent structural limitations. Here, we introduce transformable embedded ink writing (TEIW), a 3D printing strategy that bypasses these issues by triggering rapid, autonomous self-assembly of 2D-printed patterns into predefined 3D structures. TEIW employs yield-stress inks within a Newtonian-like fluid bath, where net gravitational-buoyancy forces drive the filaments to go upward or downward. Through tailored density contrasts, controlled viscosity, and mechanical coupling between structural elements, complex shape transformation is directed with physical intelligence embedded in the printed structure itself, requiring no external intervention. This strategy demonstrates broad compatibility with materials including silicone elastomers, acrylate-based resins, and hydrogels, enabling applications spanning customizable microelectronics, perfusable networks, and cryptographically encoded devices. Furthermore, TEIW's ability to integrate various components in a single print establishes a platform for next-generation systems requiring spatiotemporal multi-material control.

DOI: https://doi.org/10.1038/s41467-025-66418-z
ACS Appl Mater Interfaces. 2025 Dec 10.

Protein-Based Nanostructures: Column-free Biosynthesis of Bundlemer Peptides with Programmable, Orthogonally Reactive Handles for Nanomaterial Construction.

Caitlin D'Ambrosio, Nadim Massad, Amanda L McCahill, William Rears, Pierre Rouviere, Jeffery G Saven, Darrin J Pochan, Christopher J Kloxin, April M Kloxin, Wilfred Chen.

  Nature's protein sequences dictate structure and function across scales, from the nanometer-scale of viral capsids to micrometer- to millimeter-scale architectures of extracellular matrices and tissues. This multiscale precision underlies diverse functions, including molecular recognition, mechanical support, and dynamic responsiveness. Mimicking this complexity synthetically remains challenging. To address this, we engineered biosynthetic coiled-coil 'bundlemer' peptides as modular building blocks that can be conjugated and assembled into complex, higher-ordered materials. Using recombinant expression, we produced peptides and peptide fusion constructs that are otherwise difficult to achieve via solid-phase peptide synthesis. An N-terminal fusion protein with a pH-cleavable intein-inclusion body facilitated simple, scarless purification directly from insoluble fractions. We further incorporated SpyTag (-VPTIVMVDAYKRYK-) and sortase-recognition motifs (GGG-, -LPETGG) into the bundlemers, enabling precise, programmable assembly using genetically encoded and enzymatic ligation strategies. Using sortase-mediated ligation, we polymerized a single bundlemer into fibrillar structures, which were confirmed via TEM, SEC-MALS, SDS-PAGE, and native gels. Additionally, we constructed multicomponent architectures with a layered bundlemer and EGFP on an E2 nanocage using orthogonal linking chemistries, specifically SpyCatcher-SpyTag ligation and sortase-mediated ligation, and the associated increase in particle size and molecular weight was confirmed via TEM, DLS, and SDS-PAGE. This platform establishes a versatile framework for designing complex, protein-based nanostructures with defined architecture and function, offering possibilities in biomaterials engineering, targeted drug delivery, and synthetic biology.

Keywords:  SpyCatcher/SpyTag; biosynthesis; nanomaterials; orthogonal conjugation; peptide assembly; protein purification; sortase

DOI:  https://doi.org/10.1021/acsami.5c17204
Biomater Adv. 2025 Dec 08. pii: S2772-9508(25)00480-7. [Epub ahead of print]181 214653

Influence of mechanical properties of agarose hydrogels on bacterial growth and secretory activity.

L Dupont, V S Tadimarri, R Buret, S Sankaran, L Picton, A M Jonas, K Glinel.

  Engineered living materials (ELMs) rely on the ability to control cell behavior in material systems. ELMs containing bacteria secreting beneficial molecules are being developed for therapeutic purposes. Using commensal strains embedded in physically cross-linked agarose hydrogels, we systematically investigate how gel rigidity and initial bacterial density affect the morphology of bacterial colonies and their secretory function. Although often considered independently, these parameters jointly define the microscale environment experienced by embedded cells, influencing nutrient access, mechanical interactions, and potential cell-to-cell communication. We show that matrix rigidity effectively tunes aggregate morphology, modulating their shape and compactness, without compromising bacterial growth or secretion. In parallel, initial bacterial density determines the biomass accumulation dynamics and spatial distribution of aggregates, which in turn influence the onset and temporal profile of secretory activity, without altering its final magnitude. This decoupling between structural organization and secretory output opens new possibilities for engineering ELMs with tailored architectures and prolonged secretory and release activity.

Keywords:  Cell density; Cell encapsulation; Elafin; Engineered living material; L. plantarum; Matrix stiffness; Probiotic; S. epidermidis; Secretion

DOI:  https://doi.org/10.1016/j.bioadv.2025.214653
Nat Commun. 2025 Dec 12.

Selective infusion of spatially controlled domains via vat photopolymerization 3D-printing for chemically diverse multimaterial parts.

Sarah G Finnegan, Allison M Kinsey, Andrew J Boydston.

Creating multimaterial objects through vat photopolymerization (VP) is challenging due to difficulty transitioning between liquid resins. Multiwavelength VP has emerged as a prominent approach for achieving multimaterial parts through VP; however, the material scope has historically been limited to combinations of organic photo-resins. To address this limitation, we have developed a method that we refer to as infusion multimaterial actinic spatial control additive manufacturing (iMASC-AM). This technique uses dual wavelength light projection to create distinct material regions within a single printed part that display disparate affinity toward infusion of dissolved materials. Herein, we demonstrate the versatility of iMASC-AM with the infusion of organic dyes, silicone resins, and metal salts for patterned optical, mechanical, and conductive properties, respectively. Notably, mild thermal post-processing after infusion was found to reduce silver salts, leading to patterned combinations of electrically conductive and insulating domains and allowing for fabrication of functional circuits from a single print. The iMASC-AM method enables the creation of a wide variety of chemically diverse multimaterial parts with materials properties combinations that are generally inaccessible through VP.

DOI: https://doi.org/10.1038/s41467-025-66128-6
Nat Commun. 2025 Dec 10.

Hierarchical core-shell DNA condensates enable programmable information storage and encryption.

Likang Chu, Liqi Wan, Haixia Wang, Peng Wang, Linyi Deng, Yuan Gao, Pei Guo, Lei He, Da Han.

Utilizing DNA's molecular programmability, massive parallelism, and minimal energy requirements, it emerges as a transformative medium for secure data storage and encryption. However, practical implementation is limited by technical challenges, particularly the development of robust, programmable systems for flexible data encoding, precise molecular operations, and reliable encryption. Here, we present a molecular information storage and encryption platform that integrates hierarchical core-shell DNA condensates with biomolecular computing networks. It allows programmable and rapid execution of core operations such as information encoding, erasure, rewriting, replication, and repair within readily accessible and readable DNA-based condensates. Moreover, programmable biomolecular computing circuits endowed the system with unprecedented encryption capabilities, including multi-level logic encryption, time-dependent dynamic encryption, living system-driven encryption and fine-grained access control of information. Together, this work represents a meaningful advancement in molecular information storage and encryption, with notable advantages in dynamic editability and system scalability.

DOI: https://doi.org/10.1038/s41467-025-67093-w
ACS Appl Mater Interfaces. 2025 Dec 09.

A Hydration-Entropy Lubrication Coupling Strategy for Superhydrophilicity and Ultralow Friction of Hydrogel Coatings.

Siming Li, Xiaohui Song, Yuchen Lu, Zilong Han, Shaoxing Qu.

  Hydrogel coatings combining superhydrophilicity with ultralow friction on irregular, load-bearing biomedical surfaces are critical yet elusive. Natural mucus, with its highly glycosylated mucin network, protects complex biological surfaces from friction and wear through a uniquely structured lubrication mechanism. Here, inspired by mucin, we engineer hydrogel coatings that are easy to fabricate on diverse substrates, bear high loads, and maintain enduring superlubricity via pure structural design. We introduce a hydration-entropy lubrication coupling strategy in which long, free polymer chains synthesized in situ on the surface maintain a robust hydration layer and high configurational freedom, thereby generating strong shear-induced steric repulsion. By tuning polymerization kinetics in an oxygen-rich environment, we rapidly (≤90 s) form coatings exhibiting ultralow friction (μ = 0.008, 1/20 that of regular hydrogels) and superhydrophilicity (static contact angle = 7.9°). A densely entangled internal network preserves coating integrity and stress transfer, sustaining lubrication at a pressure of ∼0.25 MPa for over 60 days. Incorporation of degradable cross-linkers endows excellent biocompatibility and controllable degradability, fulfilling sustainability requirements for implantable systems. This strategy provides a versatile and facile approach for integrating robust superlubricity hydrogel coatings into complex biological interfaces.

Keywords:  degradability; hydrogel coatings; structural design; superhydrophilicity; ultralow friction

DOI:  https://doi.org/10.1021/acsami.5c21090
ACS Appl Mater Interfaces. 2025 Dec 07.

Double-Network Polysaccharide-Collagen Hybrid Bioink.

Fabian Tribukait-Riemenschneider, V Prasad Shastri.

  Over the past decade, three-dimensional bioprinting (3DBP) has evolved into a versatile processing tool for engineering tissues. The key component, the bioink, can be composed of many different hydrogel-forming polymers, which are mostly performant in either mechanical or biological properties but seldom both. Carboxylated agarose (CA) was combined here with collagen type 1 to simultaneously satisfy both properties and combine their attributes, without compromising on either; the result is an innovative, hybrid bioink. It can be printed with high accuracy, good layer-to-layer adhesion, and rapid gelation, enabling overhang printing. Scanning electron microscopy (SEM) and fluorescently labeled collagen demonstrated that the two components mixed well, resulting in uniformly distributed collagen fibrils and a double network. From the biological perspective, a bioink must exhibit cell-adhesion moieties to maintain proliferation and metabolism, which we could ensure through the collagen component. Here, we present an example strategy for combining an inert polysaccharide with bioactive collagen, two polymers with opposing gelation conditions, which yields a bioink that possesses beneficial properties from both without compromising the features of either. The interpenetrating structure of both molecules synergistically balances the mechanical strength of CA and the biological functionality of collagen.

Keywords:  3D bioprinting; carboxylated agarose; collagen; hybrid bioink; interpenetrating network

DOI:  https://doi.org/10.1021/acsami.5c20304
Cell. 2025 Dec 08. pii: S0092-8674(25)01308-X. [Epub ahead of print]

Biomaterial-minimalistic photoactivated bioprinting of cell-dense tissues.

Mian Wang, Wanlu Li, Jin Hao, Ling Cai, Xuan Mei, Regina Sanchez Flores, Penélope Cerón Castillo, Carlos Ezio Garciamendez-Mijares, Xuan Mu, Xiao Kuang, Xianbin Yu, Jugal Kishore Sahoo, Guosheng Tang, Zeyu Luo, Guillermo Wells, Zhongmin Liu, Alfredo Quiñones-Hinojosa, Kevin Eggan, Shaorong Gao, Yu Shrike Zhang.

  Conventional hydrogel-based bioprinting methods often suffer from insufficient cell densities, which may limit crucial cell-cell interactions and impair overall tissue functions. Here, we present an approach that modifies cell membranes with acrylate bonds, allowing living cells at physiological densities (up to ∼109 cells mL-1) to serve directly as bioinks, demonstrating photoactivated bioprinting through digital light processing using purely cellular bioinks. Our cell-dense bioinks (CLINKs) rapidly produce tissue constructs that closely mimic native tissues, characterized by strong structural relevancy and robust functionality. The high cellularity and living nature of CLINKs enable the creation of advanced biological models such as connected neural circuits and rhythmically contracting mini-hearts derived entirely from stem cells, effectively capturing essential native-like behaviors. Implants created through this method showcase the capacity to integrate with the host, thereby promoting regeneration. Our CLINK technology holds substantial promise in tissue biofabrication, opening alternative avenues for biomedical applications.

Keywords:  3D bioprinting; cardiac tissues; cardiomyocytes; cell-dense; digital light processing; liver tissues; neural cells; neural circuits; scaffold-free; skin regeneration

DOI:  https://doi.org/10.1016/j.cell.2025.11.012
Nat Commun. 2025 Dec 11. 16(1): 10955

Programmable Assembly of Multistranded Helices in Water.

Dimitri Delcourt, Reguram Arumugaperumal, Prachi Verma, Perttu Permi, Rosa M Gomila, Antonio Frontera, Fabien B L Cougnon.

Sequence-specific conformational changes underpin essential biological processes, from information storage to energy transduction, but are difficult to replicate in synthetic systems. Here, we present a simple approach to encode in the primary sequence of molecular strands all the information required to govern both the formation and dynamic behavior of multistranded helices. We demonstrate that the sequence of oligo(m-phenylene ethynylene) strands composed of hydrophobic phenylene and charged pyridinium residues reliably direct the formation of either a single structure (e.g., a double helix) or dynamic assemblies (e.g., double and triple helices in exchange). In the latter case, transitions between different helical states can be controlled by concentration, temperature, or by the presence of anionic molecules. This minimal yet versatile design strategy lays the groundwork for the construction of adaptive supramolecular systems with programmable structure and function.

DOI: https://doi.org/10.1038/s41467-025-67227-0
ACS Appl Bio Mater. 2025 Dec 12.

pH-Triggered Coassembly of Cello-oligosaccharides and Hyaluronic Acid into Hydrogels.

Takako Ida, Yuuki Hata, Thomas Sakata, Yuta Yamamoto, Takuya Katashima, Toshiki Sawada, Takeshi Serizawa.

  Polysaccharides are valuable building blocks for constructing functional hydrogel materials for diverse applications. Although many polysaccharides with high water solubility require cross-linking to be formulated into hydrogels, physically cross-linking ionic polysaccharides with biocompatible substances under mild aqueous conditions remains a significant challenge. Herein, we report the physical cross-linking of hyaluronic acid with crystalline cello-oligosaccharides via bottom-up coassembly at the molecular level. Neutralization of alkaline mixtures of cello-oligosaccharides and hyaluronate resulted in the facile preparation of translucent hydrogels with equilibrium moduli of 1-10 Pa. Structural analyses suggested that hyaluronate formed the backbone of the gel networks, while crystalline cello-oligosaccharides acted as physical cross-linkers. In vitro cytotoxicity assays demonstrated the excellent cytocompatibility of the coassembled hydrogels. Furthermore, the cationic antibiotic polymyxin B was successfully incorporated into the hydrogels, yielding antibacterial composite hydrogels. This study provides a promising strategy for the development of advanced polysaccharide-based biomaterials through physical cross-linking with crystalline oligosaccharides.

Keywords:  biomaterial; cell culture; cello-oligosaccharide; drug release; hyaluronic acid; physical gel; self-assembly

DOI:  https://doi.org/10.1021/acsabm.5c02001
Nat Commun. 2025 Dec 10. 16(1): 11073

Self-assembly of hybrid 3D cultures by integrating living and synthetic cells.

Nils Piernitzki, Ning Gao, Gilles Gasparoni, Louisa M Krauß, Julia Schulze-Hentrich, Michael Dustin, Bianca Schrul, Balázs Győrffy, Stephen Mann, Oskar Staufer.

Self-assembly is a fundamental property of living matter that drives the three-dimensional organization of cell collectives such as tissues and organs. Here, the co-assembly of synthetic and natural cells is leveraged to create hybrid living 3D cancer cultures. We screen a range of synthetic cell models for their ability to form augmented tumoroids with artificial but controllable micro-environments, and show that the balance of inter- and extracellular adhesion and synthetic cell surface tension are key material properties driving integrated co-assembly. We demonstrate that synthetic cells based on droplet-supported lipid bilayers can establish artificial tumor immune microenvironments (ART-TIMEs), mimicking immunogenic signals within tumoroids and eliminating the need to integrate complex living immune cells. Using the ART-TIME approach, we identify a AhR-ARNT-mediated co-signaling mechanism between PD-1 and CD2 as a driver in immune evasion of pancreatic ductal adenocarcinoma. Our study advances the field of hybrid organoid engineering, offers opportunities for the construction and modelling of artificial tumour environments, and marks a step towards the design of functional living/non-living cytomimetic materials.

DOI: https://doi.org/10.1038/s41467-025-66789-3
RSC Chem Biol. 2025 Nov 24.

Optimization of the genetic code expansion technology for intracellular labelling and single-molecule tracking of proteins in genomically re-coded E. coli.

Filip Ilievski, Linnea Wikström, Anneli Borg, Ivan L Volkov, Gerrit Brandis, Magnus Johansson.

Single-molecule tracking (SMT) is a powerful tool for real-time studies of protein interactions in living cells. Dye-labelled SNAP-tag and HaloTag self-labelling proteins have simplified SMT significantly, due to their superior photophysical properties compared to fluorescent proteins. However, due to their size, fusion of these tags to a protein of interest often results in loss of protein function. We introduce FLORENCE - a universal labelling method for SMT, based on genetic code expansion (GCE). We overcome significant caveats related to re-coded strains, vectors, and dyes and report successful tracking of site-specifically intracellularly labelled proteins in genomically re-coded E. coli. Our findings establish a robust in vivo protein-labelling strategy, expanding the capabilities of SMT as a method to study the dynamics of proteins in living cells. Moreover, we observe that the strain-promoted azide-alkyne click-chemistry reaction occurs as fast as 30 min in live E. coli cells and can be used as a robust labelling reaction.

DOI: https://doi.org/10.1039/d5cb00221d
Nat Mater. 2025 Dec 11.

Local and sustainable production of biomaterials.

Swathi Kumar, Lakshmi Sujeesh, Lois Hong, Jennifer L Young, Andrew W Holle.

DOI: https://doi.org/10.1038/s41563-025-02451-z
Adv Mater. 2025 Dec 09. e19281

Bioinspired Color-Changing Polymeric Hydrogel Actuators/Robots.

Zelin Li, Shuxin Wei, Patrick Théato, Tao Chen, Wei Lu.

  Many natural creatures exhibit remarkable control over their morphologies and skin colors for better adaptability in dynamic living environments, which has inspired the emergence of biomimetic color-changing soft actuators/robots. Polymeric hydrogels are ideal candidate materials owing to their extremely biological similarity such as soft wet nature and tissue-like modulus. The past 5 years have witnessed the flourishing development of synergistic color-changing polymeric hydrogel actuators/robots with huge application potentials in camouflage, locomotion, information encryption and so on. This review is intended to give an in-depth overview of this flourishing research area by classifying them into three categories based on the mechanism of color origination (pigment color, structural color, and fluorescence color). Their typical preparation strategies, synergistic multicolor-shifting and 3D shape-morphing performances, as well as demonstrated applications are thoroughly summarized. Current challenges and future prospects on synergistic shape/color-polymeric hydrogels will also be discussed to attract more research interests.

Keywords:  actuators/robots; bioinspiration; color change; fluorescence; polymeric hydrogel; structural color

DOI:  https://doi.org/10.1002/adma.202519281
Small. 2025 Dec 09. e12447

Advanced Encapsulation Technologies for Extracellular Vesicles: From Single Units to Macroscale Packaging.

Kejian Ding, Xingwang Wen, Kaizhe Wang.

  Extracellular vesicles (EVs), as natural mediators of intercellular communication, hold substantial promise for diagnostics, drug delivery, and regenerative medicine. However, their translation remains constrained by vulnerability to hostile microenvironments, rapid clearance with a short in vivo half-life, and limited control over localization and dosing. Encapsulation based on multi-scale materials engineering can endow EVs with programmable release, environmental responsiveness, and site-specific delivery. In this review, recent advances in EV encapsulation technologies are synthesized. Guided by structural design principles, encapsulation is classified into three scales comprising nanoscale, microscale, and macroscale, and each scale provides distinct mechanisms for protection and controlled release. A comparative overview of representative strategies is then offered, and their advantages and application contexts are summarized. Finally, key challenges and future directions are outlined, including elucidation of material-EV interactions, development of scalable and standardized manufacturing, and realization of on-demand, spatiotemporally precise release in response to physiological cues.

Keywords:  EV encapsulation; biomaterials; controlled release; extracellular vesicles; theranostic

DOI:  https://doi.org/10.1002/smll.202512447
RSC Appl Polym. 2025 Nov 28.

Polydimethylsiloxane gel thickness and stiffness affect the initial adhesion of Escherichia coli and Staphylococcus aureus.

Brandon Barajas, Meng-Chen Chiang, Dylan Lechner, Uzochi Uwazuruonye-Anyanwu, Jessica D Schiffman.

The persistent presence of hospital-acquired bacterial infections and the growing prevalence of antibiotic-resistant bacterial strains necessitates a greater understanding of the initial adhesion of bacteria to biomaterials. While the mechanical properties of polydimethylsiloxane (PDMS) gels have been shown to influence the initial attachment of microorganisms, to date, attachment has only been assessed on gels that are 1000× larger than the microorganisms evaluated. Here, a library of nine PDMS gels were manufactured to be thin (∼10 µm), medium (∼35 µm) and thick (∼100 µm) with distinct Young's Moduli that were considered to be soft (E = ∼60 kPa), standard (E = ∼1150 kPa), and stiff (E = ∼1700 kPa). All gels were well characterized using atomic force microscopy. Next, the initial adhesion of microorganisms to the gels was assayed using two strains of Escherichia coli (K12 MG1655 and CFT073), as well as two strains of Staphylococcus aureus (SH1000 and methicillin-resistant S. aureus, i.e., MRSA), representing both well-studied and clinically relevant microorganisms. Bacterial adhesion was the greatest on the thinnest, softest PDMS gels, with S. aureus SH1000 demonstrating the greatest changes in adhesive behavior in response to gel thinness. These findings suggest that both PDMS gel stiffness and thickness are important factors when considering the initial adhesion of these Gram-negative and Gram-positive microorganisms to hydrophobic biomaterials.

DOI: https://doi.org/10.1039/d5lp00227c
Soft Matter. 2025 Dec 10.

Genetic control of morphological transitions in a coacervating protein template.

William C Wixson, Nada Y Naser, Aditya Sonpal, Jim Pfaendtner, François Baneyx.

Nature routinely exploits liquid-liquid phase separation (LLPS) of proteins to control the assembly and mineralization of hybrid materials. Here, we show that fusion of the Car9 silica-binding peptide to an elastin-like polypeptide (ELP) yields temperature- and sequence-programmable soft matter templates for the synthesis of silicified architectures ranging in size from nanometers to micrometers. Specifically, we demonstrate unprecedented control over the diameter of silica nanoparticles (SiNP) in the 30-60 nm range with 4 nm precision, show that a single arginine residue (R4) in the Car9 sequence underpins the transition from micelles to proteinosomes, and find that substitutions in other basic residues modulate electrostatic repulsion and solvation to enable access to kinetically trapped species. These structures, which include interconnected micelles, small (∼200 nm) and large (>5 µm) vesicles, are readily visualized by SEM imaging following silicification. Molecular dynamics (MD) simulations and AlphaFold predictions reveal that mutations in positively charged residues alter interfacial packing, hydration, and conformational freedom of the silica-binding segments. Overall, our results establish sequence and thermal energy as synergistic levers for morphological control across length scales using solid-binding ELPs and establish mineralization as a powerful tool to visualize the structure of dynamic soft matter assemblies.

DOI: https://doi.org/10.1039/d5sm01047k
ACS Appl Mater Interfaces. 2025 Dec 08.

In-Material Computation: A Computational Metamaterial for Data-Efficient Tactile Interfaces.

Yongxing Guo, Baorui Li, Li Xiong, Shuang Zhang, Lin Zhang, Kun Xiao, Xiaoli Li, Rui Min, Zhuo Wang.

  Embedding computational capabilities directly into the physical structure of soft materials is a central goal for developing next-generation smart sensors and human-machine interfaces. However, achieving deterministic information processing within a compliant material remains a significant design and fabrication challenge. We introduce a "computational metamaterial" that physically performs information encoding through a deterministic process termed "mechanical compilation". This structured elastomer, embedded with a sparse optical sensing network, is engineered to deterministically map complex high-dimensional spatial pressure patterns, benchmarked using 26 distinct Braille characters, into unique low-dimensional optical signals with 100% classification accuracy. The physically encoded information is of such high quality that a synergistic physics-informed machine learning (PIML) decoder maintains over 96% accuracy with an 80% reduction in training data, demonstrating a profound enhancement in data efficiency. This work pioneers a structure-driven design paradigm for computational metamaterials, shifting the computational burden from software to the material itself and paving a new path toward highly efficient, low-complexity sensing systems.

Keywords:  compressive sensing; mechanical information encoding; morphological computation; physics-informed machine learning; sparse sensor array; tactile sensing

DOI:  https://doi.org/10.1021/acsami.5c19143
ACS Appl Mater Interfaces. 2025 Dec 11.

Brush-like Polymer Surface on Silk Fibroin Films for Controlled Release of Local Anesthetics.

Sanyukta A Patil, Longtu Chen, Christopher Foster, Xinhao Lin, Yuhang Xiao, Xiuling Lu, Bin Feng, Courtney K Rowe, Kelly A Burke.

  Postsurgical pain management remains a persistent challenge for patients and healthcare providers. This work presents an implantable, degradable drug release platform based on silk biomaterials designed to be placed at a desired surgical site intraoperatively to release the local anesthetic bupivacaine in a sustained manner to prevent and treat postsurgical pain. Methacrylate monomers containing different pendant groups are used to generate brush-like polymers on silk fibroin films by surface-initiated reversible addition-fragmentation chain transfer polymerization. These brushes have side groups to control polymer hydrophilicity and facilitate drug attachment via a hydrolyzable tether. Spectroscopy and contact angle goniometry are used to characterize the chemical composition and hydrophobicity of the synthesized films at each synthetic step. In vitro culture and in vivo implant studies show no differences in biocompatibility compared with unmodified silk films. Bupivacaine can be continually released for at least 7 days. The amount of drug released in vitro is increased by increasing the hydrophilicity of the brush-like polymer, and the released anesthetic is effective at blocking the conduction of action potentials of C-fibers and Aδ-fibers ex vivo. These degradable films show promise as a platform to achieve controllable, continuous delivery of local anesthetics for pain control after surgery.

Keywords:  brush-like polymers; drug release; local anesthetics; silk fibroin

DOI:  https://doi.org/10.1021/acsami.5c15685
Sci Adv. 2025 Dec 12. 11(50): eady9581

Loop closure grasping: Topological transformations enable strong, gentle, and versatile grasps.

Kentaro Barhydt, O Godson Osele, Sreela Kodali, Cosima du Pasquier, Chase M Hartquist, H Harry Asada, Allison M Okamura.

Grasping mechanisms must both create and subsequently hold grasps that permit safe and effective object manipulation. Existing mechanisms address the different functional requirements of grasp creation and grasp holding using a single morphology but have yet to achieve the simultaneous strength, gentleness, and versatility needed for many applications. We present "loop closure grasping," a class of robotic grasping that addresses these different functional requirements through topological transformations between open-loop and closed-loop morphologies. We formalize these morphologies for grasping, formulate the loop closure grasping method, and present principles and a design architecture that we implement using soft growing inflated beams, winches, and clamps. The mechanisms' initial open-loop topology enables versatile grasp creation via unencumbered tip movement, and closing the loop enables strong and gentle holding with effectively infinite bending compliance. Loop closure grasping circumvents the tradeoffs of single-morphology designs, enabling grasps involving historically challenging objects, environments, and configurations.

DOI: https://doi.org/10.1126/sciadv.ady9581
Small. 2025 Dec 12. e10863

Functionalizing Nucleic Acids: Synthesis and Purification Strategies for Bioconjugates as Biomaterials.

Nico Alleva, Jian Zhang, David Y W Ng, Tanja Weil, Torsten John.

  Nucleic acids are fundamental to life, encoding and storing genetic information, catalyzing biological processes, and directing protein synthesis. The primary classes, DNA and RNA, have become increasingly significant in biomedical applications due to advances in stabilizing these structures against degradation and elucidating their molecular roles. Nucleic acids can be functionalized with polymers, peptides, proteins, lipids, saccharides and other functional units to yield hybrid biomaterials with tailored properties for nanomedicine and materials science. This review summarizes conjugation strategies and provides a critical overview of purification approaches, including chromatographic, membrane-based, and electrophoretic methods, highlighting their principles, advantages, and limitations. Emphasis is placed on the relationship between synthesis route and purification choice, as well as common challenges such as solubility, aggregation, and incomplete coupling. Broadly applicable strategies for the successful synthesis and purification of nucleic acid conjugates are discussed, along with an overview of recent approaches for conjugates with polymers, peptides, proteins, lipids and saccharides. Finally, strategies are summarized for obtaining high-purity conjugates suitable for biomedical and materials applications.

Keywords:  DNA nanotechnology; click chemistry; hybrid biomaterials; nucleic acid bioconjugates; purification techniques; solid‐phase synthesis; therapeutic delivery

DOI:  https://doi.org/10.1002/smll.202510863
Nat Commun. 2025 Dec 11.

Modular programming of interaction and geometric specificity enables assembly of complex DNA origami nanostructures.

Rupam Saha, Daichi Hayakawa, Thomas E Videbæk, Mason Price, Wei-Shao Wei, Juanita Pombo, Daniel Duke, Gaurav Arya, Gregory M Grason, W Benjamin Rogers, Seth Fraden.

Self-assembly of nanoscale building blocks with programmable geometries and interactions offers a powerful route to engineer materials that mimic the complexity of biological structures. DNA origami provides an exceptional platform for this purpose, enabling precise control over subunit shape, binding angles, and interaction specificity. Here we present a modular DNA origami design approach to address the challenges of assembling geometrically complex nanoscale structures, including those with nonuniform curvatures. This approach features a core structure that completely conserves the scaffold routing across different designs and preserves more than 70% of the DNA staples between designs, dramatically reducing both cost and effort, while enabling precise and independent programming of subunit interactions and binding angles through adjustable overhang lengths and sequences. Using cryogenic electron microscopy, gel electrophoresis, and coarse-grained simulations, we validate a set of robust design rules and demonstrate the assembly of diverse self-limiting structures, including anisotropic shells, a T = 13 icosahedral shell, and a toroid with globally varying curvature. This modular strategy provides an efficient and cost-effective framework for the synthetic fabrication of complex nanostructures.

DOI: https://doi.org/10.1038/s41467-025-66195-9
Adv Mater. 2025 Dec 12. e18318

Thermally Switchable Photoactivity in Azobenzene-Functionalized DNA Condensates.

Ming-Di Gao, Chao-Yang Guan, Jia-Yao Wang, Jin-Ying Qi, Nan-Nan Deng.

  Soft materials capable of responding to diverse environmental stimuli are fundamental to advancing soft robotics and intelligent biomedical devices, enabling adaptive, life-like functions. Here, multimodal photothermal adaptability is reported in azobenzene-conjugated DNA condensates assembled via liquid-liquid phase separation (LLPS). These coacervates exhibit a striking temperature-dependent inversion of their photo-response: at elevated temperatures, the liquid-like droplets deform under visible light and dissolve under ultraviolet (UV) light, whereas at lower temperatures, the gel-like condensates are reshaped by UV light while remaining inert to visible light. This unique bidirectional control is attributed to the synergy of confined azobenzene photochemistry within DNA duplexes and a pronounced isomer-dependent shift in the system's glass transition and melting temperatures. This platform of multi-responsive photofluids opens new avenues for applications demanding exquisite spatiotemporal control.

Keywords:  DNA nanotechnology; azobenzene; liquid‐liquid phase separation; photofluids; photo‐responsiveness

DOI:  https://doi.org/10.1002/adma.202518318
ACS Nano. 2025 Dec 09.

Bioinspired Out-of-Equilibrium Conductive Hydrogels: Unlocking Fuel and Light-Responsive Transient Conducting Properties.

Ruchi Shukla, Rajarshi Chakraborty, Vijay Kumar Patel, Subrat Vishwakarma, Bhola Nath Pal, Divya B Korlepara, Pandeeswar Makam.

  The development of out-of-equilibrium supramolecular hydrogels, inspired by biological systems, has attracted considerable interest due to their potential applications in nanotechnology. Despite this, these transient hydrogels' (opto-)electronic properties remain elusive. This study introduces a bioinspired dissipative hydrogel powered by a chemical fuel, exhibiting tunable conducting and photoelectronic functionalities. A bio-organic bolaamphiphile (PA) was designed and synthesized, integrating the optoelectronic characteristics of perylene diimide (P) with the reversible gel-triggered switching capabilities of l-aspartic acid (A). Precise temporal control over the supramolecular self-assembly and disassembly of the PA hydrogel was achieved by regulating the chemical fuel dimethyl sulfate (DMS). Results demonstrate that the PA-based dissipative self-assembly can reversibly switch between an insulating sol state and a conductive gel state, accompanied by nanostructural, fluorescence, and chiroptical switching. Furthermore, a thin film derived from the hydrogel exhibited photoresponsive conductivity switching capability. PA's transient structural, chemical, and functional properties were extensively characterized using spectroscopic, microscopic, computational, and device fabrication techniques. This study not only elucidates the structure-property relationships in dissipative hydrogels but also contributes to the development of adaptive, life-like functional nanomaterials with promising applications in optoelectronics, nanotechnology, and soft robotics.

Keywords:  bioinspired materials; chiral self-assembly; fuel-driven dissipative assembly; light-responsive conductivity; out-of-equilibrium hydrogels; perylene diimide

DOI:  https://doi.org/10.1021/acsnano.5c14077
J Control Release. 2025 Dec 04. pii: S0168-3659(25)01121-6. [Epub ahead of print]390 114507

Promoting probiotic delivery and colonization through controllable polymer surface display.

Di Zhang, Tao Wang, Shenyi Zhang, Qianqian Song, Lixun Xie, Jiaheng Liu, Hui Zhao.

  Surface modification of probiotics with polymers is a promising strategy for conferring unique exogenous functions and modulating cell behavior. While current methods, such as in-situ encapsulation, have been widely adopted, they often face limitations in controllability, biocompatibility, and general applicability. Here, we develop a modular chemical modification approach for probiotics by gently co-incubating engineered Lactococcus lactis and pre-synthesized polymers. In contrast to conventional coating techniques, this approach is compatible with a broad range of polymers and allows tailored modification of L. lactis by both chemical and biological engineering. The resulting modifications exhibit favorable performance in terms of cell viability, nutrient ingestion and protease-driven release of cells. Using polydopamine as a model polymer, we demonstrate that the modified L. lactis showed improved resistance against harsh gastrointestinal environment and contributes to the alleviation of colitis symptoms in vivo. This advance not only overcomes key constraints of existing modification techniques but also provides a versatile platform for probiotic surface engineering, opening new horizons in the field of probiotic research and therapy.

Keywords:  Intestinal therapeutics; Probiotic delivery; Radical polymerization; Spy chemistry; Surface display

DOI:  https://doi.org/10.1016/j.jconrel.2025.114507
Science. 2025 Dec 11. 390(6778): 1171-1176

Mesoporous optically clear heat insulators for sustainable building envelopes.

Amit Bhardwaj, Blaise Fleury, Bohdan Senyuk, Eldho Abraham, Jan Bart Ten Hove, Taewoo Lee, Vladyslav Cherpak, Ivan I Smalyukh.

Mesoporous materials exhibit highly controlled nanoscale structures, often templated by liquid crystalline assemblies of surfactants, with emergent and often designable physical properties. However, scaling their fabrication to be suitable for uses such as envelopes of buildings is challenging. In this work, we describe fabrication of flexible square-meter-sized films and multicentimeter-thick slabs made of three-dimensional spatial graphs of mesopore tubes that have all structural features under 50 nanometers. A solution-based kinetic fabrication process templates growing networks of cylindrical surfactant micelles with thin tubes of polysiloxane-forming gel networks and, upon replacing surfactants and solvents with air, yields lightweight materials with greater than 99% visible-range optical transparency and approximately 10 milliwatts per kelvin per meter thermal conductivity. Such predesigned metamaterials enable transparent thermal barriers for wall-grade insulated glass units, square-meter window retrofits, and unconcentrated solar thermal energy harnessing.

DOI: https://doi.org/10.1126/science.adx5568
ACS Appl Mater Interfaces. 2025 Dec 06.

3D-Printed Multifunctional Hydrogel for Integrated Electromagnetic Interference Shielding, Infrared Stealth, and Wearable Sensing.

Jianshe Hao, Song Hu, Di Liu, Chaofan Yang, Yanbin Xu, Yang Lyu, Zhongying Ji, Xiaolong Wang.

  The growing demand for wearable electronics and infrared stealth technologies has highlighted the limitations of traditional electromagnetic interference (EMI) shielding materials, which often lack flexibility, lightweight design, and multifunctional integration. Although hydrogels present a promising platform due to their flexibility, adhesion, and sensing capabilities, the integration of multiple functions into a single material system through a straightforward fabrication process remains challenging. In this study, we developed a one-pot synthesized multifunctional ANE hydrogel that incorporates an ionic liquid (EBIB) as a conductive medium. Unlike conventional conductive fillers, such as silver nanowires or MXene, EBIB enhances both conductivity and interfacial polarization, achieving an EMI shielding efficiency of 34.5 dB in the X-band, surpassing many reported polymer-based shields. By combining this with vat photopolymerization 3D printing, we fabricated tailored topological structures that promote electromagnetic wave dissipation and suppress infrared thermal transmission. The hydrogel demonstrates effective infrared stealth, maintaining a low temperature increase of 24 °C on a 100 °C hot stage for 20 min, outperforming typical nonporous hydrogel coatings. Furthermore, the material exhibits strong adhesion, high strain sensitivity (gauge factor = 5.282 over 150-300% strain), fast response (165 ms), and cycling stability, exceeding the performance of many existing ionic hydrogels in motion sensing. By integration of EMI shielding, infrared camouflage, and wearable sensing in a single 3D-printable system, this study offers a competitive material solution for next-generation multifunctional sensors.

Keywords:  electromagnetic shielding; infrared thermal invisibility; multifunctional hydrogel; vat photopolymerization 3D printing; wearable flexible sensors

DOI:  https://doi.org/10.1021/acsami.5c20335
Sci Robot. 2025 Dec 10. 10(109): eadu8009

Microscopic robots that sense, think, act, and compute.

Maya M Lassiter, Jungho Lee, Kyle Skelil, Li Xu, Lucas Hanson, William H Reinhardt, Dennis Sylvester, Mark Yim, David Blaauw, Marc Z Miskin.

Although miniaturization has been a goal in robotics for nearly 40 years, roboticists have struggled to access submillimeter dimensions without making sacrifices to onboard information processing because of the unique physics of the microscale. Consequently, microrobots often lack the key features that distinguish their macroscopic cousins from other machines, namely, on-robot systems for decision-making, sensing, feedback, and programmable computation. Here, we take up the challenge of building a robot comparable in size to a single-celled paramecium that can sense, think, and act using onboard systems for computation, sensing, memory, locomotion, and communication. Built massively in parallel with fully lithographic processing, these microrobots can execute digitally defined algorithms and autonomously change behavior in response to their surroundings. Combined, these results pave the way for general-purpose microrobots that can be programmed many times in a simple setup and can work together to carry out tasks without supervision in uncertain environments.

DOI: https://doi.org/10.1126/scirobotics.adu8009
Chem Sci. 2025 Dec 08.

Programmable self-destruction of artificial cells with death signaling.

Joshua Krehan, Lorena Baranda Pellejero, Andreas Walther.

Programmed cell death is a crucial biological process that removes damaged or no longer needed cells and is orchestrated through complex intracellular signaling cascades. Mimicking such behavior in synthetic systems enables programmed disassembly after completing a task or releasing cargo on demand. Despite advances in engineering artificial cells (ACs) that mimic key cellular functions such as metabolism, homeostasis or communication, systems with a programmable lifetime remain unrealized. Here, we introduce a time-programmed self-destruction mechanism in ACs based on pH-responsive giant unilamellar vesicles, equipped with an internal UV-inducible acidification cascade. Upon light activation, photocaged glucose is enzymatically converted to gluconic acid, lowering the internal pH and destabilizing the pH-sensitive membrane, ultimately causing complete membrane collapse. The self-destruction is spatially confined and tunable in time, ranging from minutes to over an hour, depending on the light intensity. Furthermore, we demonstrate that collapse-induced release of DNA signals triggers defined downstream responses in neighboring ACs, including membrane labeling and aggregation. Our findings pave the way for ACs with programmed lifetimes, capable of on-demand release or disassembly in response to defined stimuli, allowing transmission of signals within complex synthetic environments.

DOI: https://doi.org/10.1039/d5sc08882h
Nat Commun. 2025 Dec 12. 16(1): 10848

Engineering the auxin-inducible degron system for tunable in vivo control of organismal physiology.

Jeremy Vicencio, Daisuke Chihara, Matthias Eder, Lucia Sedlackova, Julie Ahringer, Nicholas Stroustrup.

The auxin-inducible degron (AID) system is designed for the rapid and near-complete degradation of a specific target protein in vivo. However, to understand the dynamics of complex physiological networks, researchers often need methods that produce graded, quantitative changes in degradation rates for multiple proteins simultaneously. Here, we develop the AID system for in vivo, quantitative control over the abundance of multiple proteins simultaneously. First, by measuring and modeling the on- and off-target activities of different AID system variants in Caenorhabditis elegans, we characterize a variant of the E3 ubiquitin ligase subunit TIR1, which provides improved degradation activity compared to the original AID and AID2 systems. Then, we develop a TIR1 expression construct that enables simultaneous pan-somatic and germline protein degradation. Finally, we expand the AID toolkit to allow independent, simultaneous degradation of two distinct tissue-specific proteins. Together, these technologies enable new in vivo approaches for studying quantitative cellular biology and organismal dynamics.

DOI: https://doi.org/10.1038/s41467-025-66347-x
Nat Commun. 2025 Dec 12.

Chemically gated artificial nanochannels for programmable subcellular signal modulated transport regulation.

Man-Sha Wu, Xi-Chen Du, Ze-Rui Zhou, Xiao-Yuan Wang, Shi-Yu Zheng, Jian Lv, Bin-Bin Chen, Da-Wei Li, Ruo-Can Qian.

Biomimetic artificial nanochannels have been developed rapidly because of their promising potentials in biomedical applications. Here we report the design of chemically gated artificial nanochannels to perform transmembrane channel-mimetic permeability transition via the multi-functional DNA components modified at the inner surface, whereby the structure and charge of the DNA components can be tuned by multiple key chemical signals. We realize the targeted capture of a single mitochondrion in single living cells, which allows in situ response of multiple mitochondrial signals (Ca2+ / ROS / H+) and the subsequent delicate control of permeability transition. Further study of rotenone (ROT) induced ROS / Ca2+ release and mitochondrial membrane potential loss demonstrate that the nanochannels can response to complex chemical signals at a localized subcellular region in spite of the complicated intracellular environment. Finally, we report the advanced applications of nanochannels for evaluating and regulating the interaction network between mitochondria and other organelles.

DOI: https://doi.org/10.1038/s41467-025-66239-0
ACS Appl Mater Interfaces. 2025 Dec 08.

Injectable Nanocomposite Biomaterial for 3D Printing of Personalized Matrices and Their Use in Bioreactors for Bioengineering Advanced Cell Culture Models.

Elisabetta Campodoni, Andrea Mazzoleni, Margherita Montanari, Gaia Vicinelli, Valentina Possetti, Antonio Inforzato, Ivan Martin, Manuele G Muraro, Monica Sandri.

  Printing technology is a leading strategy for creating customized 3D matrices for tissue engineering. Our study developed an injectable nanocomposite hydrogel (bHAGel) for high-fidelity 3D extrusion printing composed of gelatin (Gel) and magnesium-doped biomimetic hydroxyapatite (bHA) particles that mimics a bone extracellular matrix. bHA particles, synthesized through a bioinspired mineralization process, acted as multifunctional additives, modulating rheology for printability, ensuring homogeneous phase distribution, enabling excellent model fidelity, and providing osteoinductive cues. The optimized hydrogel formulation enables the fabrication of porous scaffolds with interconnected macro- and microporosity via extrusion-based printing and freeze-drying. This key feature promoted cell infiltration and nutrient diffusion during tissue engineering procedures. Biological validation involves tailoring 3D scaffolds to fit a perfusion bioreactor chamber supporting seamless handling, seeding, and long-term culturing without scaffold removal or repositioning. Dynamic in vitro experiments with donor-derived human bone marrow stromal cells assessed the constructs' stability, ability to maintain geometry and perfusability, cytocompatibility and osteoconductivity, as well as robust osteogenic differentiation over 28 days. A more complex dynamic coculture model further demonstrated that the scaffold supports osteoclastogenesis under physiological, osteoblast-mediated conditions. Altogether, bHAGel scaffolds provided a customizable, bioactive platform suitable for engineering bone-mimetic organoids under dynamic conditions. Their modularity and biological relevance could be exploited in bone regeneration, disease modeling, and drug testing.

Keywords:  3D printing; bone organoids; bone tissue regeneration; hybrid hydroxyapatite; injectable biomaterials; osteogenic differentiation; perfusion bioreactor

DOI:  https://doi.org/10.1021/acsami.5c18437
Nat Commun. 2025 Dec 10.

Evaporation-driven generic, high-throughput and roll-to-roll printing of nanomaterials.

Xu Xiang, Jia-Hui Xin, Yu-Wei Liu, Chao Zhang, Zhi-Han Liu, Hai-Yun Ou, Hai-Feng Zhang, Chao Zheng, Chun-Wen Guo, Xiao-Bing He, Hao-Cheng Yang, Zhi-Kang Xu.

Manufacturing low-dimensional nanomaterials into macroscopic films, going beyond the limit of conventional polymer counterparts, can unleash the potential of advanced separation, energy harvesting, optical/thermal management, and soft robotics. Despite enormous achievements, it remains untouchable to achieve large-scale and high-throughput manufacturing of arbitrary nanomaterials into uniform films using a facile and generic strategy. Herein, we demonstrate an original evaporation-driven printing (EDP) approach that enables high-throughput roll-to-roll and spatially-programmable fabrication of various nanomaterials into multi-functional composite films, overcoming the limitations of conventional strategies demanding specific physicochemical properties of nanomaterials. The EDP approach leverages a ubiquitous physical phenomenon of water evaporation for driving rapid bottom-up mobility and gathering of nanomaterials toward the evaporated interface and eventually assembling into orientated nanomaterial-stacked films on the surface of porous substrates due to the presence of size-screening effect. Unlike conventional nanomaterials printing, the EDP can be applicable for arbitrary nanomaterials from 2D nanosheets to 1D nanotube and their combination for multi-materials and recyclable printing without the need of extra additives. EDP-manufactured graphene oxide films can be harnessed as desalination with over 95.0% rejection for sodium sulfate, outperforming most graphene oxide-based counterparts. Moreover, EDP is also capable of printing high-performance electromagnetic shielding materials by virtue of printed ordered lamellar structures as continuous conductive pathways.

DOI: https://doi.org/10.1038/s41467-025-66455-8
Nat Commun. 2025 Dec 12.

Photoredox-controlled alternating copolymerization enables highly crystalline structures and block copolymers from thermoplastic to elastomer.

Mengli Xu, Qiankai Chen, Shantao Han, Kaixuan Chen, Xing Guo, Mao Chen.

Ethylene-based crystalline copolymers are important materials across broad applications. However, precise control over their primary structures remains a critical challenge in advancing functional materials, limited by the intrinsic reactivity difference between ethylene and comonomers. In this work, we report the development of a light-driven organocatalyzed reversible-deactivation radical copolymerization to access well-defined ethylene-chlorotrifluoroethylene copolymer (ECTFE) under mild conditions (<5 atm, 25 °C). The rational design of a three-armed phenothiazine catalyst in combination with a fluorinated dithiocarbamate furnishes good chain-growth control in the photoredox-mediated copolymerization, yielding ECTFE of excellent alternating sequence with minimized chain defects, which resulted in high crystallinity and superior melting points (up to 263.8 °C). Importantly, the obtained ECTFE exhibits outstanding chain-end activity/fidelity, enabling chain-extension (co)polymerization to access a variety of unprecedented ECTFE-based block copolymers upon visible-light exposure, which has successfully integrated rigid and soft blocks in single chains. The ease of synthesizing such block copolymers creates a versatile and convenient platform to largely tune mechanical properties, affording polymeric materials spanning from thermoplastics to elastomers via structural tailoring.

DOI: https://doi.org/10.1038/s41467-025-66962-8
J Am Chem Soc. 2025 Dec 12.

Bioactive Artificial Cells as Autonomous Metabolic Actuators Enable Bidirectional Communication with Tumor Cells.

Lifan Hu, Wenwu Peng, Jiyao Yu, Lisa Förch, Stephen Mann, Seah Ling Kuan, Tanja Weil.

Artificial cells (ACs) offer a powerful platform to reprogram metabolic signaling in complex tissue environments by replicating key biological functions without the full complexity of living cells. However, achieving autonomous metabolite exchange and stable integration with living tissues remains a major challenge. Here, we report the development of proteinosome-based ACs equipped with a minimal metabolism to mediate bidirectional communication with glycolytic tumor cells. These tumors accumulate lactate, a metabolic byproduct that promotes immunosuppression and metastasis. Although lactate oxidase (LOx) can degrade lactate, its oxidation product, pyruvate, may inadvertently fuel tumor growth. To overcome this limitation, we engineered dual-processor ACs coencapsulating LOx and pyruvate decarboxylase (PDC), enabling selective conversion of lactate into cytotoxic acetaldehyde while suppressing pyruvate and hydrogen peroxide accumulation. These ACs demonstrate sustained catalytic activity, maintain reactive oxygen species homeostasis, and remain functional when integrated in 3D tumor spheroids. Crucially, they engage in autonomous, bidirectional metabolite exchange, preferentially with cancer cells over normal cells, dynamically rewiring important metabolites of the tumor microenvironment and suppressing cell viability. This work establishes synthetic metabolic biointerfaces as programmable actuators capable of reshaping pathological signaling in cancer tissues.

DOI: https://doi.org/10.1021/jacs.5c14609
Nat Commun. 2025 Dec 06. 16(1): 10950

Talin force coupling underlies eukaryotic cell-substrate adhesion.

Srishti Rangarajan, Lena Espeter, Hannes C A Drexler, Anna Chrostek-Grashoff, Carsten Grashoff.

Integrin-mediated cell adhesion and mechanotransduction are considered key innovations in animal evolution. Here, we show that these processes represent a specialization of an evolutionarily conserved force coupling mechanism that originated in unicellular organisms and is mediated by the actin-binding protein talin. In contrast to heterodimeric integrin receptors, talin is widely distributed in unicellular organisms, including amoebae. By comparing the molecular mechanics of talin-A from amoeboid cells with that of mammalian talin-1, we uncover a conserved role for talin in transmitting pN-scale forces, even in unicellular organisms lacking canonical integrin receptors but expressing the functional homologue SibA. Our data indicate that the critical evolutionary steps towards integrin-mediated cell adhesion in metazoan organisms were the specialization of talin as an adaptor protein allowing the activation of integrin receptors, the regulation of biochemical signaling by paxillin, FAK and YAP, and the control of cell adhesion turnover by KANK recruitment. Collectively, these experiments suggest a central but thus far underappreciated role for talin in the evolution of eukaryotic cell-substrate adhesion and force transmission.

DOI: https://doi.org/10.1038/s41467-025-67354-8
Nat Commun. 2025 Dec 12. 16(1): 11100

Mass spectrometry-based profiling of single-cell histone post-translational modifications to dissect chromatin heterogeneity.

Ronald Cutler, Laura Corveleyn, Claudia Ctortecka, Francesca LiCausi, Joshua Cantlon, Alvaro Sebastian Vaca Jacome, Dieter Deforce, Jan Vijg, Maarten Dhaenens, Malvina Papanastasiou, Steven A Carr, Simone Sidoli.

Single-cell proteomics confidently quantifies cellular heterogeneity, however quantification of post-translational modifications, such as those deposited on histone proteins, remains elusive. Here, we develop a robust mass spectrometry-based method for the unbiased analysis of single-cell histone post-translational modifications (sc-hPTM). sc-hPTM identifies both single- and combinatorial histone post-translational modifications (67 peptidoforms in total), which includes nearly all frequently studied histone post-translational modifications with comparable reproducibility to traditional bulk experiments. As a proof of concept, we treat cells with sodium butyrate, a histone deacetylase inhibitor, and demonstrate that our method can i) distinguish between treated and untreated cells, ii) identify sub-populations of cells with heterogeneous response to the treatment, and iii) reveal differential co-regulation of histone post-translational modifications in the context of drug treatment. The sc-hPTM method enables comprehensive investigation of chromatin heterogeneity at single-cell resolution and provides a further understanding of the histone code.

DOI: https://doi.org/10.1038/s41467-025-66031-0
ACS Biomater Sci Eng. 2025 Dec 08.

Negative Pressure Actuated Microfluidic Droplet Generation Enables High-Throughput and Robust Synthesis of Cell-Laden Alginate Microgels.

Pavel S Pleshakov, Stanislav V Shmakov, Nikita A Filatov, Anton S Bukatin.

  Hydrogel microparticles (microgels) have significant potential for use as building blocks in tissue engineering, as bioinks for 3D bioprinting, and as drug and cell carriers for cell-based therapies targeting damaged and diseased tissues. Various fabrication techniques have been developed for producing microgels with predefined shapes and sizes. However, for practical applications in biological laboratories and clinics, it is necessary to reduce time costs and simplify instrumentation and synthesis protocols, improving their reproducibility and reliability. Here we demonstrate a three-step experimental approach to develop microfluidic flow-focusing droplet generators that enable the introduction of all liquids by creating negative pressure in the outlet reservoir for the generation of spherical, core-shell, and Janus alginate microgels with living cells. This approach allows the use of a simple experimental setup that is easy to operate and robust and provides highly reproducible results, achieving a synthesis performance of up to 200 μL of microgels per hour. The size and the structure of the microgels were determined by the chip design and remained stable under pressure variations within the operating range of -7 to -15 kPa. This enabled the reliable and reproducible encapsulation of CT26 and HepG2 cells into core-shell and Janus alginate microgels with diameters ranging from 80 to 120 μm, maintaining over 80% cell viability during long-term incubation. Our findings offer a new perspective for the automation and scaling of multicomponent alginate microgel fabrication, paving the way for their implementation in tissue engineering and 3D bioprinting.

Keywords:  3D cell culture; Janus microparticle; cell aggregate; core−shell microparticle; droplet microfluidics; hydrogel microparticle; microgel

DOI:  https://doi.org/10.1021/acsbiomaterials.5c01427
Nat Commun. 2025 Dec 10.

Percolation transition in entangled granular networks.

Seongmin Kim, Daihui Wu, Yilong Han.

Highly nonconvex granular particles, such as staples and metal shavings, can form solid-like cohesive structures through geometric entanglement (interlocking). However, the network structure formed by this entanglement remains largely unexplored. Here, we employ network science to investigate the entanglement networks of C-shaped granular particles under vibration in experiments and simulations. Analysis of key network properties reveals that these networks undergo a percolation transition as the number of links increases logarithmically over time; the entangled particles form a giant cluster when the number of links exceeds a critical threshold. We propose a continuum percolation model of rings that effectively describes this observed transition. Furthermore, we find that the particles' opening angle significantly affects mechanical bonding and, consequently, the network structure. This work demonstrates the promise of network-based approaches for studying entangled materials, with potential applications from mechanical metamaterials to entangled robot swarms.

DOI: https://doi.org/10.1038/s41467-025-66228-3
Polymers (Basel). 2025 Nov 21. pii: 3094. [Epub ahead of print]17(23):

Materials for Yeast Immobilization in Alcoholic Fermentation: Bridging Conventional Techniques and 3D Bioprinting.

Sara I Brunet, Tamara Erceg, Ljiljana Janjušević, Slobodan Birgermajer, Mirjana Odanović, Vladimir Puškaš, Uroš Miljić.

  Immobilization of yeast cells represents a significant advance in alcoholic fermentation. Compared to traditional methods that rely on the use of free cells, immobilized systems enable higher cell density, easier separation and reuse of biocatalysts, and improved fermentation control, all while maintaining cellular activity. The choice of immobilization material plays a key role in performance. Natural polymers such as alginate provide biocompatibility, but the main drawback is their insufficient mechanical strength. On the other hand, synthetic polymers offer greater durability but raise concerns regarding food safety and cost. Three-dimensional (3D) bioprinting is emerging as a promising solution, enabling the design of structural, customizable matrices with precise cell positioning and tunable physical properties. Traditional materials are undergoing reengineering as bioinks, while new synthetic and hybrid materials are being developed to overcome the limitations of conventional carriers. These innovations combine biocompatibility with mechanical stability and functional adaptability for industrial use. Although the application of 3D bioprinting to produce such carriers has shown promising progress, challenges remain in scalability, process integration, and long-term stability under industrial fermentation conditions. For these reasons, continued interdisciplinary research is necessary to further develop advanced techniques for immobilizing yeast cells for use in alcoholic fermentation.

Keywords:  3D bioprinting; alcoholic fermentation; bioinks; biopolymers; hydrogels; yeast immobilization

DOI:  https://doi.org/10.3390/polym17233094