bims-enlima Biomed News
on Engineered living materials
Issue of 2025–08–24
thirty-two papers selected by
Rahul Kumar, Tallinna Tehnikaülikool



  1. Adv Funct Mater. 2025 Aug 07. pii: e18226. [Epub ahead of print]
      Tissue development and regeneration are governed by processes that span subcellular signaling, cell-cell interactions, and the integrated mechanical properties of cellular collectives with their extracellular matrix. Synthetic biomaterials that can emulate the hierarchical structure and supracellular mechanics of living systems are paramount to the realization of regenerative medicine. Recent reports detail directed cell alignment on mechanically anisotropic but stiff liquid crystalline polymer networks (LCNs). While compelling, the potential implementation of these materials as tissue engineering scaffolds may be hindered by the orders of magnitude larger stiffness than most soft tissue. Accordingly, this report prepares liquid crystalline hydrogels (LCHs) that synergize the anisotropic mechanical properties intrinsic to LCNs with the cytocompatibility and soft mechanics of PEG hydrogels. LCH are prepared via sequential oligomerization and photopolymerization reactions between liquid crystalline (LC) monomers and poly(ethylene glycol) (PEG)-dithiol. Despite their low liquid crystalline content, swollen LCH oligomers are amenable to rheological alignment via direct ink write 3D printing. Mechanically anisotropic LCHs support C2C12 myoblast culture on their surface and direct their alignment in the stiffest direction. Further, C2C12s can be encapsulated within LCH oligomers and 3D-printed, whereby mechanical anisotropy of the LCH directs myoblast polarization in 3D.
    Keywords:  3D bioprinting; anisotropic hydrogel; cellular alignment; liquid crystalline; tissue engineering
    DOI:  https://doi.org/10.1002/adfm.202518226
  2. Nat Commun. 2025 Aug 18. 16(1): 7665
      During development, epithelia function as malleable sheets that undergo extensive remodeling to shape developing embryos. Optogenetic control of Rho signaling provides an avenue to investigate mechanisms of epithelial morphogenesis, but transgenic optogenetic tools can be limited by variability in expression levels and deleterious effects of transgenic overexpression on development. Here, we use CRISPR/Cas9 to tag Drosophila RhoGEF2 and Cysts/Dp114RhoGEF with components of the iLID/SspB optogenetic heterodimer, permitting light-dependent control over endogenous protein activities. Using quantitative optogenetic perturbations, we uncover a dose-dependence of tissue furrow depth and bending behavior on RhoGEF recruitment, revealing mechanisms by which developing embryos can shape tissues into particular morphologies. We show that at the onset of gastrulation, furrows formed by cell lateral contraction are oriented and size-constrained by basal actomyosin. Our findings demonstrate the use of quantitative, 3D-patterned perturbations of cell contractility to precisely shape tissue structures and interrogate developmental mechanics.
    DOI:  https://doi.org/10.1038/s41467-025-62483-6
  3. Small. 2025 Aug 19. e06022
      Control of cell adhesion is essential for biomedical devices, biosensors, and anti-fouling coatings. Here, adhesion of A549 epithelial cells is systematically evaluated on silicon substrates with tunable wettability (superhydrophilic to superhydrophobic) and topography (smooth, nanostructured, and micropillared). Superhydrophobic surfaces stabilize a trapped air plastron that minimizes solid-liquid contact, enabling plastron-mediated physical repellency of cells. The most cell-repellent surface, composed of 5 µm micropillars with a 7.4% solid-liquid contact fraction, reduced cell density by ≈83% versus a smooth hydrophobic control and ≈95% versus a hydrophilic control at 4 h, and by ≈90% and ≈93%, respectively, after 24 h of incubation, corresponding to an approximate tenfold decrease in cell adhesion. Micropillar arrays outperform nanostructures in resisting cell attachment, owing to large air-filled gaps exceeding 10 µm that physically prevent cell adhesion. A trade-off is observed: lower solid-fraction micropillars provide greater short-term repellency but lose the plastron over time, enabling delayed fouling, whereas higher-fraction structures preserve the air layer beyond 72 h but are initially less cell-repellent due to higher effective cell contact area and smaller air gaps. These results establish that optimized microscale superhydrophobic textures achieve superior and time-dependent bio-repellency and introduce a rational design strategy for non-fouling materials.
    Keywords:  air plastron; biointerface; cell adhesion; microstructures; physical repellency; superhydrophobic
    DOI:  https://doi.org/10.1002/smll.202506022
  4. ACS Omega. 2025 Aug 12. 10(31): 35207-35216
      Many recent efforts toward sustainable polymer development use building blocks from renewable biomass feedstocks. However, issues arising from the processes used to extract starting materials from biomass are often overlooked, despite the safety and environmental hazards associated with energy-intensive separation processes and solvent utilization. Here, we describe a holistic approach toward using green solvents and processes to synthesize polyester thermosets from birch bark, a waste product from the paper and pulp industry. Betulin, a diol with a pentacyclic ring structure, was extracted from the bark of silver birch trees via reflux boiling using green solvents available from biobased sources. Ethanol and 1:1 ethanol:ethyl acetate mixtures were effective solvents for extraction, with additional selectivity achieved via antisolvent precipitation. Betulin-rich extracts containing 62.2-81.5 wt % betulin were produced and directly used to prepare polyester thermosets using one-pot, solventless polycondensations with 100% of the starting materials available from biomass feedstocks. The polymers prepared directly from extracts had properties comparable to those synthesized from pure betulin, suggesting that additional processing steps required to achieve higher purity betulin may not be warranted. Overall, we present an approach to polyester development from betulin-rich birch bark extracts, which incorporate green chemistry and engineering principles from feedstock to product.
    DOI:  https://doi.org/10.1021/acsomega.5c05162
  5. ACS Omega. 2025 Aug 12. 10(31): 35301-35308
      Breast reconstruction remains hindered by the limitations of conventional implant materials such as silicone, which exhibit hydrophobicity and poor tissue integration, often leading to complications, including capsular contracture. Here, we report the development of a poly-(HEMA-MA)/Fe3+ (PHM/Fe3+) hydrogel as a next-generation soft implant material. This hydrogel is synthesized via copolymerization of 2-hydroxyethyl methacrylate (HEMA) and maleic acid (MA), followed by immersion in FeCl3 to induce secondary cross-linking through Fe3+-carboxyl coordination. The resulting homogeneous ionic network effectively mitigates stress concentration and hardening, enabling enhanced mechanical energy dissipation and conferring excellent elasticity, toughness, and fatigue resistance. In vitro and in vivo assessments demonstrate that the PHM/Fe3+ hydrogel is cytocompatible and elicits minimal immune response. Compared with traditional smooth and textured silicone implants, PHM/Fe3+ hydrogels induce significantly thinner fibrous capsule formation and promote more rapid tissue stabilization, indicating a markedly reduced risk of capsular contracture. These findings highlight the potential of PHM/Fe3+ hydrogels as biocompatible and mechanically resilient alternatives for breast reconstruction.
    DOI:  https://doi.org/10.1021/acsomega.5c06268
  6. bioRxiv. 2025 Aug 13. pii: 2025.08.12.669972. [Epub ahead of print]
      Engineered programmable RNA sensors have been applied in low-cost diagnostics, endogenous RNA detection, and multi-input genetic circuits. However, designing, producing, and screening high-performance RNA sensors remains time consuming and labor intensive. Here, we present an automated plasmid assembly pipeline using liquid handling robotics to enable high-throughput construction of plasmids with arbitrary sequences. We compare automated and manual assembly methods using the NGS Hamilton Microlab STAR across two plasmid backbones to evaluate efficiency and reliability. As a proof of concept, we use this modular platform to construct 144 total plasmids encoding riboregulators targeting diverse viral targets along with their cognate trigger sequences. We further demonstrate that the assembled plasmids are functional in both bacterial and cell-free expression systems.
    DOI:  https://doi.org/10.1101/2025.08.12.669972
  7. Nat Commun. 2025 Aug 19. 16(1): 7704
      Solution-based soft matter self-assembly (SA) promises unique material structures and properties from approaches including additive manufacturing/three-dimensional (3D) printing. The 3D printing of periodically ordered porous functional inorganic materials through SA unfolding during printing remains a major challenge, however, due to the often vastly different ordering kinetics of separate processes at different length scales. Here, we report a "one-pot" direct ink writing process to produce hierarchically porous transition metal nitrides and precursor oxides from block copolymer (BCP) SA. Heat treatment protocols identified in various environments enable mesostructure retention in the final crystalline materials with periodic lattices on three distinct length scales. Moreover, embedded printing enables the first BCP directed mesoporous non-self-supporting helical oxides and nitrides. Resulting nitrides are superconducting, with record nanoconfinement-induced upper critical fields correlated with BCP molar mass and record surface areas for compound superconductors. Results suggest scalable porous functional inorganic material formation approaches for applications including catalysis, sensing, and microelectronics.
    DOI:  https://doi.org/10.1038/s41467-025-62794-8
  8. Nat Commun. 2025 Aug 19. 16(1): 7021
      Many genome-wide studies capture isolated moments in cell differentiation or organismal development. Conversely, longitudinal studies provide a more direct way to study these kinetic processes. Here, we present an approach for modeling gene-expression and chromatin kinetics from such studies: chronODE, an interpretable framework based on ordinary differential equations. chronODE incorporates two parameters that capture biophysical constraints governing the initial cooperativity and later saturation in gene expression. These parameters group genes into three major kinetic patterns: accelerators, switchers, and decelerators. Applying chronODE to bulk and single-cell time-series data from mouse brain development reveals that most genes (~87%) follow simple logistic kinetics. Among them, genes with rapid acceleration and high saturation values are rare, highlighting biochemical limitations that prevent cells from attaining both simultaneously. Early- and late-emerging cell types display distinct kinetic patterns, with essential genes ramping up faster. Extending chronODE to chromatin, we find that genes regulated by both enhancer and silencer cis-regulatory elements are enriched in brain-specific functions. Finally, we develop a bidirectional recurrent neural network to predict changes in gene expression from corresponding chromatin changes, successfully capturing the cumulative effect of multiple regulatory elements. Overall, our framework allows investigation of the kinetics of gene regulation in diverse biological systems.
    DOI:  https://doi.org/10.1038/s41467-025-61921-9
  9. ACS Appl Mater Interfaces. 2025 Aug 18.
      Biopolymer-supported deep eutectic solvent (DES)-based gels, also known as eutectogels, have emerged as promising alternatives to hydrogels and ionic-liquid-based gels for multiple applications in stretchable electronics and sensors due to many key advantages including their high ionic conductivity, tensile toughness, easy handling, simple synthesis, low cost, biocompatibility, and ultralow volatility. Particularly, gelatin-supported 1,2-propanediol (PD)-based eutectogels containing water have shown promise due to their hydrogel-like properties. They have low modulus values and biofriendly components, making them "skin-like" materials. They are optically transparent, which makes them ideal as user-friendly visual devices. Incorporation of color-tunable micropatterned opal structures into these novel gelatin-supported eutectogels enables the preparation of user-friendly, mechanically resilient, and stimuli-responsive materials for many applications via a simple color change. In this work, we utilize a simple and robust evaporative deposition-stamping technique to prepare eutectogels containing opal micropatterns to overcome limitations in existing fabrication techniques such as photolithography and soft lithography that suffer from costly equipment, harsh radical polymerization, and multistep processing and/or reliance on external forces. First, uniform and color-tunable opal micropatterns are formed via simple evaporative deposition. Scanning electron microscopy (SEM) images show the formation of a uniform hexagonal packing throughout the opal micropatterns. Next, the opal micropatterns are successfully transferred into gelatin-supported PD eutectogels via a simple hand-stamping technique to form opal eutectogels having uniform opal micropatterns due to the eutectogels' adhesive and mechanically resilient nature without the need for costly equipment. Photographs and dark-field optical micrographs, in combination with wavelength spectra measurements, illustrate the reliable nature of our simple evaporation-stamping method. Finally, sandwich eutectogels that fully encapsulate the opal micropatterns were produced by simply adding a secondary eutectogel layer to the top, yielding a reversible optical response to mechanical stimuli. We envision that this simple, reliable, and robust evaporation-stamping technique can be readily extended to manufacture biocompatible and user-friendly visual monitoring devices.
    Keywords:  eutectogels; evaporative deposition; micromolding; micropatterned opal films; stamping; stimuli-responsive materials
    DOI:  https://doi.org/10.1021/acsami.5c10273
  10. BMC Biol. 2025 Aug 20. 23(1): 261
       BACKGROUND: Evolution of microbes under laboratory selection produces genetically diverse populations, owing to the continuous input of mutations and to competition among lineages. Whole-genome whole-population sequencing makes it possible to identify mutations arising in such populations, to use them to discern functional modules where adaptation occurs, and then map gene structure-function relationships. Here, we report on the use of this approach, adaptive genetics, to discover targets of selection and the mutational consequences thereof in E. coli evolving under chronic nutrient limitation.
    RESULTS: Replicate bacterial populations were cultured for ≥ 300 generations in glucose limited chemostats and sequenced every 50 generations at 1000X-coverage, enabling identification of mutations that rose to ≥ 1% frequency. Thirty-nine genes qualified as high value targets of selection, being mutated far more often than would be expected by chance. A majority of these encode regulatory proteins that control gene expression at the transcriptional (e.g., RpoS and OmpR), post-transcriptional (e.g., Hfq and ProQ), and post-translational (e.g., GatZ) levels. The downstream effects of these regulatory mutations likely impact not only acquisition and processing of limiting glucose, but also assembly of structural elements such as lipopolysaccharide, periplasmic glucans, and cell surface appendages such as flagella and fimbriae. Whether regulatory or structural in nature, recurrent mutations at high value targets tend to cluster at sites either known or predicted to be involved in RNA-protein or protein-protein interactions.
    CONCLUSIONS: Our observations highlight the value of experimental evolution as a proving ground for inferences gathered from traditional molecular genetics. By coupling experimental evolution to whole-genome, whole-population sequencing, adaptive genetics makes it possible not only the genes whose mutation confers a selective advantage, but also to discover which residues in which genes are most likely to confer a particular type of selective advantage and why.
    Keywords:   E. coli ; Adaptive genetics; Experimental evolution; Functional genomics; Metabolic networks; Parallelism; Whole genome sequencing
    DOI:  https://doi.org/10.1186/s12915-025-02331-7
  11. Nat Commun. 2025 Aug 17. 16(1): 7654
      The development of robust catalysts that can work under harsh conditions bring promise but a challenge for photocatalytic hydrogen peroxide production. Here, we report the design of thiazole-based homologous heteropolyaromatic COFs (TTT-COF) via post-cyclization reaction for photocatalytic H2O2 production and aerobic oxidation of C(sp3)-H bonds. Our studies demonstrate that the elemental S heteroatom enables modified COF materials with high chemical stability, continuous π-conjugation, efficient electron and energy transfer, and an enhanced donor-acceptor (D-A) structure and charge separation, thus boosting their intrinsic photocatalytic activities and stability. Consequently, TTT-COF achieves a photosynthetic H2O2 production rate of 29.9 mmol g-1 h-1 with more than 200 hours of long-term stability when employing 10 % benzyl alcohol (V/V) as a sacrificial agent. Notably, the TTT-COF photocatalyst exhibits high reactivity in the oxidation of ethylbenzene derivatives. We believe this strategy offers a promising pathway to synthesize homologous heteropolyaromatic COFs and holds the potential for large-scale production of COF materials with tailored properties for broad applications in photocatalysis and beyond.
    DOI:  https://doi.org/10.1038/s41467-025-62937-x
  12. Trends Biotechnol. 2025 Aug 15. pii: S0167-7799(25)00278-1. [Epub ahead of print]
      Rare sugars are valuable for food and pharmaceutical applications. D-Mannose, a low-calorie sweetener, is traditionally produced via chemical extraction from plant biomass, which is unsustainable, while enzymatic methods suffer from low yields due to equilibrium limitations. Here, we demonstrate that Escherichia coli can naturally synthesize D-mannose from D-glucose through a phosphorylation-isomerization-dephosphorylation pathway. We enhanced D-mannose production by deleting competing pathways and overexpressing key biosynthetic genes. Unexpectedly, due to the promiscuous activity of the phosphatase HxpB, which dephosphorylates both D-mannose-6-phosphate (M6P) and D-sedoheptulose-7-phosphate (S7P), the engineered strain also produced D-sedoheptulose, a non-sweet rare sugar that inhibits C6 sugar consumption. Further metabolic engineering improved D-sedoheptulose production. These optimizations enabled the development of a co-production strain capable of producing both sugars with tunable ratios. By leveraging this unique sugar combination, our approach provides a sustainable route to rare sugar biosynthesis and opens new possibilities for functional food design and metabolic regulation.
    Keywords:  D-mannose; D-sedoheptulose; metabolic engineering; rare sugars
    DOI:  https://doi.org/10.1016/j.tibtech.2025.07.017
  13. Matter. 2025 Apr 02. pii: 102006. [Epub ahead of print]8(4):
      The threat of future coronavirus pandemics requires developing effective vaccine technologies that provide broad and long-lasting protection against circulating and emerging strains. Here we report a multivalent liposomal hydrogel vaccine technology comprising the receptor binding domain (RBD) of up to four SARS and MERS coronavirus strains non-covalently displayed on the surface of the liposomes within the hydrogel structure. The multivalent presentation and sustained exposure of RBD antigens improved the potency, neutralizing activity, durability, and consistency of antibody responses across homologous and heterologous coronavirus strains in a naïve murine model. When administrated in animals pre-exposed to wild-type SARS-CoV-2 antigens, liposomal hydrogels elicited durable antibody responses against the homologous SARS and MERS strains for over six months and elicited neutralizing activity against the immune-evasive SARS-CoV-2 variant Omicron BA.4/BA.5. Overall, the tunable liposomal hydrogel platform we report here generates robust responses against diverse coronaviruses, supporting global efforts to respond to future viral outbreaks.
    Keywords:  Coronavirus; Drug Delivery; Hydrogels; Liposomes; Vaccines
    DOI:  https://doi.org/10.1016/j.matt.2025.102006
  14. Small. 2025 Aug 18. e07210
      Small molecular π-systems are excellent building blocks for the construction of photoresponsive supramolecular materials, yielding a wide range of structures and functions relevant to smart materials and optoelectronic devices. Integration of photoresponsive units into molecular π-systems is meant to address key challenges in developing responsive and adaptive soft functional materials that dynamically respond to light. Since π-systems are optically and electronically active molecules, and light being the most precise stimulus, their combination to design photoresponsive dynamic supramolecular systems is one of the preferred choices in the emerging domain of smart materials, particularly in the field of photonics and nanoarchitectonics. Though a large number of photoresponsive systems have been reported, this review is mainly focused on supramolecular π-systems that exclusively operate on the chemical principles of photoisomerization and photocyclization reactions, and discusses the strategies and directions that govern their design and applications at the nano and microscale.
    Keywords:  nanoarchitectonics; photoresponse; self‐assembly; supramolecular systems; π‐systems
    DOI:  https://doi.org/10.1002/smll.202507210
  15. J Am Chem Soc. 2025 Aug 19.
      Hybrid organic-inorganic semiconductors present new opportunities for optoelectronic materials design not available in all-organic or all-inorganic materials. One example is silver phenylselenide (AgSePh) - or "mithrene" - a blue-emitting 2D organic-inorganic semiconductor exhibiting strong optical and electronic anisotropy. Here, we show that the bandgap of mithrene can be systematically tuned by introducing electron-donating and electron-withdrawing groups to the phenyl ligands. We synthesized nine mithrene variants, eight of which formed 2D van der Waals crystals analogous to those of AgSePh. Density functional theory calculations reveal that these 2D mithrene variants are direct-gap or nearly direct gap semiconductors. Furthermore, we identify correlations between the optical gap and three experimental observables - the Hammett constant, 77Se chemical shift, and selenium partial charge - offering predictive power for bandgap tuning. These findings highlight new opportunities for applying the tools of chemical synthesis to semiconductor materials design.
    DOI:  https://doi.org/10.1021/jacs.5c07989
  16. bioRxiv. 2025 Aug 14. pii: 2025.08.14.670357. [Epub ahead of print]
      Tissue- or cell type- specific expression of transgenes is often essential for interrogation of biological phenomenon or predictable engineering of multicellular organisms but can be stymied by cryptic enhancers that make identification of promoters that generate desired expression profiles challenging. In plants the months-to-years long timeline associated with prototyping putative tissue-specific promoters in transgenic lines deepens this challenge. We have developed a novel strategy called Ribozyme Enabled Tissue Specificity (RETS) that leverages the knowledge of where and when genes are expressed derived from transcriptomic studies to enable tissue specific expression without needing characterized promoters. It uses a split self-splicing ribozyme based on a group I intron from Tetrahymena thermophila to enable conditional reconstitution of a transgene mRNA in the presence of a secondary tissue-specific mRNA of choice. We elucidate the design features that enable flexible swapping of transgenes and targets, enhancing transgene expression, and circumventing host RNA interference responses. We then show that these innovations enable tissue-specific and dose-dependent expression of transgenes in Arabidopsis thaliana . Finally, we demonstrate the utility of RETS both for creating genetically encoded biosensors to study the spatiotemporal patterns of gene expression in planta as well as for engineering tissue-specific changes in organ size. RETS provides a novel avenue to study expression patterns of native loci with non-destructive imaging, complementing the weakness of existing approaches. Additionally, the spatiotemporal control of transgene expression afforded by RETS enables precision engineering of plant phenotypes which will facilitate enhancing crops without the trade-offs associated with constitutive expression.
    Significance Statement: We have developed a novel platform, called Ribozyme Enabled Tissue Specificity (RETS), that enables precision expression of transgenes in specific plant tissues without needing to spend months-to-years prototyping tissue-specific promoters. We elucidate how the programmability and functionality of RETS can be improved to enable tissue-specific and dose dependent transgene expression. RETS will enable novel fundamental studies of biological phenomenon by facilitating the creation of genetically encoded biosensors for in vivo studies of the spatiotemporal expression patterns of genes in their native genomic context. It will also significantly advance the engineering of plant phenotypes by enabling precision expression of transgenes, which is important for overcoming the trade-offs often associated with global constitutive expression, without needing tissue specific promoters.
    DOI:  https://doi.org/10.1101/2025.08.14.670357
  17. Proc Natl Acad Sci U S A. 2025 Aug 26. 122(34): e2512565122
      The valorization of CO2 to chemicals beyond C1-2 products is receiving significant interest; however, the direct electrosynthesis of Cn molecules (n > 4) remains a challenge. Here, we present a two-step abiotic-biotic system for upgrading CO2 into the biopolymer, poly(3-hydroxybutyrate). In the electrolysis system, CO2 is converted into C2 oxygenates using a Cu-Ag tandem electrocatalyst. The electrolysis process generates a liquid stream containing ~ 200 mM acetate in a bio-compatible electrolyte. This electrosynthesized acetate is then fed to a bioreactor, where the substrate is upgraded by Cupriavidus necator to biopolymer with a maximum rate of 32 ± 3.5 mg L-1 h-1. We further demonstrate the purification of the resulting biopolymer into a powder. The high productivity of the abiotic-biotic system demonstrates its feasibility for sustainable chemical manufacturing.
    Keywords:  CO2 fixation; abiotic-biotic; electrocatalysis
    DOI:  https://doi.org/10.1073/pnas.2512565122
  18. Adv Healthc Mater. 2025 Aug 18. e01621
      Hydrogen sulfide (H2S)-mediated gaseous therapies feature high therapeutic efficacy and biosafety in cancer treatment, but conventional H2S delivery protocols suffer from poor tumor specificity and uncontrollable release. Here, a living therapeutic biohybrid is developed that integrates engineered microbes for in situ H2S production with self-mineralized copper sulfide (CuS) nanoparticles, enabling synergistic H2S gaseous-photothermal cancer treatment. These engineered facultative anaerobic bacteria Vibrio natriegens continuously produce H2S and synthesize CuS nanoparticles, forming Bac@CuS living biohybrids that inhibit the mitochondrial electron transport chain through H2S production, leading to increased reactive oxygen species production and subsequent apoptosis of cancer cells. Concurrently, Bac@CuS-mediated photothermal effect induces hyperthermia, further impairing mitochondrial function and enhancing cancer-cell death. In vivo studies demonstrate that Bac@CuS living biohybrids feature excellent biocompatibility and have achieved a 95.4% tumor inhibition rate in the breast tumor-bearing mouse model. The biohybrid therapeutic platform enables the engineered bacteria to produce non-native effectors alongside with nanoparticles, integrating synthetic biology with nanotechnology and offering a novel approach for efficient cancer eradication.
    Keywords:  hydrogen sulfide; living biohybrid therapeutics; living biomaterials; synergy therapy; synthetic biology
    DOI:  https://doi.org/10.1002/adhm.202501621
  19. ACS Appl Mater Interfaces. 2025 Aug 18.
      Developing nonfluorinated low-surface-energy coatings with robust environmental adaptability is crucial for green and sustainable industrial applications. Despite substantial advances in hierarchical structures and low-surface-energy chemical design strategies, the specific effect of alkyl chain length bearing a tertiary amine group in nonfluorinated low-surface-energy systems on the dynamic wetting behavior and long-term stability of liquid-repellent coatings remains underexplored. Here, the impact of alkyl side-chain length on the dynamic wettability and stability of superhydrophobic coatings is investigated. Three amine-functionalized monomers with varying alkyl side-chain lengths (C3, C6, and C9) are synthesized and grafted onto nanosilica via polymerization to form organic-inorganic hybrid coatings. The results show that increasing the alkyl side-chain length enhances the dynamic antiwetting capability and droplet bouncing behavior. Notably, the coating with the longest alkyl side chain exhibits an ultralow water adhesion of 22 μN, enabling up to eight successive droplet rebounds upon impact due to the "spring-like" behavior of the extended alkyl chain. Moreover, increasing the alkyl side-chain length significantly enhances the water resistance and UV stability of the coatings. The C9-based coating demonstrates satisfactory durability, withstanding 288 h at a 5 cm depth and 192 h at a 25 cm depth of water, while maintaining stable superhydrophobicity even after 672 h of UV exposure. These findings demonstrate the critical role of alkyl side-chain length in regulating dynamic wettability and stability, providing insights for the rational design of durable fluorine-free superhydrophobic coatings for practical applications.
    Keywords:  alkyl chain engineering; durability; molecular design; structure−property relationship; superwetting coating
    DOI:  https://doi.org/10.1021/acsami.5c08629
  20. Small. 2025 Aug 20. e06259
      Chronic and complex wounds pose a major clinical challenge due to the intricate skin architecture and the multifactorial nature of healing. Conventional wound care often fails to restore native skin function and structure. Advances in 3D and 4D bioprinting have transformed wound management by enabling customized, biomimetic skin substitutes that enhance healing. This review outlines skin complexity and the sequential phases of repair, while addressing limitations of current therapies. The progression of 3D bioprinting is discussed, from basic additive manufacturing (AM) to precise biomaterial and cell deposition for skin reconstruction. Special focus is given to bioinks, including natural polymers, synthetic hydrogels, decellularized extracellular matrix (dECM), and composite formulations, all designed to mimic native skin properties. The emerging field of 4D bioprinting is highlighted, incorporating smart, stimuli-responsive materials capable of dynamic structural and functional adaptation to complex wound environments. Key cellular components and bioprinting techniques for multilayered constructs are reviewed, along with personalized approaches such as in situ handheld bioprinting and artificial intelligence (AI) assisted biofabrication. Finally, challenges in clinical translation, manufacturing, and scalability are addressed, with future perspectives on robotics, AI, and innovative biomaterials in regenerative wound care.
    Keywords:  3D Bioprinting; 4D Bioprinting; bioinks; regenerative medicine; tissue engineering; wound healing
    DOI:  https://doi.org/10.1002/smll.202506259
  21. Lab Chip. 2025 Aug 18.
      Gut-on-a-chip platforms replicate realistic gut microenvironments but face limited adoption due to their complex designs, expensive fabrication, and specialized instrumentation that increases operational complexity. In this study, we present a microfluidic chip insertable into 12-well plates with a unique radial design and a pumpless flow actuation system using an orbital shaker. We use a surface tension-driven hydrogel patterning technique to compartmentalize the chip, enabling co-culture of gut epithelium and vasculature, resulting in leak-proof monolayer tubes. Furthermore, computational fluid dynamic analysis demonstrates bidirectional peristaltic flow induced by the shaker. The platform's physiological relevance is confirmed through the evaluation of cell polarization, tight junction markers and barrier integrity, using high-magnification microscopy and electrical resistance measurements. We also demonstrate the ability of the platform to support live bacterial colonization, simulating host-microbe interactions. The model is validated for drug development by assessing gut and vascular permeability following drug overdose and inflammatory cytokine activation. Additionally, we explore nanoplastic poisoning using nano polyethylene terephthalate (PET) particles, highlighting the gut's role in limiting particle absorption into the bloodstream. The orbital gut-on-a-chip platform offers an accessible, dynamic cell culture system for drug discovery and biomimetic modeling of gut-related disease interactions.
    DOI:  https://doi.org/10.1039/d5lc00333d
  22. Macromol Rapid Commun. 2025 Aug 17. e00063
      This review aims to prospect the development and utilization of proton-conducting biopolymers as sustainable matters. Its focal point is a move to sustainable materials of environment-friendly alternatives to conventional plastics. The review explores the properties and development techniques related to proton conduction in biopolymers and highlights their practical applications. Proton conductivity, mechanical strength, thermal stability, and chemical compatibility are pivotal features for creating advanced materials where biomaterials offer a sustainable production pathway for such materials. Methods for enhancing these properties include blending with similar biomaterials, making chemical modifications, creating nanostructures, and employing hybrid fabrication techniques. Improved proton conductivity is possible by forming proton pathways, attributed to chains of water molecules. These enhanced conductive materials have applications in fuel cells, sensors, ion separation membranes, and biomedical devices. Nature-derived biomimetic materials may offer such adaptable solutions that could also be eco-friendly and support a circular economy. This study has implications for industry professionals and researchers in the fields of energy and consumer electronics, highlighting the potential of biopolymers as key elements in sustainable product development.
    Keywords:  biodegradation; bioelectronics devices; biopolymers; fuel cells; membranes; proton transport
    DOI:  https://doi.org/10.1002/marc.202500063
  23. Sci Rep. 2025 Aug 19. 15(1): 30366
      This study presents a novel piston-driven pneumatic extrusion system for direct ink writing (DIW), featuring flexible actuation and real-time monitoring of extrusion pressure. The design integrates the benefits of both pressure and feedrate control, achieving consistent linewidth while safeguarding pressure-sensitive materials such as cell-laden hydrogels. The system comprises a lightweight pneumatic syringe on the printhead and a stationary actuation unit, allowing efficient decoupling of motion and extrusion. Experiments demonstrate stable gelatin extrusion with a mean linewidth of 4.32 mm and a minimal increase ratio of 0.012 over printing distance. These findings show promise for advancing DIW with emerging soft materials, particularly in bioprinting and sustainable manufacturing.
    Keywords:  Bioprinting; Direct ink writing; Flexible actuation; In-situ monitoring; Material extrusion
    DOI:  https://doi.org/10.1038/s41598-025-15164-9
  24. Nature. 2025 Aug;644(8077): 829-832
      
    Keywords:  Genomics; Machine learning; Synthetic biology; Technology
    DOI:  https://doi.org/10.1038/d41586-025-02621-8
  25. Nat Commun. 2025 Aug 19. 16(1): 7727
      The spontaneous electrification of surfaces and interfaces is a widespread phenomenon that produces unexpected effects in chemical reactivity and mass charge transfer, revealed in abundant literature over the past twenty years. The pervasive presence of electrostatic charges originates from many sources, including friction, mechanochemical reactions, phase change, flexoelectricity, and others. Since fused deposition modeling undergoes most well-known electrification mechanisms, it would be not surprising that 3D-printed objects display large amounts of charge. Here we uncover the hitherto unexplored realm of electrostatic charging in 3D printing, underscores the impact of printing parameters on charge generation in polymers. Substrates, printing speed, temperature, and printing direction each exert distinct impacts on charge buildup, depending upon the material used for printing. We also develop simple protocols employing common multimeters for charge monitoring, while substrates subjected to corona charging or triboelectrification demonstrate effective methods for charge control or mitigation. An original development is achieved by demonstrating the ability to print quasi-electrets, indicating a potential revolution in electret technology. The implications of these findings establish the groundwork for advancements in 3D printing technology and electrostatics, creating new scientific opportunities for a better understanding of matter.
    DOI:  https://doi.org/10.1038/s41467-025-61566-8
  26. J Pharm Sci. 2025 Aug 16. pii: S0022-3549(25)00417-4. [Epub ahead of print] 103963
      Protein-based therapeutics are prone to pH-dependent intramolecular chemical degradation reactions. Knowledge of the pH around protein-based therapeutics inside sustained release (SR) formulations is necessary for assessing their suitability for sustained delivery applications. Herein, we have taken advantage of the pH-sensitive chemical reactions of a model antibody, mAb1, to infer the pH around proteins in two representative SR formulations: PLGA microparticles and hyaluronic acid hydrogel. Distinct chemical changes in mAb1 retrieved from the two SR formulations at various stages of in vitro release were measured and compared with the chemical changes in mAb1 exposed to aqueous buffers of known pH to infer the pH around mAb1 in the SR formulations. The monomer content, charge variants, and residue level chemical degradation in mAb1 were quantified using SEC, icIEF, and peptide mapping, respectively. The results suggest that mAb1 was exposed to pH 4-7 in PLGA microparticles and to pH 6-7 in hyaluronic acid hydrogels. The approach presented here will be universally applicable for characterizing pH in the vicinity of proteins inside any SR formulation.
    Keywords:  Protein stability; chemical degradation; drug delivery; pH
    DOI:  https://doi.org/10.1016/j.xphs.2025.103963
  27. Adv Healthc Mater. 2025 Aug 20. e01733
      Particularly for dynamic, shape-changing, or fibrillar tissues such as muscles and blood vessels, the development of innovative biomaterials is crucial for advancing tissue engineering and regenerative medicine. This study introduces a novel multicomponent hydrogel created from silk fibroin (SF), tyramine-modified hyaluronic acid (HA_Tyr), and tyramine-modified gelatin (G_Tyr). Using an enzymatic orthogonal covalent bonding between phenolic groups, i.e., tyrosine and tyramine moieties of SF, HA_Tyr, and G_Tyr, a dynamically stiffening SF/HA_Tyr/G_Tyr (SHG) multicomponent hydrogel is achieved with enhanced mechanical properties. Utilizing an extrusion-based 3D printing approach, the precise fabrication of constructs with tailored geometries and functionalities is demonstrated. The emerging 3D-printed hydrogels undergo morphologic changes (4D) under 37 °C/phosphate buffer saline (PBS) conditions. The observed morphological change results from the conformational change and folding of SF leading to fibrillation. These multicomponent hydrogels also show significant promise in creating bio-instructive materials that meet the mechanical and functional requirements necessary for in situ tissue engineering. The study highlights the potential of these self-stiffening biomaterials to recover dynamic and fibrillar tissues, supported by both in vitro and pre-clinical chorioallantoic membrane (CAM) model evaluations that underscore their biocompatibility and pro-angiogenic properties.
    Keywords:  3D printing; dynamic tissue engineering; phenolic biopolymers; self‐stiffening hydrogel
    DOI:  https://doi.org/10.1002/adhm.202501733
  28. Chem Mater. 2025 Aug 12. 37(15): 5487-5501
      We describe the synthesis of a functional macroporous polymer material and its potential use as a scaffold to support the 3D culture of hematopoietic stem and progenitor cells (HSPCs). Glycidyl methacrylate (GMA)-based emulsion-templated porous polymers (known as polyHIPEs) were prepared by photopolymerization and subsequently surface functionalized with hyaluronic acid (HA) using Huisgen azide-alkyne cycloaddition click reaction, inferring a high degree of functionalization based on the near-quantitative nature of the reactions. Quantitative azidation of GMA-based polyHIPEs is achieved by the ring opening reaction of epoxide rings with sodium azide. Reductive amination reaction is used to end-cap HA with alkyne functionality to be later clicked onto the azidified polyHIPE surfaces. The synthesized polyHIPE materials are characterized by 1H nuclear magnetic resonance (NMR), Fourier-transform infrared (FT-IR), Raman and X-ray photoelectron spectroscopy (XPS). Scanning electron microscopy (SEM) and compression testing are also conducted on the polyHIPE scaffolds to evaluate their morphological and mechanical characteristics, respectively. Biocompatibility and cell viability were assessed, along with preliminary stem cell culture experiments to evaluate the suitability of HA-functionalized polyHIPE scaffolds for stem cell maintenance and proliferation. These experiments revealed a notable increase of approximately 20% in CD36+ cell proliferation on HA-polyHIPE scaffolds compared to the control GMA-polyHIPE scaffolds. The multifunctionality served by HA, such as its biocompatibility, biodegradability, nonimmunogenicity, anti-inflammatory properties, antiangiogenic characteristics and binding ability to biological targets critical to mimicking stem cell environment, significantly advances the development of biological scaffolds for tissue engineering and regeneration.
    DOI:  https://doi.org/10.1021/acs.chemmater.5c00068
  29. Bioact Mater. 2025 Nov;53 831-854
      Bioprinting provides a promising tool to customize human tissues for medicine. Currently, it is expected to generate a tissue from the printed tissue construct that is consisted of biomaterials and cells. One of the major challenges is the lack of advanced printable biomaterials that allows the tissue constructs to efficiently mature into a real tissue. For the bioprinting, the commonly used biomaterials are "dead", while the cells are living. It is important to develop cell-adaptable materials that can dynamically provide space for the seeded cells to grow and migrate. In this work, we overview current cell-adaptable hydrogels for bioprinting tissue constructs including in vivo implants and in vitro disease models. Also, we discuss the key considerations for future clinical translation of bioprinting using cell-adaptable hydrogels. This work would help us to understand the opportunities and challenges of bioprinting using cell-adaptable hydrogels.
    Keywords:  Biomaterials; Bioprinting; Cell-adaptable hydrogels; Translational medicine
    DOI:  https://doi.org/10.1016/j.bioactmat.2025.07.044
  30. Nucleic Acids Res. 2025 Aug 11. pii: gkaf727. [Epub ahead of print]53(15):
      Ultraviolet (UV) crosslinking with mass spectrometry (XL-MS) has been established for identifying RNA- and DNA-binding proteins along with their domains and amino acids involved. Here, we explore chemical XL-MS for RNA-protein, DNA-protein, and nucleotide-protein complexes in vitro and in vivo. We introduce a specialized nucleotide-protein-crosslink search engine, NuXL, for robust and fast identification of such crosslinks at amino acid resolution. Chemical XL-MS complements UV XL-MS by generating different crosslink species, increasing crosslinked protein yields in vivo almost four-fold, and thus it expands the structural information accessible via XL-MS. Our workflow facilitates integrative structural modelling of nucleic acid-protein complexes and adds spatial information to the described RNA-binding properties of enzymes, for which crosslinking sites are often observed close to their cofactor-binding domains. In vivo UV and chemical XL-MS data from E. coli cells analysed by NuXL establish a comprehensive nucleic acid-protein crosslink inventory with crosslink sites at amino acid level for >1500 proteins. Our new workflow combined with the dedicated NuXL search engine identified RNA crosslinks that cover most RNA-binding proteins, with DNA and RNA crosslinks detected in transcriptional repressors and activators.
    DOI:  https://doi.org/10.1093/nar/gkaf727
  31. Environ Res. 2025 Aug 15. pii: S0013-9351(25)01861-4. [Epub ahead of print]285(Pt 4): 122609
      Here, following the waste-to-value principle, cellulose extracted from spent coffee grounds was modified to fabricate cargo-loaded hydrogel scaffolds via 3D printing, thereby enhancing resource utilization efficiency. Initially, FTIR spectroscopy confirmed the removal of non-cellulosic fractions, yielding cellulose over 10 %, which was subsequently converted into carboxymethyl cellulose through the etherification process. Furthermore, the concrete inks prepared from two hydrogel microparticles that were made from recovered carboxymethyl cellulose and their photo-crosslinked hydrogels exhibited distinct property characteristics, establishing a foundation for selecting an appropriate formulation for hydrogel scaffold printing. Notably, the structural parameters of the hydrogel scaffolds significantly influenced cargo release kinetics, with scaffolds printed using 0.3 mm and 0.6 mm nozzles demonstrating marked filling density-dependent release behaviors. The nutrient release duration increased from 0.25 to 9 h to 19 and 26 h as filling density was elevated. However, structural factors of the scaffolds were found to critically influence cargo release kinetics within the hydrodynamic field, as the spatial structure governs the surface area-to-volume ratio, thereby affecting diffusion pathways and release behaviors. Finally, the developed release model was utilized to predict the release kinetics of medicine from the hydrogel scaffold, providing a new perspective on scaffold design and manufacture aimed at optimizing performance and minimizing waste. This work, combining waste re-utilization and loss reduction, presents a promising pathway towards circular economy promotion and carbon emission mitigation to advance sustainable development goals.
    Keywords:  3D printing; Biomass waste; Cellulose; Hydrogel scaffolds; Release kinetics; Waste minimization
    DOI:  https://doi.org/10.1016/j.envres.2025.122609
  32. Phys Rev E. 2025 Jul;112(1-2): 015504
      We investigate the mechanical behavior of jammed knitted fabrics, where geometric confinement leads to an initially stiff mechanical response that softens into low stiffness behavior with additional applied stress. We show that the jammed regime is distinguished by changes in yarn geometry and contact rearrangement that must occur to allow the individual stitches to stretch. These rearrangements allow for the relaxation of high residual stresses that are present within jammed fabric, altering the low-strain response. We demonstrate that fabric jamming can be induced or reduced by changing either the constituent yarn or the fabric manufacturing parameters. Analysis of experimental samples shows that changing the "stitch size" in manufacturing affects both the in situ yarn radius and the length of yarn per stitch, both of which affect jamming.
    DOI:  https://doi.org/10.1103/g94g-c6tt