bims-enlima Biomed News
on Engineered living materials
Issue of 2025–05–25
forty-five papers selected by
Rahul Kumar, Tallinna Tehnikaülikool
  1. Hierarchical Engineering of Amphiphilic Peptides Nanofibrous Crosslinkers toward Mechanically Robust, Functionally Customable, and Sustainable Supramolecular Hydrogels.
  2. Bacterial Species in Engineered Living Materials: Strategies and Future Directions.
  3. Stiff yet stretchy dissipative metamaterials.
  4. Enabling RNA-compatible synthetic receptors through RNA editing.
  5. Host Evolution Improves Genetic Circuit Function in Complex Growth Environments.
  6. Adenosine-Triggered Dynamic and Transient Aptamer-Based Networks Integrated in Liposome Protocell Assemblies.
  7. Viscoelasticity of ECM and cells-origin, measurement and correlation.
  8. Enabling technologies for in situ biomanufacturing using probiotic yeast.
  9. High-performance recyclable polymers enabled by stereo- and sequence-controlled polymerization.
  10. Dynamic Transcription Machineries in Protocells.
  11. Engineering Supramolecular Hydrogen Bonding Interactions into Dynamic Covalent Polymers To Obtain Double Dynamic Biomaterials.
  12. Near-infrared responsive three-component supramolecular hydrogels of peptide, agarose and upconversion nanoparticles.
  13. Engineering non-viral protein nanoparticles to deliver nucleic acids and proteins to cells.
  14. High-throughput single-cell density measurements enable dynamic profiling of immune cell and drug response from patient samples.
  15. Semipermeable Membrane-Mediated Hydrogen Bonding Interface for Fabricating High-Performance Pure PEDOT:PSS Hydrogels.
  16. Single-Cell Nanoencapsulation: Chemical Synthesis of Artificial Cell-in-Shell Spores.
  17. Evolution-guided tolerance engineering of Pseudomonas putida KT2440 for production of the aviation fuel precursor isoprenol.
  18. These contact lenses give people infrared vision - even with their eyes shut.
  19. Osmosis-Induced Mechanical Disintegration of Polymer Network Gels.
  20. Multicomponent supramolecular hydrogels composed of cationic phenylalanine derivatives and anionic amino acids.
  21. Flexible and Environmentally Friendly Calcium Polyphosphate Hydrogels: Toward Inorganic Functional Materials for Wearable Devices and Soft Actuators.
  22. Nano-engineered thin-film thermoelectric materials enable practical solid-state refrigeration.
  23. Biofabrication in suspension media - a decade of advances.
  24. Intracellular Nanodelivery of DNA with Enzyme-Degradable and pH-Responsive Peptide Dendrons.
  25. Photoacid-induced Supramolecular Network Disassembly: a Systems Approach to Stimuli-responsive Polymers.
  26. Injectable and self-healable supramolecular hydrogels assembled by quaternised chitosan/alginate polyelectrolyte complexation for sustained drug delivery and cell encapsulation.
  27. A biochemical sensor with continuous extended stability in vivo.
  28. Engineering Synthetic PEG Hydrogels to Model Peri-implantation Epiblast Morphogenesis with Tunable Biophysical Properties.
  29. inCu-click: DNA-enhanced ligand enables live-cell, intracellular click chemistry reaction with copper catalyst.
  30. Light-Triggered Switching of Metallosupramolecular Polymer Systems.
  31. A generalizable approach for programming protease-responsive conformationally inhibited artificial transcriptional factors.
  32. Emerging strategies to develop novel genetically encoded biosensors.
  33. Recent advancements in electro-thermal anti-/de-icing materials.
  34. Additive manufacturing of carbon fiber-reinforced thermoset composites via in-situ thermal curing.
  35. Genetic and bioactive functionalization of bioinks for 3D bioprinting.
  36. Horizontal gene transfer of molecular weapons can reshape bacterial competition.
  37. Enhanced Near-Infrared Light-Mediated Hydrogel Curing Using Photoinitiator Integrated Upconversion Particles as Nano Initiator for 3D Bioprinting.
  38. Bioprinting.
  39. Abiotic lipid metabolism enables membrane plasticity in artificial cells.
  40. Microenvironment-responsive living hydrogel containing engineered probiotic for treatment of massive bone defects.
  41. Chaperone overexpression boosts heterologous small molecule production in Saccharomyces cerevisiae.
  42. Effect of Salt on Synthetic Cationic Antimicrobial Polymer-Cell Interactions.
  43. Micropatterning Photoconductive Peptide Assemblies on Stiff and Soft Biomaterial Substrates.
  44. Engineering cellulosic paper into a bending strain sensor using chemical additives: Metal salt-based treatment and ethanol-assisted processing.
  45. PERRC: Protease Engineering with Reactant Residence Time Control.
  1. Adv Mater. 2025 May 20. e2503324
    Hierarchical Engineering of Amphiphilic Peptides Nanofibrous Crosslinkers toward Mechanically Robust, Functionally Customable, and Sustainable Supramolecular Hydrogels.
    Yifan Zheng, Shuang Zhang, Yue Yuan, Chuang Li.
      Hierarchical architectures spanning multiple length scales are ubiquitous in biological tissues, conferring them with both mechanical robustness and dynamic functionalities via structural reorganization under loads. The design of hierarchical architectures within synthetic hydrogels to concurrently achieve mechanical reinforcement and functional integration remains challenging. Here, a biomimetic hierarchical engineering approach is reported to develop mechanically robust and function-customizable supramolecular hydrogels by utilizing strong yet dynamic fibrous nanoarchitectures of amphiphilic peptides as crosslinkers. This design, on one hand, resolves the strength-toughness trade-off in hydrogel design through energy-dissipative mechanisms involving dynamic detachment and reinsertion of peptides within their assembled nanostructures upon loading. On the other hand, the amphiphilicity and sequence programmability of peptides allow spatially orthogonal integration of multiple dynamic functionalities across distinct structural domains, including lipophilic fluorophore encapsulation, photopatterning capability, and anisotropic contraction. Capitalizing on its ultralow hysteresis and rapid recovery properties, the hydrogel's effectiveness is demonstrated as high-sensitivity strain sensors. Moreover, the fully noncovalent crosslinking strategy permits closed-loop recycling and reprocessing via reversible crosslinker disassembly-reassembly processes. Through systematic extension of this principle across diverse peptide systems, a generalized platform is demonstrated for creating advanced soft materials that synergistically integrate traditionally incompatible attributes of mechanical robustness, customable dynamic functionality, and environmental sustainability.
    Keywords:  amphiphilic peptide; fibrous crosslinker; hierarchical self‐assembly; recyclability; tough supramolecular hydrogel
    DOI:  https://doi.org/10.1002/adma.202503324
  2. Microb Biotechnol. 2025 May;18(5): e70164
    Bacterial Species in Engineered Living Materials: Strategies and Future Directions.
    Hu Wang, Chunzhong Li, Yanmin Wang, Huanming Zhang.
      In recent years, there has been a notable increase interest in engineered living materials (ELMs) owing to their considerable potential. One key area of research within this field is the utilisation of various species of bacteria to create innovative living materials. In order to accelerate the advancement of bacterial-based living materials, a systematic summary of bacterial species and their design strategies is essential. Yet, up to this point, no applicable reviews have been documented. This review offers a concise introduction to living materials derived from bacteria, delves into the strategies and applications of each bacterial species in this realm, and provides perspectives and future outlooks in this field.
    Keywords:  bacteria; biofilm; engineered living materials
    DOI:  https://doi.org/10.1111/1751-7915.70164
  3. Nat Mater. 2025 May 21.
    Stiff yet stretchy dissipative metamaterials.
    Damiano Pasini.
      
    DOI:  https://doi.org/10.1038/s41563-025-02247-1
  4. Nat Rev Mol Cell Biol. 2025 May 21.
    Enabling RNA-compatible synthetic receptors through RNA editing.
    Xiaowei Zhang, Luis S Mille-Fragoso.
      
    DOI:  https://doi.org/10.1038/s41580-025-00863-y
  5. ACS Synth Biol. 2025 May 20.
    Host Evolution Improves Genetic Circuit Function in Complex Growth Environments.
    Joanna T Zhang, Andrew Lezia, Philip Emmanuele, Muyao Wu, Elina C Olson, Aayush Somani, Adam M Feist, Jeff Hasty.
      The systematic design of genetic circuits with predictable behaviors in complex environments remains a significant challenge. Here, we engineered a population control circuit and used a combination of evolutionary and rational engineering approaches to enhance Escherichia coli for robust genetic circuit behavior in nontraditional growth environments. We utilized adaptive laboratory evolution (ALE) on E. coli MG1655 in minimal media with a sole carbon source and saw improved dynamics of the circuit after host evolution. Additionally, we applied ALE to E. coli Nissle, a probiotic strain, in a more complex medium environment with added reactive oxygen species (ROS) stress. In combination with directed mutagenesis and high-throughput microfluidic screening, we observed restored circuit function and improved tolerance of the circuit components. These findings serve as a framework for the optimization of relevant bacterial host strains for improved growth and gene circuit performance in complex environments.
    Keywords:  adaptive laboratory evolution; circuit design; microfluidics; microscopy; strain optimization
    DOI:  https://doi.org/10.1021/acssynbio.5c00168
  6. J Am Chem Soc. 2025 May 22.
    Adenosine-Triggered Dynamic and Transient Aptamer-Based Networks Integrated in Liposome Protocell Assemblies.
    Yu Ouyang, Yang Sung Sohn, Xinghua Chen, Rachel Nechushtai, Eli Pikarsky, Fan Xia, Fujian Huang, Itamar Willner.
      The development of transient dissipative nucleic-acid-based reaction circuits and constitutional dynamic networks attracts growing interest as a means of emulating native dynamic reaction circuits. Recent efforts applying enzymes, DNAzymes, or light as catalysts controlling the transient, dissipative functions of DNA networks and circuits were reported. Moreover, the integration of the dynamic networks in protocell assemblies and the identification of potential applications are challenging objectives. Here, we introduce the adenosine (AD) aptamer subunit complex coupled with adenosine deaminase (ADA) as a versatile recognition/catalytic framework for driving transient allosterically AD-stabilized DNAzyme circuits or dissipative AD-stabilized constitutional dynamic networks. In addition, the AD/ADA-driven transient frameworks are integrated into liposome assemblies as protocell models. Functionalized liposomes carrying allosterically ATP-stabilized DNAzymes cleaving EGR-1 mRNA are fused with MCF-7 breast cancer cells, demonstrating effective gene therapy and selective apoptosis of cancer cells.
    DOI:  https://doi.org/10.1021/jacs.5c05090
  7. Mechanobiol Med. 2024 Dec;2(4): 100082
    Viscoelasticity of ECM and cells-origin, measurement and correlation.
    Zhiqiang Liu, Si Da Ling, Kaini Liang, Yihan Chen, Yudi Niu, Lei Sun, Junyang Li, Yanan Du.
      The extracellular matrix (ECM) and cells are crucial components of natural tissue microenvironments, and they both demonstrate dynamic mechanical properties, particularly viscoelastic behaviors, when exposed to external stress or strain over time. The capacity to modify the mechanical properties of cells and ECM is crucial for gaining insight into the development, physiology, and pathophysiology of living organisms. As an illustration, researchers have developed hydrogels with diverse compositions to mimic the properties of the native ECM and use them as substrates for cell culture. The behavior of cultured cells can be regulated by modifying the viscoelasticity of hydrogels. Moreover, there is widespread interest across disciplines in accurately measuring the mechanical properties of cells and the surrounding ECM, as well as exploring the interactive relationship between these components. Nevertheless, the lack of standardized experimental methods, conditions, and other variables has hindered systematic comparisons and summaries of research findings on ECM and cell viscoelasticity. In this review, we delve into the origins of ECM and cell viscoelasticity, examine recently developed methods for measuring ECM and cell viscoelasticity, and summarize the potential interactions between cell and ECM viscoelasticity. Recent research has shown that both ECM and cell viscoelasticity experience alterations during in vivo pathogenesis, indicating the potential use of tailored viscoelastic ECM and cells in regenerative medicine.
    Keywords:  Cell; Correlation; Extracellular matrix; Measurement; Origin; Viscoelasticity
    DOI:  https://doi.org/10.1016/j.mbm.2024.100082
  8. Adv Drug Deliv Rev. 2025 May 16. pii: S0169-409X(25)00090-0. [Epub ahead of print] 115605
    Enabling technologies for in situ biomanufacturing using probiotic yeast.
    William Parker, Amanda Taylor, Aryan Razdan, Jose Escarce, Nathan Crook.
      Saccharomyces boulardii (Sb) is a Generally Regarded As Safe (GRAS) probiotic yeast currently used to alleviate symptoms from various gastrointestinal diseases. Sb is a promising platform for probiotic and biotherapeutic engineering as it is the only probiotic eukaryote and carries with it a unique set of advantages compared to bacterial strains, including resistance to phage, high protein secretion abilities, and intrinsic resistance to antibiotics. While engineered Sb has not been studied as extensively as its close relative Saccharomyces cerevisiae (Sc), many genetic engineering tools developed for Sc have also shown promise in Sb. In this review, we address recent research to develop tools for genetic engineering, colonization modulation, biomarker sensing, and drug production in Sb. Ongoing efforts, especially those that overcome gut-specific challenges to engineered performance, are highlighted as they advance this chassis as a scalable platform for treating gastrointestinal diseases.
    Keywords:  Drug Discovery; Probiotics; Synthetic Biology; Therapeutics; Yeast
    DOI:  https://doi.org/10.1016/j.addr.2025.115605
  9. Nat Chem. 2025 May 16.
    High-performance recyclable polymers enabled by stereo- and sequence-controlled polymerization.
    Meng-Yuan Wang, Yi-Min Tu, Qing-Qian Zeng, Kun Li, Wei Xiong, Zhongzheng Cai, Jian-Bo Zhu.
      Monomer design strategy has become a powerful tool to access chemically recyclable polymers with desired and diverse properties. The presence of two or multiple stereogenic centres in one monomer offers a new dimension to fine-tune the polymer performance. However, it is still a formidable challenge in synthetic polymer chemistry to achieve precise stereocontrol and sequence control over the polymer microstructure. Here we report a stereo- and sequence-controlled polymerization of 5H-1,4-benzodioxepin-3(2H)-one-based monomers with two stereogenic centres (M) to furnish a series of isoenriched AB diblock polymers P(cis-M)-b-P(trans-M) and ABA triblock polymers P(trans-M)-b-P(cis-M)-b-P(trans-M). Notably, P(cis-M2)900-b-P(trans-M2)38 delivered impressive toughness and ductility, comparable to the commodity plastic isotactic polypropylene; the ABA triblock P(trans-M2)26-b-P(cis-M2)900-b-P(trans-M2)26 appeared to be softer and resembled low-density polyethylene. These various materials could fully convert to the monomer M. The establishment of stereo- and sequence-controlled polymerization not only provides an effective and robust strategy to tailor polymer properties on the molecular level, but also delivers various chemically recyclable materials that can be converted back to monomers.
    DOI:  https://doi.org/10.1038/s41557-025-01828-6
  10. J Am Chem Soc. 2025 May 23.
    Dynamic Transcription Machineries in Protocells.
    Jiantong Dong, Fan Xia, Fujian Huang, Itamar Willner.
      Transcription machineries play key roles in nature by regulating diverse cellular processes, including cell cycle progression, the control of intracellular metabolic balance, and cell differentiation and growth. These processes are regulated by the programmed transcription factor-mediated operation of transcription machineries and cellular environmental cues dictating spatiotemporal gene expression, demonstrating amplification and bistable, switchable, and transient dynamic features. Emulating these native pathways through artificial means not only advances the area of Systems Chemistry by providing principles for the evolution of life but also introduces novel catalytic and theranostic applications of the system. The perspective addresses recent advances in developing transcription-machinery-loaded protocell assemblies, consisting of liposomes, microdroplets, proteinsomes, and microcapsules. Stimuli-responsive transcription machineries integrated into liposomes, Fe3+-cross-linked tannic acid membranes, and nucleic acid-functionalized hydrogel microcapsules acting as protocells are triggered by light, redox agents, and switchable refiguration of transcription templates. Moreover, temporally modulated oscillatory transcription circuitries integrated in microemulsion droplets acting as protocells were demonstrated, and the transcription-guided transient assembly and disassembly of DNA nanotubes mimicking formation and dissociation of motor filaments in native cells was accomplished. In addition, the dynamic transcription-mediated diffusive signaling and communication of microdroplets and proteinosome-based protocell assemblies are presented. Future challenges of the topic and potential practical applications of these systems are addressed in the conclusion section.
    DOI:  https://doi.org/10.1021/jacs.5c03622
  11. J Am Chem Soc. 2025 May 23.
    Engineering Supramolecular Hydrogen Bonding Interactions into Dynamic Covalent Polymers To Obtain Double Dynamic Biomaterials.
    Jasper G M Aarts, Maritza M Rovers, Martin G T A Rutten, Patricia Y W Dankers.
      Inspired by dynamic systems in nature, we can introduce dynamics into synthetic biomaterials through dynamic covalent bonds or supramolecular interactions. Combining both types of dynamic interactions may allow for advanced and innovative networks with multiple levels of dynamicity. Here we present two types of solid materials consisting of either dynamic covalent imine bonds or a combination of these dynamic covalent bonds with supramolecular hydrogen bonding ureido-pyrimidinone (UPy) units to obtain double dynamic materials. We showed the facile synthesis and formulation of both materials at room temperature. The thermal and physical properties of each material are highly tunable by altering the ratio and type of cross-linker. Interestingly, we showed that minimal amounts of UPy units result in a drastic increase in material mechanics. Furthermore, we show that both types of materials are suitable as biomaterials through functionalization with cell-adhesive peptides, through either a dynamic covalent imine bond or a supramolecular UPy moiety.
    DOI:  https://doi.org/10.1021/jacs.4c15102
  12. Faraday Discuss. 2025 May 20.
    Near-infrared responsive three-component supramolecular hydrogels of peptide, agarose and upconversion nanoparticles.
    Ivo Rosenbusch, Dominik Mählmann, Bart Jan Ravoo.
      Self-assembled, low molecular weight hydrogels are of particular interest for the development of responsive materials because they exhibit tunable viscoelasticity, high water content, and shear-thinning behavior, which make them suitable for various applications as biomimetic materials. Moreover, such hydrogels are quite easy to prepare. Here, a three-component gel is prepared by adding the peptide AAP-FGDS to an agarose polymer network. The photoresponsive peptide hydrogel exhibits excellent reversible properties. The photoisomerization of the peptide is enabled by lanthanide-doped upconversion nanoparticles (UCNP) added as a third component in the gel. UCNP can convert excitation in the near infrared (NIR) range into emission of higher energy through the process of upconversion. Irradiation with an NIR laser dissolves the self-assembled three-dimensional network structure of the peptide, resulting in a softer hydrogel. The three-component supramolecular gel can potentially be used for in vivo applications considering the fact that (unlike harmful UV light) NIR light can penetrate deeply into tissue.
    DOI:  https://doi.org/10.1039/d4fd00203b
  13. Nat Biotechnol. 2025 May 16.
    Engineering non-viral protein nanoparticles to deliver nucleic acids and proteins to cells.
      
    DOI:  https://doi.org/10.1038/s41587-025-02665-1
  14. Nat Biomed Eng. 2025 May 20.
    High-throughput single-cell density measurements enable dynamic profiling of immune cell and drug response from patient samples.
    Weida Wu, Sarah H Ishamuddin, Thomas W Quinn, Smitha Yerrum, Ye Zhang, Lydie L Debaize, Pei-Lun Kao, Sarah Marie Duquette, Mark A Murakami, Morvarid Mohseni, Kin-Hoe Chow, Teemu P Miettinen, Keith L Ligon, Scott R Manalis.
      Cell density, the ratio of cell mass to volume, is an indicator of molecular crowding and a fundamental determinant of cell state and function. However, existing density measurements lack the precision or throughput to quantify subtle differences in cell states, particularly in primary samples. Here we present an approach for measuring the density of 30,000 single cells per hour by integrating fluorescence exclusion microscopy with a suspended microchannel resonator. This approach achieves a precision of 0.03% (0.0003 g ml-1) for cells larger than 12 μm in diameter. In human lymphocytes, we discover that cell density and its variation decrease as cells transition from quiescence to a proliferative state, suggesting that the level of molecular crowding decreases and becomes more regulated upon entry into the cell cycle. Using a pancreatic cancer patient-derived xenograft model, we find that the ex vivo density response of primary tumour cells to drug treatment can predict the in vivo tumour growth response. Our method reveals unexpected behaviour in molecular crowding during cell state transitions and suggests density as a biomarker for functional precision medicine.
    DOI:  https://doi.org/10.1038/s41551-025-01408-6
  15. Adv Mater. 2025 May 20. e2505635
    Semipermeable Membrane-Mediated Hydrogen Bonding Interface for Fabricating High-Performance Pure PEDOT:PSS Hydrogels.
    Mingze Zeng, Jie Ding, Yuan Tian, Yusheng Zhang, Xiaoyin Liu, Zhihong Chen, Jing Sun, Chengheng Wu, Liangxue Zhou, Huabing Yin, Dan Wei, Hongsong Fan.
      Conductive poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) hydrogels are potential bioelectronic interface materials because of their favorable mechanical properties and tunable electrochemical performances. Owing to intrinsic core-shell colloidal microstructure composed of insulative phase and conductive phase, inducing phase separation via diverse methods are proposed to improve their performances. However, fabrication of high-performance pure PEDOT:PSS hydrogels via a simple, mild strategy remains challenges. Here, we report a straightforward strategy to yield high-performance pure PEDOT:PSS hydrogels via the formation of semipermeable membrane-mediated hydrogen bonding interface. In this method, ethanol-attracted PSS is free to accumulate at the man-made interface provided by the semipermeable membrane, to realize controllable hierarchical PEDOT and PSS two-phase distribution. The separated PEDOT aggregates via π-π conjugation, followed by the removal of rearranged insulative PSS phase easily, to form PEDOT:PSS hydrogels with satisfactory mechanical and electrochemical performances. This work presents a universal, effective, and controlled strategy to design conductive hydrogels for bioelectronic applications.
    Keywords:  PEDOT:PSS hydrogel; bioelectronics; conductive polymer; phase separation
    DOI:  https://doi.org/10.1002/adma.202505635
  16. Chem Rev. 2025 May 22.
    Single-Cell Nanoencapsulation: Chemical Synthesis of Artificial Cell-in-Shell Spores.
    Hyeong Bin Rheem, Nayoung Kim, Duc Tai Nguyen, Ghanyatma Adi Baskoro, Jihun H Roh, Jungkyu K Lee, Beom Jin Kim, Insung S Choi.
      Nature has evolved adaptive strategies to protect living cells and enhance their resilience against hostile environments, exemplified by bacterial and fungal spores. Inspired by cryptobiosis in nature, chemists have designed and synthesized artificial "cell-in-shell" structures, endowed with the protective and functional capabilities of nanoshells. The cell-in-shells hold the potential to overcome the inherent limitations of biologically naı̈ve cells, enabling the acquisition of exogenous phenotypic traits through the chemical process known as single-cell nanoencapsulation (SCNE). This review highlights recent advancements in the development of artificial spores, with sections organized based on the categorization of material types utilized in SCNE, specifically organic, hybrid, and inorganic types. Particular emphasis is placed on the cytoprotective and multifunctional roles of nanoshells, demonstrating potential applications of SCNEd cells across diverse fields, including synthetic biology, biochemistry, materials science, and biomedical engineering. Furthermore, the perspectives outlined in this review propose future research directions in SCNE, with the goal of achieving fine-tuned precision in chemical modulation at both intracellular and pericellular levels, paving the way for the design and construction of customized artificial spores tailored to meet specific functional needs.
    DOI:  https://doi.org/10.1021/acs.chemrev.4c00984
  17. Metab Eng. 2025 May 19. pii: S1096-7176(25)00083-7. [Epub ahead of print]
    Evolution-guided tolerance engineering of Pseudomonas putida KT2440 for production of the aviation fuel precursor isoprenol.
    Hyun Gyu Lim, Aparajitha Srinivasan, Russel Menchavez, Ian S Yunus, Myung Hyun Noh, Megan White, Yan Chen, Jennifer W Gin, Bernhard O Palsson, Taek Soon Lee, Christopher J Petzold, Thomas Eng, Aindrila Mukhopadhyay, Adam M Feist.
      Isoprenol (3-methyl-3-buten-1-ol) is a precursor to aviation fuels and other commodity chemicals and can be microbially synthesized from renewable carbon streams. Its production has been demonstrated in Pseudomonas putida KT2440 but its titers, rates, and yields have yet to reach commercially viable levels, potentially due to toxicity to the bacterial chassis. We hypothesized that utilization of Tolerization Adaptive Laboratory Evolution (TALE) would generate P. putida hosts more tolerant to isoprenol and suitable for enhanced production phenotypes. Here, we performed a comprehensive TALE campaign using three strains, the wild-type and two strains lacking subsets of known isoprenol catabolism and transport functions in quadruplicate independently evolved lineages. Several evolved clones from each starting strain displayed robust growth (up to 0.2 h-1) at 8 g/L of isoprenol, where starting strains could not grow. Whole genome resequencing of the 12 independent strain lineages identified convergent mutations. Reverse engineering each of the four commonly mutated regions individually (gnuR, ttgB-PP_1394, PP_3024-PP_5558, PP_1695) resulted in a partial recovery of the tolerance phenotypes observed in the evolved strains. Additionally, a proteomics-guided deletion of the master motility regulator, fleQ, in an evolved clone alleviated the tolerance vs. production trade-off, restoring isoprenol titers and consumption to levels observed in the starting strains. Collectively, this work demonstrated that an integrated strategy of laboratory evolution and rational engineering was effective to develop robust biofuel production hosts with minimized product toxicity.
    Keywords:  3-methyl-3-buten-1-ol; Adaptive laboratory evolution; Pseudomonas putida; isoprenol; sustainable aviation fuel (SAF); tolerance engineering
    DOI:  https://doi.org/10.1016/j.ymben.2025.05.007
  18. Nature. 2025 May 22.
    These contact lenses give people infrared vision - even with their eyes shut.
    Elizabeth Gibney.
      
    Keywords:  Materials science; Nanoparticles
    DOI:  https://doi.org/10.1038/d41586-025-01630-x
  19. Small. 2025 May 19. e2503209
    Osmosis-Induced Mechanical Disintegration of Polymer Network Gels.
    Shou Ohmura, Kosei Oikawa, Takuya Nishimura, Ryuji Kiyama, Jian Ping Gong, Tasuku Nakajima.
      A polymer network soaked in its good solvent absorbs the solvent molecules to swell up. The structurally possible swelling range of a polymer network is from its dried state to the structural swelling limit where its network strands reach their stretching limit. However, swelling of a polymer network to near its structural limit has not been realized due to the thermodynamic limitation. Here, this research succeeds in excessive swelling of polymer networks to or even beyond their structural swelling limit. For the excess swelling, dense linear polymers are repeatedly introduced inside a polymer network of interest. The linear polymers, trapped inside the polymer network, generate extremely high osmotic pressure and make the polymer network swell excessively. The resulting polymer networks, overswollen beyond their structural limit, disintegrate into microgels due to catastrophic scission of the polymer network strands, analogous to osmotic hemolysis of red blood cells in a hypotonic solution. This research is expected to contribute to osmosis-induced mechanodegradation of polymer network materials and well-controlled, swelling-based mechanochemistry.
    Keywords:  degradation; gel; mechanochemistry; osmotic pressure; polymer; swelling
    DOI:  https://doi.org/10.1002/smll.202503209
  20. Faraday Discuss. 2025 May 21.
    Multicomponent supramolecular hydrogels composed of cationic phenylalanine derivatives and anionic amino acids.
    Shruti Ghosh, Hannah E Distaffen, Christopher W Jones, Bradley L Nilsson.
      Supramolecular hydrogels composed of self-assembled fluorenylmethoxycarbonyl phenylalanine (Fmoc-Phe) derivatives have been the focus of intense study as novel materials for biological applications that include drug delivery, tissue engineering, and regenerative medicine. Cationic Fmoc-Phe derivatives functionalized with diaminopropane (Fmoc-Phe-DAP) have been shown to undergo self-assembly and hydrogelation upon an increase in solution ionic strength by the addition of inorganic salts that provide cation-shielding counterions. Further, the identity of the inorganic salts modifies the assembly morphology and emergent viscoelastic properties of the resulting materials. Herein, we report multicomponent hydrogels composed of Fmoc-Phe-DAP derivatives in which hydrogelation is promoted by the addition of anionic amino acids, monosodium aspartate or monosodium glutamate. Aspartate and glutamate salts both support supramolecular gelation of Fmoc-Phe-DAP derivatives, although only the glutamate gels remain stable over periods longer than one hour. The assemblies formed by Fmoc-Phe-DAP derivatives in the presence of aspartate and glutamate are morphologically distinct relative to those formed in the presence of sodium chloride. The viscoelastic properties of stable glutamate/Fmoc-Phe-DAP derivative hydrogels are sensitive to the ratios of glutamate to Fmoc-Phe-DAP derivative, with increased concentrations of glutamate corresponding to higher viscoelastic strength. These multicomponent systems demonstrate that comixing unfunctionalized amino acids with self-assembling Fmoc-Phe-DAP derivatives is yet another effective method to modify the emergent properties of the resulting materials.
    DOI:  https://doi.org/10.1039/d4fd00198b
  21. Adv Healthc Mater. 2025 May 19. e2501332
    Flexible and Environmentally Friendly Calcium Polyphosphate Hydrogels: Toward Inorganic Functional Materials for Wearable Devices and Soft Actuators.
    Tongtong Zhou, Jiulong Zhou, Song Zhang, Shuxun Cui.
      Inorganic hydrogels have attracted significant interest in materials science. However, it is a big challenge to fabricate flexible and multifunctional inorganic hydrogels due to the inherent rigidity of traditional inorganic materials. Herein, a flexible inorganic hydrogel is proposed, which is prepared by crosslinking long-chain polyphosphate (LPP) with Ca2+ ions. This pure-inorganic CaLPP hydrogel exhibits excellent self-healing ability, arbitrarily shapable ability, conductivity, degradability and biocompatibility. Furthermore, the CaLPP hydrogel can be used as strain sensors to monitor dynamic deformations (e.g., stretching and bending) with high sensitivity and reliability. The CaLPP hydrogel can also be used as ionic skins to detect human motions, such as bending of the joints and facial expressions. After functionalization, the CaLPP hydrogel can be used as a magnetic actuator. This fundamental work provides an environmentally friendly soft material with a purely inorganic composition, which can be used as a complement to organic-based soft materials for wearable devices and actuators.
    Keywords:  conductivity; degradability; inorganic hydrogel; polyphosphate; self‐healing ability; wearable devices
    DOI:  https://doi.org/10.1002/adhm.202501332
  22. Nat Commun. 2025 May 21. 16(1): 4421
    Nano-engineered thin-film thermoelectric materials enable practical solid-state refrigeration.
    Jake Ballard, Matthew Hubbard, Sung-Jin Jung, Vanessa Rojas, Richard Ung, Junwoo Suh, MinSoo Kim, Joonhyun Lee, Jonathan M Pierce, Rama Venkatasubramanian.
      Refrigeration needs are increasing worldwide with a demand for alternates to bulky poorly scalable vapor compression systems. Here, we demonstrate the first proof of practical solid-state refrigeration, using nano-engineered controlled hierarchically engineered superlattice thin-film thermoelectric materials. With 100%-better thermoelectric materials figure of merit, ZT, than the conventional bulk materials near 300 K, we demonstrate (i) module-level ZT greater than 75% and (ii) a system-level refrigeration ZT 70% better than that of bulk devices. Thin-film thermoelectric modules offer 100-300% better coefficient-of-performance than bulk devices depending on operational scenarios; system-level coefficient-of-performance is ~15 for temperature differentials of 1.3 °C. The thin-film devices enable more heat pumping per P-N couple, relevant for distributed and portable refrigeration, and electronics cooling. Beyond the demonstration of nano-engineered materials for a system-level advantage, we utilize 1/1000th active materials with scalable microelectronic manufacturing. The improved efficiency and ultra-low thermoelectric materials usage herald a new beginning in solid-state refrigeration.
    DOI:  https://doi.org/10.1038/s41467-025-59698-y
  23. Biofabrication. 2025 May 22.
    Biofabrication in suspension media - a decade of advances.
    Megan Elin Cooke, Morgan B Riffe, Manuela E Gomes, Rui M A Domingues, Jason A Burdick.
      Suspension bath bioprinting, defined as extrusion bioprinting into a suspension bath consisting of a yield-stress material with fast recovery, emerged over a decade ago. Since this time, many suspension baths have been developed from molecular assemblies to granular media and across a range of synthetic and natural polymers. These suspension baths have been applied to the printing of a wide variety of inks for applications in tissue engineering, from in vitro tissue models to implantable constructs. In a scoping search of published literature over the past decade, 254 articles were identified that met various definitions related to suspension baths for biofabrication in order to gain a perspective on the various materials used and their applications; however, the literature is much more broad than this due to the disperse terminology that has been applied to the approach. This article gives a perspective on the progress that has been made in suspension bath printing, including applications of the technology and challenges that exist across the field, as well as provides a look to the future of where such printing methods will make an impact.
    Keywords:  Bioinks; Bioprinting; Embedded printing; Suspension bath
    DOI:  https://doi.org/10.1088/1758-5090/addc42
  24. Biomacromolecules. 2025 May 17.
    Intracellular Nanodelivery of DNA with Enzyme-Degradable and pH-Responsive Peptide Dendrons.
    M A Urello, H J Vaughan, L T Dockery, A J Ciciriello, Y Rui, B Keyser, I Ramos, E E Bosco, N Peterson, C Webster, J Anand Subramony, M Rice, M Marelli, R James Christie.
      Effective DNA delivery requires functional materials to package and transport genetic cargo into cells. However, many synthetic systems rely on heterogeneous mixtures, lack biodegradability, and pose toxicity concerns. Here, we introduce a peptide dendron single-molecule transfection reagent that enables targeted DNA delivery via pH-responsive, degradable nanoparticles with minimal toxicity. Peptide dendrons for intracellular delivery (PDIDs) incorporate ionizable non-natural amino acids for DNA binding and pH sensitivity. PDIDs formed stable nanoparticles that released DNA upon lysosomal acidification, facilitating cytoplasmic entry and subsequent gene expression. Rationally designed triamino acid blocks promoted protease degradation, reducing toxicity in preclinical models. Targeting ligands further enhanced the transfection efficiency by increasing cell uptake. In a lung metastasis model, targeted PDID-DNA nanoparticles selectively delivered therapeutic gene cargo to the lung, reducing tumor burden and extending survival. This platform demonstrates the potential to integrate natural and non-natural peptide features to enable safe and efficient DNA delivery in vivo.
    DOI:  https://doi.org/10.1021/acs.biomac.5c00013
  25. Angew Chem Int Ed Engl. 2025 May 22. e202506981
    Photoacid-induced Supramolecular Network Disassembly: a Systems Approach to Stimuli-responsive Polymers.
    Marta Oggioni, Luca Bertossi, Derek J Kiebala, Adelle Kirshner, Andrea Dodero, Georges J M Formon, Christoph Weder.
      The introduction of supramolecular motifs allows the design of stimuli-responsive polymers whose physical properties can be changed by external triggers that affect the supramolecular binding. However, using this approach to create light-responsive materials that can be switched under isothermal conditions proves to be challenging. Here, we report a material systems approach to achieve this. Thus, supramolecular polymer networks, in which optically inert ureidopyrimidinone (UPy) groups assemble into reversible cross-links, are combined with a trigger molecule, the photoacid generator (PAG) 2-(4-methoxy-styryl)-4,6-bis(trichloromethyl)-1,3,5-triazine (MBTT). Model experiments with a fluorescent, self-reporting UPy motif elucidate the sequence of processes that result from optical triggering, namely acid generation, protonation of UPy groups, and ultimately dissociation of the supramolecular cross-links. The optically stimulated transformation of gels and rubbery films into viscous liquids was quantitatively monitored by opto-rheological measurements, showing that the optical stimulation and resultant mechanical responses are intimately coupled. The potential usefulness of this approach to create materials with spatially graded mechanical characteristics and as the basis for debonding-on-demand adhesives was explored in proof-of-concept experiments.
    Keywords:  Polymer; Stimuli-responsive; hydrogen-bonding; supramolecular; ureidopyrimidinone
    DOI:  https://doi.org/10.1002/anie.202506981
  26. Biomater Sci. 2025 May 19.
    Injectable and self-healable supramolecular hydrogels assembled by quaternised chitosan/alginate polyelectrolyte complexation for sustained drug delivery and cell encapsulation.
    Cristiana F V Sousa, João Borges, João F Mano.
      Hydrogels formed through phase separation during the complexation of oppositely charged polymers have unique properties, including fast self-assembly, hierarchical microstructures, and tunable properties. These features make them highly attractive materials for various biomedical applications, such as drug delivery, protective coatings, and surface adhesives. Notably, injectable polyelectrolyte complex (PEC) supramolecular hydrogels stand out for their minimally invasive administration and reduced trauma and side effects, providing attractive alternatives to covalent hydrogels, which are constrained by the irreversibility of their crosslinks, limiting their versatility and broader applicability. Sustainable marine-origin polysaccharides have been used for developing hydrogels due to their proven biocompatibility, non-cytotoxicity and wide bioavailability from renewable resources. In particular, chitosan (CHT) and alginate (ALG) have been widely employed to develop hydrogels, taking advantage of their opposite charge nature. However, the limited solubility of CHT under physiological conditions limits the range of bioapplications. Herein, we report the development of size- and shape-tunable PEC supramolecular hydrogels encompassing water-soluble quaternised CHT and ALG biopolymers, under physiological conditions, by polyelectrolyte complexation. The rheological and mechanical properties of the PECs are studied, demonstrating their injectability, self-healing behaviour, and cytocompatibility towards human adipose-derived stem cells. A sustained and controlled release of encapsulated fluorescein isothiocyanate-labelled bovine serum albumin is observed over fourteen days. This work paves the way for the design and development of advanced CHT-based injectable biomaterial platforms for a wide array of biomedical and biotechnological applications.
    DOI:  https://doi.org/10.1039/d5bm00072f
  27. Nat Biomed Eng. 2025 May 23.
    A biochemical sensor with continuous extended stability in vivo.
    Yihang Chen, Kaiyu X Fu, Renee Cotton, Zihao Ou, Jean Won Kwak, Jun-Chau Chien, Vladimir Kesler, Hnin Yin Yin Nyein, Michael Eisenstein, H Tom Soh.
      The development of biosensors that can detect specific analytes continuously, in vivo, in real time has proven difficult due to biofouling, probe degradation and signal drift that often occur in vivo. By drawing inspiration from intestinal mucosa that can protect host cell receptors in the presence of the gut microbiome, we develop a synthetic biosensor that can continuously detect specific target molecules in vivo. The biomimetic multicomponent sensor features the hierarchical nano-bio interface design with three-dimensional bicontinuous nanoporous structure, polymer coating and aptamer switches, balancing small-molecule sensing and surface protection in complex biological environments. Our system is stable for at least 1 month in undiluted serum in vitro or 1 week implanted within the blood vessels of free-moving rats, retaining over 50% baseline signal and reproducible calibration curves. We demonstrate that the implanted system can intravenously track pharmacokinetics in real time even after 4 days of continuous exposure to flowing blood within rat femoral vein. In this way, our work provides a generalizable design foundation for biosensors that can continuously operate in vivo for extended durations.
    DOI:  https://doi.org/10.1038/s41551-025-01389-6
  28. Methods Mol Biol. 2025 May 22.
    Engineering Synthetic PEG Hydrogels to Model Peri-implantation Epiblast Morphogenesis with Tunable Biophysical Properties.
    Michael Patrick Seitz, Zhen Ma, Era Jain.
      Implantation triggers critical morphological transformations in the embryo, where the epiblast transitions from a cluster of unpolarized cells into a highly organized, polarized epithelium characterized by a central lumen. Human pluripotent stem cells (hPSCs) are valuable models for studying this process, but conventional matrices like Matrigel have significant limitations, including variability and poor control over mechanical properties. To overcome these challenges, we developed a synthetic polyethylene glycol (PEG) hydrogel system with tunable mechanical stiffness to model peri-implantation epiblast morphogenesis.Our platform enables hPSCs to form unpolarized 3D aggregates that undergo stiffness-dependent transformation into lumen-forming, apicobasal-polarized structures resembling epiblast morphogenesis during peri-implantation. Unlike natural ECMs, PEG hydrogels maintain hPSC pluripotency for extended periods and support trilineage differentiation upon induction. The modular hydrogel design facilitates targeted mechanistic studies on the biophysical and biochemical regulation of cell morphogenesis. We present a comprehensive protocol for fabricating PEG hydrogels, encapsulating hPSCs, and assessing cell polarity, lumen formation, and pluripotency using immunostaining and RT-PCR. This platform provides a robust, cost-effective, and versatile tool for advancing developmental biology and regenerative medicine.
    Keywords:  Hydrogels; In vitro embryo model; Mechanobiology; Pluripotency; Stem cells; hiPSC
    DOI:  https://doi.org/10.1007/7651_2025_640
  29. Nat Commun. 2025 May 23. 16(1): 4788
    inCu-click: DNA-enhanced ligand enables live-cell, intracellular click chemistry reaction with copper catalyst.
    Keqing Nian, Yifang Liu, Yuchen Qiu, Zhuoyu Zhang, Laura Brigandi, Meni Wanunu, Sara H Rouhanifard.
      Labeling cellular biomolecules via copper-catalyzed azide-alkyne cycloaddition (CuAAC) offers rapid reaction kinetics and uses small azide and alkyne probes that minimally disturb molecular function, making it ideal for tracking biomolecules. However, applying CuAAC inside living cells has been hindered by the high copper levels required, which compromise cell health. To overcome this barrier, here, we develop inCu-click, an intracellular CuAAC approach that employs a DNA-conjugated ligand (BTT-DNA) to localize and concentrate copper ions at the reaction site. This design permits efficient click chemistry at low intracellular copper concentrations without added copper salts and supports template-driven proximity and liposomal delivery of the ligand into cells. Here we show that inCu-click enables robust fluorescent labeling of nascent phospholipids and proteins in live cells with negligible impact on viability, establishing a platform for real-time visualization of biomolecule dynamics in complex, live cell environments.
    DOI:  https://doi.org/10.1038/s41467-025-60143-3
  30. ACS Macro Lett. 2025 May 20. 765-772
    Light-Triggered Switching of Metallosupramolecular Polymer Systems.
    Luca Bertossi, Marta Oggioni, Georges J M Formon, Christoph Weder.
      Metallosupramolecular polymers (MSPs) are formed through the formation of coordination complexes between monomers that contain multiple ligands and suitable metal salts. The assembly of MSPs is generally dynamic and reversible, which leads to stimuli-responsive materials and enables functions such as healing or recycling. Heat is arguably the most widely employed stimulus to manipulate MSPs, but the level of control that can be achieved is limited. Here, we report light-responsive MSP systems, whose response is based on an opto-chemical transduction principle. We combined the photoacid generator 2-(4-methoxystyryl)-4,6-bis(trichloromethyl)-1,3,5-triazine (MBTT) with poly(acrylates) that comprise a few mol % of the 2,6-bis(1'-methyl-benzimidazolyl)pyridine (Mebip) ligand. The latter forms supramolecular cross-links upon the addition of metal salts, such as Zn2+, Eu3+, and Cu2+. We utilized titration experiments, optical spectroscopy, and rheology on model compounds and polymer systems to demonstrate that the MSP network can be rapidly disassembled upon optical activation of the photoacid generator, on account of protonation of the ligand and dissociation of the ML complex. Optorheological experiments reveal that the rheological properties of gels based on the MSP network, MBTT, and chlorobenzene can be drastically altered in an on-demand fashion by exposure to UV light.
    DOI:  https://doi.org/10.1021/acsmacrolett.5c00205
  31. Nat Commun. 2025 May 17. 16(1): 4604
    A generalizable approach for programming protease-responsive conformationally inhibited artificial transcriptional factors.
    Yinxia Liu, Lingyun Zhao, Jinshan Long, Zhenye Huang, Ying Long, Jianjun He, Jian-Hui Jiang.
      Synthetic genetic circuits that harness programmable protein modules and artificial transcription factors (ATF) to devise event-triggerable cascaded pathways represent an essential class of tools for studying cell biology. Fine-tuning the general structural functionality of ATFs is important for constructing orthogonal and composable transcriptional regulators. Here, we report the design of a protease-responsive conformationally inhibited system (PRCIS). By intramolecularly linking the free DNA-binding domains of ATF to confined dimerized regions, the transcriptional binding is conformationally inactivated. The function of DNA binding is reinstated upon proteolytic cleavage of linkages, activating the downstream gene expressions. The versatility of PRCIS design is demonstrated through its adaptability to various ATFs and proteases, showcasing high activation ratios and specificity. Furthermore, the development of PRCIS-based triple-orthogonal protease-responsive and dual-orthogonal chemical-inducible platforms and Boolean logic operations are elaborated in this paper, providing a generalizable design for synthetic biology.
    DOI:  https://doi.org/10.1038/s41467-025-59828-6
  32. Trends Biotechnol. 2025 May 15. pii: S0167-7799(25)00159-3. [Epub ahead of print]
    Emerging strategies to develop novel genetically encoded biosensors.
    Lili Chang, Jin Wang, Meng Wang, Yue Zhang.
      The current biosensor inventory is inadequate for the multitude of metabolites and proteins needing detection. Assisted by new technologies and research paradigms such as multi-omics analysis and de novo protein design, emerging strategies provide a promising avenue for the development of novel, tailored genetically encoded biosensors for various applications.
    Keywords:  artificial intelligence; chimeric biosensor; de novo protein design; genetically encoded biosensor; multi-omics technology
    DOI:  https://doi.org/10.1016/j.tibtech.2025.04.014
  33. RSC Adv. 2025 May 21. 15(22): 17102-17115
    Recent advancements in electro-thermal anti-/de-icing materials.
    Hui Gao, Yuqin Zhou, Jieyin Ma, Haichuan Jin, Jiayi Bao, Dongsheng Wen.
      Icing is a common phenomenon in daily life, but the formation and accumulation of ice on critical surfaces can lead to catastrophic failures, economic losses, and safety issues. It is essential to implement effective anti-/de-icing strategies to solve these problems. Electro-thermal anti-/de-icing is a typical method and widely utilized in different engineering areas but still faces challenges like inefficiency, high energy cost, and poor temperature uniformity. Increasing studies have focused on design and fabrication of new electro-thermal materials with better performance for anti-/de-icing. This review summarizes recent advancements and applications of electro-thermal anti-/de-icing materials. First of all, the mechanism of electro-thermal anti-/de-icing is briefly presented. Subsequently, various electro-thermal anti-/de-icing materials are introduced according to the material types, i.e., carbonaceous materials, metallic materials, and other materials. Furthermore, advances in the application of electro-thermal anti-/de-icing materials in aircraft, electric transmission-lines, wind power generation equipment and others are provided. To end, we summarize potential challenges and future perspectives in the design and fabrication of electro-thermal anti-/de-icing materials.
    DOI:  https://doi.org/10.1039/d5ra01330e
  34. Nat Commun. 2025 May 20. 16(1): 4691
    Additive manufacturing of carbon fiber-reinforced thermoset composites via in-situ thermal curing.
    Carter F Dojan, Morteza Ziaee, Alireza Masoumipour, Samuel J Radosevich, Mostafa Yourdkhani.
      Fiber-reinforced polymer composites are lightweight structural materials widely used in the transportation and energy industries. Current approaches for the manufacture of composites require expensive tooling and long, energy-intensive processing, resulting in a high cost of manufacturing, limited design complexity, and low fabrication rates. Here, we report rapid, scalable, and energy-efficient additive manufacturing of fiber-reinforced thermoset composites, while eliminating the need for tooling or molds. Use of a thermoresponsive thermoset resin as the matrix of composites and localized, remote heating of carbon fiber reinforcements via photothermal conversion enables rapid, in-situ curing of composites without further post-processing. Rapid curing and phase transformation of the matrix thermoset, from a liquid or viscous resin to a rigid polymer, immediately upon deposition by a robotic platform, allows for the high-fidelity, freeform manufacturing of discontinuous and continuous fiber-reinforced composites without using sacrificial support materials. This method is applicable to a variety of industries and will enable rapid and scalable manufacture of composite parts and tooling as well as on-demand repair of composite structures.
    DOI:  https://doi.org/10.1038/s41467-025-59848-2
  35. Bioprocess Biosyst Eng. 2025 May 20.
    Genetic and bioactive functionalization of bioinks for 3D bioprinting.
    Pawan Kumar, Jitender Sharma, Ravinder Kumar, Jan Najser, Jaroslav Frantik, Nagaraju Sunnam, Anil Sindhu, Seepana Praveenkumar.
      3D bioprinting is revolutionizing tissue engineering and regenerative medicine by enabling the precise fabrication of biologically functional constructs. At its core, the success of 3D bioprinting hinges on the development of bioinks, hydrogel-based materials that support cellular viability, proliferation, and differentiation. However, conventional bioinks face limitations in mechanical strength, biological activity, and customization. Recent advancements in genetic engineering have addressed these challenges by enhancing the properties of bioinks through genetic modifications. These innovations allow the integration of stimuli-responsive elements, bioactive molecules, and extracellular matrix (ECM) components, significantly improving the mechanical integrity, biocompatibility, and functional adaptability of bioinks. This review explores the state-of-the-art genetic approaches to bioink development, emphasizing microbial engineering, genetic functionalization, and the encapsulation of growth factors. It highlights the transformative potential of genetically modified bioinks in various applications, including bone and cartilage regeneration, cardiac and liver tissue engineering, neural tissue reconstruction, and vascularization. While these advances hold promise for personalized and adaptive therapeutic solutions, challenges in scalability, reproducibility, and integration with multi-material systems persist. By bridging genetics and bioprinting, this interdisciplinary field paves the way for sophisticated constructs and innovative therapies in tissue engineering and regenerative medicine.
    Keywords:  3D bioprinting; Bioink; Gel; Genetics; Tissue engineering
    DOI:  https://doi.org/10.1007/s00449-025-03180-y
  36. PLoS Biol. 2025 May;23(5): e3003095
    Horizontal gene transfer of molecular weapons can reshape bacterial competition.
    Elisa T Granato, Jacob D Palmer, Christian Kirk, Connor Sharp, George Shillcock, Kevin R Foster.
      Bacteria commonly use molecular weaponry to kill or inhibit competitors. Genes encoding many weapons and their associated immunity mechanisms can be transmitted horizontally. These transfer events are striking because they appear to undermine bacterial weapons when given to competing strains. Here, we develop an ecological model of bacterial warfare to understand the impacts of horizontal gene transfer. Our model predicts that weapon gene transfer from an attacker to a target strain is possible, but will typically occur at a low rate such that transfer has a negligible impact on competition outcomes. We tested the model empirically using a transmissible plasmid encoding colicin E2, a potent antibacterial toxin produced by Escherichia coli. As predicted by the model, we find that toxin plasmid transfer is feasible during warfare, but the resulting transconjugants remain rare. However, exploring the model further reveals realistic conditions where transfer is predicted to have major impacts. Specifically, the model predicts that whenever competing strains have access to unique nutrients, transconjugants can proliferate and reach high abundances. In support of these predictions, short- and long-term experiments show that transconjugants can thrive when nutrient competition is relaxed. Our work shows how horizontal gene transfer can reshape bacterial warfare in a way that benefits a weapon gene and strains that receive it. Interestingly, we also find that there is little cost to a strain that transfers a weapon gene, which is expected to further enable the horizontal gene transfer of molecular weapons.
    DOI:  https://doi.org/10.1371/journal.pbio.3003095
  37. Biomacromolecules. 2025 May 17.
    Enhanced Near-Infrared Light-Mediated Hydrogel Curing Using Photoinitiator Integrated Upconversion Particles as Nano Initiator for 3D Bioprinting.
    Xiong Xiao, Ziwei Huang, Hongying Duan, Liping Yang, Yuchu Yang, Yushang Lai, Chenxi Li, Li Feng.
      In vivo three-dimensional (3D) bioprinting is a promising strategy that can enable personalized organ repair with minimal injury. The current in vivo 3D bioprinting based on upconversion nanoparticles (UCNPs) mediating near-infrared (NIR) light curing is still limited by the low hydrogel cross-linking efficiency. Herein, we introduced a bioink system that allows enhanced NIR light curing by utilizing thiol-ene cross-linkable polymers and photoinitiator-modified UCNPs@LAP nano initiator. The norbornene functionalized hyaluronic acid (NorHA) and thiolated gelatin (GelSH) were first synthesized to prepare the thiol-ene polymer solution. Compared to radical cross-linkable gelatin methacryloyl (GelMA), the NorHA/GelSH exhibited much higher reactivity under weak photoinitiating conditions. With the addition of surface-modified UCNPs@LAP nano initiator, the bioinks showed improved NIR curing performances, which is beneficial to reduce potential thermal damage. Furthermore, in vitro evaluation showed that the NIR light-cured 3D scaffolds preserved excellent bioactivity, suggesting that the hybrid bioink holds great promise to serve as a candidate for in vivo 3D bioprinting.
    DOI:  https://doi.org/10.1021/acs.biomac.4c01775
  38. Nat Biotechnol. 2025 May;43(5): 684
    Bioprinting.
      
    DOI:  https://doi.org/10.1038/s41587-025-02662-4
  39. Nat Chem. 2025 May 22.
    Abiotic lipid metabolism enables membrane plasticity in artificial cells.
    Alessandro Fracassi, Andrés Seoane, Roberto J Brea, Hong-Guen Lee, Alexander Harjung, Neal K Devaraj.
      The plasticity of living cell membranes relies on complex metabolic networks fueled by cellular energy. These metabolic processes exert direct control over membrane properties such as lipid composition and morphological plasticity, which are essential for cellular functions. Despite notable progress in the development of artificial systems mimicking natural membranes, the realization of synthetic membranes capable of sustaining metabolic cycles remains a challenge. Here we present an abiotic phospholipid metabolic network that generates and maintains dynamic artificial cell membranes. Chemical coupling agents drive the in situ synthesis of transiently stable non-canonical phospholipids, leading to the formation and maintenance of phospholipid membranes. We find that phospholipid metabolic cycles can drive lipid self-selection, favouring the enrichment of specific lipid species. Moreover, we demonstrate that controlling lipid metabolism can induce reversible membrane phase transitions, facilitating lipid mixing between distinct populations of artificial membranes. Our work demonstrates that a simple lipid metabolic network can drive dynamic behaviour in artificial membranes, offering insights into mechanisms for engineering functional synthetic compartments.
    DOI:  https://doi.org/10.1038/s41557-025-01829-5
  40. Bioact Mater. 2025 Aug;50 556-570
    Microenvironment-responsive living hydrogel containing engineered probiotic for treatment of massive bone defects.
    Haoyu Fang, Yanyi Wang, Li Li, Xiaotong Qin, Daoyu Zhu, Pei Liu, Qianhao Yang, Youshui Gao, Zhongmin Shi, Xin Ma, Chao Zhong, Yixuan Chen.
      Self-activating and microenvironment-responsive biomaterials for tissue regeneration would address the escalating need for bone grafting, but remain challenging. The emergence of microbial living therapeutics offers vast potential in regenerative medicine, as genetically engineered probiotics possess efficient stimuli-responsiveness and tunable biological functions. Here, using elevated endogenous nitric oxide (NO) signals as a biological trigger in bone fracture injuries, a Living Responsive Regenerative Medicine (LRRM) strategy for in situ bone defect repair through real-time controlled release of bone morphogenetic protein-2 (BMP2) is proposed. The Escherichia coli Nissle 1917 (EcN) strain, genetically engineered to sense NO signals and correspondingly produce and secrete BMP2, was firstly encapsulated in gelatin methacryloyl (GelMA) microspheres and then embedded in a bulky hyaluronic acid methacryloyl (HAMA) hydrogel to form a living hydrogel device that circumvents immune attack and prevents bacterial leakage. In vivo multiple bone defect models demonstrated the efficacy of the living hydrogel in enhancing the maturation of bone callus, promoting neovascularization, and facilitating full-thickness bone union. Strategic incorporation of engineered probiotics and the bilayer-structured encapsulation system may emerge as an effective and microenvironment-responsive medicine approach for tissue regeneration.
    Keywords:  Bacterial engineering; Living hydrogel; Regenerative medicine; Sensing-reporting; Smart biomaterial
    DOI:  https://doi.org/10.1016/j.bioactmat.2025.04.020
  41. Microb Cell Fact. 2025 May 19. 24(1): 112
    Chaperone overexpression boosts heterologous small molecule production in Saccharomyces cerevisiae.
    Andreas M Vestergaard, Wasti Nurani, Paul Cachera, Uffe H Mortensen.
       BACKGROUND: Chaperones play an important role in maintaining cellular proteostasis by mediating protein folding. As a result, chaperone overexpression has been widely used as a tool for enhancing folding and improving production of heterologous proteins in host organisms such as Saccharomyces cerevisiae. In contrast, this strategy has been much less explored for small molecule (SM) production. This is surprising, as SM pathways typically depend on multiple enzymes including large multi-domain synthases or synthetases, which may all benefit from folding assistance to enhance the catalytic power of the pathway.
    RESULTS: We have established an S. cerevisiae strain library of 68 strains overexpressing endogenous cytosolic chaperones and a mating-based method that allows the chaperone library to be combined with a query strain that contains the pathway of a desirable SM. Using the small molecule aspulvinone E from Aspergillus terreus as a model compound, we screened the chaperone library for chaperones that improve production of aspulvinone E. Screening of the library identified several chaperones and chaperone combinations that improved aspulvinone E production. Specifically, the combined overexpression of YDJ1 and SSA1 was identified as the best hit in our screen. Subsequently, we demonstrated that overexpression of YDJ1 and SSA1 improved aspulvinone E production by 84% in 1.5 mL scale batch fermentations. The observed increase is likely due to higher levels of the MelA synthetase responsible for aspulvinone E synthesis, as overexpression of YDJ1 and SSA1 increases the amounts of fluorescent MelA-mRFP in cells producing this fusion protein.
    CONCLUSION: The endogenous cytosolic chaperone overexpression library and mating based screening method presented in this report constitute a tool allowing for fast and efficient identification of specific chaperones and chaperone combinations that benefit production of a given SM in S. cerevisiae-based cell factories.
    Keywords:   Saccharomyces cerevisiae ; Aspulvinone E; Cell factory engineering; Chaperone overexpression; Library screening.; Mating
    DOI:  https://doi.org/10.1186/s12934-025-02728-7
  42. Biomacromolecules. 2025 May 19.
    Effect of Salt on Synthetic Cationic Antimicrobial Polymer-Cell Interactions.
    Zachary Benmamoun, Thomas Kinard, Prem Chandar, Joe Jankolovits, William A Ducker.
      Cationic antiseptics are deployed in a variety of settings, where salinity ranges from almost pure water to hypertonic salt. Here, we examine how dissolved NaCl affects the antimicrobial action of a model antimicrobial, polydiallyldimethylammonium chloride (PDADMAC) to the bacterium Escherichia coli (E. coli). Fluorescence microscopy is used to measure the time course of both the adsorption of PDADMAC to E. coli and the cell viability. NaCl decreases the density of adsorbed PDADMAC and diminishes its efficacy. At NaCl concentrations at or above 0.15 M, PDADMAC no longer kills bacteria but still prevents reproduction by halting the growth in cell length. Reproduction can be restarted if PDADMAC is removed. Fluorescence depolarization measurements show that PDADMAC rigidifies model membranes, but salt reduces the rigidity. We therefore attribute the halt in cell growth to reversible bridging by the polymer on the cell surface that prevents expansion of the cell membrane.
    DOI:  https://doi.org/10.1021/acs.biomac.4c01706
  43. ACS Appl Mater Interfaces. 2025 May 20.
    Micropatterning Photoconductive Peptide Assemblies on Stiff and Soft Biomaterial Substrates.
    Emil M Lundqvist, Kathryn K Lee, Lanie Le, Krystal Nguyen, Sujeung Lim, Natalie Celt, Yuyao Kuang, Ze-Fan Yao, Haotian Wu, Sheng Wei Tang, Jian Pei, Herdeline Ann M Ardoña.
      The propagation of electrical signals in the human heart relies on organized conduction pathways to optimally function and pump blood into the rest of the body. Mimicking this directionality across interconnected myocytes in vitro is currently achieved by patterning the cells themselves, which are often subjected to external stimulatory cues that are rarely localized or have controlled anisotropy. Here, we demonstrate an approach to interface micropatterned optoelectronic peptides with cardiomyocytes, whereby the engineered biomolecular structures dictate the organization of cells in a substrate, while also presenting photocurrent-generating electrodes of defined microscale geometries. To this end, we utilized surface modification strategies that allowed for the creation of stable micropatterns of quaterthiophene-bearing peptide assemblies on both glass (∼GPa range) and gelatin hydrogel (∼20 kPa) substrates that last for multiple days within an aqueous environment. The pH-sensitive assembly behavior of π-conjugated peptides was also investigated as to how it evolves at various stages of the patterning process and impacts material scattering once they are imprinted on different substrates. Neonatal rat ventricular myocytes (NRVMs) seeded on gelatin scaffolds that had been interfaced with π-conjugated peptide micropatterns saw improvements to their orientational order parameter (OOP) of both the actin cytoskeleton and z-lines, which were not observed for those cultured on isotropic controls or on microgrooved gelatin samples. Additionally, the micropatterned π-conjugated peptide platform was shown to exhibit photocurrent-generating properties on both gelatin and glass substrates in aqueous cell culture environments. The peptide-based platform discussed here provides a potential approach to confine conductive biomaterials within microscale features in vitro while simultaneously providing an avenue for light-based localized stimulation of electroactive tissues.
    Keywords:  biomaterials; cardiac tissue engineering; patterning; peptides; photoconductive materials
    DOI:  https://doi.org/10.1021/acsami.5c05693
  44. Carbohydr Polym. 2025 Jun 15. pii: S0144-8617(25)00220-6. [Epub ahead of print]358 123439
    Engineering cellulosic paper into a bending strain sensor using chemical additives: Metal salt-based treatment and ethanol-assisted processing.
    Jianmin Peng, Xin Fu, Xiaoyan Yu, Zhongfei Yuan, Xueren Qian, Yonghao Ni, Zhibin He, Jing Shen.
      The pulp and paper industry, traditionally focused on basic material production, is now expanding into innovative areas, such as advanced functional materials. Papermaking wet-end chemistry & chemical additives is a specialized field that integrates process control in wet-end paper production with the versatile use of chemical additives, which can be tailored for both wet-end and non-wet-end applications. By combining the optimization of wet-end processes with the adaptability of chemical additives-designed specifically for papermaking or adapted from other industries-this field offers immense potential for bridging traditional papermaking with emerging technologies. This study introduces a cellulosic paper-based bending strain sensor enabled by two simple chemical additives: metal salt and ethanol. The sensor is fabricated through a treatment process that engineers the fiber network, enhancing its conductive properties. By transforming the paper's porous structure into a denser network, efficient conductive pathways are established. The resulting material demonstrates features like bending strain detection, isotropic sensitivity, low hysteresis, and high-frequency responsiveness. Additionally, it can sense temperature changes between 20-60 °C and remains functional at subzero temperatures. Encapsulation with polyimide further improves its waterproof and environmental stability. The metal salt-ethanol approach offers a scalable, sustainable, and cost-effective method for producing cellulosic sensors and wearable devices, providing a robust foundation for the practical adoption of innovative sensing technologies.
    Keywords:  Anhydrous ethanol; Cellulosic materials; Conductive paper; Flexible electronics; Metal salt; Papermaking wet-end chemistry & chemical additives; Pulp and paper industry; Wearable sensors
    DOI:  https://doi.org/10.1016/j.carbpol.2025.123439
  45. ACS Synth Biol. 2025 May 19.
    PERRC: Protease Engineering with Reactant Residence Time Control.
    Sage Nelson, Jokent Gaza, Seyednima Ajayebi, Ronald Masse, Raymond Pho, Cianna Scutero, Samantha Martinusen, Lawton Long, Amor Menezes, Alberto Perez, Carl Denard.
      Proteases with engineered specificity hold great potential for targeted therapeutics, protein circuit construction, and biotechnology applications. However, many proteases exhibit broad substrate specificity, limiting their use in such applications. Engineering protease specificity remains challenging because evolving a protease to recognize a new substrate, without counterselecting against its native substrate, often results in high residual activity on the original substrate. To address this, we developed Protease Engineering with Reactant Residence Time Control (PERRC), a platform that exploits the correlation between endoplasmic reticulum (ER) retention sequence strength and ER residence time. PERRC allows precise control over the stringency of protease evolution by adjusting counterselection to selection substrate ratios. Using PERRC, we evolved an orthogonal tobacco etch virus protease variant, TEVESNp, that selectively cleaves a substrate (ENLYFES) that differs by only one amino acid from its parent sequence (ENLYFQS). TEVESNp exhibits a remarkable 65-fold preference for the evolved substrate, marking the first example of an engineered orthogonal protease driven by such a slight difference in substrate recognition. Furthermore, TEVESNp functions as a competent protease for constructing orthogonal protein circuits in bacteria, and molecular dynamics simulations analysis reveals subtle yet functionally significant active site rearrangements. PERRC is a modular dual-substrate display system that facilitates precise engineering of protease specificity.
    Keywords:  high-throughput screening; protease engineering; synthetic biology; tobacco etch virus (TEV) protease; yeast surface display
    DOI:  https://doi.org/10.1021/acssynbio.5c00154
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