bims-enlima Biomed News
on Engineered living materials
Issue of 2025–04–06
twenty-six papers selected by
Rahul Kumar, Tallinna Tehnikaülikool



  1. Nat Chem Biol. 2025 Mar 28.
      Inspired by the power of transcriptional synthetic receptors and hoping to complement them to expand the toolbox for cell engineering, we establish LIDAR (Ligand-Induced Dimerization-Activating RNA editing), a modular post-transcriptional synthetic receptor platform that harnesses RNA editing by adenosine deaminases acting on RNA. LIDAR is compatible with various receptor architectures in different cellular contexts and enables the sensing of diverse ligands and the production of functional outputs. Furthermore, LIDAR can sense orthogonal signals in the same cell and produce synthetic spatial patterns, potentially enabling the programming of complex multicellular behaviors. Lastly, LIDAR is compatible with compact encoding and can be delivered as synthetic mRNA. Thus, LIDAR expands the family of synthetic receptors, holding the promise to empower basic research and therapeutic applications.
    DOI:  https://doi.org/10.1038/s41589-025-01872-w
  2. bioRxiv. 2025 Mar 21. pii: 2025.03.21.644572. [Epub ahead of print]
      Biological systems use protein circuits to organize cellular activities in space and time, but engineering synthetic dynamics is challenging due to stochastic effects of genetic and biochemical variation on circuit behavior. Genetically encoded oscillators (GEOs) built from bacterial MinDE-family ATPase and Activator modules generate fast orthogonal protein waves in eukaryotic cells, providing an experimental model system for genetic and biochemical coordination of synthetic protein dynamics. Here, we use budding yeast to experimentally define and model phase portraits that reveal how the breadth of frequencies and amplitudes available to a GEO are genetically controlled by ATPase and Activator expression levels and noise. GEO amplitude is encoded by ATPase absolute abundance, making it sensitive to extrinsic noise on a population level. In contrast, GEO frequency is remarkably stable because it is controlled by the Activator:ATPase ratio and thus affected primarily by intrinsic noise. These features facilitate noise-guided design of different expression strategies that act as filters on GEO waveform, enabling us to construct clonal populations that oscillate at different frequencies as well as independently tune frequency and amplitude variation within a single population. By characterizing 169 biochemically distinct GEOs, we provide a rich assortment of phase portraits as starting points for application of our waveform engineering approach. Our findings suggest noise-guided design may be a valuable strategy for achieving precision control over dynamic protein circuits.
    DOI:  https://doi.org/10.1101/2025.03.21.644572
  3. bioRxiv. 2025 Mar 14. pii: 2025.03.12.642522. [Epub ahead of print]
      Trogocytosis, the transfer of plasma membrane fragments during cell-cell contact, offers potential for macromolecular delivery but is limited by uncertain fate of trogocytosed molecules, constraints to membrane cargo, and unclear generalizability. Here, we demonstrate that donor cells engineered with designed receptors specific to intrinsic ligands can transfer proteins to recipient cells through direct contact. We identified key principles for enhancing contact-mediated transfer and subsequent functionalization of transferred macromolecules, including receptor design, pH-responsive membrane fusion, inducible cargo localization, release, and subcellular translocation. Exploiting these findings, we developed TRANSFER, a versatile delivery system that integrates logic gate-based control to sense multiple ligand inputs and deliver diverse functional cargos for genome editing and targeted cell ablation across cell types. The study establishes trogocytosis as a novel, programmable framework for cell-based macromolecular delivery.
    DOI:  https://doi.org/10.1101/2025.03.12.642522
  4. ACS Appl Mater Interfaces. 2025 Mar 30.
      Multifunctional antibodies, capable of simultaneously engaging multiple targets, are a unique class of antibodies that have sparked growing interest. Current approaches for making multifunctional antibodies, including chemical conjugation or genetic modifications, suffer from low product yield, complex structure design, and complicated manufacturing processes. In this study, we report a modular post-translational platform with highly specific protein-protein interactions for multifunctional antibody assembly and an elastin-like polypeptide (ELP) for easy purification. We generated and purified multifunctional antibodies with over 90% assembled scaffold and overall product purity. Additionally, we assembled antibodies with diverse applications, including detecting cancer, inhibiting cancer cell growth, and directing T cells to cancer cells for enhanced therapeutic efficacy. This platform offers high assembly efficiency, easy purification, and modularity for the redesign of antibody functions.
    Keywords:  antibody engineering; elastin-like polypeptide (ELP); nanobody; protein purification; protein−protein interaction
    DOI:  https://doi.org/10.1021/acsami.4c21958
  5. Proc Natl Acad Sci U S A. 2025 Apr 08. 122(14): e2424112122
      Microbial colony development hinges upon a myriad of factors, including mechanical, biochemical, and environmental niches, which collectively shape spatial patterns governed by intricate gene regulatory networks. The inherent complexity of this phenomenon necessitates innovative approaches to comprehend and compare the mechanisms driving pattern formation. Here, we unveil the multistability of bacterial colony patterns, where bacterial colony patterns can stabilize into multiple distinct types including ring-like patterns and sector-like patterns on hard agar, orchestrated by a simple synthetic bistable switch. Utilizing quantitative imaging and spatially resolved transcriptome approaches, we explore the deterministic process of a ring-like colony pattern formation from a single cell. This process is primarily driven by bifurcation events programmed by the gene regulatory network and microenvironmental cues. Additionally, we observe a noise-induced process amplified by the founder effect, leading to patterns of symmetry-break during range expansion. The degrees of asymmetry are profoundly influenced by the initial conditions of single progenitor cells during the nascent stages of colony development. These findings underscore how the process of range expansion enables individual cells, exposed to a uniform growth-promoting environment, to exhibit inherent capabilities in generating emergent, self-organized behavior.
    Keywords:  cell fate decision; pattern formation; range expansion; synthetic biology
    DOI:  https://doi.org/10.1073/pnas.2424112122
  6. Small. 2025 Mar 31. e2501172
      Structural colors are bright and possess a remarkable resistance to light exposure, humidity, and temperature such that they constitute an environmentally friendly alternative to chemical pigments. Unfortunately, upscaling the production of photonic structures obtained via conventional colloidal self-assembly is challenging because defects often occur during the assembly of larger structures. Moreover, the processing of materials exhibiting structural colors into intricate 3D structures remains challenging. To address these limitations, rigid photonic microparticles are formulated into an ink that can be 3D printed through direct ink writing (DIW) at room temperature to form intricate macroscopic structures possessing locally varying mechanical and optical properties. This is achieved by adding small amounts of soft microgels to the rigid photonic particles. To rigidify the granular structure, a percolating hydrogel network is formed that covalently connects the microgels. The mechanical properties of the resulting photonic granular materials can be adjusted with the composition and volume fraction of the microgels. The potential of this approach is demonstrated by 3D printing a centimeter-sized photonic butterfly and a temperature-responsive photonic material.
    Keywords:  design of experiment; extrusion‐based printing; mechanics; rheology; stiff microparticles; structural colors; temperature sensor
    DOI:  https://doi.org/10.1002/smll.202501172
  7. Curr Opin Biotechnol. 2025 Mar 29. pii: S0958-1669(25)00043-6. [Epub ahead of print]93 103299
      One-carbon (C1) greenhouse gases are the primary driver of global climate change. Fermenting these gases into higher-value products is an attractive strategy for climate action and sustainable development. C1 gas-fermenting bacteria are promising chassis organisms, but various technical challenges hinder scale-up to industrial production levels. Bacterial microcompartments (MCPs), proteinaceous organelles that encapsulate enzymatic pathways, may confer several metabolic benefits to increase the industrial potential of these bacteria. Many species of gas-fermenting bacteria are already predicted to natively produce MCPs. Here, we describe how these organelles can be identified and engineered to encapsulate pathways that convert C1 gases into valuable chemical products.
    DOI:  https://doi.org/10.1016/j.copbio.2025.103299
  8. bioRxiv. 2025 Mar 17. pii: 2025.03.17.643471. [Epub ahead of print]
      Cell-free biosensing systems are being engineered as versatile and programmable diagnostic technologies. A core component of cell-free biosensors are programmable molecular circuits that improve biosensor speed, sensitivity and specificity by performing molecular computations such as logic evaluation and signal amplification. In previous work, we developed one such circuit system called Polymerase Strand Recycling (PSR) which amplifies cell-free molecular circuits by using T7 RNA polymerase off-target transcription to recycle nucleic acid inputs. We showed that PSR circuits can be configured to detect RNA target inputs as well as be interfaced with allosteric transcription factor-based biosensors to amplify signal and enhance sensitivity. Here we expand the development of PSR circuit design principles to generalize the platform for detecting a diverse set of model microRNA inputs. We show that PSR circuit function can be enhanced through engineering T7 RNAP, and present troubleshooting strategies to optimize PSR circuit performance.
    DOI:  https://doi.org/10.1101/2025.03.17.643471
  9. ACS Appl Mater Interfaces. 2025 Apr 01.
      Many organisms have evolved sophisticated structural colors that adapt to input signals in their environment for communication, camouflage, and/or aposematism. However, replicating such an ability remains an engineering and materials challenge. This study presents an approach for building and controlling structural color using pigment-impregnated polystyrene (PS) particles stabilized with a triblock copolymer (TBC). These hybrid particles exhibit robust, reversible color shifts under an applied electric field, by leveraging electrophoretic mobility to modulate structural color. The incorporation of a bioinspired pigment xanthommatin (Xa) into the PS particles expands the color profile of the system, while the TBC provides enhanced reversibility under electrophoretic control. A prototype pixel array with staggered connections further demonstrates the controllable color shift potential in a practical display setup. This work advances the field of adaptive materials by offering a strategy that combines bioinspired coloration principles with electrophoretic control for responsive displays and coatings.
    Keywords:  adaptive; bioinspired; electrophoresis; structural color; xanthommatin
    DOI:  https://doi.org/10.1021/acsami.5c00995
  10. Adv Sci (Weinh). 2025 Apr 03. e2412566
      Rapid advances in biomedical applications and soft robotics demand load-bearing soft materials that can be processed into complex 3D shapes. Direct ink writing (DIW) enables the fabrication of customizable shapes with locally varying compositions. Hydrogels that are formulated as microgels meet the rheological requirements that DIW imparts on the inks if they are jammed. However, most granular hydrogels are soft because inter-particle interactions are weak. These hydrogels can be reinforced with a second hydrogel, yielding double network granular hydrogels (DNGHs). Yet, DNGHs suffer from low fracture energy. This limitation is addressed by electrostatically reinforcing them. The resulting materials exhibit Young's moduli and fracture energies similar to values of cartilage and muscles. An empirical model is proposed to predict the fracture energy of these reinforced DNGHs, based on the dissipation zone size, contact area, and adhesion energy. These DNGHs can be 3D-N, N-methylene bisacrylamideprinted into free-standing structures exhibiting tuneable mechanical properties at the centimeter scale without the need for supporting structures.
    Keywords:  additive manufacturing; fracture energy; granular hydrogel; interfacial reinforcement
    DOI:  https://doi.org/10.1002/advs.202412566
  11. Cell Stem Cell. 2025 Mar 25. pii: S1934-5909(25)00092-X. [Epub ahead of print]
      Human engineered tissues hold great promise for therapeutic tissue regeneration and repair. Yet, development of these technologies often stalls at the stage of in vivo studies due to the complexity of engineered tissue formulations, which are often composed of diverse cell populations and material elements, along with the tedious nature of in vivo experiments. We introduce a "plug and play" platform called parallelized host apposition for screening tissues in vivo (PHAST). PHAST enables parallelized in vivo testing of 43 three-dimensional microtissues in a single 3D-printed device. Using PHAST, we screen microtissue formations with varying cellular and material components and identify formulations that support vascular graft-host inosculation and engineered liver tissue function in vivo. Our studies reveal that the cellular population(s) that should be included in engineered tissues for optimal in vivo performance is material dependent. PHAST could thus accelerate development of human tissue therapies for clinical regeneration and repair.
    Keywords:  3D printing; biomaterial; bioprinting; high-throughput; hydrogel; in vivo; liver; microenvironment; tissue engineering; vascularization
    DOI:  https://doi.org/10.1016/j.stem.2025.03.002
  12. Biochemistry. 2025 Apr 02.
      Cell surface oligosaccharides and related polymers are commonly decorated with acyl esters that alter their structural properties and influence their interactions with other molecules. In many cases, these esters are added to polymers that are already positioned on the extracytoplasmic side of a membrane, presenting cells with a chemical challenge because the high-energy acyl donors used for these modifications are made in the cytoplasm. How activated acyl groups are passed from the cytoplasm to extra-cytoplasmic polymers has been a longstanding question. Recent mechanistic work has shown that many bacterial acyl transfer pathways operate by shuttling acyl groups through two covalent intermediates to their final destination on an extracellular polymer. Key to these and other pathways are cross-membrane acyltransferases─enzymes that catalyze transfer of acyl groups from a donor on one side of the membrane to a recipient on the other side. Here we review what has been learned recently about how cross-membrane acyltransferases in polymer acylation pathways function, highlighting the chemical and biosynthetic logic used by two key protein families, membrane-bound O-acyltransferases (MBOATs) and acyltransferase-3 (AT3) proteins. We also point out outstanding questions and avenues for further exploration.
    Keywords:  AT3; MBOAT; SGNH; acetyltransferase; acyltransferase; bacteria; cell envelope; cell surface; enzyme mechanism; glycopolymer; polysaccharide; transferase
    DOI:  https://doi.org/10.1021/acs.biochem.4c00731
  13. Chemistry. 2025 Apr 01. e202500884
      The regulation of hydrogen-bonding networks in molecular switches is critical for adaptive materials. However, most of the reported molecular switches do not are not capable of modulating hydrogen-bonding networks in energetic materials, limiting their use in high-demand applications such as energetic systems. In this work, the first high-energy nitroamino-based molecular switch is reported. It can control the complex hydrogen bonding systems of energetic materials by reversible cycling for property modulation. Through alkali-acid stimulation, the nitroamino-based switch undergoes dynamic transitions, which reconfigure H-bond networks and separate twin crystals (in X-ray verification). Supported by crystallography and theorical modeling (e.g., the density of states), this switching mechanism modulates molecular planarity (Δθ>60°) and optimizes the energy-stability balance, obtaining a compound 6-β with comprehensive properties comparable to classical explosives (e.g., RDX and HMX). By linking hydrogen-bonding engineering and energetic materials science through the nitroamino-based molecular switch, it facilitates superior energetic compounds that can be applied to defense equipments. In addition, our work establishes the nitroamino-based switch as a generalized tool for molecular engineering, bridging dynamic hydrogen-bonding control and self-assembly materials design.
    Keywords:  Self-assembly; energetic compounds; explosives; hydrogen-bonding modulation; molecular switches
    DOI:  https://doi.org/10.1002/chem.202500884
  14. Sci Adv. 2025 Apr 04. 11(14): eads4735
      Suppressing plasmid transfer in microbial communities has profound implications due to the role of horizontal gene transfer (HGT) in spreading and maintaining diverse functional traits such as metabolic functions, virulence factors, and antibiotic resistance. However, existing tools for inhibiting HGT are limited in their modes of delivery, efficacy, and scalability. Here, we present a versatile denial-of-spread (DoS) strategy to target and eliminate specific conjugative plasmids. Our strategy exploits retrotransfer, whereby an engineered DoS plasmid is introduced into host cells containing a target plasmid. Acting as a predatory gene drive, DoS propagates itself at the expense of the target plasmid, through competition or active elimination. Once the target plasmid is eradicated, DoS is removed via induced plasmid suicide, resulting in a community containing neither plasmid. The strategy is tunable and scalable for various conjugative plasmids, different mechanisms of plasmid inheritance interruption, and diverse environmental contexts. DoS represents a new tool for precise control of gene persistence in microbial communities.
    DOI:  https://doi.org/10.1126/sciadv.ads4735
  15. Carbohydr Polym. 2025 Jun 01. pii: S0144-8617(25)00219-X. [Epub ahead of print]357 123438
      Microorganisms can induce biomineralization of inorganic ions to form a lipophobic layer on the surface of cave rocks. Mimicking this, we developed and propose a protocol that produces a highly lipophobic hybrid layer of CaCO3 nanoparticles on hydrogel surfaces. This lipophobic layer endows hydrogels with an oil contact angle of 162°, causing oil droplets placed on the surface to bead up and roll off immediately. The lipophobic surface effectively resists staining from lipophilic dyes, and does not adhere to double-sided tapes. A lipophobic layer on hydrogel tubes effectively prevents the adhesion of thrombus and axunge during a three-day implantation period in rabbits. The hydrogel tubes, made of biodegradable sodium alginate, can serve as implantable scaffolds, degrading in the body, and avoiding the need for removal surgery. These properties make hydrogel tubes promising for medical devices like absorbable stents and catheters.
    Keywords:  Biomineralization; Hollow hydrogel tubes; Lipophobicity; Medical devices
    DOI:  https://doi.org/10.1016/j.carbpol.2025.123438
  16. Microb Cell Fact. 2025 Mar 29. 24(1): 75
      Isoflavones such as daidzein and genistein are naturally occurring compounds found in plants such as legumes. They have diverse pharmacological activities, making them valuable in the food, pharmaceutical, and cosmetic industries. Currently, isoflavones are mainly obtained through the extraction of plant biomass. Chemical synthesis is challenging for most isoflavones due to the complexity of their structures. The limited supply of isoflavones cannot meet the market demands. Advances in synthetic biology have provided a sustainable and efficient solution for the production of isoflavones, with yeasts often serving as the microbial chassis for biosynthesis. This review summarizes the pharmacological properties of specific isoflavones, their biosynthetic pathways, and the technical strategies used in engineered yeasts for isoflavone production. In addition, the development of synthetic biology and state-of-the-art biotechnological strategies for the environmentally friendly production of bioactive isoflavones is discussed.
    Keywords:  Engineered yeasts; Isoflavones; Metabolic pathways; Synthetic biology
    DOI:  https://doi.org/10.1186/s12934-025-02692-2
  17. Nat Microbiol. 2025 Mar 31.
      The gut microbiome changes with age and has been proposed to mediate the benefit of lifespan-extending interventions such as dietary restriction. However, the causes and consequences of microbiome ageing and the potential of such interventions remain unclear. Here we analysed 2,997 metagenomes collected longitudinally from 913 deeply phenotyped, genetically diverse mice to investigate interactions between the microbiome, ageing, dietary restriction (caloric restriction and fasting), host genetics and a range of health parameters. Among the numerous age-associated microbiome changes that we find in this cohort, increased microbiome uniqueness is the most consistent parameter across a second longitudinal mouse experiment that we performed on inbred mice and a compendium of 4,101 human metagenomes. Furthermore, cohousing experiments show that age-associated microbiome changes may be caused by an accumulation of stochastic environmental exposures (neutral theory) rather than by the influence of an ageing host (selection theory). Unexpectedly, the majority of taxonomic and functional microbiome features show small but significant heritability, and the amount of variation explained by host genetics is similar to ageing and dietary restriction. We also find that more intense dietary interventions lead to larger microbiome changes and that dietary restriction does not rejuvenate the microbiome. Lastly, we find that the microbiome is associated with multiple health parameters, including body composition, immune components and frailty, but not lifespan. Overall, this study sheds light on the factors influencing microbiome ageing and aspects of host physiology modulated by the microbiome.
    DOI:  https://doi.org/10.1038/s41564-025-01963-3
  18. Science. 2025 Apr 04. 388(6742): 74-81
      Colonization of the intestinal lumen precedes invasive infection for a wide range of enteropathogenic and opportunistic pathogenic bacteria. We show that combining oral vaccination with engineered or selected niche-competitor strains permits pathogen exclusion and strain replacement in the mouse gut lumen. This approach can be applied either prophylactically to prevent invasion of nontyphoidal Salmonella strains, or therapeutically to displace an established Escherichia coli. Both intact adaptive immunity and metabolic niche competition are necessary for efficient vaccine-enhanced competition. Our findings imply that mucosal antibodies have evolved to work in the context of gut microbial ecology by influencing the outcome of competition. This has broad implications for the elimination of pathogenic and antibiotic-resistant bacterial reservoirs and for rational microbiota engineering.
    DOI:  https://doi.org/10.1126/science.adp5011
  19. ACS Nano. 2025 Mar 31.
      Synthetic nano- and microparticles have become essential tools in biotechnology. Protein-based compartments offer distinct advantages over synthetic particles, such as biodegradability and biocompatibility, but their development is still in its infancy. Bacterial microcompartments (BMCs) are protein-based organelles consisting of a protein shell encapsulating an enzymatic core. BMCs are self-assembling, selectively permeable, and modular, making them ideal candidates for the development of protein compartments for biotechnology. Indeed, several groups have engineered BMC shells and individual shell proteins into synthetic nanoreactors and functionalized molecular scaffolds. Expanding the variety of architectures assembled from BMC shell proteins will increase their versatility as building blocks in biotechnology. Here, we developed a method for the in vitro assembly of single-component monodisperse microparticles using only CcmK2, the major hexameric shell protein of the β-carboxysome BMC. We report the controlled assembly of a single type of BMC shell protein into a solid microparticle. High-resolution imaging revealed CcmK2 particles to be assemblies of radially clustered nanotubes. Through biochemical characterization, we determined the conditions for reversible assembly and residues mediating assembly. We found that pH is a key regulator of final particle size and disassembly. Our study situates CcmK2 particles as precisely controlled and self-assembling monodisperse solid protein particles for future applications in biotechnology.
    Keywords:  Bacterial microcompartment; carboxysome; microparticle; nanoparticle; pH-responsive; self-assembly
    DOI:  https://doi.org/10.1021/acsnano.4c18021
  20. Nat Commun. 2025 Apr 01. 16(1): 3134
      The direct reduction of CO2 into one-carbon molecules is key to highly efficient biological CO2-fixation. However, this strategy is currently restricted to anaerobic organisms and low redox potentials. In this study, we introduce the CORE cycle, a synthetic metabolic pathway that converts CO2 to formate at aerobic conditions and ambient CO2 levels, using only NADPH as a reductant. Combining theoretical pathway design and analysis, enzyme bioprospecting and high-throughput screening, modular assembly and adaptive laboratory evolution, we realize the CORE cycle in vivo and demonstrate that the cycle supports growth of E. coli by supplementing C1-metabolism and serine biosynthesis from CO2. We further analyze the theoretical potential of the CORE cycle as a new entry-point for carbon in photorespiration and autotrophy. Overall, our work expands the solution space for biological carbon reduction, offering a promising approach to enhance CO2 fixation processes such as photosynthesis, and opening avenues for synthetic autotrophy.
    DOI:  https://doi.org/10.1038/s41467-025-57549-4
  21. Nat Chem. 2025 Apr 03.
      Transcriptional regulation is a dynamic process that coordinates diverse cellular activities, and the use of small molecules to perturb gene expression has propelled our understanding of the fundamental regulatory mechanisms. However, small molecules typically lack the spatiotemporal precision required in highly non-invasive, controlled settings. Here we present the development of a cell-permeable small-molecule DNA G-quadruplex (G4) binder, termed G4switch, that can be reversibly toggled on and off by visible light. We have biophysically characterized the light-mediated control of G4 binding in vitro, followed by cellular, genomic mapping of G4switch to G4 targets in chromatin to confirm G4-selective, light-dependent binding in a cellular context. By deploying G4switch in living cells, we show spatiotemporal control over the expression of a set of G4-containing genes and G4-associated cell proliferation. Our studies demonstrate a chemical tool and approach to interrogate the dynamics of key biological processes directly at the molecular level in cells.
    DOI:  https://doi.org/10.1038/s41557-025-01792-1
  22. bioRxiv. 2025 Mar 10. pii: 2025.03.06.641880. [Epub ahead of print]
       Purpose: In muscle tissues, anisotropic cell alignment is essential for optimal muscle fiber development and function. Biomaterials for muscle tissue engineering must guide cellular alignment while supporting cell proliferation and myogenic differentiation.
    Methods: Here, we describe the fabrication of a tissue-engineered construct consisting of a scaffold of aligned poly(ε-caprolactone) (PCL) microfibers coated in a dynamic covalent hydrazone crosslinked hyaluronic acid (HA) hydrogel to support myoblast attachment, alignment, and differentiation. Norbornene modification of HA further enabled functionalization with fibronectin-derived arginine-glycine-aspartic acid (RGD) peptide. Scaffolds were fabricated using melt electrowriting (MEW), a three-dimensional (3D)-printing technique that uses stabilization of fluid columns to produce precisely aligned polymeric microfibers. We evaluated scaffolds with fiber diameters of 10 μm, 20 μm, and 30 μm of non-coated, HA-coated, and HA-RGD-coated MEW scaffolds through immunocytochemistry and creatine kinase activity assays.
    Results: HA-coated and HA-RGD-coated scaffolds showed increased cellular attachment of C2C12 mouse skeletal myoblasts on all fiber diameters compared to non-coated scaffolds, with HA-RGD-coated scaffolds demonstrating the highest cell attachment. All scaffolds supported cellular alignment along the fibers. Cells differentiated on scaffolds showed anisotropic alignment with increased myotube formation on HA-RGD-coated scaffolds as seen by myosin heavy chain (MHC) staining. Highest creatine kinase (CK) activity on day 5 signified the successful differentiation of C2C12 cells into mature myotubes.
    Conclusion: This unique combination of tunable biophysical and biochemical cues enables the creation of a biomimetic tissue engineered scaffold, providing a platform for new therapeutic approaches for muscle regeneration.
    Keywords:  Muscle regeneration; cellular alignment; hyaluronic acid; melt electrowriting; microfiber scaffold; polycaprolactone
    DOI:  https://doi.org/10.1101/2025.03.06.641880
  23. Nat Chem. 2025 Apr;17(4): 477-492
      Developing new generic methodologies for organizing molecules into nano- to mesoscale structures of precise shapes and sizes is a research topic at the forefront of modern chemistry. Creating hierarchical molecular assembly, especially at the mesoscale, is important to realize functions reminiscent of those manifested by biomolecular assemblies in the mesoscopic regime. However, this is challenging due to the difficulty in maintaining stringent controllability over the organization of molecules at higher hierarchical levels, wherein weak non-directional intermolecular interactions rather than strong directional interactions typically play a predominant role. Recent studies have revealed that secondary nucleation, often experienced by one-dimensional assemblies such as supramolecular polymers that grow with spontaneous nucleation, is effective in the hierarchical construction of higher-order structures. Here we illustrate how secondary nucleation can be combined with the well-established precision synthesis of supramolecular polymers to realize precise control over hierarchical structures in the mesoscopic regime. We present a roadmap for creating hierarchical supramolecular polymers by exploiting secondary nucleation-elongation processes and discuss future prospects for the field.
    DOI:  https://doi.org/10.1038/s41557-025-01764-5
  24. ACS Nano. 2025 Mar 31.
      Organoids are 3D artificial miniature organs composed of a cluster of self-renewing and self-organizing cells in vitro, which mimic the functions of real organs. Nanotechnologies, including the preparation of nanomaterials and the fabrication of micro/nanostructures, have been proven to promote cell proliferation, guide cell differentiation, and regulate cell self-organization, showing great promise in engineering organoids. In this Perspective, different types of nanocomposite hydrogels for organoid culture are summarized, the effects of micro/nanostructures on organoid growth and development are discussed, and 3D bioprinting technologies for constructing organoid models are introduced.
    Keywords:  Nanomaterials; cell self-organization; hydrogels; micro/nanostructures; organoids
    DOI:  https://doi.org/10.1021/acsnano.4c17587
  25. Biochemistry. 2025 Apr 03.
      Lipid nanoparticle (LNP)-based mRNA delivery has a lot of potential in combating a wide range of diseases, but delivering mRNA to specific cell types continues to be challenging. Despite recent advances in organ and cell specificity, the majority of clinical LNP systems cannot fully release their payload to a targeted site. Incorporating active targeting moieties into LNPs is highly desired to expand nanomedicine applications. In this Letter, we developed LNPs that harness the power of bioorthogonal "click" azide-alkyne chemical reactions. We show that the plasma membranes of cancer cells can be labeled with azide groups by metabolic sugar labeling, and these azide groups can react with dibenzocyclooctyne (DBCO) on LNPs to achieve specific binding. To achieve this, we synthesized new and versatile lipids by functionalizing DBCO groups to phospholipids with or without a poly(ethylene glycol) (PEG) linker. The DBCO lipids were successfully formulated into DBCO-LNPs comprising other standard lipid compounds. When using these DBCO-LNPs to deliver mRNA to metabolically labeled cells, DBCO-LNPs showed a remarkable ability to preferentially deliver mRNA to azide-labeled cells. Removing PEG linkers from DBCO lipids enables better integration and retention in the LNP, and the higher the amount of DBCO lipid, the stronger the targeting effect. This work demonstrates that cell-specific targeting can be achieved utilizing azide-alkyne ″click″ chemistry and could inspire the development of the next generation of LNPs for active cyto-tropic nanomedicines.
    DOI:  https://doi.org/10.1021/acs.biochem.4c00699