bims-livmat Biomed News
on Living materials
Issue of 2025–06–15
nine papers selected by
Sara Trujillo Muñoz, Leibniz-Institut für Neue Materialien



  1. Glob Chall. 2025 Jun;9(6): 2400384
      Engineered Living Materials (or ELMs) are an emerging class of materials that utilize microorganisms that can either generate their own structure (such as biofilms) or that can be incorporated into synthetic matrices using technologies (such as 3D printing). ELMs can be designed to have multiple functions, such as biosensing, self-repair, or bioremediation. Such materials have the potential to address a variety of problems related to sustainability, including water security, energy, and health. One major challenge to widescale social acceptance and adoption of these materials is the so-called yuck factor, or the propensity these materials may have to elicit disgust reactions. This Perspective provides an overview of social science research directed at the yuck factor to identify the drivers and demographics of disgust experiences and to examine how each of these are likely to arise in relation to ELMs. Strategies for overcoming these challenges are also addressed. Finally, areas where future empirical research is needed to better understand disgust toward ELMs, or particular ELM applications, are identified.
    Keywords:  disgust; living materials; social acceptance of materials; yuck factor
    DOI:  https://doi.org/10.1002/gch2.202400384
  2. bioRxiv. 2025 Jun 04. pii: 2025.06.04.657808. [Epub ahead of print]
      Engineered living materials (ELMs) at the multicelluar level represent an innovation that promises programmable properties for biomedical, environmental, and consumer applications. However, the rational tuning of the mechanical properties of such ELMs from first principles remains a challenge. Here we use synthetic cell-cell adhesins to systematically characterize how rheological and viscoelastic properties of multicellular materials made from living bacteria can be tuned via adhesin strength, cell size and shape, and adhesion logic. We confirmed that the previous results obtained for non-living materials also apply to bacterial ELMs. Additionally, the incorporation of synthetic adhesins, combined with the adaptability of bacterial cells in modifying various cellular parameters, now enables novel and precise control over material properties. Furthermore, we demonstrate that rheology is a powerful tool for actively shaping the microscopic structure of ELMs, enabling control over cell aggregation and particle rearrangement, a key feature for complex material design. These results deepen our understanding of tuning the viscoelastic properties and fine structure of ELMs for applications like bioprinting and microbial consortia design including natural systems.
    DOI:  https://doi.org/10.1101/2025.06.04.657808
  3. Soft Matter. 2025 Jun 11.
      The proliferation of microorganisms in hydrogels is crucial for the design of engineered living materials and biotechnological processes, and may provide insights into cellular growth in aquatic environments. While the mechanical properties of the gel have been shown to affect the division of entrapped cells, research is still needed to understand the impact and the origin of mechanical forces controlling the growth of microorganisms inside hydrogels. Using diatoms as model microorganisms, we investigate the viability, time to division and growth dynamics of cells entrapped in agar hydrogels with tuneable mechanical properties. Cell culture experiments, confocal optical microscopy and particle tracking velocimetry are performed to uncover the role of stress relaxation and residual stresses in the gel and how these affect diatom proliferation. Our experiments reveal that the interplay between the internal pressure of the dividing cell and the mechanical response of the hydrogel control the proliferation behaviour of the entrapped diatoms. By providing quantitative guidelines for the selection of hydrogels for the entrapment and growth of microorganisms, this study offers new insights on the design of living materials for established and emerging biotechnologies.
    DOI:  https://doi.org/10.1039/d5sm00391a
  4. J Agric Food Chem. 2025 Jun 13.
      Lacto-N-fucopentaose I (LNFP I), a fucosylated neutral human milk oligosaccharide (HMO) with diverse biological functions, was biosynthesized through metabolic engineering in Escherichia coli BL21star (DE3). A de novo pathway was constructed by chromosomal integration of three key enzymes: lgtA (β-1,3-N-acetylglucosaminyltransferase), wbdO (β-1,3-galactosyltransferase), and galE (UDP-galactose-4-epimerase), generating a plasmid-free strain that achieved a lacto-N-tetraose (LNT) titer of 109.80 g/L in a 5 L bioreactor, the highest yield reported to date. Subsequent screening identified α-1,2-fucosyltransferase (FutC) from Helicobacter pylori as the optimal catalyst for LNFP I biosynthesis. Multidimensional optimization strategies were systematically implemented, including copy number balancing of rate-limiting transferases, promoter-RBS engineering, enhanced intracellular cofactor regeneration, and knockout of competing pathways. Fed-batch fermentation under optimized conditions yielded 77 g/L LNFP I with 93.05% LNT-to-LNFP I conversion efficiency, representing both the highest reported titer and precursor utilization efficiency for LNFP I.
    Keywords:  Escherichia coli; human milk oligosaccharide; lacto-N-fucopentaose I; lacto-N-tetraose; metabolic engineering
    DOI:  https://doi.org/10.1021/acs.jafc.5c03851
  5. Sci Adv. 2025 Jun 13. 11(24): eads8651
      Programming microorganism adhesions to engineer multicellular microbial communities holds promise for synthetic biology and medicine. Current chemical and genetic engineering approaches often lack specificity or require engineered bacteria, making the design of responsive interactions challenging. Here, we demonstrate the use of functional DNA as programmable surface receptors to regulate the patterns and behaviors of microbial communities. Using metabolic labeling and hydrophobic insertion, we modified various microorganisms with DNA, including Gram-positive and Gram-negative bacteria, and dormant spores. By incorporating distinct sequences, we achieved precise spatial control of bi- and tricomponent microbial assemblies, forming diverse morphologies like core-shell and selective clusters. Stimuli-responsive clustering was successfully realized using aptamers, strand displacement, and reverse-Hoogsteen base pairing, with oligonucleotides or small molecules as exogenous cues. This work extends the use of functional DNA to control microbial interactions, enabling living communities with dynamic biofunctions, such as biofilm formation, antibiotic sensitivity, and quorum sensing, in response to biological triggers.
    DOI:  https://doi.org/10.1126/sciadv.ads8651
  6. Methods Mol Biol. 2025 ;2942 187-197
      Humans are colonized by trillions of microbes that compose the human microbiome. Much of the microbiome inhabits the mucus layers. Mucus layers, covering digestive, reproductive, ocular, and respiratory tracts, are viscous networks consisting mainly of water and mucin glycoproteins. Mucins assemble into a dense, cross-linked network that can affect bacterial swimming patterns, and studying this behavior provides valuable insights into how the body regulates interactions with both harmful and beneficial microbes. Here we present the use of time-lapse imaging to track individual bacterial cells within mucin and discuss techniques for accurately extracting cell trajectory data from these images. By integrating theoretical and experimental approaches, we also describe how to quantify bacterial movement in terms of speed, persistence, and randomness.
    Keywords:  Bacteria; Cell motility; Cell tracking; Diffusion; Fluorescence microscopy; Microbiome; Mucin; Mucus
    DOI:  https://doi.org/10.1007/978-1-0716-4627-4_16
  7. Gut Microbes. 2025 Dec;17(1): 2517377
      The three main types of live bacterial therapies - probiotics, fecal/microbiome transplants, and engineered bacterial therapies - hold immense potential to revolutionize medicine. While offering targeted and personalized treatments for various diseases, these therapies also carry risks such as adverse immune reactions, antibiotic resistance, and the potential for unintended consequences. Therefore, developing and deploying these therapies necessitates a robust regulatory framework to protect public health while fostering innovation. In this paper, we propose a novel conceptual tool - the Ladder of Regulatory Stringency and Balance-which can assist in the design of robust regulatory regimes which encompass medicine practices based not only on definitive Randomized Controlled Trials (RCTs), but also on meta-analyses, observational studies, and clinicians experience. Regulatory stringency refers to the strictness of regulations, while regulatory balance concerns the degree of alignment between the regulatory framework governing a technology and the actual risks posed by specific products within that technology. Focusing on the US regulatory environment, we subsequently position the three types of live bacterial therapies on the Ladder. The insight gained from this exercise demonstrates that probiotics are generally positioned at the bottom of the Ladder, corresponding to low-stringency regulation, with a proportionate regulatory balance. However, probiotics intended for high-risk populations are currently subject to low-stringency regulations, resulting in under-regulation. Our analysis also supports the conclusion that fecal microbiota transplants (FMT) for recurrent Clostridium difficile infection should be positioned close to but below the threshold for under regulation by the U.S. Food and Drug Administration (FDA), and we recommend improved donor screening procedures, preservation and processing, storage, and distribution. Our framework can serve as a scale to assess regulatory gaps for live bacterial therapies and to identify potential solutions where such gaps exist.
    Keywords:  C difficile; FDA; fecal microbiota transplants; genetically modified organisms; probiotics; regulation
    DOI:  https://doi.org/10.1080/19490976.2025.2517377
  8. Mol Syst Biol. 2025 Jun 09.
      Synthetic biology approaches such as whole-cell biosensing and 'sense-and-respond' therapeutics aim to enlist the vast sensing repertoire of gut microbes to drive cutting-edge clinical and research applications. However, well-characterised circuit components that sense health- and disease-relevant conditions within the gut remain limited. Here, we extend the flexibility and power of a biosensor screening platform using bacterial memory circuits. We construct libraries of sensory components sourced from diverse gut bacteria using a bespoke two-component system identification and cloning pipeline. Tagging unique strains using a hypervariable DNA barcode enables parallel tracking of thousands of unique clones, corresponding to ~150 putative biosensors, in a single experiment. Evaluating sensor activity and performance heterogeneity across various in vitro and in vivo conditions using mouse models, we identify several biosensors of interest. Validated hits include biosensors with relevance for autonomous control of synthetic functions within the mammalian gut and for non-invasive monitoring of inflammatory disease using faecal sampling. This approach will promote rapid biosensor engineering to advance the development of synthetic biology tools for deployment within complex environments.
    Keywords:  Bacterial Biosensor; Gut Microbiome; Inflammation; Synthetic Biology
    DOI:  https://doi.org/10.1038/s44320-025-00123-3
  9. Bioact Mater. 2025 Sep;51 575-597
      The burgeoning field of algal biomedicine capitalizes on evolutionarily refined biological systems to address critical challenges in therapeutic delivery and tissue regeneration. As autotrophic biosystems, unicellular algae uniquely possess multi-functions, including oxygen generation, dynamic motility, fluorescence imaging, and programmable biosynthesis. Their photosynthetic systems not only generate therapeutic oxygen/hydrogen gradients but also facilitate chlorophyll-mediated therapeutics through inherent fluorescence and photodynamic effects. Beyond their metabolic versatility, flagellar propulsion systems, unique morphologies (e.g., helical, elongated), and easily modified surfaces enable precision engineering of algae-based biohybrid microswimmers for spatiotemporally controlled drug delivery. This review comprehensively elucidates mechanistic foundations and biomedical applications of algae-based therapeutic platforms. Spontaneous and persistent oxygen production of algae could rescue hypoxic neurons or cardiomyocytes in myocardial infarction and ischemic stroke lesions, while ameliorating the hypoxia of skin fibroblasts to accelerate wound healing. In addition, increased oxygen levels enable the improvement of hypoxic tumor microenvironments to enhance the sensitivity of chemotherapy/radiotherapy to malignancies. Moreover, many versatile algae-based microswimmers have been developed for delivering therapeutic agents to treat gastrointestinal diseases and bacterial infections. It is believed that these photosynthetic microorganisms have great potential for being developed as next-generation platforms to address growing biomedical challenges.
    Keywords:  Algae; Drug delivery; Microswimmers; Oxygen generation; Photosynthesis
    DOI:  https://doi.org/10.1016/j.bioactmat.2025.05.023