bims-livmat 2026-01-18 papers

AIMS Microbiol. 2025 ;11(4): 946-962

Engineered bacteria as living therapeutics: Next-generation precision tools for health, industry, environment, and agriculture.

Imen Zalila-Kolsi.

Synthetic biology has revolutionized precision medicine by enabling the development of engineered bacteria as living therapeutics, dynamic biological systems capable of sensing, responding to, and functioning within complex physiological environments. These microbial platforms offer unprecedented adaptability, allowing for real-time detection of disease signals and targeted therapeutic delivery. This review explores recent innovations in microbial engineering across medical, industrial, environmental, and agricultural domains. Key advances include CRISPR-Cas systems, synthetic gene circuits, and modular plasmid architectures that provide fine-tuned control over microbial behavior and therapeutic output. The integration of computational modeling and machine learning has further accelerated design, optimization, and scalability. Despite these breakthroughs, challenges persist in maintaining genetic stability, ensuring biosafety, and achieving reproducibility in clinical and industrial settings. Ethical and regulatory frameworks are evolving to address dual-use concerns, public perception, and global policy disparities. Looking forward, the convergence of synthetic biology with nanotechnology, materials science, and personalized medicine is paving the way for intelligent, responsive, and sustainable solutions to global health and environmental challenges. Engineered bacteria are poised to become transformative tools not only in disease treatment but also in diagnostics, biomanufacturing, pollution mitigation, and sustainable agriculture.

Keywords: CRISPR-Cas systems; Engineered bacteria; living therapeutics; microbiome engineering; synthetic biology

DOI: https://doi.org/10.3934/microbiol.2025042

ACS Synth Biol. 2026 Jan 13.

Design and Modeling of Biosensor-Driven Encapsulation Systems for Systemic Delivery of Bacterial Cancer Therapy.

Jaeseung Hahn, Tetsuhiro Harimoto, Yu-Yu Chen, Filippo Liguori, Kam W Leong, Tal Danino.

Advances in synthetic biology continue to potentiate bacterial cancer therapy. Here, we constructed biosensor-driven encapsulation systems for autonomous control of capsular polysaccharides of Escherichia coli Nissle 1917 to improve pharmacokinetic profiles. The engineered bacteria were programmed to express capsular polysaccharides for immune evasion upon intravenous administration to reach tumors and then turn off gene expression upon colonizing the tumors based on quorum-sensing or acid-sensing to prevent dissemination of bacteria into the systemic circulation. Because a classical pharmacokinetic model could not capture the dynamic nature of living therapeutics, a two-state pharmacokinetic model was developed to simulate the autonomous control of capsular polysaccharides in different biological compartments and their impact on biodistribution. Using this model, we identified parameters in gene circuit dynamics and immune clearance that influence tumor colonization and systemic bacterial persistence. In a "humanized" pharmacokinetic model with an increased rate of complement-mediated lysis of bacteria, biosensor-driven systems achieved tumor seeding densities comparable to wild-type bacteria while reducing bacterial loads in blood and liver by several orders of magnitude, highlighting their potential for safe systemic delivery. The biosensor-driven systems represent a more effective strategy to control living drugs than inducible systems, and the two-state pharmacokinetic model is a first step to capture the autonomous nature of this new class of therapeutics for clinical translation.

Keywords: biosensor; cancer; capsular polysaccharides; engineered bacteria; pharmacokinetic modeling

DOI: https://doi.org/10.1021/acssynbio.5c00598

Small Methods. 2026 Jan 15. e01450

Rapid Generation of Fusable Cell Beads for Multi-Scale Human Living Materials Assembly.

Beatriz S Moura, Maria V Monteiro, Joana F Soeiro, Nuno J O Silva, Vítor M Gaspar, João F Mano.

Three-dimensional self-assembled cellular aggregates, such as spheroids, provide unique building blocks for bottom-up tissue engineering and in vitro disease modeling. Nevertheless, traditional spheroid production methods require prolonged cell aggregation times and are highly dependent on cell type, requiring frequent optimization steps. Additionally, spheroids' size is dependent on their cell density, preventing a control over their final volume. Herein, a methodology combining metabolic glycoengineering and click chemistry with superhydrophobic surfaces is described to rapidly create spherically structured living bead units, that can surpass the fabrication constraints of conventional spheroids. Compared to spheroids produced in low attachment settings, the living beads comprising various cell types (i.e., stem, endothelial, and cancer cells) are rapidly produced and demonstrate enhanced cell viability and cell spreading over 14 days, while maintaining principal spheroid characteristics, namely the fusion into multi-scale living materials and cellular migration capabilities. In addition, this methodology enables the production of living beads with controlled size, independently of cell density, overcoming a key limitation of current spheroid production methods. The enhanced reproducibility, reduced cell assembly time, and improved handling make these spherically structured living beads a valuable alternative, with broad application in bottom-up tissue engineering approaches and disease modeling applications.

Keywords: bottom‐up assembly; cellgel beads; hierarchical constructs; living materials; metabolic glycoengineering

DOI: https://doi.org/10.1002/smtd.202501450

Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2026 Jan-Feb;18(1):18(1): e70049

Living Organs as Micro-Factories: Material-Producing Organoids.

Quentin M Perrin, Ali Miserez.

Self-organizing tissues, such as organoids, offer transformative potential beyond healthcare by enabling the sustainable production of advanced materials. Resource scarcity and global warming drive the need for innovative fabrication solutions. This prospective review explores developmental biology as a manufacturing process, where the material (e.g., spider silk) and its production unit are self-organized (e.g., silk glands). Biological systems orchestrate the emergence of hierarchical materials with superior mechanical properties and biodegradability, using abundant and renewable resources. Tissue engineering enables the creation of biological systems that surpass current synthetic designs in complexity. We highlight application opportunities, focusing on spider silk as a model to demonstrate how organs synthesize and assemble next-generation materials. The concept of growing both a material and its organ production units is exemplified by hair-bearing organoids, self-organized from induced pluripotent stem cells (iPSCs). Key challenges in expanding organoid research to new model species and scaling-up production are discussed alongside potential solutions. We propose a simplified description of these complex systems to help address key challenges. Furthermore, synthetic and hybrid approaches are explored, considering the ethical, societal, and technological impacts. Though still in their infancy, material-producing organoids present a promising avenue for sustainable, high-value products, fostering new interdisciplinary collaborations among bioengineers, developmental biologists, and material scientists. This work aims to inspire further exploration into the applications of self-organized biological systems in addressing global challenges. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Nanotechnology Approaches to Biology > Cells at the Nanoscale.

Keywords: biological material; organoid; self‐assembly; self‐organization; tissue engineering

DOI: https://doi.org/10.1002/wnan.70049