bims-livmat 2026-08-30 papers

Nat Commun. 2026 Jul 23. pii: 8958. [Epub ahead of print]17(1):

A programmable living force sensor fabricated with surface engineered microbial network.

Si Shi, Changhong Wang, Qiliner Feng, Hailin Li, Aike Shi, Jie Liu, Yongzheng Ma, Xiangjun Gong, Zifu Li, Baizhu Chen.

Engineered living materials have recently expanded into the field of bioelectronics when incorporating the rationally rewired microbes inside. Integrating living materials with force sensing provides an alternative route to overcome limitations of traditional sensors, such as fragility and stretching-sensitivity. Here, we present a programmable living force sensor fabricated by surface engineered microbial network with a bottom-up design for human-machine interfaces. Bacterial cells are genetically rewired to display surface-anchored affinity pairs that mediate the assembly of bacteria to macroscale. Functioning as the conductive and sensing layer, the microbial network is encapsulated in elastic tubes to fabricate the macroscopic force sensor. The resulting living sensor features a tunable measuring range, rapid self-recovery capacity within tens of milliseconds, and remarkably, excellent stretching-insensitivity with only ~30% increase in resistance under 800% of elongation. This bio-integrated approach enables microbes to prepare robust and reconfigurable force sensor suitable for tensile, dynamic and extreme mechanical conditions.

DOI: https://doi.org/10.1038/s41467-026-75944-3

J Control Release. 2026 Aug 24. pii: S0168-3659(26)00678-4. [Epub ahead of print] 115274

Living drug carriers: Microbial and bioengineered platforms redefining precision therapeutic and immunomodulatory delivery.

Lahanya Guha, Jonaid Ahmad Malik, Bipasha Bose.

Microbial living therapeutics are a new class of drug-delivery materials that combine synthetic biology, immunomodulation, and advanced formulations to achieve controllable therapeutic effects in space and time. In the broad field of living drug-delivery systems, therapeutic platforms include engineered microorganisms, mammalian immune cells, stem cells, viral vectors, extracellular-vesicle-producing cells, and hybrid bioengineered living materials. This review focuses on engineered microbial living drug carriers, including genetically modified bacteria and probiotic platforms, because these systems uniquely integrate programmable biosensing, in situ therapeutic synthesis, adaptive immunomodulation, and controllable drug delivery within a single living chassis. Designed microbes and consortia possess other unique functions, such as microenvironment sensing, programmed control of gene expression, and long-lasting in situ manufacturing of therapeutic payloads not available with small-molecule or biologic drugs. Recent progress in microbial chassis engineering, genetic circuit design, and biocontainment has enabled fine-tuning of immune responses, metabolic pathways, and tissue-specific signaling in a wide range of diseases from cancer to autoimmune and inflammatory diseases, to metabolic and endocrine disorders, neuro-immunological conditions (e.g., amyotrophic lateral sclerosis), infectious diseases including infectious threats without existing approved vaccines (Zika virus) as well as rare genetic disorders. Advances in formulation science, including encapsulation technologies, biomaterial-microbe hybrids, and stimuli-responsive release platforms, have enabled overcoming key translation challenges concerning microbial viability, biodistribution, safety, and controlled activation in complex physiological milieus like the gut (for enteric pathogens), tumor microenvironment (for oncolytic organisms), or injured tissues (for tissue-targeting organisms). Increasing numbers of clinical-stage LBP studies are now conducted under good manufacturing practice, standardized QC, and clinical conditions, ranging from emerging PK, biodistribution, and biomarker-driven studies to those adapted to living entities. The addition of host microbiome profiling, multi-omics analysis, and computational modeling is anticipated to increase therapeutic predictability and patient stratification. Taken together, these advances position live microbial therapeutics as programmable biological medicines with the potential for adaptive, context-specific administration and warrant further clinical development and increased integration within precision medicine-informed therapeutic approaches.

Keywords: Engineered probiotics and consortia; Immunomodulatory drug delivery; LMTs; Programmable gene circuits; Targeted and controlled release systems

DOI: https://doi.org/10.1016/j.jconrel.2026.115274

Biomaterials. 2026 Aug 20. pii: S0142-9612(26)00589-2. [Epub ahead of print]337 124565

Multidimensional interactions of living materials with biological entities.

Shuqing Du, Yanfei Liu, Yongbo Liu, Yifu Tan, Yunqi Man, Zhirou Zhang, Zexiang Lv, Luke P Lee, Qi-Wen Chen, Zhenbao Liu.

Living materials, defined by dynamic biological activity and responsive capabilities, are emerging as pivotal therapeutic agents in biomedicine. Their therapeutic effects are driven by active interactions with biological entities at multiple levels. However, most existing reviews focus narrowly on fabrication methods or specific applications, lacking a comprehensive, integrated analysis of the complex, multidimensional interactions between living materials and host cells, tissues, disease microenvironments, and the organism as a whole. This gap impedes the full understanding of the regulatory mechanisms that govern the relationship between these interactions and therapeutic outcomes. This work aims to bridge this gap by systematically analyzing the core interaction mechanisms of living materials-ranging from bacteria, bacteriophages, and viruses to cells and microalgae-with their host environments. We explore four-dimensional interactions: living material-cell, living material-tissue, living material-disease microenvironment, and living material-host. By synthesizing insights across these dimensions, we propose a unified framework linking living-material properties to host interactions and disease intervention. This study provides foundational principles and identifies key technical challenges for optimizing living materials, facilitating their rational design and clinical translation. Ultimately, this research seeks to accelerate the innovative application of living materials in the treatment of major diseases.

Keywords: Biological entities; Biomedical applications; Disease intervention; Living materials; Multidimensional interactions

DOI: https://doi.org/10.1016/j.biomaterials.2026.124565

Pharmaceutics. 2026 Jul 24. pii: 915. [Epub ahead of print]18(8):

Single-Step Chromosomal Engineering Integrates Biocontainment and Therapeutic Function for Regulatory-Oriented Live Biotherapeutic Chassis Design.

Gabriela Christina Kuhl, Ciarán Devoy, Munawar Abbas, Emilene Da Silva Morais, Mark Tangney.

Background: Live biotherapeutic products (LBPs) require robust genetic stability and effective biocontainment to support safe clinical translation and regulatory acceptance. Aim: This study presents a single-step chromosomal engineering strategy that integrates auxotrophy-mediated biocontainment with therapeutic gene insertion to support regulatory-oriented live biotherapeutic chassis design. Methods: A no-SCAR genome-editing approach combining CRISPR/Cas9 and λ-Red recombineering was used to generate an Escherichia coli MG1655 ΔilvC::hlyA strain by replacing ilvC with the hlyA gene encoding listeriolysin O. Chromosomal and episomal expression systems were compared for auxotrophy, growth, haemolytic activity, plasmid stability, and intracellular DNA delivery to RAW 264.7 macrophages. Results: Auxotrophy was successfully established and restored by branched-chain amino acid supplementation. Chromosomal integration preserved haemolytic activity and bacterial growth while improving long-term genetic stability and plasmid maintenance compared with episomal expression. Both systems supported intracellular DNA delivery, whereas the chromosomal construct showed improved host-cell preservation under higher bacterial challenge. Conclusions: This proof-of-concept study supports the feasibility of using a single-step chromosomal engineering strategy to combine intrinsic biocontainment with therapeutic-gene integration in an engineered bacterial chassis.

Keywords: auxotrophy; bacterial DNA delivery; bactofection; biosafety; genetic stability; genome engineering; listeriolysin O; live biotherapeutic products; microbial chassis; synthetic biology

DOI: https://doi.org/10.3390/pharmaceutics18080915

Microorganisms. 2026 Jul 24. pii: 1621. [Epub ahead of print]14(8):

Recent Advances in Encapsulation Strategies for Synbiotic Formulation Containing Lactiplantibacillus plantarum.

Kairat Saparkhanovich Zhakipbekov, Murat Zulpidinovich Ashirov, Baurzhan Kalzhanovich Makhatov, Karlygash Manapovna Akpayeva, Aziza Mukataikyzy Omari, Rakatzhan Duisenbekuly Abdikalykov, Zhanar Kasymbekovna Shimirova, Gulmira Marsovna Abdrakhmanova, Yerbolat Abibillayevich Tulebayev, Sabit Bekseitovich Pazilov, Bazarkhan Imangaliyeva, Marzhan Bauyrzhan, Bauyrzhan Kuanishbekovich Toizhanov, Zhanat Sadebekovna Toxanbayeva, Sulushash Dauletiyarkyzy Butanbayeva.

Lactiplantibacillus plantarum is one of the most studied probiotic organisms due to its adaptability, gastrointestinal tolerance, antimicrobial activity, and health-promoting properties. However, the survival and efficacy of this probiotic can be significantly reduced during processing, storage, and gastrointestinal transit, limiting its effectiveness in food, nutraceutical, and pharmaceutical products. Synbiotic formulations, which are prepared by combining probiotics with prebiotics, have emerged as a promising approach to enhance the survival and efficacy of probiotics. In this context, encapsulation technologies play a crucial role in protecting probiotic cells from environmental and physiological stresses and in enabling controlled release at targeted sites within the gastrointestinal tract. This review describes recent developments in encapsulation strategies for L. plantarum-based synbiotic formulations, including traditional methods such as spray drying, freeze drying, extrusion and emulsion-based systems, as well as emerging methods such as nanoencapsulation and hydrogel-based delivery systems. The properties of commonly used encapsulating materials, and functional applications in food, nutraceutical and pharmaceutical products are also described. Furthermore, current challenges and future prospects are also highlighted. Overall, encapsulation represents an effective strategy to improve the stability, delivery and therapeutic potential of L. plantarum-based synbiotic formulations.

Keywords: Lactiplantibacillus plantarum; encapsulation; functional food; nutraceuticals; prebiotics; probiotic; synbiotics

DOI: https://doi.org/10.3390/microorganisms14081621

Research (Wash D C). 2026 ;9 1413

Programmed Probiotics Generate Interleukin-37b-Bearing Nanovesicles In Situ for Precision Immunomodulation in Colitis.

Xiaojing Zhang, Liufei Gong, Haiyi Zhang, Yang Luo, Tengfei Long, Qian He, Yang Luo, Lu Han, Zhipeng Li, Cang Li, Xiaoyu Wang, Zijian Zheng, Yao Deng, Xiaoping Liao, Hao Ren, Jian Sun.

Genetically engineered probiotic bacteria are promising living therapeutics. However, their therapeutic potential is frequently confined to their colonization sites, and limitations in efficacy, controllability, and robustness remain major barriers to translation. Anti-inflammatory cytokines play a crucial role in mitigating the pathogenesis of inflammation-related diseases, yet their application is limited by their vulnerability in the mammalian gastrointestinal tract. In this regard, we first found that interleukin-37b (IL-37b) mitigated inflammatory responses at picogram concentrations in primary intestinal cells, supporting its translational potential for the oral treatment of inflammatory diseases. Then, we harnessed the probiotic bacterium Escherichia coli Nissle 1917 as a chassis and further engineered it into a hypervesiculating strain, ΔECIL-37b, capable of efficiently secreting IL-37b-bearing bacterial outer membrane vesicles (OMVs) in situ. These OMVs facilitated IL-37b penetration across the intestinal barrier, enabling it to reach the inflamed mucosa and interact with target cells. In both acute and chronic murine colitis models, we demonstrated that ΔECIL-37b achieved anti-inflammatory efficacy comparable to direct IL-37b injection while enabling local intestinal delivery. Mechanistically, ΔECIL-37b exerted anti-inflammatory effects by attenuating myeloid differentiation primary response 88 (MyD88)-related downstream extracellular-signal-regulated kinase/nuclear factor κB signaling and inflammatory-immune cross-talk. Together, these findings provide a proof-of-concept strategy to harness the anti-inflammatory activity of IL-37b via probiotic-derived OMV delivery and offer insights into a precision anti-inflammatory approach integrating cytokine and probiotic functions.

DOI: https://doi.org/10.34133/research.1413