bims-livmat 2026-03-15 papers

bims-livmat

Biomed News

on Living materials

Issue of 2026–03–15
six papers selected by
Sara Trujillo Muñoz, Leibniz-Institut für Neue Materialien

Programmable Semi-Interpenetrating Living Materials With Robust Stability for Versatile Bioremediation and Biotherapeutics.
Biofilm-inspired encapsulation enhances the viability of probiotic Lacticaseibacillus paracasei NN4-1 under simulated gastrointestinal conditions.
A yeast synthetic biotic platform for delivery of therapeutic nanobodies to ameliorate gastrointestinal inflammation.
Engineered Bacteria-Driven Biohybrid Microrobots Potentiate IL-2 Immunotherapy by Evoking Pyroptosis.
Multi-Targeting Non-Specific Genome Engineering in Bacteria.
Associate toxin-antitoxin with CRISPR-Cas to harness (ATTACH) engineered microbes.

Adv Sci (Weinh). 2026 Mar 13. e24320

Programmable Semi-Interpenetrating Living Materials With Robust Stability for Versatile Bioremediation and Biotherapeutics.

Zixian Bao, Shengfeng Yang, Dandan Hu, Jiezheng Liu, Bo Jiang, Xinyue Sui, Qingsheng Qi, Lai Li, Guang Zhao.

  The practical application of engineered living materials (ELMs) is currently hindered by some critical challenges, such as streamlining fabrication processes and achieving long-term stability. Here, a semi-interpenetrating ELM was developed relying on thermosensitive self-assembly of hydroxybutyl chitosan (HBC) and spontaneous covalent protein interactions. This semi-interpenetrating network provided superior mechanical properties over HBC hydrogels. Furthermore, this material can be adapted for diverse scenarios based on engineered bacteria encapsulated, and its applications in biotherapy treatment and environmental remediation were validated. Compared to planktonic bacteria or enzymes, this ELM presented enhanced tolerance to harsh environments, including high temperatures, extreme pH values, high salinity, and digestive fluids, resulting in improved therapeutic efficacy with excellent biosafety in ulcerative colitis treatment and long-term degradation of the pollutant paraoxon. In summary, our material offers advantages including simple preparation, excellent mechanical properties, high stability, customizability, and biosafety, laying a foundation for the application of ELMs.

Keywords:  SpyCatcher/SpyTag; bioremediation; engineered living materials; hydroxybutyl chitosan; ulcerative colitis treatment

DOI:  https://doi.org/10.1002/advs.202524320
Food Res Int. 2026 Apr 30. pii: S0963-9969(26)00325-X. [Epub ahead of print]230 118649

Biofilm-inspired encapsulation enhances the viability of probiotic Lacticaseibacillus paracasei NN4-1 under simulated gastrointestinal conditions.

Fedrick C Mgomi, Chunlei Lu, Anqi Tang, Shu Xu, Fei Chen, Lei Yuan, Zhen-Quan Yang.

  The survival of probiotics during transit through the gastrointestinal tract (GIT) remains a significant challenge, limiting their in vivo functional efficacy. Microorganisms often resist adverse conditions by forming biofilms. Leveraging this property, the current study introduces a novel biofilm-inspired encapsulation approach using single- and multilayer-coated sodium alginate gel beads (SAGBs) to promote in situ biofilm formation by Lacticaseibacillus paracasei NN4-1. Comparative analyses were conducted to assess bacterial viability in SAGBs, planktonic cells, and biofilm cells under simulated GIT conditions. In vitro studies showed enhanced resistance in SAGBs, with a survival rate of 81.48% compared to unencapsulated cells. Additionally, biofilm encapsulation increased biochemical production, yielding average protein and polysaccharide concentrations of 0.633 mg/mL and 1.056 mg/mL, respectively. The scanning electron microscope revealed clusters of bacterial colonization inside the SAGBs. Whole-genome sequencing revealed multiple genes associated with biofilm formation, stress tolerance, adhesion, acid, and bile salt resistance. Multilayer of SAGBs reduced bacterial leakage by 52.52%, slowed small-molecule diffusion, and slightly improved textural properties without compromising bacterial metabolic activity or growth. Furthermore, SAGBs exhibited markedly higher survival (99.43%) than planktonic (76.3%) and biofilm cells (77.5%) after 21 days of refrigerated storage in milk. This approach offers promising applications in designing next-generation functional foods and targeted probiotic delivery systems, warranting higher viability of probiotics under adverse conditions of the GIT.

Keywords:  Genome sequence; Gut survival; Lacticaseibacillus paracasei; Probiotic biofilm; Probiotic delivery

DOI:  https://doi.org/10.1016/j.foodres.2026.118649
Dis Model Mech. 2026 Feb 01. pii: dmm052620. [Epub ahead of print]19(2):

A yeast synthetic biotic platform for delivery of therapeutic nanobodies to ameliorate gastrointestinal inflammation.

Roger Palou, Almer M van der Sloot, Aline A Fiebig, Megan T Zangara, Naseer Sangwan, María Sánchez-Osuna, Bushra Ilyas, Haley Zubyk, Michael Cook, Gerard D Wright, Brian K Coombes, Mike Tyers.

  Protein-based pharmaceuticals, such as engineered antibodies, form a major drug class of steadily increasing market share. However, these biologic medicines are costly to manufacture, are subject to strict supply chain and storage constraints, and often require invasive administration routes. Engineered microbes that secrete bioactive products directly within the microbiome milieu may mitigate these challenges. Here, we describe a cell microfactory platform based on the probiotic yeast Saccharomyces boulardii for the production of nanobody biologics in the gastrointestinal (GI) tract. High-level secretion of nanobodies by S. boulardii was achieved by optimizing promoters, secretion signals and antibody formats. In mice, oral gavage of S. boulardii allowed efficient and transient colonization of the colonic compartment, and in situ production of a therapeutic nanobody directed against tumor necrosis factor (TNF). In a mouse model of chemical-induced colitis, GI-delivery of anti-murine TNF nanobody via live S. boulardii improved both survival and disease severity without causing overt perturbation of microbiome composition. These results position S. boulardii as a synthetic biotic platform for the in situ production and delivery of protein-based therapeutics to the GI tract.

Keywords:   Saccharomyces boulardii ; Inflammatory bowel disease; Synthetic biotic; TNF; VHH nanobody

DOI:  https://doi.org/10.1242/dmm.052620
ACS Nano. 2026 Mar 12.

Engineered Bacteria-Driven Biohybrid Microrobots Potentiate IL-2 Immunotherapy by Evoking Pyroptosis.

Ping Li, Qianying Li, Lu Ding, Shiyu Peng, Hui Wei, Tingtao Chen, Yonghua Xiong, Ben Zhong Tang, Xiaolin Huang.

  Interleukin-2 (IL-2) immunotherapy offers considerable potential for metastatic cancers; however, its efficacy is limited by low response rates, dose-dependent toxicity, short half-life, poor tumor accumulation, and off-target immune activation. In this work, we present a biohybrid microrobot (IL-2@Z/C/A) engineered through biomimetic mineralization of IL-2 variant-secreting Escherichia coli Nissle 1917 (EcN) with a zeolitic imidazolate framework-8 (ZIF-8) shell coloaded with an aggregation-induced emission photosensitizer and catalase. The ZIF-8 coating preserves bacterial viability tumor-homing capability while preventing premature drug leakage and systemic exposure, thus minimizing off-target effects. Upon accumulation in the acidic tumor microenvironment (TME), the framework degrades to release engineered bacteria and therapeutic cargo. Locally delivered zinc ion release, light-triggered reactive oxygen species and EcN derived pathogen-associated molecular patterns act synergistically to induce Cle-caspase/GSDMD mediated pyroptosis, resulting in immunogenic cell death accompanied by damage-associated molecular pattern release and pro-inflammatory cytokine production. Simultaneously, catalase-driven oxygen generation alleviates hypoxia and suppresses HIF-1α-induced immunosuppression. In combination with PD-L1 blockade, IL-2@Z/C/A achieves near-complete tumor regression in a B16F10 melanoma model via a coordinated immune cascade: pyroptosis-mediated antigen exposure primes adaptive immunity, hypoxia reversal counteracts immunosuppression, and sustained local IL-2 release reverses T cell exhaustion, collectively reprogramming the immunosuppressive TME and eliciting strong antitumor immunity. This work establishes a distinct paradigm for spatially controlled immunotherapy and highlights the potential of this biohybrid microrobot in converting immunologically "cold" tumors into responsive niches.

Keywords:  aggregation-induced emission photosensitizer; engineered bacteria; immunotherapy; interleukin-2; pyroptosis

DOI:  https://doi.org/10.1021/acsnano.5c21475
Adv Sci (Weinh). 2026 Mar 09. e21532

Multi-Targeting Non-Specific Genome Engineering in Bacteria.

Runze Sun, Ruixiang You, Yiwen Zhou, Huiyan He, Wenfang Wang, Xudong Qu, Yinhua Lu, Lei Li.

  Genome engineering plays a crucial role in the rapidly growing fields of metabolic engineering and synthetic biology. Chromosomal integration and stable expression of functional genes or large metabolic pathways necessitate the development of host-independent enabling technologies in diverse bacteria. Here, a generalizable genome engineering approach, MNGE (Multi-targeting Non-specific Genome Engineering), is developed based on the multi-targeting integrase (MTI) systems for multi-copy (at least three copies), highly random (only requiring the core TT dinucleotide) integration of metabolic genes or pathways in both Gram-positive bacteria (i.e., Streptomyces and Saccharopolyspora) and Gram-negative bacteria (i.e., Burkholderia and Chromobacterium). Using MNGE, the fungicide UK-2 BGC (41 kb) and the polyether antibiotic salinomycin BGC (106 kb) were randomly integrated into a heterologous host Streptomyces albus, significantly enhancing their fermentation levels based on chromosome position effects. Furthermore, the potent Gq/11-signaling inhibitor FR900359 BGC (66 kb) was successfully expressed in Burkholderia gladioli by the MTI1 system. Together, the MNGE approach exhibits broad applicability for next-generation genome engineering in diverse bacteria, thereby achieving highly efficient production of high-value compounds.

Keywords:  bacteria; genome engineering; microbial drugs; multi‐targeting integrases; synthetic biology

DOI:  https://doi.org/10.1002/advs.202521532
Nucleic Acids Res. 2026 Feb 24. pii: gkag213. [Epub ahead of print]54(5):

Associate toxin-antitoxin with CRISPR-Cas to harness (ATTACH) engineered microbes.

Huiwei Zhao, Tao Zhou, Ming Zhang, Chengqiang Wang, Rui Wang, Xian Shu, Feiyue Cheng, Qiong Xue, Chao Liu, Jing Xu, Xinyue Cao, Jun Du, Liangliang Wang, Hongwei Liu, Ming Li.

Robust biocontainment is essential for the safe use of engineered microbes, but existing strategies suffer from genetic instability and/or laborious construction. Here, we present ATTACH, a kill switch that associates toxin-antitoxin with CRISPR-Cas to harness engineered microbes. Our approach employs a CRISPR-repressed toxin-antitoxin (CreTA) module to make microbes addicted to the type I-F Cas effector proteins, and places both the Cas3 nuclease and the chromosome-targeting guide RNA under inducible promoters, thereby improving the genetic stability and stringency of the CRISPR-based suicidal program. Additionally, we have developed a single-plasmid, antibiotic-independent ATTACH device, which shows robust, stringent containment of a microbial chassis in murine gut, and negligible impacts on culture growth or lycopene production during batch fermentation. Our data highlight the potential of CreTA to stabilize CRISPR-based kill switches, advancing their development into more portable and reliable biocontainment tools for engineered microbes.

DOI: https://doi.org/10.1093/nar/gkag213