bims-livmat Biomed News
on Living materials
Issue of 2025–11–30
eleven papers selected by
Sara Trujillo Muñoz, Leibniz-Institut für Neue Materialien
  1. Genetically-Programmed Hypervesiculation of Lactiplantibacillus Plantarum Increases Production of Bacterial Extracellular Vesicles with Therapeutic Efficacy in a Preclinical Inflammatory Bowel Disease Model.
  2. Silk Fibroin-Derived Smart Living Hydrogels for Regenerative Medicine and Organoid Engineering: Bioactive, Adaptive, and Clinically Translatable Platforms.
  3. Fabrication of Single-Bacterium Microgel with Gas-Shearing Strategy for Precision Probiotic Delivery in IBD Therapy.
  4. Evaluating Cytocompatibility of Corynebacterium glutamicum-poly Vinyl Alcohol Living Biomaterials for Ocular Use.
  5. Immunostimulatory Activity of Solubilized Peptidoglycan Derivatives Prepared From Lactic Acid Bacteria.
  6. Wireless in-body sensing through genetically engineered bacteria.
  7. Probiotic-based oral vaccine mucosal delivery system enabling genetically encoded dual-antigen arrays.
  8. One-Step Biological Upcycling of Chitin Wastes into Violacein by Engineered Chromobacterium violaceum.
  9. Engineering butyrate-producing Lachnospiraceae to treat metabolic disease.
  10. A Screening Assay for Bile Acid-Transforming Microorganisms Using Engineered Bacterial Biosensors.
  11. Improving T cell expansion by optogenetically engineered bacteria-loaded MMP-2-responsive cyclophosphamide for antitumor immunotherapy.
  1. Adv Sci (Weinh). 2025 Nov 26. e12679
    Genetically-Programmed Hypervesiculation of Lactiplantibacillus Plantarum Increases Production of Bacterial Extracellular Vesicles with Therapeutic Efficacy in a Preclinical Inflammatory Bowel Disease Model.
    Nicholas H Pirolli, Daniel Levy, Alyssa Schledwitz, Natalia Sampaio Moura, Mitali Sarkar, Talia J Solomon, Emily H Powsner, Raith Nowak, Zuzanna Mamczarz, Christopher J Bridgeman, Sulayman Khan, Andrew Hui, Nidhi Anne, Laura Reus, William E Bentley, Jean-Pierre Raufman, Steven M Jay.
      Inflammatory bowel diseases (IBD) affect over 6 million people globally and current treatments achieve only 10-20% rates of durable disease remission. Bacterial extracellular vesicles (BEVs) from probiotic lactic acid bacteria (LAB) are a promising novel therapeutic with mechanisms holding potential to drive increased rates of durable disease remission, including immunomodulation and intestinal epithelial tissue repair. However, translation of these cell-secreted nanovesicles is limited by long standing biomanufacturing hurdles, especially low production yields due to low biogenesis rates from cells. Here, Lactiplantibacillus plantarum is identified as a candidate LAB producing BEVs effective in treating acute dextran sulfate sodium (DSS)-induced murine colitis with greater efficacy than BEVs from probiotic Escherichia coli Nissle 1917. Genetic engineering of L. plantarum to create a hypervesiculating strain via inducible expression of a peptidoglycan-modifying enzyme is shown to enable a 66-fold increase in BEV productivity. Finally, hypervesiculating L. plantarum BEVs are confirmed to be therapeutically effective in the acute DSS mouse model of colitis, with superior reduction of mucosal tissue damage compared to live L. plantarum cells. These findings demonstrate that BEVs from genetically engineered hypervesiculating strain of L. plantarum are a promising preclinical therapeutic candidate for IBD that overcomes historical biomanufacturing limitations of BEV therapeutics.
    Keywords:  IBD; bacterial membrane vesicles; colitis; extracellular vesicles; lactic acid bacteria
    DOI:  https://doi.org/10.1002/advs.202512679
  2. Gels. 2025 Nov 13. pii: 908. [Epub ahead of print]11(11):
    Silk Fibroin-Derived Smart Living Hydrogels for Regenerative Medicine and Organoid Engineering: Bioactive, Adaptive, and Clinically Translatable Platforms.
    Asim Mushtaq, Khai Ly Do, Abdul Wahab, Muhammad Yousaf, Abdul Rahman, Hamid Hussain, Muhammad Ali, Pingfan Du, Miao Su.
      Silk fibroin (SF) has evolved from a traditional biopolymer to a leading regenerative medicine material. Its combination of mechanical strength, biocompatibility, tunable degradation, and molecular adaptability makes SF a unique matrix that is both bioactive and intelligent. Advances in hydrogel engineering have transformed SF from a passive scaffold into a smart, living hydrogel. These systems can instruct cell fate, sense microenvironmental signals, and deliver therapeutic signals as needed. By incorporating stem cells, progenitors, or engineered immune and microbial populations, SF hydrogels now serve as synthetic niches for organoid maturation and as adaptive implants for tissue regeneration. These platforms replicate extracellular matrix complexity and evolve with tissue, showing self-healing, shape-memory, and stimuli-responsive properties. Such features are redefining biomaterial-cell interactions. SF hydrogels are used for wound healing, musculoskeletal repair, neural and cardiac patches, and developing scalable organoid models for disease and drug research. Challenges remain in maintaining long-term cell viability, achieving clinical scalability, and meeting regulatory standards. This review explores how advances in SF engineering, synthetic biology, and organoid science are enabling SF-based smart living hydrogels in bridging the gap between research and clinical use.
    Keywords:  living hydrogel; organoid; regenerative medicine; silk fibroin; tissue engineering
    DOI:  https://doi.org/10.3390/gels11110908
  3. Research (Wash D C). 2025 ;8 0955
    Fabrication of Single-Bacterium Microgel with Gas-Shearing Strategy for Precision Probiotic Delivery in IBD Therapy.
    Jialin Wu, Lili Wu, Ruiying Liu, Leyan Xuan, Jiamin Qian, Chenchen Fang, Huaibin Wang, Jie Guo, Lingran Du, Yingling Miao, Bin Liu, Yutao Liu, Guosheng Tang.
      The human gut microbiome is essential for maintaining health, as it substantially impacts immune regulation and overall balance within the body. Accordingly, disruptions in this microbial community are associated with various diseases. Probiotics offer a promising solution, but their effectiveness is often hampered by challenges related to gastrointestinal delivery. To overcome the issue of probiotic survival in the gastrointestinal system, researchers have explored various encapsulation techniques. However, traditional coarse encapsulation techniques lack precision and effective targeting, limiting the delivery of viable organisms to the colon. Current methods face challenges such as inadequate particle size control, leakage, and poor survival in complex gastrointestinal environments. This research introduces a novel approach for encapsulating individual bacteria to create single-bacterium microgels, utilizing gas-shearing technology to enhance the survival and targeting capabilities of probiotics. This approach also demonstrates the capability to coat multiple microbial species, including bacteria and fungi, while ensuring good biocompatibility and mechanical support. Focusing on Escherichia coli Nissle 1917, we demonstrate that this method significantly improves therapeutic efficacy in treating inflammatory bowel disease compared to unencapsulated strains. Our results suggest that gas-shearing encapsulation represents a promising strategy for the fabrication of single-bacterium microgels, facilitating the development of effective probiotic therapies with potential applications in both biomedical and nutraceutical fields.
    DOI:  https://doi.org/10.34133/research.0955
  4. Adv Healthc Mater. 2025 Nov 29. e03831
    Evaluating Cytocompatibility of Corynebacterium glutamicum-poly Vinyl Alcohol Living Biomaterials for Ocular Use.
    Krupansh Desai, Lorely Garcia-Sanchez, Maryam Amini, Lara Luana Teruel-Enrico, Silke Siegrist, Aránzazu Del Campo, Sara Trujillo.
      In ophthalmology, living biomaterials have appeared as promising drug delivery and biosensor devices to tackle dynamic sensing and delivery of compounds. Their living character complicates their assessment with the also dynamic ocular tissues. The use of animal experiments increases complexity, and most animal ocular models are anatomically different from humans. Thus, in vitro ocular systems applied specifically to living biomaterials are required to assess their safety, compatibility and efficacy. Here, we report on an in vitro cornea model for co-cultures with Corynebacterium glutamicum-polyvinyl alcohol living biomaterials, which are reported as suitable living contact lenses, to study their cytocompatibility to the eye. We co-cultured this living biomaterial with human primary corneal cells (epithelial and fibroblasts) for 7 days, mimicking contact lens extended wear. We studied bacterial proliferation, biocontainment and biosafety. We investigated potential cytotoxicity and pro-inflammatory responses of living biomaterials to corneal cells. Our results revealed that the living biomaterial does not trigger cytotoxicity or pro-inflammatory phenotypes on corneal cells during the 7-day co-culture. We placed the living biomaterial on top of the corneal epithelium, observing no cytotoxic effects. Overall, these findings highlight the potential of in vitro investigations for living biomaterials and the applicability of these devices for ophthalmology purposes.
    Keywords:  corynebacterium glutamicum; co‐cultures; cytocompatibility; immunogenicity; living biomaterials; poly vinyl alcohol
    DOI:  https://doi.org/10.1002/adhm.202503831
  5. Microbiol Immunol. 2025 Nov 26.
    Immunostimulatory Activity of Solubilized Peptidoglycan Derivatives Prepared From Lactic Acid Bacteria.
    Sho Noguchi, Momoko Nakayama, Masahiro Eguchi, Sakura Onoue, Hiroaki Kouzai, Kazuyoshi Kawahara.
      To develop vaccine adjuvants from bacterial peptidoglycan (PG) the immunostimulatory activity of lysozyme-solubilized PG derived from Levilactobacillus brevis and Lactiplantibacillus plantarum was investigated. Solubilized PG from both bacteria induced IL-8 in THP-1 cells, and periodate oxidation of L. plantarum PG reduced the activity, suggesting that muramyl dipeptide was partially destroyed. Periodate-oxidized L. plantarum PG showed reduced IL-8 inducing activity in NOD2-expressing cells, while it remained in NOD1-expressing cells, suggesting that γ-d-glutamyl-meso-diaminopimelic acid structure was maintained. All PG preparations stimulated RAW264.7 cells to proliferate, suggesting that they could be potent candidates for vaccine adjuvants.
    Keywords:  IL‐8; lactic acid bacteria; muramyl dipeptide; peptidoglycan
    DOI:  https://doi.org/10.1111/1348-0421.70025
  6. Nat Commun. 2025 Nov 25. 16(1): 10432
    Wireless in-body sensing through genetically engineered bacteria.
    Ahmet Bilir, Merve Yavuz, Urartu Ozgur Safak Seker, Sema Dumanli.
      This paper introduces a class of wireless implantable sensors that integrate genetically engineered cells capable of detecting specific molecules for continuous monitoring. While synthetic biology enables cells to sense molecular targets, wireless communication of this information remains a challenge. Electromagnetic (EM) waves at cellular-scale wavelengths are strongly attenuated in tissue, necessitating centimeter-scale wavelengths for in-body links. Aligning cellular responses with these longer EM wavelengths enables effective interaction. In this work, the response of Escherichia coli is harnessed to trigger the controlled degradation of a passive microwave antenna, which is then monitored via backscatter communication. This approach converts cellular activity into detectable EM signals, eliminating the need for batteries or circuits. We demonstrate a wireless link between a passive, cell-based sensor in a human body phantom and an external receiver, achieving molecular-level sensing at 25 mm implant depth. Future implementations could couple bacterial responses to diverse molecular targets.
    DOI:  https://doi.org/10.1038/s41467-025-65416-5
  7. Nat Commun. 2025 Nov 22.
    Probiotic-based oral vaccine mucosal delivery system enabling genetically encoded dual-antigen arrays.
    Yale Yue, Qi Xin, Yuanyuan Zhu, Dandan Zhu, Baohua Zhang, Xiyun Yan, Bing Jiang.
      Oral vaccines provide a non-invasive approach for cancer immunotherapy but face challenges in gastrointestinal stability, antigen presentation, and mucosal delivery. Here, we present an engineered probiotic-based oral vaccine system, BacOR-Fn-T+phiX174, featuring genetically encoded dual-antigen ferritin arrays and inducible bacterial lysis. Upon oral administration and arabinose induction, the probiotic strain lyses in situ, releasing OVA/TRP2-decorated ferritin nanoparticles that efficiently traverse the intestinal barrier via M-cell targeting and activate mucosal dendritic cells. This platform robustly stimulates CD8+ and CD4+ T-cell responses, enhances B-cell and macrophage activation, reduces regulatory T cells, and provides therapeutic efficacy against melanoma in both lung metastasis and subcutaneous tumor models. It also establishes durable immunological memory without disrupting systemic or mucosal homeostasis. This work offers a programmable bacterial chassis for precise antigen array presentation and controlled delivery, representing a promising strategy for next-generation, needle-free cancer vaccines.
    DOI:  https://doi.org/10.1038/s41467-025-66622-x
  8. ACS Synth Biol. 2025 Nov 24.
    One-Step Biological Upcycling of Chitin Wastes into Violacein by Engineered Chromobacterium violaceum.
    Ru Li He, Bao-Cheng Huang, Jing Wu, Dan Sun, Hui-Hui Li, Jia-Qi Liu, Jie Wu, Dong-Feng Liu, Wen-Wei Li.
      Existing technologies for the valorization of organic wastes have been focused mainly on degradable wastes, while an efficient, low-carbon approach for the upcycling of shell waste is still lacking. Here, we report a one-step chitin biological fermentation process (CBFP), based on the construction of Chromobacterium violaceum engineered strain, for efficiently converting shell waste-derived chitin into high-value violacein. A high-efficiency CRISPR cytosine-base editor (pRK2-BE, 97% editing efficiency) was developed for C. violaceum, which demonstrated cv_4240, cv_1440, and cv_2935 as the major chitin hydrolysis genes and phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS) as the major N-acetyl-glucosamine uptake pathway. The engineered strain WT/pBAD-4, co-overexpressing of cv_4240, cv_1440, cv_2935, and vioABCDE, efficiently utilized colloidal chitin and crystalline chitin as the sole carbon and nitrogen source, achieving violacein yields of 159.78 and 120.95 mg·L-1, respectively. This study provided an economically viable and environmentally sustainable solution for green upcycling of shell waste.
    Keywords:  Chitin bioconversion; Chromobacterium violaceum; Circular economic; Shell waste upcycling; Violacein biosynthesis
    DOI:  https://doi.org/10.1021/acssynbio.5c00472
  9. bioRxiv. 2025 Nov 09. pii: 2025.11.08.687059. [Epub ahead of print]
    Engineering butyrate-producing Lachnospiraceae to treat metabolic disease.
    Jack Arnold, Sandra McClure, Joshua Glazier, Recep E Ahan, Sadiksha Shakya, David Villegas, Tracy Leidan Chen, Jay Fuerte-Stone, Rory McGann, Mark Mimee.
      Engineering native gut bacteria offers a route to persistent, programmable therapeutics, yet many dominant taxa remain genetically intractable. Lachnospiraceae are a prevalent and abundant family in the human gut microbiome, possessing metabolic functions generally associated with health 1 . Despite their promise as engineered live biotherapeutics, genetic manipulation of Lachnospiraceae remains challenging. Here, we develop a modular toolkit for Lachnospiraceae engineering, including constitutive and inducible expression and chromosomal integration systems. Applying this toolkit to the native commensal Coprococcus comes , we program secretion of the mammalian cytokine interleukin-22 (IL-22) in the mouse intestinal tract where it elicits ileal transcriptional responses consistent with cytokine signaling. In a mouse model of metabolic associated steatotic liver disease, IL-22-secreting C. comes improves glucose homeostasis and attenuates hepatic steatosis. This work demonstrates that a native Lachnospiraceae chassis can be genetically programmed to modulate host metabolic and immune physiology. The toolkit provides a generalizable foundation for Lachnospiraceae-derived microbiome therapeutics and for probing causal links between Lachnospiraceae gene programs and host phenotypes.
    DOI:  https://doi.org/10.1101/2025.11.08.687059
  10. Biosensors (Basel). 2025 Oct 29. pii: 716. [Epub ahead of print]15(11):
    A Screening Assay for Bile Acid-Transforming Microorganisms Using Engineered Bacterial Biosensors.
    Debora Dallera, Daniele Pastorelli, Massimo Bellato, Angelica Frusteri Chiacchiera, Francesca Usai, Maria Gabriella Cusella De Angelis, Paola Brun, Paolo Magni, Lorenzo Pasotti.
      Bile salt hydrolase (BSH) enables microbial-mediated deconjugation of bile acids (BAs) in the gastrointestinal tract. BSH enzymes initiate bile acid metabolism by catalyzing the first, essential deconjugation step. Due to the strict connection between dysregulations of the BA pool and human or animal diseases, identification and characterization of strains with BSH activity are relevant for both healthcare and agroindustry. However, current methods are expensive, poorly sensitive, or require complex procedures. Here, a BSH screening assay for cultivated microbes is proposed, based on a bacterial biosensor that reports the concentration of different BA types via fluorescence. Although the biosensor is broadly responsive to various bile acids, the assay was designed to guarantee specificity by testing individual primary BAs within controlled concentration ranges. The assay was evaluated on two recombinant Escherichia coli strains bearing BSH genes from Lactobacillus johnsonii PF01 and a BSH-positive probiotic strain (Lactobacillus rhamnosus GG). Data showed a consistent activity pattern with previous assays on these enzymes. A crucial aspect addressed was the matrix effect, i.e., the impact of the growth media of the BSH-containing strains on biosensor output. This assay is expected to be a reproducible and accessible option, compatible with automated protocols.
    Keywords:  Escherichia coli; TcpH; TcpP; bacterial sensor; bile salts; calibration curve; fluorimetric assay; lactic acid bacteria; specificity; synthetic biology
    DOI:  https://doi.org/10.3390/bios15110716
  11. J Nanobiotechnology. 2025 Nov 28.
    Improving T cell expansion by optogenetically engineered bacteria-loaded MMP-2-responsive cyclophosphamide for antitumor immunotherapy.
    Jiawen Chen, Renjiang Kong, Yuzhi Qiu, Sihan Chen, Yidi Liu, Xi Yu, Xiangliang Yang, Yan Zhang, Yanhong Zhu.
      The efficacy of antitumor immunotherapy is closely associated with the expansion of tumor-infiltrating CD8+ T cells. However, within the tumor microenvironment, CD8+ T cells often exhibit reduced proliferation due to persistent exposure to tumor antigens. The cytokine IL-2 is a potent growth factor that can drive the expansion of tumor-infiltrating lymphocytes. While its clinical application has been severely limited by systemic toxicity and in vivo instability. To address these challenges, we have developed a dual-responsive system (EcNIL-2@UCNP/Gel-CTX) leveraging the hypoxic tropisms of E. coli Nissle 1917(EcN). This system is capable of producing IL-2 in situ upon near-infrared (NIR) irradiation and releasing low-dose cyclophosphamide (CTX) in response to matrix metalloproteinase-2 (MMP-2) in the tumor microenvironment. The EcNIL-2@UCNP/Gel-CTX system not only drives the expansion of CD8+ T cells and boost the activity of NK cells but also reduces Treg cell populations, thereby remodeling the immune microenvironment and eliciting robust tumor-specific immune responses in H22 subcutaneous tumors in mice and confers long-term protection against tumor rechallenge by promoting the generation of durable memory T cells. Our findings provide an both light and tumor microenvironment responsive platform for enhanced cancer immunotherapy.
    Keywords:  Cyclophosphamide; Engineered bacteria; Interleukin-2(IL-2); Optogenetic; Tumor immunotherapy
    DOI:  https://doi.org/10.1186/s12951-025-03801-4
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