bims-livmat 2025-10-05 papers

bims-livmat

Biomed News

on Living materials

Issue of 2025–10–05
seven papers selected by
Sara Trujillo Muñoz, Leibniz-Institut für Neue Materialien

Biohybrid Bacteria as Living Nanofactories for Disrupting Diabetic Wound Pathological Cascade via Antimicrobial-Regenerative Coupling.
Microencapsulated Lactiplantibacillus plantarum ZGP-Lpl.19 modulates growth and virulence gene expression of Shigella flexneri ATCC 12022 in vitro.
An Inflammation-Targeting Engineered Probiotic Escherichia coli Nissle 1917 with High Anti-TNF-α Nanobody Secretion Efficacy Alleviates Ulcerative Colitis.
Metabolic engineering of microorganisms for tailor-made biopolymer production: A review.
Designer probiotic-based living drugs for uric acid homeostasis control in hyperuricemic mice and rats.
Targeted Enrichment of Engineered Bacteria on Triple-Negative Breast Cancer Turns Immunologically Cold Tumors Hot.
Co-encapsulation of probiotics with functional components: design strategies, synergistic mechanisms, biomedical applications, and challenges for industrialization.

Adv Healthc Mater. 2025 Sep 30. e03107

Biohybrid Bacteria as Living Nanofactories for Disrupting Diabetic Wound Pathological Cascade via Antimicrobial-Regenerative Coupling.

Wendi Xuan, Yupei Hu, Sicong Li, Xiaozhen Zhou, Meng Chen, Chenyao Wu, Xiang Gao, Gaoyan Xu, Jine Zhao, Lili Xia, Wei Feng, Yu Chen.

  Diabetic wound healing remains a formidable clinical challenge due to persistent biofilm formation, chronic inflammation, and excessive reactive oxygen species (ROS) accumulation. Current therapeutic approaches often lack synchronized antimicrobial-regenerative mechanisms and fail to provide sustained efficacy. Here, this work engineers a bioengineered living hydrogel system (BMB181@ALG) that leverages genetically modified Bacillus thuringiensis strain BMB181 as a melanin nanofactory, enabling in situ biosynthesis of multifunctional melanin nanoparticles (MNPs). Encapsulation within the hydrogel preserves bacterial metabolic activity, ensuring continuous MNPs production. These nanoparticles exhibit a dual-mode therapeutic action, including photothermal antibacterial activity under near-infrared irradiation for biofilm disruption and pathogen eradication, and ROS scavenging and antioxidant effects to modulate the inflammatory microenvironment. The sustained release of MNPs further promotes angiogenesis, enhances tissue regeneration, and dynamically regulates the diabetic wound microenvironment. Notably, the self-replenishing nature of this biohybrid system ensures long-term therapeutic efficacy, minimizing the need for frequent interventions. This study establishes a bacteria-driven therapeutic paradigm, demonstrating the translational potential of living microbial systems for next-generation precision wound management.

Keywords:  anti‐bacteria; catalytic nanomedicine; living biomaterials; photothermal; wound management

DOI:  https://doi.org/10.1002/adhm.202503107
Naunyn Schmiedebergs Arch Pharmacol. 2025 Oct 03.

Microencapsulated Lactiplantibacillus plantarum ZGP-Lpl.19 modulates growth and virulence gene expression of Shigella flexneri ATCC 12022 in vitro.

Zahra Ghorbani, Mohammad Shayestehpour, Mohammad Esmaeil Shahaboddin, Azad Khaledi, Merat Karimi, Reyhaneh Maleki, Mitra Motallebi.

  Encapsulation of Lactiplantibacillus plantarum (L. plantarum) ZGP-Lpl.19 in alginate-pectin-chitosan microcapsules significantly improved its survival under simulated gastrointestinal conditions and attenuated Shigella flexneri (S. flexneri) growth and pathogenicity through downregulation of the mdoH and IcsA virulence genes. Microencapsulation was achieved via extrusion using a polysaccharide blend, yielding an encapsulation efficiency of 98.44%. Structural integrity of the microcapsules was confirmed by scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR). Encapsulation markedly enhanced probiotic survivability, with viable counts of 5.37 log CFU/mL after 60 min in gastric fluid and 120 min in intestinal fluid, compared with 2.25 log CFU/mL for free cells. Both encapsulated and free L. plantarum ZGP-Lpl.19 demonstrated potent antimicrobial activity against S. flexneri ATCC 12022, with comparable antimicrobial metabolite production. The minimum inhibitory concentration (MIC) of cell-free supernatants from both forms was 1/8 of the original concentration. Importantly, real-time PCR analysis confirmed that both encapsulated and free cells significantly downregulated mdoH and IcsA expression. Overall, these findings demonstrate that alginate-pectin-chitosan microencapsulation provides effective protection for L. plantarum and enhances its functional delivery, positioning encapsulated L. plantarum as a promising therapeutic strategy to mitigate S. flexneri infections.

Keywords:   Lactiplantibacillus plantarum ; Shigella flexneri ; Alginate/chitosan; Microencapsulation; Probiotics; Virulence genes

DOI:  https://doi.org/10.1007/s00210-025-04623-9
Adv Sci (Weinh). 2025 Sep 29. e12360

An Inflammation-Targeting Engineered Probiotic Escherichia coli Nissle 1917 with High Anti-TNF-α Nanobody Secretion Efficacy Alleviates Ulcerative Colitis.

Siqi Hua, Kaiqiang Li, Pengyou Shang, Lina Liu, Jiayu Pan, Bo Zhu, Zichun Hua.

  The probiotic Escherichia coli Nissle 1917 (EcN), clinically used for ulcerative colitis (UC) due to its safety and genetic tractability, exhibits limited therapeutic efficacy owing to poor targeting and colonization at inflamed sites. Phosphatidylserine (PS) exposure increases on apoptotic colon epithelial cells during UC progression, suggesting PS-targeting could enhance EcN localization. Here, EcN is engineered to surface-display Annexin A5 (ANXA5), a PS-binding protein, to improve inflammation targeting and colonization. Since TNF-α drives UC pathogenesis and anti-TNF-α biologics face cost and safety limitations, the secretion-hindering lpp gene is concurrently knocked out in ANXA5-expressing EcN, creating the inflammation-targeted, secretion-enhanced EcNΔlpp::A5. This base strain is further modified to secrete an anti-TNF-α nanobody (aTN), generating EcNΔlpp::A5-aTN. Both engineered strains demonstrate significantly stronger colonic colonization versus wild-type EcN, effectively attenuating oxidative stress-mediated epithelial apoptosis, restoring mucosal barriers, improving immune-microbiota balance, and alleviating murine colitis. EcNΔlpp::A5-aTN shows superior efficacy to EcNΔlpp::A5. This study develops an engineered EcN system with enhanced targeting, colonization, and secretion. By efficiently delivering anti-TNF-α nanobodies, EcNΔlpp::A5-aTN exhibits strong therapeutic potential for UC, overcoming limitations that hinder the clinical application of wild-type EcN.

Keywords:  Escherichia coli Nissle 1917; annexin A5; anti‐TNF‐α nanobodies; inflammatory bowel disease; targeted drug delivery

DOI:  https://doi.org/10.1002/advs.202512360
Int J Biol Macromol. 2025 Sep 30. pii: S0141-8130(25)08479-X. [Epub ahead of print] 147922

Metabolic engineering of microorganisms for tailor-made biopolymer production: A review.

Mădălina Lorena Medeleanu, Lavinia-Florina Călinoiu, Gheorghe-Adrian Martău, Dan-Cristian Vodnar.

  Growing environmental concerns and the short lifespan of synthetic polymers have intensified the search for sustainable, biodegradable alternatives. Microbially produced biopolymers, such as bacterial cellulose, hyaluronic acid, polyhydroxyalkanoates, and poly-γ-glutamic acid, have gained attention due to their biocompatibility, non-toxicity, and renewability. This review highlights recent advances in metabolic engineering aimed at improving the yield, quality, and functionality of these biopolymers. Key strategies include genetic modifications (e.g., gene overexpression, gene deletion, CRISPR-Cas9) and systems biology tools (e.g., proteomics, genomics, synthetic biology). These approaches enable the development of optimized materials for food, medical, and industrial applications. The review also addresses important factors such as molecular weight control, scalability, biocompatibility, and eco-friendly degradation. By comparing natural and engineered microbial platforms, we provide insights into their advantages and limitations. This work underscores the crucial role of microbial metabolic engineering in advancing next-generation biopolymers, supporting both industrial innovation and global sustainability goals.

Keywords:  Bacterial cellulose; Biopolymers; Engineered microorganisms; Hyaluronic acid; Poly-γ-glutamic acid; Polyhydroxyalkanoates

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.147922
Cell Rep Med. 2025 Oct 01. pii: S2666-3791(25)00452-5. [Epub ahead of print] 102379

Designer probiotic-based living drugs for uric acid homeostasis control in hyperuricemic mice and rats.

Xianyun Gao, Yiyu Jin, Mengyao Liu, Wenbo Ma, Deqiang Kong, Yang Zhou, Lingxue Niu, Jianli Yin, Haibing Chen, Haifeng Ye, Ningzi Guan.

  Engineered probiotics can effectively manage hyperuricemia, a condition characterized by increased serum uric acid (UA) levels, leading to several chronic diseases. In this study, we design a probiotic-based UA level sensing and adjustment (PULSE)-engineered bacterium to maintain UA homeostasis. We generate a UA sensor in the E. coli Nissle 1917 strain based on a UA-responsive transcriptional repressor HucR, integrated with a synthetic promoter. Upon oral administration of engineered probiotics, PULSE cells dynamically regulate urate oxidase expression, reducing UA in the gastrointestinal tract in response to increased serum levels. We have demonstrated the potential of PULSE-engineered bacteria in maintaining UA balance in acute and chronic hyperuricemic mouse and rat models, highlighting the potential for long-term oral administration in reducing hyperuricemia-associated renal damage. Our probiotic-based living drug supports the progress of engineered probiotics as a safe, effective, and patient-friendly alternative to typical therapeutics for chronic disease management.

Keywords:  UA homeostasis; designer cells; engineered probiotics; hyperuricemic rat model; living therapeutics; renal damage; synthetic biology; urate oxidase; uric acid sensor

DOI:  https://doi.org/10.1016/j.xcrm.2025.102379
Adv Sci (Weinh). 2025 Sep 30. e10171

Targeted Enrichment of Engineered Bacteria on Triple-Negative Breast Cancer Turns Immunologically Cold Tumors Hot.

Xuanxiang Zhai, Xiaoyi Shi, Xiao Liu, Xiaotong Gu, Wenting Li, Xiangjun Chen, Wei Hong.

  Tumor immunotherapy has garnered significant attention, however, several notable challenges remain to be addressed, including: 1) enhancing active targeting, 2) effectively shielding immune checkpoints, and 3) inducing the transformation of "cold" tumor into "hot". In this study, an "all-in-one" extracellular anaerobic bacterial nanocomposite system is constructed. Escherichia coli Nissle 1917 (EcN) is enveloped with polydopamine via self-polymerization (PDAEcN), subsequently conjugated with a chitosan oligosaccharide (COS) nanoparticle immunostimulant backpack, denoted as PDAEcN/COS. The PDA coating is capable of concealing EcN polysaccharides, masking the immunogenic bacterial surface antigens, and inducing a mild photothermal therapy (PTT) effect. Moreover, PDAEcN/COS exhibits targeted accumulation in hypoxic regions of solid tumors and demonstrates pronounced enrichment on tumor cell surfaces, attributed to the bacterial hypoxic region targeting ability and adhesive properties of PDA, physically obstructing the immune checkpoint. Simultaneously, both EcN and COS markedly enhanced the transformation of M2 macrophages into the M1 phenotype, whereas mild PTT-induced immunogenic cell death (ICD) further mitigated the immunosuppressive nature of the hypoxic tumor microenvironments (TMEs). This integrated therapeutic approach eradicated tumors without eliciting metastasis or discernible side effects following a single injection and laser irradiation in a murine 4T1 cancer model. Ultimately, the immunostimulatory capacity of PDAEcN/COS is considered to hold significant potential for developing novel and efficacious therapies for immunologically "cold" triple-negative breast cancer (TNBC).

Keywords:  engineered bacteria; in situ activation; mild photothermal immunotherapy; self‐blocking immune checkpoint; triple‐negative breast cancer

DOI:  https://doi.org/10.1002/advs.202510171
J Mater Chem B. 2025 Oct 01.

Co-encapsulation of probiotics with functional components: design strategies, synergistic mechanisms, biomedical applications, and challenges for industrialization.

Chenyang Ji, Danyuan Li, Ying Liang, Yangchao Luo.

Chronic diseases such as depression, diabetes, inflammatory bowel disease, and colorectal cancer are closely associated with gut microbiota dysbiosis and impaired intestinal barrier function. Probiotic supplementation represents an effective therapeutic approach for modulating gut microecology and alleviating disease symptoms. However, their limited survival rates and colonization efficiency in the gastrointestinal tract compromise their functional efficacy. Co-encapsulation of probiotics with functional components is an effective approach to enhance stability and has gradually become a major focus in current delivery system research. This review summarizes the co-encapsulation strategies of probiotics with functional components, including metabolites, prebiotics, and polyphenols. It also examines the applications of advanced manufacturing technologies such as microfluidics, 3D printing, layer-by-layer encapsulation, and electrospinning/electrospraying in this field. Through functional evaluation methods, including ex vivo gastrointestinal models, in vivo imaging, and metabolic tracking, the advantages of co-encapsulation in improving probiotic survival rates, targeted release capabilities, and functional stability have been demonstrated. Furthermore, this review explores the application potential of co-encapsulation in chronic disease intervention and identifies the challenges that remain in industrial scale-up, safety standardization, and clinical translation. This review aims to provide a scientific foundation for the clinical translation and industrial application of probiotic co-encapsulation technologies.

DOI: https://doi.org/10.1039/d5tb01747e