bims-livmat 2025-06-29 papers

bims-livmat

Biomed News

on Living materials

Issue of 2025–06–29
twelve papers selected by
Sara Trujillo Muñoz, Leibniz-Institut für Neue Materialien

Engineered Marine Biofilms for Ocean Environment Monitoring.
Living Cell Materials for Advanced Biomedical Applications in Disease Diagnosis, Treatment, and Prevention.
Development of Sucrose-Utilizing Escherichia coli Nissle 1917 for Efficient Heparosan Biosynthesis.
Programmable cell aggregation by a synthetic biosilicification approach.
Probiotics-embedded polymer films for oral health: Development, characterization, and therapeutic potential.
A Multilayered Biocontainment System for Laboratory and Probiotic Yeast.
Probiotic-Enhanced Porous Bio-Hybrids with Inflammatory Targeting, ROS Scavenging, and Long-Term Drug Release for Ulcerative Colitis Treatment.
[Construction of an engineered probiotic strain for efficiently delivering chemokine CXCL12 and application of the strain in diabetic chronic wound healing].
Microencapsulation of Lactiplantibacillus plantarum BXM2 in Bamboo Shoot-Derived Nanocellulose Hydrogel to Enhance Its Survivability.
Microbial Dynamic Regulatory Tools: Design, Applications, and Prospects.
Engineered Endosymbionts that Modulate Primary Macrophage Function and Attenuate Tumor Growth by Shifting the Tumor Microenvironment.
Oral Nanoarmored Live Bacterial Biotherapeutics Bearing Polyphenol-Based Supraparticles Enhance Chemotherapy via Reestablishing Immuno-Oncology-Microbiome Axis.

ACS Synth Biol. 2025 Jun 22.

Engineered Marine Biofilms for Ocean Environment Monitoring.

Guillermo Nevot, Maria Pol Cros, Lorena Toloza, Nil Campamà-Sanz, Maria Artigues-Lleixà, Laura Aguilera, Marc Güell.

  Marine bacteria offer a promising alternative for developing Engineered Living Materials (ELMs) tailored to marine applications. We engineered Dinoroseobacter shibae to increase its surface-associated growth and develop biosensors for ocean environment monitoring. By fusing the endogenous extracellular matrix amyloidogenic protein CsgA with mussel foot proteins, we significantly increased D. shibae biofilm formation. Additionally, D. shibae was engineered to express the tyrosinase enzyme to further enhance microbial attachment through post-translational modifications of tyrosine residues. By exploiting D. shibae's natural genetic resources, two environmental biosensors were created to detect temperature and oxygen. These biosensors were coupled with a CRISPR-based recording system to store transient gene expression in stable DNA arrays, enabling long-term environmental monitoring. These engineered strains highlight D. shibae's potential in advancing marine microbiome engineering for innovative biofilm applications, including the development of natural, self-renewing biological adhesives, environmental sensors, and "sentinel" cells equipped with CRISPR-recording technology to capture and store environmental signals.

Keywords:  Dinoroseobacter shibae; ELMs; biofilm; biosensors; marine bacteria; surface colonization

DOI:  https://doi.org/10.1021/acssynbio.5c00192
Adv Healthc Mater. 2025 Jun 23. e2502358

Living Cell Materials for Advanced Biomedical Applications in Disease Diagnosis, Treatment, and Prevention.

Fanhui Kong, Jiani Jiang, Ekaterina Chernova, Stefan Wuttke, Wei Zhu, Qi Lei.

  Tailored and personalized therapies have gained significant attention for their great potential to minimize treatment-related side effects, mitigate immunological rejection, and improve disease prognosis. In this context, living cell materials (LCMs)-comprising living cells integrated with synthetic or non-biological components-synergistically combine the intrinsic properties of living cells with the superior functionalities of synthetic materials, enabling precise disease diagnosis and customized therapies. In this review, the characteristics and advantages of various living mammalian and bacterial cells utilized in the fabrication of living materials are summarized. Different methodologies (encapsulation, surface coating, intracellular loading, and cell backpack) for constructing LCMs, highlighting the benefits and limitations of each approach, along with their diverse applications in diagnosis and treatment are also discussed. Finally, the potential strategies are addressed to enhance the safety of living cell therapies, exploit novel functionalities, and facilitate the translation of fundamental research into clinical practice.

Keywords:  biomedical applications; diagnosis and treatment; living cell materials (LCMs); living mammalian and bacterial cells; tailored and personalized therapy

DOI:  https://doi.org/10.1002/adhm.202502358
Metabolites. 2025 Jun 18. pii: 410. [Epub ahead of print]15(6):

Development of Sucrose-Utilizing Escherichia coli Nissle 1917 for Efficient Heparosan Biosynthesis.

Yaozong Chen, Zihua Wan, Zheng-Jun Li.

  Background/Objectives: Heparosan is a component of the capsular polysaccharide in Escherichia coli K5 and Pasteurella multocida Type D. It shares a similar glycan structure with heparin and can be enzymatically modified to produce bioactive heparin. Methods: In this study, the probiotic strain E. coli Nissle 1917 (EcN), which naturally produces heparosan, was genetically engineered to utilize sucrose as a carbon source for growth while achieving high-yield heparosan biosynthesis. Results: By expressing the sucrose hydrolase genes sacA (from Bacillus subtilis) or spI (from Bifidobacterium adolescentis), EcN was enabled to utilize sucrose, achieving heparosan titers of 131 mg/L and 179 mg/L, respectively. Further metabolic engineering was performed to block the glycolytic and pentose phosphate pathways, thereby redirecting sucrose-derived glucose-6-phosphate and fructose-6-phosphate toward heparosan biosynthesis, while glycerol was supplemented as an auxiliary carbon source to support cell growth. Finally, the key biosynthesis genes galU, kfiD, and glmM were overexpressed, resulting in an engineered strain with a heparosan titer of 622 mg/L. Conclusions: This study represents the first successful engineering of EcN to utilize sucrose as the carbon source for growth, while achieving enhanced heparosan production through synergistic carbon source utilization. These findings establish a foundational strategy for employing this strain in the sucrose-based biosynthesis of other glycosaminoglycans.

Keywords:  Nissle 1917; carbon co-utilization; heparosan; sucrose

DOI:  https://doi.org/10.3390/metabo15060410
iScience. 2025 Jun 20. 28(6): 112519

Programmable cell aggregation by a synthetic biosilicification approach.

Qing Wang, Jing Sun, Lei Zang, Huaxiong Yao, Lin Wang, Runtao Zhu, Jie Li, Simin Zeng, Hongting Tang, Teng Wang, Ji Liu, Bo Wang, Bo Li, Zhiyuan Liu, Zhuojun Dai.

  Programmable cell aggregation offers valuable insights into the natural development of synthetic multicellular systems and enables precise control over spatial organization and material structuring. Previous efforts have focused on modifying cells with designed organic-based adhesive modules and assembling cells into defined patterns. Here, we present a different approach to guide cell assembly by tuning the organic-inorganic interactions. Our method involves engineering cells to express a silicifying peptide on their surfaces, which promotes silica deposition on the cell walls. This peptide simultaneously binds to the silica synthesized on adjacent cells, triggering cell clustering. The engineered cells exhibit rapid aggregation, with approximately 95% of cells assembling within 15 min. We further show that this capability can facilitate materials assembly and chemical production. Our biosilicification-based approach offers novel insights into natural multicellularity mechanisms and holds potential for applications in biomanufacturing and materials engineering.

Keywords:  Bioengineering; Biomaterials; Synthetic biology

DOI:  https://doi.org/10.1016/j.isci.2025.112519
Colloids Surf B Biointerfaces. 2025 Jun 17. pii: S0927-7765(25)00393-5. [Epub ahead of print]255 114886

Probiotics-embedded polymer films for oral health: Development, characterization, and therapeutic potential.

Charlotte Eckermann, Christof Johannes Klein, Florian Schäfer, Marc Thiel, Agnes-Valencia Weiss, Christian Motz, Karen Lienkamp, Matthias Hannig, Marc Schneider.

  The oral microbiome plays a crucial role in maintaining homeostasis, and microbial imbalances contribute to diseases such as periodontitis. Probiotic strains such as Lactobacillus rhamnosus and Lactobacillus reuteri have shown potential in restoring microbial balance in the oral cavity. However, their application remains challenging due to limited survival and adherence under intraoral conditions. Thus, we aimed to develop and evaluate mucoadhesive polymer films for local probiotic delivery. L. rhamnosus and L. reuteri were microencapsulated via spray drying and embedded in films composed of hydroxypropyl methylcellulose-polyvinyl alcohol (HPMC-PVA) and foamed polyvinyl alcohol (PVA). The films were characterized in terms of bacterial viability, tensile strength, folding endurance, and mucoadhesive properties. A proof-of-concept in vivo study was conducted by intraorally exposing enamel samples to two volunteers for eight hours, followed by confocal imaging and morphological analysis of adherent bacteria. Microencapsulation preserved high bacterial viability. The resulting films exhibited suitable mechanical properties and strong mucoadhesion. Biological evaluation revealed clear effects: films containing microencapsulated bacteria led to a statistically significant increase in adherent rod-shaped lactobacilli and a consistent reduction in coccoid bacteria associated with dysbiosis. The foamed PVA formulation showed the most pronounced modulation of the enamel-associated microbiota. These findings demonstrate that probiotic films can enable both bacterial stabilization and effective oral delivery. The system enhances colonization by beneficial bacteria while reducing potentially pathogenic cocci. This approach presents a promising strategy for microbiome-based prevention of oral diseases and merits further clinical investigation.

Keywords:  Lactobacillus reuteri; Lactobacillus rhamnosus; Microencapsulation; Mucoadhesive polymer films; Oral microbiome; Periodontitis

DOI:  https://doi.org/10.1016/j.colsurfb.2025.114886
Metab Eng. 2025 Jun 25. pii: S1096-7176(25)00095-3. [Epub ahead of print]

A Multilayered Biocontainment System for Laboratory and Probiotic Yeast.

Carla Maneira, Sina Becker, Alexandre Chamas, Gerald Lackner.

  The containment of genetically engineered microorganisms to designated environments of action is a paramount step in preventing their spread to nature. Physical barriers were traditionally employed to solve this issue, nevertheless, the growing number of biotechnological operations in open dynamic environments calls for intrinsic biocontainment. Here we describe the development of genetically embedded safeguard systems for both a laboratory strain of Saccharomyces cerevisiae and the commercial probiotic Saccharomyces cerevisiae var. boulardii. In a stepwise approach, single-input metabolic circuits based either on a synthetic auxotrophy or a CRISPR-based kill switch were developed before their combination into an orthogonal two-input system. All circuits are based on gut-active molecules or environmental cues, making them amenable to microbiome therapy applications. The final two-input system is stable for more than a hundred generations while achieving less than one escapee in 109 CFUs after incubation under restrictive conditions for at least six days. Biocontained strains can robustly produce heterologous proteins under permissive conditions, supporting their future use in the most varied applications, like in-situ production and delivery of pharmaceutically active metabolites.

Keywords:  Biocontainment; Engineered live biotherapeutic products; Saccharomyces boulardii; Saccharomyces cerevisiae; Synthetic biology

DOI:  https://doi.org/10.1016/j.ymben.2025.06.009
Adv Sci (Weinh). 2025 Jun 27. e04802

Probiotic-Enhanced Porous Bio-Hybrids with Inflammatory Targeting, ROS Scavenging, and Long-Term Drug Release for Ulcerative Colitis Treatment.

Luna Quan, Yang Ouyang, Weiwen Liang, Zixin Chen, Dongtian Miao, Bingna Zheng, Dingcai Wu, Rongkang Huang.

  Functional porous materials hold significant promise for biomedical applications owing to their high surface area and customizable pore architectures. However, the complex gastrointestinal environment poses considerable challenges for conventional nanomaterials in achieving targeted accumulation and controlled drug release. Herein, a kind of novel probiotic-enhanced porous bio-hybrids (E-xPAM@ASA) is designed via bio-hybridization of 5-aminosalicylic acid-loaded hairy microporous nanospheres (xPAM@ASA) with probiotic Escherichia coli Nissle 1917. Benefiting from the intrinsic inflammatory-targeting capability of EcN, the E-xPAM@ASA can accumulate in the inflammatory sites of the intestine. The unique porous architecture of xPAM@ASA not only facilitates high drug loading and long-term release but also provides abundant adsorption sites for effective reactive oxygen species scavenging. In a dextran sulfate sodium-induced ulcerative colitis murine model, E-xPAM@ASA demonstrate superior therapeutic outcomes, including mucosal repair, inflammation alleviation, and microbiota regulation. These findings highlight the potential of the multifunctional nanocomposite as a precise therapeutic platform for the treatment of intestinal inflammation.

Keywords:  ROS scavenging; hyper‐cross‐linking polymers; inflammatory targeting; long‐term drug release; ulcerative colitis

DOI:  https://doi.org/10.1002/advs.202504802
Sheng Wu Gong Cheng Xue Bao. 2025 Jun 25. 41(6): 2334-2348

[Construction of an engineered probiotic strain for efficiently delivering chemokine CXCL12 and application of the strain in diabetic chronic wound healing].

Shengjie Li, Huijuan Su, Xiaoting Li, Jing Wei, Tingtao Chen.

  Diabetic chronic wounds are characterized by difficult healing, recurrent progression, and high rates of disability and mortality, which make their clinical treatment a medical challenge urgent to be addressed. However, the complex local microenvironment conditions of chronic wounds, such as high protease activity and persistent inflammatory responses, result in low bioavailability of exogenous cytokines (e.g., chemokine CXCL12) at the wound site, limiting their clinical application. In this study, we utilized Lactobacillus plantarum WCFS1 as the chassis to develop an efficient CXCL12 delivery system based on synthetic biology. Subsequently, we evaluated the role of the engineered probiotic strain in promoting the chronic wound healing in diabetic mice. Firstly, we fused the endogenous secretion signal peptide lp_3050 (SPlp_3050) of L. plantarum WCFS1 and the commonly used secretion signal peptide usp45 (SPusp45) of lactic acid bacteria with the reporter gene gusA and inserted them into the pTRK892-P32(pgm) plasmid by molecular cloning. Then, we prepared the engineered strains and characterized the efficacy of the two signal peptides in driving the secretion of GusA. The results showed that SPlp_3050 efficiently drove the secretion of GusA in L. plantarum WCFS1, increasing the activity of GusA in the culture supernatant by nearly five times compared with that of SPlp_3050. Further, we fused SPlp_3050 and codon-optimized CXCL12 gene to construct an engineered probiotic strain Lpw-CXCL12 for CXCL12 delivery. The results demonstrated that the content of CXCL12 in the culture supernatant reached (13.40±0.20) μg/mL. Finally, we found that the engineered probiotic strain Lpw-CXCL12 accelerated chronic wound healing in a diabetic mouse model. In conclusion, these results support an engineered probiotic strain in promoting diabetic chronic wound healing, providing a new strategy and technological foundation for the management of diabetic chronic wounds in the future.

Keywords:  chemokine CXCL12; chronic wound healing; drug delivery; engineered probiotic strain; synthetic biology

DOI:  https://doi.org/10.13345/j.cjb.240632
Gels. 2025 Jun 18. pii: 465. [Epub ahead of print]11(6):

Microencapsulation of Lactiplantibacillus plantarum BXM2 in Bamboo Shoot-Derived Nanocellulose Hydrogel to Enhance Its Survivability.

Yajuan Huang, Qiao Guan, Yirui Wu, Chaoyang Zheng, Lingyue Zhong, Wen Xie, Jiaxin Chen, Juqing Huang, Qi Wang, Yafeng Zheng.

  This study presents a novel approach for enhancing the survivability of Lactiplantibacillus plantarum BXM2 using bamboo shoot-derived nanocellulose hydrogels. Nanocellulose hydrogels, composed of cellulose nanofibers (CNFs), cellulose nanocrystals (CNCs), and polyvinyl alcohol (PVA), were developed as protective matrices for probiotics. Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) confirmed the successful formation of hydrogen-bonded networks between PVA and nanocelluloses, while scanning electron microscopy (SEM) revealed that the ternary PVA-CNF-CNC hydrogel exhibited a dense, hierarchical porous structure, effectively encapsulating probiotics with an encapsulation efficiency of 92.56 ± 0.53%. Under simulated gastrointestinal digestion, the encapsulated probiotics maintained 8.04 log CFU/g viability, significantly higher than that of free bacteria (3.54 log CFU/mL). The hydrogel also enhanced heat tolerance (6.58 log CFU/mL at 70 °C) and freeze-drying survival (86.92% viability), outperforming binary systems. During 60-day storage at 4 °C and 25 °C, encapsulated probiotics retained viability above the critical threshold (≥6 log CFU/unit), whereas free cells declined rapidly. These findings highlight the potential of PVA-CNF-CNC hydrogel as an efficient delivery system to improve probiotic stability in food applications.

Keywords:  hydrogel; nanocellulose; probiotics; viability

DOI:  https://doi.org/10.3390/gels11060465
ACS Synth Biol. 2025 Jun 24.

Microbial Dynamic Regulatory Tools: Design, Applications, and Prospects.

Haibin Qin, Junping Zhou, Aiping Pang, Lianggang Huang, Zhiqiang Liu, Yuguo Zheng.

  Establishing efficient microbial cell factories for the production of functional nutraceuticals, pharmaceuticals, biofuels, and chemical products requires precise regulation to adapt key enzymes and pathway modules. Dynamic regulatory strategies are a promising and effective approach to achieve balanced cell growth and metabolite production. Dynamic regulatory tools, as the executors of regulatory strategies, usually require rationally designed modification strategies to provide libraries of tools with reliable quality. Here, typical dynamic regulatory tools at the DNA level (transcriptional level), the RNA level (post-transcriptional and translational level), and the protein level (post-translational) are presented. The regulatory mechanisms and design modification strategies of each tool are highlighted. Subsequently, strategies for applying regulatory tools to construct dynamic regulatory networks of metabolic pathways are summarized. Finally, the limitations of current dynamic regulatory tools are discussed and future trends are outlooked.

Keywords:  dynamic regulatory tools; genetic circuits; metabolic engineering; microbial cell factories; synthetic biology

DOI:  https://doi.org/10.1021/acssynbio.5c00219
ACS Appl Bio Mater. 2025 Jun 24.

Engineered Endosymbionts that Modulate Primary Macrophage Function and Attenuate Tumor Growth by Shifting the Tumor Microenvironment.

Cody S Madsen, Ashley V Makela, Chima V Maduka, Emily M Greeson, Anthony Tundo, Evran Ural, Satyajit Hari Kulkarni, Ahmed A Zarea, Matti Kiupel, Maryam Sayadi, Christopher H Contag.

  Modulating gene expression in macrophages can be used to improve tissue regeneration and redirect tumor microenvironments (TMEs) toward positive therapeutic outcomes. We have developed Bacillus subtilis as an engineered endosymbiont (EES) capable of residing inside the eukaryotic host cell cytoplasm and controlling the fate of macrophages. Secretion of mammalian transcription factors (TFs) from B. subtilis that expresses listeriolysin O (LLO; allowing the EES to escape destruction by the macrophage) modulated expression of surface markers, cytokines, and chemokines, indicating functional changes in a macrophage/monocyte cell line. The engineered B. subtilis LLO TF strains were evaluated in murine bone marrow-derived macrophages (BMDMs) by flow cytometry, chemokine/cytokine profiling, metabolic assays, and RNA-Seq delivery of TFs by the EES shifted BMDM gene expression, production of cytokine and chemokines, and metabolic patterns, indicating that the TF strains could guide primary macrophage function. Thereafter, the ability of the TF strains to alter the TME was characterized in vivo in an orthotopic murine model of triple-negative breast cancer to assess therapeutic effects. The TF strains altered the TME by shifting immune cell composition and attenuating tumor growth. Additionally, multiple doses of the TF strains were well-tolerated by the mice. The use of B. subtilis LLO TF strains as EES showed promise as a unique cancer immunotherapy by directing the immune function intracellularly. The uses of EES could be expanded to modulate other mammalian cells over a range of biomedical applications.

Keywords:  bacterial immunotherapy; bacteriotherapy; bone marrow-derived macrophages; engineered endosymbiont; immune modulation; immunometabolism; transcription factors; tumor microenvironment

DOI:  https://doi.org/10.1021/acsabm.5c00590
ACS Nano. 2025 Jun 26.

Oral Nanoarmored Live Bacterial Biotherapeutics Bearing Polyphenol-Based Supraparticles Enhance Chemotherapy via Reestablishing Immuno-Oncology-Microbiome Axis.

Qinling Liu, Yue Wu, Qingxin Fan, Jialing Liu, Yan Chen, Yuanmeng He, Wenqi Wei, Haojie Zhang, Yueling Zhao, Yunxiang He, Xiao Du, Junling Guo.

  The immuno-oncology-microbiome (IOM) axis, referring to the gut microbiota-regulated immune interactions on the tumor microenvironment and systemic immunity, is essential for cancer therapies. However, the cytotoxicity of chemotherapeutic agents (Chemos) disrupts the gut microbiota- and gut microbiota-manipulated IOM axis, further diminishing the therapeutic efficacy. Here, we developed oral nanoarmored live bacterial biotherapeutics (supraLBT), to reshape the tumor microenvironment and enhance chemotherapy via reestablishing the IOM axis. The cyto-adhesive polyphenol-based supraparticles, made from green tea polyphenol and food-grade milk protein, attached on microbes (Escherichia coli Nissle1917, EcN) resisted a range of clinically relevant Chemos via phenolic-mediated noncovalent interactions, enhancing supraLBT survival by 27-fold compared with bare EcN. SupraLBT restored the intestinal microbiota and the disrupted IOM axis, thereby reducing the infiltration of regulatory T cells, increasing the recruitment of cytotoxic CD8+ T cells to the tumor bed, and further inhibiting tumor proliferation and demonstrating enhanced systemic immune responses. Notably, oral supraLBT combined with chemotherapy (doxorubicin) exhibited 2.35-fold greater tumor regression than that of doxorubicin alone, indicating that oral supraLBT can enhance the chemotherapeutic effect. Further investigations revealed that supraLBT reprogrammed the immune tumor microenvironment by upregulating antitumor cytokines and altering the gut microbial composition. Given the intricate interplay between gut microbiota, host immune system, and tumor microenvironment, this work presents a facile and biomaterial-engineered microorganism-based strategy to enhance the synergistic immuno-chemotherapy effects.

Keywords:  IOM axis; armored probiotics; chemo-immunotherapy; gut barrier; polyphenol

DOI:  https://doi.org/10.1021/acsnano.5c01158