bims-livmat 2026-04-26 papers

bims-livmat

Biomed News

on Living materials

Issue of 2026–04–26
nine papers selected by
Sara Trujillo Muñoz, Leibniz-Institut für Neue Materialien

Photosynthetic engineered living materials incorporating recombinant Chlamydomonas reinhardtii enable long-term semi-continuous photobiotransformation.
Living Microbial Drugs.
Construction of an engineered Escherichia coli strain with enhanced intestinal colonization and anti-inflammatory efficacy in colitis.
Unveiling the mechanistic principles and engineered exploitation of bacteria and derivatives in precision drug delivery.
Focused Ultrasound-Triggered Burst Release and Enrichment of Engineered Bacteria for Tumor Therapy.
Improved efficacy and long-term protective effects of CXCR4/IL10 bioengineered mesenchymal stromal cells in a model of inflammatory bowel disease.
Advances in single-cell surface engineering: nano-coating and core-shell strategies for probiotics delivery in inflammatory bowel disease.
Employing synthetic biology to modulate metabolic flux: Current strategies and applications.
Marine Polysaccharides: A Promising Source for Probiotic Delivery Systems.

N Biotechnol. 2026 Apr 21. pii: S1871-6784(26)00050-6. [Epub ahead of print]

Photosynthetic engineered living materials incorporating recombinant Chlamydomonas reinhardtii enable long-term semi-continuous photobiotransformation.

Vilja Siitonen, Tiia Siivola, Pornpan Napaumpaiporn, Tekla Tammelin, Yagut Allahverdiyeva.

  Photosynthetic engineered living materials (ELMs) present an attractive platform for producing valuable compounds and fuels using solar energy. Compared to traditional suspension cultures, ELMs enable long-term biocatalytic activity, more efficient light utilization, and facilitate downstream processing. In this study, we developed photosynthetic ELMs by entrapping Chlamydomonas reinhardtii in either alginate or TEMPO-oxidized cellulose nanofibers (TCNF). The strain utilized was converting cyclohexanone to ε-caprolactone via photobiotransformation. The cell loading and matrix material were evaluated in short-term reactions and during a semi-continuous bioproduction in vials. We showed that the entrapped cells remain photosynthetically active and catalytically competent over extended periods. By replenishing the substrate and collecting the product every 24hours we achieved semi-continuous photobiotransformation for over two weeks, reaching an average productivity of 2.31 ± 0.26gm-2 d-1 and accumulating 0.31 ± 0.03molm-2 corresponding to 3.49 ± 0.31gL-1 of ε-caprolactone. These findings establish photosynthetic ELMs as a viable approach for long-term whole-cell photobiotransformation.

Keywords:  Alginate; Baeyer-Villiger monooxygenase BVMO; Chlamydomonas reinhardtii; Cyclohexanone monooxygenase (CHMO); TEMPO-oxidized cellulose nanofibers (TCNF); engineered living materials; immobilization

DOI:  https://doi.org/10.1016/j.nbt.2026.04.004
Chemistry. 2026 Apr 22. e03523

Living Microbial Drugs.

Cemile Elif Özçelik, Nazlıcan Tunç, Senem Şen, Urartu Özgür Şafak Şeker.

  Living microbial therapeutics have arisen as a novel category of medications that extend beyond traditional small molecules and biologics. Advancements in synthetic biology have facilitated the rational engineering of microorganisms to detect host or disease-related signals and administer therapeutic chemicals in situ. In contrast to conventional pharmaceuticals, these live biotherapeutic agents engage in dynamic interactions with both the host and its microbiota, allowing context-specific, self-regulating therapies. This review emphasizes the progression of the field from conventional probiotics to advanced, designed living therapeutics. We examine principal microbiological platforms, including bacteria, yeasts, and alternative systems such as phages and archaea, delineating their relative benefits and constraints as therapeutic hosts. Key design principles, genetic logic circuits, quorum-sensing-based regulation, and synthetic memory devices that enable microorganisms to possess context-dependent and self-adjusting therapeutic capabilities, are discussed alongside present and emerging therapeutic applications in infectious diseases, metabolic disorders, inflammatory illnesses, and cancer immunotherapy, where engineered microorganisms have demonstrated significant preclinical effectiveness and first clinical promise. Despite these advancements, obstacles remain, including biosafety, biocontainment, regulatory approval, and patient acceptability. Engineered living microbial therapeutics signify a swiftly evolving domain in medicine, set to transform treatment paradigms via intelligent, flexible, and sustainable methodologies for human health.

Keywords:  cell engineering; living microbial therapeutics; probiotic engineering; synthetic biology; synthetic circuit design

DOI:  https://doi.org/10.1002/chem.202503523
Cell Mol Immunol. 2026 Apr 22.

Construction of an engineered Escherichia coli strain with enhanced intestinal colonization and anti-inflammatory efficacy in colitis.

Peijun Yu, Wenjing Zhou, Chunyang Li, Qiang Sun, Yunpeng Yang.

  Engineered probiotics are considered effective and safe therapeutic strategies for the treatment of various diseases. Escherichia coli Nissle 1917 (EcN) has been widely used as a chassis strain because of its safety and well-established genetic manipulation system. However, the limited intestinal colonization ability of EcN limits its potential as a chassis for the construction of synthetic probiotics. Here, an engineered EcN strain (EcN-CPM) with enhanced gastric acid and bile salt tolerance and improved intestinal adhesion was constructed. Oral administration of EcN-CPM to mice with colitis alleviated disease severity and reshaped the disordered gut microbiome by decreasing the abundance of Escherichia-Shigella while increasing the abundance of norank_f_Muribaculaceae. Mechanistically, the EcN-CPM supernatant directly promoted the proliferation of norank_f_Muribaculaceae, a short-chain fatty acid (SCFA)-producing genus. Targeted metabolomics revealed that EcN-CPM restored the DSS-induced depletion of SCFAs, which were negatively correlated with the abundance of Escherichia-Shigella and positively correlated with the abundance of norank_f_Muribaculaceae. Consistent with these findings, EcN-CPM treatment upregulated the expression of Treg-associated markers (Foxp3, Ctla4, and Cd25) and downregulated the expression of Th17-related genes (IL-17A and Roryt) in colonic tissues, restoring the IL-17A/Foxp3 ratio to homeostasis. Untargeted metabolomics further demonstrated that EcN-CPM uniquely restored the levels of seven anti-inflammatory metabolites depleted by DSS treatment. Collectively, these findings demonstrate that EcN-CPM alleviates intestinal inflammation by remodeling the gut microbiota to increase the production of SCFAs and anti-inflammatory metabolites, thereby driving a shift in Th17- and Treg-associated transcriptional signatures. This study establishes a platform for precision-designed synthetic probiotics with enhanced probiotic properties.

Keywords:   Escherichia coli Nissle 1917 (EcN); Colitis; Intestinal colonization ability; Synthetic probiotics; Th17- and Treg-associated transcriptional signatures

DOI:  https://doi.org/10.1038/s41423-026-01415-w
Biotechnol Adv. 2026 Apr 20. pii: S0734-9750(26)00108-4. [Epub ahead of print]90 108902

Unveiling the mechanistic principles and engineered exploitation of bacteria and derivatives in precision drug delivery.

Wen Yang, Anlong Li, Beihan Dong, Xiao Feng, Feng Jiang.

  The core of precision medicine lies in the efficient and specific delivery of therapeutic agents to disease sites. Traditional synthetic nanocarriers face inherent limitations in navigating complex biological barriers and responding to dynamic disease microenvironments. This review systematically explores the engineering strategies and application potential of four cutting-edge bacterial-derived delivery systems. Live biotherapeutic products (LBPs) serve as "living factories", utilizing genetic circuits to sense the disease microenvironment and produce therapeutic molecules in situ. Bacterial secretion systems (T1SS-T7SS) are repurposed as precise "molecular syringes" to directly translocate effector proteins, nucleic acids, and other cargoes into target cell cytosol or specific compartments. Extracellular contractile injection systems (eCISs) function as autonomous, pre-assembled "nanosyringes" that utilize a spring-loaded mechanism for direct cytosolic injection, offering a non-viral, high-efficiency delivery platform. Bacterial extracellular vesicles (bEVs), as natural nanocarriers, are engineered for targeted drug delivery and immunomodulation. The article compares the delivery mechanisms, payload characteristics, engineering flexibility, and clinical translation challenges of these platforms. The future advancement of this field will rely on the deep integration of synthetic biology, nanotechnology, and immunology to develop intelligent therapeutic platforms that are simultaneously potent, safe, and controllable.

Keywords:  Bacterial drug delivery; Bacterial extracellular vesicles (bEVs); Engineered nanoplatforms; Extracellular contractile injection systems (eCISs); Live biotherapeutic products (LBPs); Modular secretion system

DOI:  https://doi.org/10.1016/j.biotechadv.2026.108902
Biomater Res. 2026 ;30 0354

Focused Ultrasound-Triggered Burst Release and Enrichment of Engineered Bacteria for Tumor Therapy.

Jinhee Yoo, Yunhee Hwang, Mihyeon Park, Honghyeon Ha, Myeong Ryeol Choi, Sung In Lim, Byullee Park, Yong Joo Ahn, Won Jong Kim, Gyoo Yeol Jung, Hyung Ham Kim.

Ultrasound has been widely used in bacteria-based tumor therapy for targeted drug delivery due to its noninvasive ability to control bacteria. However, current approaches achieve only gradual release of therapeutic agents and rely on limited natural homing ability, resulting in poor treatment efficacy. Here, we demonstrate that focused ultrasound (FUS) can simultaneously induce burst release within tumors and local enrichment of therapeutics, enhancing precise and controllable spatiotemporal drug delivery efficiency within tumor microenvironments in living-therapeutic biomaterial system. We achieved FUS-triggered bacterial burst release by coexpressing gas vesicles (GVs), protein nanostructures that induce cavitation, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which increases antitumor efficacy. Furthermore, we show that FUS enhances enrichment of therapeutics at the tumor site by manipulating bacteria toward tumor vessel walls and increasing tumor permeability via sonopermeation. In a mouse model, we demonstrated clinical potential by achieving a 40% reduction in tumor volume using probiotic Escherichia coli Nissle (EcN) 1917 with a short 2-min FUS exposure and no exogenous agents. This work shows that physical ultrasound control provides an intuitive, highly efficient, and easily applicable biohybrid approach to bacteria-based tumor therapy, offering a simple and widely accessible strategy that can be broadly adapted to diverse living biomaterial systems.

DOI: https://doi.org/10.34133/bmr.0354
Bioeng Transl Med. 2026 Mar;11(2): e70083

Improved efficacy and long-term protective effects of CXCR4/IL10 bioengineered mesenchymal stromal cells in a model of inflammatory bowel disease.

Mercedes Lopez-Santalla, Marta C Ordoñez-Velasco, Maria Fernandez-Garcia, Miriam Hernando-Rodriguez, Juan A Bueren, Rosa M Yañez, Marina I Garin.

  Mesenchymal stromal cell (MSCs)-based therapies have emerged as a promising approach for inflammatory bowel disease (IBD) treatment due to their immunosuppressive and regenerative properties. However, clinical trials have shown limited therapeutic effectiveness, largely because of low efficiency in penetrating the inflamed colon and their inconsistent in vivo immunomodulatory ability. In this study, we generated genetically engineered adipose-derived human MSCs constitutively expressing CXC chemokine receptor 4 and interleukin 10 (CXCR4-IL10-MSCs) to promote their delivery to the inflamed colon and enhance their immunosuppressive capability. Compared to unmodified MSCs, CXCR4-IL10-MSCs exhibited enhanced trafficking to the inflamed colon and achieved improved therapeutic effects in dextran sulfate sodium (DSS)-challenged colitic mice. Upon a chronic DSS re-challenge, CXCR4-IL10-MSCs showed enhanced long-term protective effects. These findings demonstrate that stable ectopic expression of CXCR4 and IL10 enhances the therapeutic efficacy of MSCs and supports the development of an optimized MSC-based product capable of inducing an improved long-term protective immune memory in IBD.

Keywords:  CXCR4; IL10; immunomodulation; inflammatory bowel disease; mesenchymal stromal cell‐based therapy

DOI:  https://doi.org/10.1002/btm2.70083
Arch Microbiol. 2026 Apr 24. pii: 352. [Epub ahead of print]208(7):

Advances in single-cell surface engineering: nano-coating and core-shell strategies for probiotics delivery in inflammatory bowel disease.

Keke Wang, Chao Yan.



Keywords:  Biomedical material; Delivery system; Inflammatory bowel disease; Probiotics

DOI:  https://doi.org/10.1007/s00203-026-04907-5
J Biosci Bioeng. 2026 Apr 21. pii: S1389-1723(26)00130-1. [Epub ahead of print]

Employing synthetic biology to modulate metabolic flux: Current strategies and applications.

Divya Ojha, Ram Kulkarni, Ambadas B Rode.

  The world's increasing demand for petrochemical, pharmaceutical, and nutraceutical products necessitates the development of new strategies for producing these high-value chemicals. The depletion of the natural fossil reserves and environmental pollution associated with their procurement further compel us to find sustainable, greener, and cost-effective alternatives. In light of this, a shift has been witnessed in deriving these products from fossil-based sources or chemical synthesis to biomanufacturing (production using living systems). However, to fully utilize the potential of biomanufacturing, novel tools and strategies that can function in bacteria, archaea, and eukaryotes, regulate multi-enzyme pathways, offer precise and conditional gene regulation, and possess versatility are highly required. This review presents a comprehensive summary of the latest gene modulation tools and strategies used by metabolic engineers, along with a mechanistic overview and their applications. In addition, we presented the tools that have the potential to be used for pathway optimization but are still less explored. Within this context, we categorized these tools based on their molecular level of gene regulation, i.e., at and beyond the central dogma. We believe that a deeper understanding of the design, development, and application of these tools would be beneficial for metabolic engineers to reprogram biosynthetic pathways by adopting system-specific approaches, as a single strategy cannot be applied to all systems. Lastly, we discussed the challenges and future prospects of developing these gene regulatory tools to further advance the biomanufacturing field.

Keywords:  Biomanufacturing; Biosynthetic pathways; Central dogma; Conditional gene regulation; Gene modulation

DOI:  https://doi.org/10.1016/j.jbiosc.2026.03.012
Probiotics Antimicrob Proteins. 2026 Apr 23.

Marine Polysaccharides: A Promising Source for Probiotic Delivery Systems.

Sathish Kumar Venkatachalam, Shantkriti Srinivasan, Murali Santhoshkumar, Nallusamy Duraisamy, Ramachandran Vinayagam, Dharmaraj Senthilkumar.



Keywords:  Delivery systems; Encapsulation; Gut health; Gut microbiome; Probiotics; Seaweed polysaccharides

DOI:  https://doi.org/10.1007/s12602-026-11030-w