bims-livmat 2026-10-11 papers

bims-livmat

Biomed News

on Living materials

Issue of 2026–10–11
eleven papers selected by
Sara Trujillo Muñoz, Leibniz-Institut für Neue Materialien

An Antimicrobial, Cell-Adhesive, and Growth Factor-Producing Living Material Engineered From Bacillus subtilis Biofilms for Wound Healing.
A living hydrogel platform for wireless light-controlled microbial therapy in the stomach.
Formation of a swelling gel underlies a morphological transition in Bacillus subtilis biofilms.
Programmable genetic control of tumor-colonizing Bifidobacterium longum for intratumoral therapeutic delivery and biocontainment.
Sonogenetic Control of Engineered Probiotics for the Treatment of MASH by Modulating the Gut-Liver Axis.
Advances and perspectives in genetically encoded biosensors for biomarker detection and theranostic circuits.
Reprogramming the therapeutic fate of living biotherapeutic products for intestinal diseases via biomaterials.
Engineered probiotics couple photothermal cuproptosis with biomechanical disruption and immune activation.
Engineered Bacillus subtilis Spores Surface-Displaying a PRRSV GP3/GP4/GP5 Fusion Antigen: A Preliminary Immunogenicity Evaluation in Mice and Piglets.
Mining Microbial Transcriptomes to Engineer Cell-Based Bacterial Biosensors in Gut-Resident Bacteroidaceae.
DNA nanodevice-engineered macrophages as living sensors for dual-mode in vivo monitoring of tumor-associated macrophage polarization.

Adv Healthc Mater. 2026 Oct 09. e71823

An Antimicrobial, Cell-Adhesive, and Growth Factor-Producing Living Material Engineered From Bacillus subtilis Biofilms for Wound Healing.

Mélanie Côté-Cyr, Marie-Jeanne Archambault, Caroline Dupuis, Steve Bourgault.

  Chronic wounds represent a burden for healthcare systems and critically impair quality of life of patients. Engineered living materials (ELMs) show great potential as scaffolds and delivery systems in tissue regeneration. As a generally regarded safe biofilm-producing organism, Bacillus subtilis (B. subtilis) presents interesting properties to develop functional ELMs in biomedicine. In this study, we engineer B. subtilis to design a protein-based living matrix eluting bioactive sequences for wound healing. Accordingly, we create a biofilm-deficient B. subtilis strain that expressed the biofilm scaffold protein, TasA in fusion with a cell-adhesive motif (TasA-PRb), which results in biofilms with cell-adhesive properties for fibroblasts and keratinocytes. Besides, B. subtilis is known to elicit antimicrobial properties against strains of E. coli and S. epidermidis, which are not impeded by biofilm engineering. We also incorporate secretion of fibroblast growth factor 2 (FGF2), known to promote wound healing, in the biofilm-deficient strain. Co-culture of FGF2-expressing and TasA-PRb producing strains resulted in biofilms secreting bioactive FGF2. Chronic wound healing assays in diabetic mice reveal accelerated wound closure in mice treated with the TasA-PRb/FGF2 biofilms, with absence of observable adverse effects. This underlines the potential of the B. subtilis biofilm for the design of functional ELMs in biomedicine.

Keywords:  Bacillus subtilis; FGF2; TasA; biofilms; living materials; protein fibers; wound healing

DOI:  https://doi.org/10.1002/adhm.71823
J Colloid Interface Sci. 2026 Oct 07. pii: S0021-9797(26)01897-7. [Epub ahead of print]728 141720

A living hydrogel platform for wireless light-controlled microbial therapy in the stomach.

Hongxiang Li, Chao Zhang, Haihan Yao, Yihao Wang, Yue Jiang, Guijie Bai, Long Li, Zhijie Feng, Duo Liu, Hanjie Wang.

  Engineered microbial therapies provide a promising strategy for in situ production of therapeutic molecules at disease sites; however, their clinical translation remains limited by insufficient retention at target tissues and the lack of external control after administration. Here, we develop a wearable bioelectronic-assisted living hydrogel platform that enables rapid in situ immobilization and remote regulation of engineered bacteria. Optogenetically engineered bacteria capable of green-light-induced anti-interleukin-6 (anti-IL-6) secretion were encapsulated within a photoresponsive Gelatin Methacryloyl/Sodium Alginate (GelMA/SA) hydrogel precursor. Upon external green-light stimulation, the precursor rapidly transformed into a stable living hydrogel within 5 s while activating the therapeutic protein expression program of engineered bacteria, thereby coordinating hydrogel formation with microbial functional regulation. This rapid in situ gelation strategy enhanced bacterial retention in the stomach and provided a protective microenvironment to maintain bacterial viability and sustained functional output. Combined with a lightweight wireless-powered wearable LED device, the system allowed non-invasive optical control after gastric administration, overcoming the limited spatiotemporal controllability of conventional microbial therapies. The platform preserved bacterial activity, enabled on-demand modulation of inflammatory responses, and demonstrated therapeutic benefits in full-thickness skin wound and ethanol-induced gastritis models. Compared with bacteria or hydrogel treatment alone, optically activated bacterial therapy further reduced inflammation and promoted tissue repair. This work establishes a rapidly assembled and remotely programmable living bioelectronic interface by combining photocrosslinkable biomaterials, optogenetic engineering, wearable electronics, and engineered microbes, offering a controllable approach for microbial therapy of gastrointestinal diseases.

Keywords:  Engineering bacteria; Green light; Hydrogel; Stomach

DOI:  https://doi.org/10.1016/j.jcis.2026.141720
Proc Natl Acad Sci U S A. 2026 Oct 13. 123(41): e2608188123

Formation of a swelling gel underlies a morphological transition in Bacillus subtilis biofilms.

Ayantika Saha, Joshua M Jones, Abigail Plummer, Joseph W Larkin.

  Microbes across diverse species and environments form biofilms, living materials composed of cells and extracellular polymers. Biofilm-dwelling cells benefit from emergent soft matter physics, which sculpts three-dimensional morphologies and facilitates osmotic nutrient uptake. Although biofilms are modeled as viscoelastic gels, the physical origins of the phase transition underlying their conversion from groups of cells to living gels have not been systematically investigated. Here, we show that Bacillus subtilis biofilms use polymer composition to tune their physical properties and drive gel formation. Using imaging, water immersion experiments, and rheological measurements with matrix knockout strains, we demonstrate the complementary roles of two polymers in this developmental transition: hydrophilic poly-γ-glutamic acid swells colonies by absorbing water while exopolysaccharides serve as effective cross-linkers, causing a sol-gel-like phase transition that imparts structural integrity. With matrix knockout coculture biofilms, we independently modulate the production of each polymer and reveal a phase space of biofilm morphologies. Colonies that produce both polymers develop macroscopic wrinkles. A thin-film model predicts biofilm wrinkling from swelling-induced internal strain coupled with elasticity. The model reproduces the shape of our observed morphological phase diagram. Our results demonstrate that bacteria leverage gelation to vary their material properties and morphologies, with implications for microbial ecology and engineering living matter.

Keywords:  gelation; hydrogel swelling; living material; microbial communities; phase transition

DOI:  https://doi.org/10.1073/pnas.2608188123
bioRxiv. 2026 Aug 13. pii: 2026.08.12.744520. [Epub ahead of print]

Programmable genetic control of tumor-colonizing Bifidobacterium longum for intratumoral therapeutic delivery and biocontainment.

Jaehyun Lee, Joshua Glazier, Ralph R Weichselbaum, Mark Mimee.

Engineered bacteria offer a distinct modality for cancer therapy by exploiting the ability of certain species to colonize tumors and deliver therapeutic payloads. Improving their efficacy and safety requires control over bacterial activity after tumor colonization, yet few microbial chassis permit it. Bifidobacterium longum , a probiotic with intrinsic tumor-targeting and antitumor activity, is a promising chassis but lacks such control. Here, we develop a genetic control system that regulates B. longum activity within tumors, from gene expression to bacterial abundance. A human-isolate-derived replicon supports plasmid maintenance without antibiotic selection, and promoter and ribosome-binding-site libraries provide ∼150-fold and ∼48-fold expression ranges, respectively. Signal peptides enable secretion of structurally diverse therapeutic payloads and B. longum secreting CCL21 or an anti-PD-L1 nanobody reduces tumor growth relative to PBS controls. Anhydrotetracycline delivered in drinking water induces transgene expression in tumor-resident bacteria and reduces intratumoral bacterial load through CRISPRi targeting essential genes. Together, these results establish a tumor-homing probiotic as an externally controllable therapeutic chassis.

DOI: https://doi.org/10.64898/2026.08.12.744520
Adv Sci (Weinh). 2026 Oct 08. e78100

Sonogenetic Control of Engineered Probiotics for the Treatment of MASH by Modulating the Gut-Liver Axis.

Chunya Ji, Yan Fang, Shen Zhang, Weichen Xu, Wenyun Guo, Jing Chen, Mingrui Zhu, Congjian Wen, Siming Chen, Yuli Zhu, Huixiong Xu, Haohao Yin.

  Metabolic dysfunction-associated steatohepatitis (MASH) currently lacks effective targeted therapeutics, while interleukin-22 (IL-22) as a potential treatment approach faces challenges in the clinical translation due to off-target risks associated with systemic delivery. To address this limitation, we developed an intelligent oral biologics platform centered on an engineered probiotic strain (Escherichia coli Nissle 1917) capable of producing therapeutic IL-22 in situ, encapsulated within an inulin hydrogel to resist gastric degradation. Critically, we integrated a sonogenetic control module that enables non-invasive, spatiotemporally precise activation of IL-22 expression in the gut via remote ultrasound stimulation. In MASH model, this targeted, on-demand IL-22 delivery effectively remodeled the gut microbiota and improved intestinal barrier function. This led to significantly reduced portal lipopolysaccharide (LPS) levels, which in turn decreased hepatic IL-6 production. Mechanistically, this strategy inhibited the pathological overactivation of the PI3K-AKT-mTOR signaling pathway, thereby markedly ameliorating hepatic steatosis, inflammation, and fibrosis. Notably, by confining IL-22 production to the gut, this strategy completely circumvented the off-target effects of conventional IL-22 therapy. We observed reversal of MASH-associated cognitive impairment, highlighting systemic benefits of restoring gut-liver axis homeostasis. This study establishes a transformative, multi-beneficial MASH therapy paradigm by modulating the gut-liver axis, offering a safe, effective, clinically translatable strategy.

Keywords:  MASH; engineered probiotics; gut‐liver axis; interleukin‐22; sonogenetics

DOI:  https://doi.org/10.1002/advs.78100
Synth Syst Biotechnol. 2027 May;19 1-20

Advances and perspectives in genetically encoded biosensors for biomarker detection and theranostic circuits.

Jianping Xu, Qingsheng Qi, Qian Wang.

  Effective biomarker detection is critical for timely and accurate clinical disease diagnosis. However, conventional analytical methodologies are often constrained by laborious procedures, reliance on specialized equipment, and an inherent inability to perform continuous in situ monitoring. To circumvent these limitations, synthetic biology has pioneered the development of genetically encoded biosensors as a rapid, highly sensitive, and cost-effective alternative. This review specifically focuses on transcriptional regulation-based biosensors, primarily those utilizing allosteric transcription factors (aTFs) and two-component systems (TCSs). By integrating these regulatory sensing modules into engineered microbial chassis, researchers can achieve continuous, real-time biomarker monitoring even within complex and otherwise inaccessible physiological environments. This review particularly focuses on microbial chassis rather than mammalian systems due to their highly tractable genetics, rapid response kinetics, and their unique potential to be deployed as autonomous living probiotics for in situ theranostics. Furthermore, coupling these sensors with engineered actuator genes enables the construction of intelligent therapeutic genetic circuits. This closed-loop theranostic paradigm facilitates simultaneous, real-time diagnosis and autonomous, localized therapeutic interventions, paving the way for personalized and dose-adaptive precision medicine. Finally, we summarize recent advancements in these biosensor platforms, explore their applications in targeted disease interventions, and discuss the contemporary challenges alongside future perspectives for their clinical translation.

Keywords:  Biomarker detection; Engineered probiotics; Genetically encoded biosensors; Synthetic biology; Theranostic circuits

DOI:  https://doi.org/10.1016/j.synbio.2026.09.006
Biomaterials. 2026 Oct 01. pii: S0142-9612(26)00699-X. [Epub ahead of print]338(Pt A): 124675

Reprogramming the therapeutic fate of living biotherapeutic products for intestinal diseases via biomaterials.

Xiyu Cheng, Yunqi Yang, Haitao Ding, Ruisheng Huang, Shuangshuang Cao, Runxuan Shi, Guobin Qi, Shuang Wang, Guanghui Ma, Wei Wei, Diwei Zheng.

  Live biotherapeutic products (LBP) hold great promise for the treatment of intestinal diseases such as inflammatory bowel disease and colorectal cancer, owing to their unique abilities to modulate the gut microbiota, regulate host immunity, and influence drug metabolism. However, the use of natural strains remains constrained by several challenges, including poor survival, limited colonization efficiency, immune clearance and non-specific targeting. Rational engineering of bacteria can overcome these limitations, while biomaterials, owing to their safety and versatile functionalities, provide powerful tools for bacterial modification. Recent studies have focused on developing biomaterial-modified bacteria (BMB) using lipid-based coatings, hydrogels, organic-inorganic hybrid materials, antibody or functional protein and cell membrane. This review systematically summarizes strategies for modifying bacterial surfaces with these biomaterials, elucidates the underlying mechanisms by which they enhance bacterial performance, and highlights recent advances in this field, offering insights that may inspire the design of the next generation of BMB based on high-throughput platforms, synthetic biology, and artificial intelligence (AI).

Keywords:  Biomaterial; Colorectal cancer; Inflammatory bowel disease; Microbiota therapy; Surface modification; Synthetic biology

DOI:  https://doi.org/10.1016/j.biomaterials.2026.124675
Bioact Mater. 2027 Feb;68 931-950

Engineered probiotics couple photothermal cuproptosis with biomechanical disruption and immune activation.

Xiaoyang Zhang, Xiaohui Liu, Ke Huang, Baijiang Jin, Nan Ma, Hao Liu, Hui Jiang, Xuemei Wang.

  Living bacterial therapeutics face limitations from poor surface functionalization and a hostile tumor microenvironment. Here, we engineer EPACS (EcN@PDA/Au-CuS) by coating E. coli Nissle 1917 with polydopamine, which acts as an adhesive interfacial platform to direct the uniform in situ growth of Au-CuS heterojunctions across the bacterial surface. EPACS combines tumor colonization, high photothermal conversion, and stimuli-responsive Cu2+ release for combined cuproptosis-mediated photothermal therapy. Mechanistically, EPACS induces oxidative stress and mitochondrial dysfunction, triggering both cuproptosis and apoptosis, while atomic force microscopy (AFM) reveals dynamic biomechanical changes-an initial RhoA/F-actin-dependent cellular stiffening that is subsequently reversed by laser irradiation into irreversible cytoskeletal disruption and enhanced cell killing. In vivo, EPACS achieves effective tumor accumulation and photothermal heating, resulting in substantial tumor suppression with favorable biosafety. When combined with laser irradiation, EPACS reduces collagen deposition and α-SMA expression, indicating stromal remodeling, and AFM confirms photothermal disruption of tumor matrix mechanics. This biomechanical remodeling is accompanied by immune modulation-decreased M2-like macrophages and regulatory T cells-suggesting enhanced antitumor immunity. Overall, EPACS integrates biochemical damage, cuproptosis/apoptosis, biomechanical regulation, and immunomodulation, offering a promising combined cancer therapy.

Keywords:  Cytoskeletal disruption; Engineered probiotics; Mechanophenotypic reprogramming; Photothermal–cuproptosis combinatorial therapy; Tumor microenvironment

DOI:  https://doi.org/10.1016/j.bioactmat.2026.09.021
Probiotics Antimicrob Proteins. 2026 Oct 03.

Engineered Bacillus subtilis Spores Surface-Displaying a PRRSV GP3/GP4/GP5 Fusion Antigen: A Preliminary Immunogenicity Evaluation in Mice and Piglets.

Yicen Tang, Yuhan Wang, Zhenhua Wang, Pengfei Fang, Lei Fei, Jianzhen Li, Yang Yang, Cheng Ma, Dongmei Zhang, Bo Jing, Xueqin Ni, Jinlong Yang, Yan Zeng, Kangcheng Pan.

  Bacillus subtilis is a safe, non-pathogenic probiotic capable of forming highly resistant spores, making it an attractive chassis for oral antigen delivery and mucosal immune modulation. In this study, we engineered a recombinant B. subtilis strain, RG, to display an optimized PRRSV fusion antigen, E5, on the spore surface using CotB as the anchoring protein. E5 was designed by tandemly linking selected GP3, GP4, and GP5 fragments. The recombinant spores were evaluated in mice and piglets as part of a proof-of-concept immunogenicity study of an oral antigen-display platform, rather than a vaccine efficacy study. In mice, oral administration of RG induced antigen-specific serum IgG and intestinal secretory IgA responses, accompanied by detectable in vitro neutralizing activity against PRRSV R98 and NADC30-like strains. RG administration was also associated with changes in selected ileal cytokines and splenic CD3⁺, CD4⁺, and CD8⁺ staining patterns, indicating immune-related modulation following oral delivery. In piglets, RG similarly induced PRRSV E5-specific serum IgG and fecal secretory IgA responses and elicited detectable serum neutralizing activity against both R98 and NADC30-like strains. Overall, these findings support the preliminary immunogenicity and technical feasibility of engineered B. subtilis spores as a spore-based oral antigen-display platform for inducing systemic and mucosal antibody responses with detectable in vitro neutralizing activity. However, neither homologous nor heterologous PRRSV challenge experiments were performed; therefore, the present findings support immunogenicity but do not establish protection against infection or vaccine efficacy. This study provides a foundation for the further development of spore-based functional microbial systems for PRRSV-related mucosal antigen delivery and presentation.

Keywords:   Bacillus subtilis ; Engineered probiotics; Oral antigen delivery; PRRSV; Spore surface display

DOI:  https://doi.org/10.1007/s12602-026-11221-5
bioRxiv. 2026 Aug 11. pii: 2026.08.10.744002. [Epub ahead of print]

Mining Microbial Transcriptomes to Engineer Cell-Based Bacterial Biosensors in Gut-Resident Bacteroidaceae.

Joshua Glazier, David Villegas, Sandra McClure, Joyce Ghali, Jay Fuerte-Stone, Mark Mimee.

The gastrointestinal tract is rich in metabolic, immune, and microbiome-derived signals that can inform the design of live biotherapeutics and diagnosis of intestinal disorders. Engineered cell-based biosensors can tap into this molecular information and report on their environment, yet their development in gut-resident symbionts has been limited by a lack of validated sensor systems. Here, we present a generalizable pipeline that leverages bacterial transcriptional profiling to identify environment-responsive systems for biosensor engineering. Candidate Sensors Systems (CSSs) mined from healthy, disease, and in vitro transcriptomes were assembled into a barcoded library in Bacteroidaceae chassis and screened in high-throughput in vivo to identify responsive promoters. A unique Bacteroidales ECF-type sigma factor operon with ties to sphingolipid metabolism and flux was highly responsive in chemically-induced colitis models. The biosensor responded robustly to disease and returned to baseline upon recovery, establishing an in vivo -driven strategy for discovering functional biosensors in non-model gut-resident bacteria.

DOI: https://doi.org/10.64898/2026.08.10.744002
Sci Adv. 2026 Oct 09. 12(41): eaej8942

DNA nanodevice-engineered macrophages as living sensors for dual-mode in vivo monitoring of tumor-associated macrophage polarization.

Qiaomei Wei, Xixi Chen, Ping Xie, Li Wang, Li-Juan Tang, Tingting Chen, Lan Liu, Jian-Hui Jiang, Xia Chu.

Exploiting macrophages as cell-autonomous reporters of their polarization states represents a promising strategy for interrogating tumor-associated macrophage (TAM) phenotypes in cancer. Here, we develop a macrophage-based sensing platform, termed eMφ. This platform is created by engineering macrophages with a modular and multiplexable DNA origami nanodevice to report TAM polarization states within the tumor microenvironment. Upon tumor infiltration, microenvironmental cues drive macrophage polarization, triggering the engineered system to convert endogenous signals (e.g., Arg1 or iNOS mRNA) into distinct, state-specific reporter outputs. The integration of local and circulating reporters enables compartment-resolved, multiscale readouts of macrophage state. Following intravenous administration, eMφ facilitates tumor detection across multiple murine models, including B16F10 melanoma and lung metastasis, and enables precise evaluation of macrophage-reprogramming immunotherapy. Overall, this work establishes DNA nanodevice-programmed macrophages as a novel class of synthetic-living hybrid systems, paving the way for programmable and precise immune-state diagnostics and therapy.

DOI: https://doi.org/10.1126/sciadv.aej8942