bims-livmat 2025-09-28 papers

bims-livmat

Biomed News

on Living materials

Issue of 2025–09–28
seven papers selected by
Sara Trujillo Muñoz, Leibniz-Institut für Neue Materialien

Probiotic-Based Materials as Living Therapeutics.
Encapsulation-enhanced switchable protein release from engineered probiotic lactobacilli.
Theranostic Probiotic Engineered Living Materials That Dynamically Respond to Inflammation Markers.
Dual-responsive engineered bacteria with spatiotemporal controlled release of Cytolysin-A for orally management of colorectal cancer.
Microalgae-Based 3D Bioprinting: Recent Advances, Applications and Perspectives.
Living Textures and Mycelium Skin Co-Creation: Designing Colour, Pattern, and Performance for Bio-Aesthetic Expression in Mycelium-Bound Composites.
Core-shell engineered Col/Cs@ECM microspheres for macrophage-targeted intracellular drug release in RA therapy.

Adv Mater. 2025 Sep 25. e08500

Probiotic-Based Materials as Living Therapeutics.

Laura Sabio, Graham J Day, Manuel Salmeron-Sanchez.

  The growing demand for safer, more targeted therapeutics requires the development of advanced biomaterials. Among these, Engineered Living Materials (ELMs)-which integrate synthetic biology with material science-are emerging as promising platforms for biomedical applications. This review focuses on a subclass of ELMs based on genetically engineered probiotics combined with matrices, that are termed Probiotic Living Materials (PLMs) to differentiate them from Living Biotherapeutic Products (LBPs). Recent studies highlight PLM's potential in addressing different health conditions, offering targeted and dynamic therapies. However, PLMs face multiple challenges to be implemented in clinics, including a lack of robust genetic toolkits for probiotic engineering, concerns about biosafety (e.g., horizontal gene transfer or non-desirable biological activity), difficulties in translating preclinical results to humans, and the absence of clear regulatory guidance for clinical use. This review first explores the fundamental features of ELMs, then provides an overview of probiotics, followed by recent advances in the design of engineered PLMs for biomedical applications, particularly in biosensing development, infection treatment, bone repair, wound healing, vaginal imbalances, gut-related conditions, and cancer therapy. Finally, biosafety issues and current gaps in regulatory frameworks to ensure safe and effective use of PLMs, with a particular focus on vulnerable populations, are discussed.

Keywords:  engineered living materials; probiotics; therapeutics

DOI:  https://doi.org/10.1002/adma.202508500
J Control Release. 2025 Sep 24. pii: S0168-3659(25)00876-4. [Epub ahead of print] 114264

Encapsulation-enhanced switchable protein release from engineered probiotic lactobacilli.

Marc Blanch-Asensio, Varun Sai Tadimarri, Roberto Martinez, Gurvinder Singh Dahiya, Cao Nguyen Duong, Rahmi Lale, Shrikrishnan Sankaran.

  Living microbial therapeutics promise precise, programmable interventions at disease sites, yet most demonstrations of on demand drug release still rely on Escherichia coli, whose rich genetic toolkit is unmatched among probiotics. In particular, genetic parts to regulate in situ protein production are severely lacking in non-model probiotic bacteria like lactobacilli. Here, we equip the probiotic Lactiplantibacillus plantarum with high-performance genetic switches and show how material encapsulation can further enhance their behavior. By integrating cumate or vanillate-responsive operators and repressors with the strongest constitutive promoter in L. plantarum (Ptec), we generated two switches that support micromolar range induction. In rapidly growing culture conditions, acidification-associated leakiness of the switch was observed, which could compromise their applicability for precise on-demand delivery of drugs. Furthermore, such leakiness also limits the duration for which these engineered probiotics can be reliably used. By restricting growth through mild temperature or nutrient limitation, acidification and leakiness were suppressed. Strikingly, immobilizing the engineered cells in core-shell alginate beads (Protein Eluting Alginate with Recombinant Lactobacilli, PEARLs) almost eliminated leakiness, enabling day-scale, reversible control of intracellular reporters and secreted enzymes. This leakiness suppression persisted when two strains carrying orthogonal switches were co-encapsulated and even after miniaturization to submillimeter beads. These results expand the genetic toolbox of probiotic L. plantarum, demonstrate the synergy between genetic circuit design and material encapsulation, and advance lactobacilli toward stimuli-responsive therapeutic platforms.

Keywords:  Alginate; Engineered living materials; Genetic switch; Probiotic lactobacilli; Protein secretion

DOI:  https://doi.org/10.1016/j.jconrel.2025.114264
Adv Healthc Mater. 2025 Sep 26. e03809

Theranostic Probiotic Engineered Living Materials That Dynamically Respond to Inflammation Markers.

Gokce Altin-Yavuzarslan, Sierra M Brooks, James O Park, Kevin B Reed, McKenna Flynn, Olivia L Lanier, Hongyuan Lu, Hal S Alper, Alshakim Nelson.

  The development of smart, implantable devices localized at the site of inflammation to conditionally and proactively combat active inflammation for inflammatory bowel disease (IBD), has the potential to transform the patient's quality of life compared to conventional treatment modalities. Engineered probiotic organisms can enable dynamic production of therapeutic compounds in response to inflammatory biomarkers. However, delivery and localization of these engineered organisms to the site of inflammation requires their integration into a material or device that sustains their viability and metabolic activity. To this end, a 3D printed engineered living material (ELM) is developed using an engineered probiotic organism (E. coli Nissle 1917) with genetic circuits to sense biomarkers for inflammation and respond with the production of anti-inflammatory compounds. These organisms are incorporated into poly(ethylene glycol) diacrylate (PEGDA) resins for the light-based 3D printing of 3D constructs. The organisms are physically encapsulated within the PEGDA and are fully viable and metabolically active. The 3D printed ELM devices are able to detect clinically relevant amounts of nitric oxide as an inflammatory biomarker and respond with the production of tryptamine or 1-acetyl-3-carboxyl-β-carboline as representative anti-inflammatory agents. Additionally, the ELM devices are efficacious in treating in vitro models of inflammation, including murine macrophages and intestinal epithelial cells. Looking forward, these ELM devices could serve as theranostic modalities for the long-term treatment of inflammatory disorders such as IBD.

Keywords:  E. coli nissle 1917; engineered living materials; inflammation treatment; probiotic therapy; smart drug delivery; stimuli‐responsive materials; theranostics

DOI:  https://doi.org/10.1002/adhm.202503809
J Control Release. 2025 Sep 24. pii: S0168-3659(25)00877-6. [Epub ahead of print] 114265

Dual-responsive engineered bacteria with spatiotemporal controlled release of Cytolysin-A for orally management of colorectal cancer.

Haoxiang Chen, Qingxia Shi, Jingtong Wu, Tao Zhou, Junya Feng, Xi Zhou, Miao Wang, Yanyun Fan, Shuntian Cai, Hongzhi Xu, Lei Ren.

  Bacterial therapy is an emerging, promising option for tumor management. Enhancing the controllability of engineered bacteria to improve therapeutic efficacy and minimize undesirable side effects is essential to facilitate the clinical translation of bacterial therapies. In this work, a dual-responsive engineered bacteria based on the E. coli Nissle 1917 probiotic was constructed for tumor therapy. The therapeutic activity of this engineered bacteria is cis-controlled by lactic acid molecules and photothermal signaling. The engineered bacteria produce and accumulate cytolysin-A in the tumor lactate-rich microenvironment, followed by the self-lysis release of cytolysin-A by near-infrared light-initiated bacterial expression of melittin. This process makes the engineered bacteria highly tumor-suppressive and promotes necrotic apoptosis of tumor cells. This strategy allows the production and release of pharmaceutical proteins from engineered bacteria to be precisely confined in tumor tissues, improving the precision and safety of engineered bacteria-based therapies. This double-instruction confirmation platform could provide a flexible and safe personalized approach for applying multiple protein drugs to tumor therapy.

Keywords:  Controlled lysis; Engineered bacteria; Spatiotemporal controlled release; Tumor therapy

DOI:  https://doi.org/10.1016/j.jconrel.2025.114265
Mar Drugs. 2025 Aug 27. pii: 342. [Epub ahead of print]23(9):

Microalgae-Based 3D Bioprinting: Recent Advances, Applications and Perspectives.

Jinhui Tang, Jiahui Sun, Jinyu Cui, Xiangyi Yuan, Guodong Luan, Xuefeng Lu.

  Three-dimensional bioprinting integrating living cells and bioactive materials enables the fabrication of scaffold structures supporting diverse cellular growth and metabolism. Microalgae are among the most promising microbial platforms for the construction of photosynthetic cell factories, while the current industrial-scale cultivation of microalgae remains predominantly dependent on traditional liquid submerged systems, imposing limitations on commercial viability due to both process and economic constraints. Encapsulation of microalgae within bioactive matrices combined with 3D bioprinting to fabricate customized structures has been explored to address the limitations of submerged cultivation, which are expected to expand microalgal applications and establish new research directions in microalgal biotechnology. This review analyzes both matrices and methods of 3D bioprinting, summarizing the advancement of microalgae-based 3D bioprinting into six main domains including living building materials, biophotovoltaics, photosynthetic biosynthesis, bioremediation, tissue engineering, and food engineering. Lastly, synthetic biology-informed perspectives are provided on future developments of 3D bioprinting technologies and their potential in microalgal research.

Keywords:  3D bioprinting; engineered living materials; microalgae; spatially customized structure

DOI:  https://doi.org/10.3390/md23090342
Biomimetics (Basel). 2025 Aug 29. pii: 573. [Epub ahead of print]10(9):

Living Textures and Mycelium Skin Co-Creation: Designing Colour, Pattern, and Performance for Bio-Aesthetic Expression in Mycelium-Bound Composites.

Anastasia Globa, Eugene Soh, Hortense Le Ferrand.

  Natural materials present sustainable opportunities in architectural design, but often lack the aesthetic controllability associated with synthetic alternatives. This research explores the bio-aesthetic potential of mycelium-bound composites (MBCs) cultivated from Ganoderma Steyaertanum (Reishi mushroom), focusing on how external stimuli and surface treatments influence material expression. This investigation was carried out through interdisciplinary collaboration involving design, architecture, and material science. Two post-demolding surface treatment strategies were applied to MBC samples: 'Delayed Growth' and 'Accelerated Growth'. These treatments were designed to assess the mycelium's responsiveness in terms of colour and texture development. A controlled set of samples was analysed using scanning electron microscopy, Fourier-transform infrared spectroscopy, and hydrophobicity testing to evaluate changes in microstructure, chemical composition, and surface properties. The results demonstrate that mycelium exhibits a measurable capacity for aesthetic adaptation, with distinct variations in pigmentation and texture emerging under different treatment conditions. These findings highlight the potential for co-creative design processes with living materials and offer new insights into the integration of biological responsiveness in design practices. The study contributes to the advancement of sustainable material systems and expands the possibilities for bio-design through controlled interaction with bio-materials.

Keywords:  MBC; bio aesthetics; bio-materials; living materials; mycelium; mycelium skin; sustainable materials

DOI:  https://doi.org/10.3390/biomimetics10090573
Bioact Mater. 2025 Dec;54 715-729

Core-shell engineered Col/Cs@ECM microspheres for macrophage-targeted intracellular drug release in RA therapy.

Xiyue Duan, Kepeng Hu, Jiawei Wang, Xiaozhao Wang, Xiaojun Long, Weiming Lin, Chengwei Wu, Wenjian Weng, Zhangfa Song, Kui Cheng.

  The imbalance of macrophage polarization between M1 and M2 phenotypes in rheumatoid arthritis (RA) results in a persistent inflammatory cascade. Activating M2 anti-inflammatory polarization, which remove excess extracellular matrix (ECM) via phagocytosis, represents a potential therapeutic target for RA. This study introduces Col/Cs@ECM microspheres, a novel drug delivery system designed for macrophage recognition via a tailored ECM surface, enhancing phagocytic efficiency and accumulation. Moreover, the Col/Cs@ECM microspheres are composed of biocompatible and fully degradable materials, ensuring their safety profile within the physiological environment. Following cell phagocytosis, the collagen/chitosan (Col/Cs) core release the drug (Dexamethasone, Dex) intracellularly to inhibit M1 polarization by inhibiting the NF-κB signaling pathway and to facilitate M2 polarization. This macrophage targeted and intracellular release approach offers a significant advantage over traditional medications by reducing systemic side effects and improving the therapeutic index. The strategy prompts macrophages to express anti-inflammatory cytokines like IL-10 while suppressing pro-inflammatory cytokines such as TNF-α, thereby remodeling the immune microenvironment. Additionally, the specially engineered ECM shell of the microspheres extends the anti-inflammatory response by prolonging macrophage lifespan, a feature that is not present in conventional treatments. This results in improved treatment outcomes in an in vivo RA animal model. This research presents a possible intracellular anti-inflammatory treatment approach for rheumatoid arthritis injection therapy with the potential to outperform existing treatments in terms of efficacy and safety.

Keywords:  Drug delivery; Extracellular matrix; Intracellular immune therapy; Macrophage polarization remodel; Microsphere

DOI:  https://doi.org/10.1016/j.bioactmat.2025.08.043