bims-livmat 2026-09-06 papers

Adv Mater. 2026 Sep 01. e74812

Self-Feeding Living Materials Enabled by Cell Responsive Glycogen Nanoparticles as Metabolic Batteries.

Melvin Gurian, Niels G A Willemen, Isa R Porsul, Nicole Bassous, Jarno Hiemstra, Yu Na, Debby Gawlitta, Su Ryon Shin, Jeroen Leijten.

Scaling engineered living materials to clinically relevant dimensions is limited by diffusion-dependent depletion of oxygen and nutrients, which rapidly induces metabolic failure. We introduce glycogen as a nutritional nanoparticle that provides cell-mediated, autonomous nutrient release to support long-term survival under extreme metabolic stress. We demonstrate that human mesenchymal stromal cells (hMSCs) survive for weeks in anoxia and serum deprivation when provided extracellular glycogen. Contrary to long-held assumptions, hMSCs secrete glycogen-degrading enzymes, enabling cell-density-controlled extracellular glycogenolysis and sustained release of glucose and metabolic intermediates, positioning glycogen as the first-of-its-kind metabolic battery. This cell-responsive process maintains metabolic activity, limits glycolytic acidosis, and enhances pro-angiogenic signaling. To translate this mechanism into a versatile materials platform, we engineered core-shell dextran-tyramine microcapsules that stably encapsulate glycogen while permitting diffusion of enzymes and degradation products. Integrated into centimeter-scale GelMA constructs, these microcapsules maintained hMSC viability and function for at least 1 month under anoxia. In vivo, glycogen-loaded implants promote deep cellular infiltration, enhanced matrix remodeling, increased M2 macrophage polarization, and orchestrated accelerated vascularization. This work establishes the novel concept of glycogen-based nutritional nanoparticles as metabolic batteries to endow engineered tissues with autonomous self-feeding capacity, enabling scalable and functional living materials for regenerative medicine and related technologies.

Keywords: MSC; glucose; polysaccharides; tissue engineering; vascularization

DOI: https://doi.org/10.1002/adma.74812

Acta Biomater. 2026 Aug 29. pii: S1742-7061(26)00583-0. [Epub ahead of print]

A living therapeutic material to coordinate metabolic oxygenation and regenerative signaling in diabetic wounds.

Xi Zeng, Nana Gong, Guangyu Zhang, Yanhong Lu, Mingdong Cheng, Xiaohan Fan, Yujie Wang, Anwei Huang, Chi Hu, Jing Wang, Jing Zhang, Ming Zeng, Ziyi Yu.

Diabetic chronic wounds remain difficult to treat because hypoxia and insufficient regenerative signaling persist. Although live biotherapeutics offer a promising route to local oxygenation therapy, current methods largely support a single microbial function rather than coordinate microbial oxygenation with regenerative cues. Here, we report a hydrogel living therapeutic material in which a crosslinked hyaluronic acid matrix coordinates a living metabolic module of Synechococcus elongatus with a regenerative module of platelet-rich plasma (PRP). The matrix enables injectability and rapid gelation while supporting microbial metabolic activity and modulating the local retention and release of PRP-derived growth factors. The resulting material sustains oxygen generation and preserves the viability of the living module. Particularly, it reduces intracellular ROS accumulation, promotes fibroblast migration, and enhances endothelial tube formation in vitro. In diabetic wounds, it accelerates wound closure and improves re-epithelialization, collagen remodeling, and angiogenesis. Transcriptomic analysis further reveals coordinated regulation of stimulus-response, immune-related, and cytokine- and chemokine-associated pathways. This work establishes a living therapeutic material framework for integrating microbial oxygenation with regenerative signaling for pathological wound microenvironment remodeling. STATEMENT OF SIGNIFICANCE: Diabetic wounds are difficult to heal because damaged tissues often lack both oxygen and regenerative signals. Current living wound therapies mainly focus on microbial oxygen production, but they rarely coordinate oxygen supply with growth-factor-mediated tissue repair. This study develops an injectable living hydrogel that combines photosynthetic Synechococcus elongatus with platelet-rich plasma in a hyaluronic acid matrix. The material continuously generates oxygen, retains and releases regenerative factors, reduces oxidative stress, and promotes cell migration, angiogenesis, collagen remodeling, and wound closure. By integrating metabolic oxygenation with regenerative signaling, this work provides a strategy for remodeling pathological wound microenvironments and designing living therapeutic materials for chronic tissue repair.

Keywords: Diabetic chronic wounds; Living therapeutic material; Oxygenation therapy; Regenerative signaling

DOI: https://doi.org/10.1016/j.actbio.2026.08.052

Cell Rep Med. 2026 Sep 03. pii: S2666-3791(26)00433-7. [Epub ahead of print] 103016

Surface display of co-stimulatory ligand B7H2 on engineered bacteria enhances tumor immunotherapy.

Qiliner Feng, Chen Wang, Zexi Li, Dingran Sheng, Si Shi, Jie Liu, Baizhu Chen.

Bacteria-based living therapeutics exhibit outstanding potential for tumor immunotherapy when combined with functional materials or rewired with rationally designed gene circuits. To stimulate T cells precisely and effectively, herein, we report the surface-engineered bacteria as the living therapeutic for tumor immunotherapy. Escherichia coli cells are genetically programmed to display surface-anchored B7H2 to provide immunological co-stimulation signal of T cells and Histag to coordinate with ZnS quantum dots. In tumors, B7H2 induces the co-stimulatory ICOS-B7H2 signal at the molecular level and triggers the stimulation of cytotoxic T cells, the polarization of helper T cells, the release of cytokines, and long term antitumor immunological memory. Meanwhile, the coordinated ZnS quantum dots image tumors and synergize with B7H2 to enhance immune effects by activating the cGAS/STING pathway. With functional domains displaying on the bacterial surface, we establish an efficient living therapeutic approach for tumor immunotherapy.

Keywords: B7H2; cGAS/STING pathway; co-stimulatory ligand; engineered bacteria; living therapeutics; surface display; tumor immunotherapy

DOI: https://doi.org/10.1016/j.xcrm.2026.103016

Front Microbiol. 2026 ;17 1891602

Engineered strains as living factories: efficient biosynthesis and modification of natural products via synthetic biology and one-pot chemical tandem reactions.

Sha Liu, Pan Chen, Haitao Li, Wenting Dong, Qiaoqiao Xu.

Natural products are a crucial source for drug discovery, but their traditional development is limited by resource availability, efficiency, chemical complexity, and the difficulty of rapidly diversifying biologically active scaffolds. This review addresses the central question of how biosynthetic precision and chemical diversification can be coupled when conventional metabolic engineering alone cannot fully overcome low titers, enzyme promiscuity limits, intermediate toxicity, and scale-up heterogeneity. We examine engineered strains as microbial living factories that construct stereochemically complex cores from renewable feedstocks, and one-pot chemical tandem reactions as complementary tools for post-biosynthetic functionalization, skeletal remodeling, and rapid analog generation. The review compares natural-product classes with distinct bottlenecks, analyzes mass-transfer and oxygen-limitation challenges during industrial translation, and explains domino, multicomponent, and sequential one-pot mechanisms for a microbiology-oriented readership. Recent advances in biocompatible catalysis, chemoenzymatic cascades, artificial metalloenzymes, photobiocatalysis, flow biocatalysis, and cell-free synthetic platforms are discussed as three integration paradigms: post-fermentation modification, one-pot chemoenzymatic coupling, and open cell-free manufacturing. Finally, the review outlines a roadmap for catalyst compatibility, process scale-up, regulatory assessment, and automated design-build-test-learn workflows to promote sustainable natural-product production and lead discovery.

Keywords: cell-free biomanufacturing; chemoenzymatic synthesis; engineered strains; natural products; one-pot tandem catalysis; synthetic biology

DOI: https://doi.org/10.3389/fmicb.2026.1891602