bims-livmat 2025-11-16 papers

FEMS Microbiol Rev. 2025 Nov 06. pii: fuaf055. [Epub ahead of print]

Strength in diversity: unlocking the full potential of engineered living materials with multi-strain collaboration.

Hannelore Wilssens, Lien De Wannemaeker, Marjan De Mey.

In the innovative field of Engineered Living Materials (ELMs) microbiology and material sciences meet. These materials incorporate living organisms, such as bacteria, fungi, plants, or algae, to enable unique functions like self-assembly, actuation, and dynamic interaction. By utilizing (micro)biological systems in material design, ELMs promise to transform industries including healthcare, construction, and agriculture. In the early phase of ELM technology development, researchers implemented a single living strain in an already established user material. However, the complexity and potential of these materials is limited by the abilities of this single strain. Even though synthetic biology brings the opportunity to add a range of non-native bioactivities to these cells and thus the material, the increasing metabolic burden upon implementation of multiple non-native pathways limits the capacity of a single strain. Furthermore, higher organisms and non-standard hosts are often desired in material settings for their native physical or metabolic advantages. However these are not always straightforward to further engineer. Thus, the use of multiple, specialised strains broadens the functionalities and thus the applicability of ELMs. Multi-strain ELMs are a brand-new technology, with many promising applications.

Keywords: bio-ELM; division of labour; engineered living materials; microbial consortia; sustainable materials; synthetic biology

DOI: https://doi.org/10.1093/femsre/fuaf055

ACS Appl Bio Mater. 2025 Nov 12.

Synergistic Therapeutic Efficacy of Engineered Probiotics Embedded in Self-Assembling Keratin Hydrogels for Ulcerative Colitis Treatment.

Yijiao Wen, Chunhua Zhang, Xuanting Wang, Yi Shen, Huiwen Luo, Siyuan Liu, Famin Ke, Qin Wang, Xiaowei Gao.

Efficient oral delivery and sustained viability of probiotics remain significant obstacles to the clinical translation of live biotherapeutics. Therefore, in this study, we developed self-assembling keratin hydrogels derived from feather waste using a disulfide shuffling strategy for probiotic encapsulation. This cost-effective and scalable approach substantially improved the gastrointestinal tolerance and oral bioavailability of multiple probiotics, including Escherichia coli Nissle 1917 (EcN), Bacillus licheniformis, Lactococcus lactis, and Bifidobacterium bifidum. To achieve site-specific release in the intestinal tract, EcN was engineered to express keratinase (EcNker), enabling hydrogel degradation in the gut. In dextran sulfate sodium-induced colitis model mice, hydrogel-encapsulated EcNker exhibited markedly superior therapeutic efficacy over unencapsulated probiotics, as indicated by the amelioration of clinical symptoms, restoration of colon histology, attenuation of intestinal apoptosis, and normalization of inflammatory cytokine profiles. Mechanistically, hydrogel-encapsulated EcNker treatment restored the gut barrier integrity by upregulating the tight junction protein levels, modulating gut microbiota by increasing the number of beneficial genera, and enhancing short-chain fatty acid production. Collectively, our findings highlight the potential of keratin hydrogels as universal biocompatible and efficient delivery platforms for orally engineered probiotics to treat colonic colitis and other diseases.

Keywords: Antimicrobial peptides; Colonic colitis; Encapsulated probiotics; Gut microbiota; Keratin hydrogel; Keratinase

DOI: https://doi.org/10.1021/acsabm.5c01614

Biomater Adv. 2025 Nov 09. pii: S2772-9508(25)00426-1. [Epub ahead of print]180 214599

Living biomaterials: A promising approach to promoting wound healing.

Qingxin Wu, Yibing You, Haiyan Hu, Lantao Wang, Zhengfeng Lu, Xiaofei Qin.

Wound healing plays an important role in re-establishing the structure and physiological function of damaged tissues during the repair process. However, certain extrinsic factors (e.g., pathogenic infection or persistent inflammatory response) may interfere with this repair process and even trigger secondary tissue damage. Therefore, exploring innovative therapeutic strategies for wound recovery has become an important direction of current medical research. Living organism therapy is a promising technique that utilizes the unique biological activity of living organisms to modulate the wound microenvironment and promote tissue repair. Despite the current remarkable breakthroughs in the field of bioengineering and regenerative medicine, there are still some critical problems with living organism-based wound therapies, such as immune response, inability to control their proliferation, and poor targeting. Biomaterials are capable of interacting with biological systems and their good biocompatibility can be used as delivery vehicles for living organisms to enhance their therapeutic efficacy. Living biomaterials, which combine living organisms with biomaterials, show considerable promise in wound healing. In this review, we firstly describe the physiological process of wound healing and its conventional therapies, and provide an overview of the types of living organisms commonly used in wound healing. Then, we comprehensively summarize the different delivery systems used for living organisms. Moreover, the various strategies of living biomaterials in promoting wound healing are systematically summarized. Finally, we analyze the application of living biomaterials in clinical translation and discuss current challenges, potential solutions, and future research directions in this area.

Keywords: Co-delivery; Living biomaterials; Living organism delivery; Living organisms; Wound healing

DOI: https://doi.org/10.1016/j.bioadv.2025.214599

Bioresour Technol. 2025 Nov 07. pii: S0960-8524(25)01546-9. [Epub ahead of print]441 133579

Engineering a living therapeutic: calcium phosphate-mineralized phycocyanobilin-producing E. coli as a self-contained photodynamic system.

Yifan Wei, Nana Pan, Jingjing Du, Chao Wang, Xin Chen, Jin-Ao Li, Li Lu, Baosheng Ge, Fang Huang, Xiaojuan Wang.

The complex synthesis, purification, and delivery of photosensitizers remain major bottlenecks for clinical photodynamic therapy (PDT). Here, we develop PCB@Ecoli@CaP, an engineered Escherichia coli-based living therapeutic that autonomously biosynthesizes the natural photosensitizer phycocyanobilin (PCB) and is encapsulated within a calcium phosphate (CaP) shell to form a self-contained photodynamic system. Under 660 nm laser irradiation, PCB@Ecoli@CaP efficiently generates reactive oxygen species (ROS), which induce potent oxidative stress to eradicate 4T1 tumor cells and simultaneously trigger bacterial self-killing, thereby establishing a self-limiting therapeutic platform. The CaP coating enhances biocompatibility and stability while modulating light penetration and ROS release, as confirmed by DPBF photobleaching, intracellular ROS imaging, and CCK-8 viability measurements. This dual-function system integrates in situ photosensitizer biosynthesis, on-demand photodynamic activation, and built-in safety through self-elimination into a single, programmable microbial platform, offering a simplified, scalable, and safer strategy for next-generation PDT.

Keywords: Calcium phosphate biomineralization; Genetically engineered bacteria; Microbial drug delivery system; Photodynamic therapy; Reactive oxygen species

DOI: https://doi.org/10.1016/j.biortech.2025.133579

Br J Dermatol. 2025 Nov 13. pii: ljaf451. [Epub ahead of print]

From prebiotics to engineered microbes: microbe-inspired therapies for atopic dermatitis.

Noor E van Hout, Guillermo Nevot, Patrick A M Jansen, Ahmad A Mannan, Patrick L J M Zeeuwen, Dirk Jan Hijnen, Reiko J Tanaka, Marc Güell, Ellen H van den Bogaard.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with diverse clinical and histological features. While primarily immune-mediated, genetic studies have also highlighted the role of epithelium-expressed gene abnormalities (e.g., filaggrin mutations) as a key factor. The approaches to treat AD are multifaceted, involving barrier restoration, local anti-inflammatory treatment, and, if needed, systemic immunosuppressive therapy. Genetic variations in the stratum corneum and the immune system are linked to an unbalance between the host and its microbiota, known as dysbiosis. An impaired skin barrier and immune responses can alter the microbial composition, while the skin microbiota itself can influence skin immunity and barrier formation. A hallmark of AD is increased bacterial colonization with Staphylococcus aureus (S. aureus), which is found on lesional skin in over 90% of patients. It contributes to disease severity driving further breakdown of the skin barrier and immune stimulation. The most common treatment for S. aureus infections in AD is topical or systemic antibiotic administration. While these treatments are typically reserved for active infections, they are sometimes prescribed to AD patients without clear skin infection. However, these treatments can disrupt commensal skin and gut microbiota, which play a critical role in maintaining skin and gut health. In this review we describe various therapies targeting the skin microbiome to reduce infection and inflammation in AD, including transplantation of microbiota, and the use of prebiotics, probiotics, and postbiotics. In addition, we provide a perspective to engineer and to harness bacteria of the skin microbiome as next-generation probiotics, also known as engineered live biotherapeutic products (eLBPs), using synthetic biology to create strains that can sense skin signals, such as immune signals, and environmental factors, and produce therapeutic treatments for AD on demand.

DOI: https://doi.org/10.1093/bjd/ljaf451