bims-livmat 2026-02-01 papers

Genome Biol. 2026 Jan 28.

Rational engineering of combinatorial bacterial therapies for cancer.

Paige Steppe, Katherine O'Connor, Jeff Hasty.

Engineered bacteria are emerging as a transformative class of cancer therapeutics. Recent advances in synthetic biology have expanded the genetic circuit toolbox, enabling the programmable control of attenuation, payload release, and immunomodulation. These developments have transformed bacteria from simple, colonizing agents into a versatile chassis for complex therapeutic functions. In this review, we examine recent circuit-based strategies for enhancing tumor specificity, regulating therapeutic delivery and engaging the host immune system, with emphasis on programming spatiotemporal control and consortia behavior. We consider current barriers to clinical translational and discuss how rational engineering can guide the next generation of microbial therapeutics.

Keywords: Bacteria; CAR-T; Cell therapy; Immunotherapy; Synthetic Biology; Tumor microenvironment

DOI: https://doi.org/10.1186/s13059-026-03951-0

Probiotics Antimicrob Proteins. 2026 Jan 27.

A Microbial Odyssey: Reshaping Probiotic Destinies through Advanced Delivery Technologies.

Ao Zhang, Yuting Rong, Yueyue Gao, Guibo Fan, Ayang Zhao, Sihua Qi.

Probiotics have attracted considerable attention in recent years due to their potential in modulating the gut microbiota, enhancing immune function, and contributing to the management of metabolic disorders, inflammatory diseases, and neuropsychiatric conditions. However, their clinical efficacy is often compromised by harsh gastrointestinal conditions such as gastric acid, bile salts, and digestive enzymes that significantly reduce probiotic viability. Moreover, current formulations face challenges in terms of bioavailability, targeted delivery, and consistency of therapeutic outcomes. To address these limitations, a variety of delivery strategies have been developed, including colon- and inflammation-targeted systems, genetically engineered and surface-modified probiotics, microencapsulation technologies with material innovations and functional enhancements, as well as inorganic and organic nanocarrier platforms. In parallel, interdisciplinary approaches such as smart-responsive systems, biomimetic technologies, microbiota remodeling, and synthetic biology have been increasingly employed to achieve precise release and sustained colonization in the host. This review systematically summarizes recent advances in probiotic delivery technologies, covering diverse engineering strategies and material platforms. It also critically examines key challenges in clinical translation, including formulation stability, inter-individual variability, regulatory inconsistencies, and long-term safety concerns, aiming to provide a comprehensive reference for the optimization and high-quality development of probiotic delivery systems. Aiming to provide a comprehensive reference and a forward-looking framework to guide the rational design of next-generation probiotic biotherapeutics.

Keywords: Biomaterial; Delivery Technologies; Probiotics; Smart-responsive

DOI: https://doi.org/10.1007/s12602-026-10926-x

J Control Release. 2026 Jan 22. pii: S0168-3659(26)00054-4. [Epub ahead of print] 114653

Bioprinted dressing with symbiotic microbes for oxygen supply and antibacterial therapy for enhanced diabetic wound healing.

Kaifeng Lin, He Xu, Hai Liu, Hejin Jiang, Hongxiang Mei, Linli Jiang, Zhongyang Du, Weiwei Tan, Xiaojie Li, Jiajing Zhou, Juan Li.

Diabetic chronic wounds exhibit delayed healing due to the high blood sugar, persistent inflammation, and bacterial infections, drawing remarkable attention worldwide. Current therapeutic approaches (e.g., surgical debridement, offloading treatment, antibiotic therapy) commonly target individual factors but fall short of modulating the complex wound microenvironment, particularly the chronic hypoxia. The symbiotic relationship between photosynthetic microorganisms and antibacterial probiotics offers a unique approach to this clinical challenge. Here, we engineer a 3D-printed bioactive microbial hydrogel (BMH) dressing by embedding Chlorella zofingiensis and Bacillus subtilis in gelatin methacryloyl as an artificial symbiotic system for modulating the diabetic wound microenvironment to promote wound healing. This BMH system demonstrates photosynthetic self‑oxygenation capability and potent antibacterial activity, thus boosting fibroblast migration and angiogenesis under hyperglycemic conditions. In diabetic rat models, BMH mitigates wound hypoxia and inflammation while enhancing vascularization and collagen deposition, thereby accelerating the healing of diabetic chronic wounds. RNA sequencing results further suggest the upregulation of genes in immune-regulation and skin-regeneration pathways. This study presents a multimodal therapeutic strategy for diabetic chronic wounds, offering insights into the design of living materials for regenerative engineering and clinical translation.

Keywords: 3D bioprinting; Algae−bacteria; Chronic wound healing; Hydrogel; Symbiotic relationship

DOI: https://doi.org/10.1016/j.jconrel.2026.114653

Adv Mater. 2026 Jan 29. e18817

Quinone-Grafted Chitosan Polymers Enhance Microbial Extracellular Electron Transfer for Living Bioelectronic Devices.

Xinyuan Zuo, Siliang Li, Abdullah Alazmi, Fiona Chen, Ravindra Saxena, Harsh Vardhan, Titus Szobody, Jaime Guel, Caroline Ajo-Franklin, Rafael Verduzco.

Microbial bioelectronics using electroactive bacteria provide robust and sustainable solutions for sensing, power generation, and chemical production. While most rely on a limited group of Gram-negative bacteria, Gram-positive species offer devices with additional functionality and broader environmental ranges. However, their thick, nonconductive cell walls hinder efficient extracellular electron transfer (EET). Here, a living bioelectronic device using a redox-active polymer to encapsulate Gram-positive bacteria near an electrode while simultaneously enhancing EET is reported. The redox-active polymer NQ-Chit contains naphthoquinone redox groups grafted onto a chitosan backbone and can be ionically cross-linked to produce redox- active hydrogels. To fabricate living bioelectronic devices, NQ-Chit is blended with the Gram-positive bacterium Lactiplantibacillus plantarum, deposited on an electrode, and ionically cross-linked in situ. The NQ-Chit hydrogel enhances EET current compared to both pure Chit-encapsulated bacteria and planktonic bacteria with NQ-Chit-coated electrodes, and Michaelis-Menten kinetics can describe the dependence of EET current on the concentration of quinone units. The devices remain functional after multiple medium exchanges. Additionally, the redox polymer enhances EET across diverse electroactive bacteria and enables a proof-of-concept for detecting environmental chemicals. This work demonstrates that encapsulating electroactive bacteria with redox-active hydrogels enhances EET and can be implemented in practical bioelectronic devices.

Keywords: bioelectronics; biosensors; redox‐active hydrogels; redox‐active polymers

DOI: https://doi.org/10.1002/adma.202518817

Pharmaceuticals (Basel). 2025 Dec 29. pii: 66. [Epub ahead of print]19(1):

Topical Delivery of Autochthonous Lactic Acid Bacteria Using Calcium Alginate Microspheres as a Probiotic Carrier System with Enhanced Therapeutic Potential.

Sigita Jeznienė, Emilija Mikalauskienė, Aistė Jekabsone, Aušra Šipailienė.

Background/Objectives: Three distinct strains of lactic acid bacteria (LAB), isolated from naturally fermented bread sourdough and representing the local autochthonous microflora, were selected to evaluate their potential probiotic properties. In addition, we evaluated whether these strains could be used in topical formulations. Methods: We evaluated probiotic properties such as the ability to co-aggregate with pathogens, antimicrobial activity, inhibition of pathogenic biofilms, and ability to adhere to human keratinocyte cells. Further, bacteria were encapsulated in calcium alginate microspheres using the emulsification/external gelation method, and their viability in topical formulations was assessed. Results: LAB significantly inhibited biofilm formation by the tested pathogens with complete inhibition observed in certain cases. The strength and specificity of these probiotic effects varied depending on the LAB strain and the target pathogen. Furthermore, among the tested strains, L. reuteri 182 exhibited the highest adhesion rates, reaching 77.94 ± 1.84%. In the context of potential topical applications, the preservative present in the formulation completely inactivated the planktonic cells of L. reuteri 182. In contrast, encapsulation within a biopolymeric system conferred protection against the preservative's bactericidal effect. After 35 days of storage at room temperature, viable cell counts reached 5.94 ± 0.06 lg CFU/g. Conclusions: Our findings confirm that local LAB strains, specifically L. reuteri 182 and L. plantarum F1, possess essential probiotic characteristics and can be effectively incorporated into preservative-containing topical formulations via efficient encapsulation strategies. This underscores the potential of these topical probiotics for skin health and highlights the need for clear regulatory guidance to ensure their safe and effective application.

Keywords: adhesion; encapsulation; probiotic; skin cells; topical formulation

DOI: https://doi.org/10.3390/ph19010066