bims-livmat 2025-09-07 papers

ACS Appl Mater Interfaces. 2025 Sep 02.

Photodegradable Hydrogel Matrices for Spatiotemporal Control of Bacteria Transport and Delivery.

Jeffrey A Reed, Scott T Retterer, Ryan R Hansen.

Stimuli-responsive hydrogels that provide controlled degradation can be used as bacteria delivery systems for advanced therapeutic applications. Here, we report the first use of photodegradable hydrogels as materials that can direct bacterial movement, tune mean bacteria speed, and control bacteria delivery through spatiotemporal control of degradation. Hydrogels were formed using base-catalyzed Michael addition reactions between photodegradable poly(ethylene glycol) (PEG) o-nitrobenzyl diacrylate macromers and PEG tetra-thiol cross-linkers within microfluidic channels. Nutrient gradients were generated across the channel, and micron-scale regions of the hydrogel were partially degraded by exposure to controlled doses (2.1-168 mJ/mm2) of patterned 365 nm light. Hydrogel degradation was then characterized in situ using fluorescence visualization of fluorescein-labeled hydrogels. Following characterization, Bacillus subtilis expressing green fluorescent protein was introduced into the device, and its movement up the nutrient gradient was monitored using time-lapse fluorescence microscopy to enable a systematic study of bacteria chemotaxis through the hydrogels at varied levels of degradation. B. subtilis showed minimal adhesion to partially degraded PEG hydrogels, and bacteria mean speed and mean directional change were tunable according to the level of hydrogel photodegradation, with a 2.6-fold difference in mean cell speed measured across the partially degraded hydrogel regions. Finally, the ability to alter bacteria speed and directionality through tunable degradation and without significant adhesion was used to achieve controlled release profiles of bacteria to delivery sites. These findings advance the use of PEG-based hydrogel materials as delivery vehicles for bacterial therapeutic applications and other living material applications that require controlled bacteria transport.

Keywords: bacteria; biotherapeutics; chemotaxis; hydrogels; living materials; photodegradation; poly(ethylene glycol)

DOI: https://doi.org/10.1021/acsami.5c14670

Adv Sci (Weinh). 2025 Aug 28. e07820

Engineering Bacteria as Living Therapeutics in Cancer Therapy.

Jiangfeng Chen, Jiaqi Chen, Yixuan Chen, Wenxuan Yuan, Jiao Zhang, Guoqing Wang, Zhuojun Dai.

Cancer is the second-leading cause of death globally, yet traditional therapies like chemotherapy face significant limitations. Recent advances in synthetic biology enable the design of various genetic circuits and the reprogramming of biological systems. Collectively, these efforts have led to the repurposing of engineered bacteria as therapeutics to achieve tumor targeting, tumor microenvironment modulation, and anticancer drug release. Here, these recent efforts are reviewed and discussed the challenges and future opportunities.

Keywords: cancer immunotherapy; engineered bacteria; synthetic biology; targeted drug delivery; tumor microenvironment modulation

DOI: https://doi.org/10.1002/advs.202507820

ACS Appl Bio Mater. 2025 Sep 01.

Probiotic Bacteria as Therapeutics and Biohybrid Drug Carriers: Advances, Design Strategies, and Future Outlook.

Deepsundar Sahoo, Edgar Rodriguez, Kytai Nguyen, Uday Chintapula.

Probiotic bacteria have emerged as versatile and biocompatible platforms for drug delivery, offering a safe and efficient means of targeting diseased tissues. Advances in nanotechnology and genetic engineering have significantly expanded the potential of probiotic bacteria in precision medicine, enabling the delivery of therapeutics, proteins, antigens, and nanoparticles (NPs). This review explores diverse strategies for utilizing probiotics as drug carriers, including bacterial ghosts, outer membrane vesicles (OMVs), surface membrane proteins, and spores, focusing on applications in cancer therapy, vaccine development, and gastrointestinal disorders. We primarily focus on the strategy of integrating probiotics into nanoparticle-based delivery systems, examining key design considerations, such as functionalization strategies, targeting efficiency, and biocompatibility. Additionally, we highlight genetic engineering approaches, including plasmid-based expression and genomic integration, that enhance the probiotic functionality for targeted therapy, immunomodulation, and nanoparticle-mediated drug delivery. Further advancements in synthetic biology, biohybrid coatings, and stimulus-responsive mechanisms that could optimize the therapeutic efficacy of these systems will be discussed briefly. This review comprehensively analyzes recent progress and the outlook for harnessing probiotics for next-generation targeted drug delivery applications.

Keywords: cancer; drug delivery; nanoparticles; probiotics; synthetic biology; vaccines

DOI: https://doi.org/10.1021/acsabm.5c00959

Exploration (Beijing). 2025 Aug;5(4): e20240045

Synthetic Biology-Based Engineering Living Therapeutics for Antimicrobial Application.

Shun Huang, Shuihao Zhao, Haijie Zhao, Mingzhang Wen, Zhong Guo.

There is currently a pressing issue of antimicrobial resistance, with numerous pathogenic superbugs continually emerging, posing significant threats to both human health and the economy. However, the development of new antibiotics has not kept up in pace with the development of microbial resistance, necessitating the exploration of more effective approaches to combat microbes. Synthetic biology offers a novel paradigm by employing selective screening and assembling diverse biological components to redesign biological systems that can specifically target and eliminate microbes. In particular, engineering living therapeutics enables the detection and precise eradication of pathogenic microorganisms in a controlled means. This review provides an overview of recent advancements in engineering living therapeutics using synthetic biology for antibacterial treatment. It focuses on modifying bacteriophages, microbes, and mammalian cells through engineering approaches for antibacterial therapy. The advantages of each approach are delineated along with potential challenges they may encounter. Finally, a prospective outlook is presented highlighting the potential impact and future prospects of this innovative antimicrobial strategy.

Keywords: antimicrobial therapy; engineering living therapeutics; synthetic biology

DOI: https://doi.org/10.1002/EXP.20240045