bims-livmat 2025-07-13 papers

ACS Appl Mater Interfaces. 2025 Jul 08.

Controlled Release of Microorganisms from Engineered Living Materials.

Manivannan Sivaperuman Kalairaj, Iris George, Sasha M George, Sofía E Farfán, Yoo Jin Lee, Laura K Rivera-Tarazona, Suitu Wang, Mustafa K Abdelrahman, Seelay Tasmim, Asaf Dana, Philippe E Zimmern, Sargurunathan Subashchandrabose, Taylor H Ware.

Probiotics offer therapeutic benefits by modulating the local microbiome, the host immune response, and the proliferation of pathogens. Probiotics have the potential to treat complex diseases, but their persistence or colonization is required at the target site for effective treatment. Although probiotic persistence can be achieved by repeated delivery, no biomaterial that releases clinically relevant doses of metabolically active probiotics in a sustained manner has been previously described. Here, we encapsulate stiff probiotic microorganisms within relatively less stiff hydrogels and show a generic mechanism where these microorganisms proliferate and induce hydrogel fracture, resulting in microbial release. Importantly, this fracture-based mechanism leads to microorganism release with zero-order release kinetics. Using this mechanism, small (∼1 μL) engineered living materials (ELMs) release >108 colony-forming-units (CFUs) of Escherichia coli in 2 h. This release is sustained for at least 100 days. Cell release can be varied by more than 3 orders of magnitude by varying initial cell loading and modulating the mechanical properties of the encapsulating matrix. As the governing mechanism of microbial release is entirely mechanical, we demonstrate the controlled release of model Gram-negative, Gram-positive, and fungal probiotics from multiple hydrogel matrices.

Keywords: controlled release; engineered living materials; probiotics; sustained release; zero-order release

DOI: https://doi.org/10.1021/acsami.5c11155

Biotechnol Adv. 2025 Jul 07. pii: S0734-9750(25)00126-0. [Epub ahead of print]83 108640

Engineering encapsulated living bacteria for advanced healthcare management.

Ming Teng, Xiaomin Luo, Jiang Chang, Chen Yang, Xiaomeng Zhang, Liuying Li, Xudan Liu, Ruizhi Zhi, Xu Guo, Xinhua Liu.

Bacterial therapies are emerging as promising alternatives to conventional treatments, particularly in the areas of intestinal therapy, oncology, and wound management. However, gastric acid, bile salts, immune cells, and reactive oxygen species in the human body hinder the colonization and growth of foreign probiotics, thereby compromising the efficacy of bacteriotherapy. Recent advancements in engineering encapsulated live bacteria strategies utilizing biopolymers to construct protective shells on the bacterial surface to significantly address the aforesaid challenges have gained unprecedented attention. The scrumptious integration of multiple probiotic species, bioencapsulation biomaterials, and on-demand encapsulation technologies offers tremendous advantages over conventional living bacterial counterparts, such as precise targeting, rapid immune activation, and synergistic therapeutic effects. This review presents the essential natures and response mechanism selectivity for encapsulation biomaterials from the design perspective of engineered bacterial therapeutics, including pH-responsive, enzyme-responsive, and reactive oxygen species (ROS)-responsive materials. Engineering bacterium requires a uniquely tailored design strategy within the polymer-targeted delivery platform. Meanwhile, the review provides an account of its recent developments and advancements in the biomedical fields, with emphasis on tissue repair, anti-inflammatory, antibacterial, anti-tumor, and other therapeutic applications. Finally, challenges and emerging trends in its clinical translation are expounded. By highlighting the potential of bacteria to revolutionise the therapeutic landscape, this review offers valuable insights into the design of innovative disease treatment paradigms and alternatives to conventional drug therapy, and facilitates the clinical applications of engineering encapsulated living bacteria.

Keywords: Encapsulation; Engineering encapsulated bacteria; Human-health management; bacteria therapies

DOI: https://doi.org/10.1016/j.biotechadv.2025.108640

Probiotics Antimicrob Proteins. 2025 Jul 11.

Enhancing the Adhesion/Colonization Efficacy of Probiotics by Polysaccharide Surface Decoration for Remission from Ulcerative Colitis.

Ting Liu, Qiang Meng, Yijun Zhang, Jianming Ye, Yingju Shang, Wei Song, Yane Luo.

Ulcerative colitis (UC) is a chronic inflammatory disease in the colon, with a rising global incidence. Probiotics have been explored for treat UC due to their regulation roles on the gut microbiota. However, issues such as low survival rate, limited colonization time, and poor therapeutic effects have been observed following the oral administration of free probiotics. Thus, techniques for surface modification of probiotics have emerged to enhance the adhesion of encapsulation materials at inflammation sites, thereby to improve the retention time of probiotics and their therapeutic effects on UC. Here, we investigated the altered physio-biochemistry environments in the gastrointestinal tract of UC patients, and the factors influencing the molecular interactions between probiotics and the mucosa. We also clarified that encapsulation materials such as chitosan, sodium alginate, and thiolated hyaluronic acid could target the colon wall through electrostatic adsorption, hydrogen bonding, or the formation of disulfide bonds, thereby elongating the adhesion time of probiotics in the intestine. Additionally, the degradation patterns, potential beneficial or harmful impacts of these encapsulation materials were summarized. Finally, the current status of probiotics and polysaccharide-based treatments for UC in clinical trials were discussed. This research will facilitate the preparation of probiotic microcapsules with colon adhesion properties and also provide recommendations for the clinical application of encapsulation materials.

Keywords: Adhesion; Colonization; Probiotics; Surface modification; Ulcerative colitis

DOI: https://doi.org/10.1007/s12602-025-10653-9

J Control Release. 2025 Jul 04. pii: S0168-3659(25)00625-X. [Epub ahead of print]385 114004

Optimized bacterial delivery approaches for precision immunotherapy in breast cancer models.

Jam-Eon Park, Soo-Ji Kang, Jun-Seong Ahn, Seung-Hyeon Choi, Jung-Sook Lee, Ji-Sun Kim, Seung-Hwan Park.

Bacteria-mediated cancer therapy is an innovative approach that exploits the tumor-targeting ability of bacteria to deliver anti-cancer drugs directly to tumors. Cytolysin A (ClyA), a bacterial pore-forming toxin, has demonstrated therapeutic efficacy in colorectal cancer but has limited effectiveness in breast cancer. To address this limitation, we engineered an attenuated Salmonella strain to express Clostridium perfringens enterotoxin (CPE), which selectively targets CLDN-4, a tight junction protein overexpressed in breast cancer, thereby minimizing off-target effects. In a 4T1 breast tumor mouse model, CPE-secreting bacteria demonstrated significantly greater therapeutic efficacy than ClyA-secreting bacteria. Mechanistic investigations revealed that ClyA and CPE induced distinct patterns of immune cell infiltration depending on tumor type. In 4T1 tumors, CPE significantly increased the infiltration of CD4+ T cells, CD8+ T cells, and NK cells, while reducing neutrophil infiltration. In contrast, ClyA promoted immune cell infiltration in CT26 tumors but had negligible effects in 4T1 tumors. Furthermore, CPE treatment markedly reduced granulocyte-colony stimulating factor (G-CSF) expression in 4T1 tumors, a key regulator of neutrophil recruitment, tumor growth, and chemotherapy resistance. Our findings demonstrate that CPE-secreting bacteria exert superior therapeutic efficacy through two synergistic mechanisms: (1) direct tumor cell lysis via pore formation and apoptosis induction, and (2) modulation of the tumor immune microenvironment by enhancing tumor-infiltrating lymphocytes and suppressing neutrophil-associated tumor progression. These results highlight the importance of tailoring bacteria-mediated cancer therapy to tumor specific molecular characteristics to maximize therapeutic efficacy.

Keywords: Bacteria-mediated cancer therapy; Breast cancer; Clostridium perfringens enterotoxin; Cytolysin a; Drug delivery; Tumor-associated immune cells

DOI: https://doi.org/10.1016/j.jconrel.2025.114004

Lab Chip. 2025 Jul 10.

Active implantable drug delivery systems: engineering factors, challenges, opportunities.

Fabiana Del Bono, Nicola Di Trani, Danilo Demarchi, Alessandro Grattoni, Paolo Motto Ros.

Implantable drug delivery systems represent a transformative approach in modern pharmacology, offering precise and controlled drug administration tailored to individual patient needs. By circumventing physiological barriers such as the gastrointestinal tract and the blood-brain barrier, these systems enhance bioavailability and therapeutic efficacy while reducing systemic side effects. Key features include sustained or on-demand drug release, remote activation, and programmable dosing, which collectively improve patient compliance and minimize the frequency of interventions. Innovations in actuation mechanisms, powering technologies, and biocompatible materials have advanced the field, enabling the development of miniaturized, energy-efficient, and scalable devices. Applications range from chronic disease management to localized therapies for neurological and cardiovascular conditions. Despite significant progress, challenges remain in integrating power systems, communication protocols, and regulatory compliance for clinical translation. This review synthesizes the current state of active implantable drug delivery systems, discussing engineering trade-offs, system requirements, and future research directions toward achieving reliable, patient-centered solutions to guide system designers toward developing reliable, scalable, and patient-centered solutions that bridge the gap between cutting-edge research and clinical application.

DOI: https://doi.org/10.1039/d5lc00131e