bims-livmat 2026-03-22 papers

Small. 2026 Mar 20. e12642

Orthogonal Tri-Modular Coiled-Coil Assembly for Programmable Multi-Cargo Display on Escherichia coli Nissle 1917.

Yong Joon Cho, Gyu-Jin Lee, Jong-Ha Park, Sung In Lim.

Live biotherapeutic products (LBPs) represent emerging living medicines capable of site-specific intervention; however, current strategies for surface functionalization rely predominantly on static genetic fusion or covalent modification, limiting multiplexing and dynamic reconfiguration. Here, we engineer TriSCs (Tri-specific Scaffold Cells), a tri-modular and orthogonally programmable living scaffold based on Escherichia coli Nissle 1917. Three distinct α-helical motifs are displayed on the bacterial outer membrane, forming a reconfigurable biointerface that enables spontaneous, highly specific, and reversible payload assembly via coiled-coil interactions. This mix-and-go strategy allows simultaneous and selective recruitment of multiple functional modules without structural interference. Spatial co-display of a DR5 agonistic nanobody and an EGFR-targeting nanobody produces enhanced anticancer activity compared to soluble combinations, underscoring the impact of surface-organized signaling. In parallel, modular incorporation of a fluorescent reporter enables real-time bioimaging. By integrating orthogonality, reversibility, and multiplex capability within a single living chassis, TriSCs establish a dynamic and programmable LBP platform for precision theranostics and next-generation bioengineered therapeutics.

Keywords: coiled‐coil interactions; live biotherapeutic products; multiplex surface display; orthogonal assembly; programmable living scaffold

DOI: https://doi.org/10.1002/smll.202512642

Arch Microbiol. 2026 Mar 17. pii: 265. [Epub ahead of print]208(6):

Harnessing engineered cyanobacteria for next-generation therapeutics.

Alka Bhardwaj, Arun Kumar Mishra.

Keywords: Biomanufacturing; Biosynthetic gene clusters; Cyanobacteria; Metabolic engineering; Synthetic biology

DOI: https://doi.org/10.1007/s00203-026-04790-0

J Control Release. 2026 Mar 17. pii: S0168-3659(26)00238-5. [Epub ahead of print] 114836

Red-light-activated living bacterial electron generator for on-demand drug release in colonic inflammation.

Haibin Lu, Yun Zhang, Wenyuan Huang, Yuanyuan Jiang, Luqiao Chen, Zhaozhong Zhu, Fei Yang, Xizi Long.

Inflammatory bowel disease demands spatiotemporally precise drug delivery, yet the variable gut redox environment limits stimuli-responsive nanocarriers. Here we report a living biohybrid platform in which optogenetically engineered Shewanella oneidensis MR-1 is electrostatically conjugated with azo-bond covalent organic frameworks (TA-COFs) loaded with anti-inflammatory drugs magnolol or 4-iodobenzoic acid. Under intestinal conditions and non-invasive red-light irradiation (660 nm), light-induced restoration of the metal-reducing pathway promotes extracellular electron transfer, thereby cleaving azo bonds in the COF. This triggers rapid structural disassembly and a 2.8-fold increase in drug release. Although wild-type Shewanella is thermally inactivated at 37 °C and cannot utilize abundant colonic acetate, expression of heat-shock genes (groES/thiF) and an acetate-to-TCA pathway (ato1/ato2/gltA) confers 37 °C tolerance and robust metabolism in the gut. In DSS-induced colitis mice, oral administration of the biohybrid significantly alleviates inflammation, restores epithelial barrier integrity, rebalances gut microbiota (enrichment of Akkermansia, Muribaculaceae, and Lachnospiraceae). This work presents a generalizable strategy for constructing electroactive living composites by integrating microbial electron generation with stimuli-responsive nanomaterials, offering a new paradigm for light-programmed smart therapeutics and programmable living materials in biomedical applications.

Keywords: Covalent organic frameworks; Extracellular electron transfer; Optogenetics; Shewanella; Stimuli-responsive drug delivery; Ulcerative colitis

DOI: https://doi.org/10.1016/j.jconrel.2026.114836

Int J Pharm. 2026 Mar 15. pii: S0378-5173(26)00227-9. [Epub ahead of print]695 126779

Single-cell probiotic encapsulation with a sandwich-structured nanocoating for intestinal-targeted delivery and inflammatory-responsive drug release.

Xuan Gu, Yunchao Wu, Jiaying Liu, Xun Yan, Rilwanu Lukman, Zhihao Chen, Yutong Fu, Fengyi Du, Kai Yin, Jiangang Li, Miaomiao Zhang.

Surface-engineered probiotics represent a promising therapeutic strategy for treating ulcerative colitis (UC). However, their therapeutic efficacy is often compromised by the complex pathological conditions and limited drug integration capacity. To overcome these therapeutic challenges, we developed a single-cell probiotic encapsulation system featuring with a sandwich-structured nanocoating (LGG@PLD-AS/ALG). The inner poly (L-dopa) (PLD) layer not only exhibited potent radical-scavenging capability, but also facilitated the dynamic loading of anti-inflammatory small molecule drugs (5-aminosalicylic acid, 5-ASA). Specifically, pathological reactive oxygen species (ROS) at the UC site triggered the cleavage of covalent bonds, resulting in on-demand 5-ASA release. Meanwhile, the outer alginate layer enabled intestinal-targeted delivery of probiotics and preventing premature 5-ASA leakage by undergoing pH-responsive degradation. In a dextran sulfate sodium (DSS)-induced murine colitis model, LGG@PLD-AS/ALG effectively promoted restoration of the intestinal barrier, rebalanced gut microbiota and alleviated colonic inflammation. This work proposes a novel single-cell probiotic encapsulation system with a sandwich-structured nanocoating, paving a new avenue for UC therapy.

Keywords: 5-Aminosalicylic acid; Nanocoating; Probiotics; Ulcerative colitis

DOI: https://doi.org/10.1016/j.ijpharm.2026.126779

J Control Release. 2026 Mar 12. pii: S0168-3659(26)00224-5. [Epub ahead of print]393 114822

Optimizing genetic engineering approaches for protein loading into bacterial extracellular vesicles for vaginal drug delivery.

Darby Steinman, Varunaa Sri Hemanth Kumar, Ryan A McIlvaine, Pranshu Tyagi, Hahnbit Kang, Raifah Alam, Anguo Liu, Christopher M Jewell, Amy Plotkin, Irina Burd, Sara Molinari, Hannah C Zierden.

There is a critical gap in the development of new therapeutic platforms designed to treat gynecologic and obstetric diseases. Compared to systemic drug delivery, vaginal administration of nanoparticle formulations limits off-target side effects while increasing therapeutic concentration in target tissues, showing promise for clinical translation. However, these formulations suffer from limited scalability, high-cost reagents, and long optimization timelines. Recent work highlights the potential of bacterial extracellular vesicles (bEVs) as a low-cost, tunable platform for therapeutic applications. Here, we evaluate bEVs as a therapeutic carrier for vaginal drug delivery. We demonstrate the loading of the model protein moxNeonGreen into Escherichia coli Nissle 1917-derived bEVs. By optimizing growth parameters, we increase protein loading into bEVs. We evaluate the effect of bEVs on the vaginal microenvironment, and observe no negative impact on vaginal epithelial cells, endocervical cells, or vaginal bacteria in vitro. Additionally, we observe the retention of bEVs in the murine female reproductive tract for more than six hours. This study provides a framework for using genetically engineered bEVs to rapidly generate customizable therapies for a range of gynecologic and obstetric conditions, addressing longstanding challenges in women's health therapeutics.

Keywords: Bacterial extracellular vesicles; Genetic engineering; Vaginal drug delivery

DOI: https://doi.org/10.1016/j.jconrel.2026.114822

Int Wound J. 2026 Mar;23(3): e70887

Microalgae as a Novel Therapy for Chronic Wound Healing.

Saskia Pearl, Yang Jae Kang, Jungnam Cho.

Chronic wounds pose a substantial global health challenge, marked by persistent inflammation, infection, hypoxia, and impaired tissue regeneration. Traditional oxygen-based therapies, including hyperbaric and topical oxygen treatments, often suffer from limited efficacy, high costs, restricted accessibility, and difficulties in achieving sustained oxygen delivery. In contrast, microalgae offer a promising and sustainable alternative, owing to their biocompatibility, glucose consumption, and continuous oxygen production via photosynthesis. Innovative delivery platforms, such as hydrogels, scaffolds, sutures, microneedles, and microrobots, have demonstrated enhanced wound healing by mitigating hypoxia, reducing infection, and modulating inflammation. Recent advances in genetic engineering and 3D bioprinting further enhance the therapeutic potential of these systems. This review explores current progress in microalgae-based wound healing approaches, with a particular focus on photosynthesis-driven oxygen delivery technologies.

Keywords: chronic wound; hypoxia; microalgae; photosynthesis‐based oxygen delivery

DOI: https://doi.org/10.1111/iwj.70887