Living therapeutic hydrogels that safely encapsulate drug-producing biofactories and sustain their function long-term

A fundamental question for LTM development is how to control the growth and activity of encapsulated biofactories in a nutrient-rich environment. In the LSC we demonstrated that this can be achieved by tailoring the spatial confinement, mechanical and diffusion properties of the encapsulating materials. We identified hydrogel composition windows and physical requirements needed to maximize drug production and maintain a steady-state bacteria number with a constant drug release profile from the LTM.

Examples of technologies used in the LSC and images of LTM laboratory prototypes containing functional biofactories.
Related Publications

Kafrashian Z, Brück S, Rogin P, Khamdan M, Farrukh HSUB, Pearson S, Del Campo A. Segmented, Side-Emitting Hydrogel Optical Fibers for Multimaterial Extrusion Printing. Adv Mater. 2025 Jan;37(4):e2309166. doi: 10.1002/adma.202309166. Epub 2024 Dec 4. PMID: 39632473; PMCID: PMC11775871.

Puertas-Bartolomé M, Gutiérrez-Urrutia I, Teruel-Enrico LL, Duong CN, Desai K, Trujillo S, Wittmann C, Del Campo A. Self-Lubricating, Living Contact Lenses. Adv Mater. 2024 Jul;36(27):e2313848. doi: 10.1002/adma.202313848. Epub 2024 Apr 21. PMID: 38583064.

Eckert N, Rebets Y, Horbal L, Zapp J, Herrmann J, Busche T, Müller R, Kalinowski J, Luzhetskyy A. Discovery and overproduction of novel highly bioactive pamamycins through transcriptional engineering of the biosynthetic gene cluster. Microb Cell Fact. 2023 Nov 14;22(1):233. doi: 10.1186/s12934-023-02231-x. PMID: 37964282; PMCID: PMC10644645.

Bhusari S, Hoffmann M, Herbeck-Engel P, Sankaran S, Wilhelm M, Del Campo A. Rheological behavior of Pluronic/Pluronic diacrylate hydrogels used for bacteria encapsulation in engineered living materials. Soft Matter. 2024 Feb 7;20(6):1320-1332. doi: 10.1039/d3sm01119d. PMID: 38241053.

Bhusari S, Sankaran S, Del Campo A. Regulating Bacterial Behavior within Hydrogels of Tunable Viscoelasticity. Adv Sci (Weinh). 2022 Jun;9(17):e2106026. doi: 10.1002/advs.202106026. Epub 2022 Apr 11. PMID: 35404519; PMCID: PMC9189655.

Bhusari S, Kim J, Polizzi K, Sankaran S, Del Campo A. Encapsulation of bacteria in bilayer Pluronic thin film hydrogels: A safe format for engineered living materials. Biomater Adv. 2023 Feb;145:213240. doi: 10.1016/j.bioadv.2022.213240. Epub 2022 Dec 20. PMID: 36577192

Groß S, Panter F, Pogorevc D, Seyfert CE, Deckarm S, Bader CD, Herrmann J, Müller R. Improved broad-spectrum antibiotics against Gram-negative pathogens via darobactin biosynthetic pathway engineering. Chem Sci. 2021 Aug 12;12(35):11882-11893. doi: 10.1039/d1sc02725e. PMID: 34659729; PMCID: PMC8442675.

Ahmed Y, Rebets Y, Estévez MR, Zapp J, Myronovskyi M, Luzhetskyy A. Engineering of Streptomyces lividans for heterologous expression of secondary metabolite gene clusters. Microb Cell Fact. 2020 Jan 9;19(1):5. doi: 10.1186/s12934-020-1277-8. PMID: 31918711; PMCID: PMC6950998.