LTMs capable of on-demand drug delivery

A unique advantage of biofactories is the possibility to integrate sensors and switches for on-demand therapeutic release. The synthetic biology expertise in this topic is provided to the LSC by the Independent Junior Group of Dr. Shrikrishnan Sankaran. The group has engineered switches for light- and heat-responsive bacterial activity in ClearColi and probiotic E. coli Nissle 1917 strains. Controlled release of the antibiotic darobactin, a pro-angiogenic vascular endothelial growth factor (VEGF)-mimetic protein and the flavonoid pinocembrin has been achieved in living hydrogels. Novel genetic parts for the probiotic L. plantarum, for which the genetic toolbox is underdeveloped, have also been engineered, including heat- and sugar-responsive gene expression systems. These results have led to a patent application. Thermoplasmonic hydrogel composites were used to encapsulate E. coli and demonstrate NIR-regulated protein production. These examples demonstrate the flexibility of LTMs for controlled delivery using different external triggers.

Demonstration of a light-regulated LTM being developed for promoting blood vessel regeneration in chronic wounds
Related Publications

Tadimarri VS, Blanch-Asensio M, Deshpande K, Baumann J, Baumann C, Müller R, Trujillo S, Sankaran S. PEARL: Protein Eluting Alginate with Recombinant Lactobacilli. Small. 2025 Jan 28:e2408316. doi: 10.1002/smll.202408316. Epub ahead of print. PMID: 39871788.

Blanch-Asensio M, Tadimarri VS, Wilk A, Sankaran S. Discovery of a high-performance phage-derived promoter/repressor system for probiotic lactobacillus engineering. Microb Cell Fact. 2024 Feb 7;23(1):42. doi: 10.1186/s12934-024-02302-7. PMID: 38326819; PMCID: PMC10848424.

Blanch-Asensio M, Dey S, Tadimarri VS, Sankaran S. Expanding the genetic programmability of Lactiplantibacillus plantarum. Microb Biotechnol. 2024 Jan;17(1):e14335. doi: 10.1111/1751-7915.14335. Epub 2023 Aug 28. PMID: 37638848; PMCID: PMC10832526.

P. Dhakane, V. S. Tadimarri, S. Sankaran Light-Regulated Pro-Angiogenic Engineered Living Materials Advanced Functional Materials 2023, 2212695

Basaran S, Dey S, Bhusari S, Sankaran S, Kraus T. Plasmonic stimulation of gold nanorods for the photothermal control of engineered living materials. Biomater Adv. 2023 Apr;147:213332. doi: 10.1016/j.bioadv.2023.213332. Epub 2023 Feb 14. PMID: 36801796.

Riedel F, Bartolomé MP, Enrico LLT, Fink-Straube C, Duong CN, Gherlone F, Huang Y, Valiante V, Del Campo A, Sankaran S. Engineered living materials for the conversion of a low-cost food-grade precursor to a high-value flavonoid. Front Bioeng Biotechnol. 2023 Nov 28;11:1278062. doi: 10.3389/fbioe.2023.1278062. PMID: 38090710; PMCID: PMC10715425.

Dey S, Blanch-Asensio M, Balaji Kuttae S, Sankaran S. Novel genetic modules encoding high-level antibiotic-free protein expression in probiotic lactobacilli. Microb Biotechnol. 2023 Jun;16(6):1264-1276. doi: 10.1111/1751-7915.14228. Epub 2023 Feb 1. PMID: 36722614; PMCID: PMC10221531.

Rodrigo-Navarro, A., Sankaran, S., Dalby, M.J. et al. Engineered living biomaterials. Nat Rev Mater 6, 1175–1190 (2021). https://doi.org/10.1038/s41578-021-00350-8

S. Pearson, J. Feng, A. del Campo Lighting the Path: Light Delivery Strategies to Activate Photoresponsive Biomaterials In Vivo Advanced Functional Materials, 2021, 31, (50), 2105989