3D Hydrogel Culture System Recapitulates Key Tuberculosis Phenotypes and Demonstrates Pyrazinamide Efficacy

Gupta, VK and Vaishnavi, VV and Arrieta-Ortiz, ML and Abhirami, PS and Jyothsna, KM and Jeyasankar, S and Raghunathan, V and Baliga, NS and Agarwal, R (2024) 3D Hydrogel Culture System Recapitulates Key Tuberculosis Phenotypes and Demonstrates Pyrazinamide Efficacy. In: Advanced Healthcare Materials .

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Abstract

The mortality caused by tuberculosis (TB) infections is a global concern, and there is a need to improve understanding of the disease. Current in vitro infection models to study the disease have limitations such as short investigation durations and divergent transcriptional signatures. This study aims to overcome these limitations by developing a 3D collagen culture system that mimics the biomechanical and extracellular matrix (ECM) of lung microenvironment (collagen fibers, stiffness comparable to in vivo conditions) as the infection primarily manifests in the lungs. The system incorporates Mycobacterium tuberculosis (Mtb) infected human THP-1 or primary monocytes/macrophages. Dual RNA sequencing reveals higher mammalian gene expression similarity with patient samples than 2D macrophage infections. Similarly, bacterial gene expression more accurately recapitulates in vivo gene expression patterns compared to bacteria in 2D infection models. Key phenotypes observed in humans, such as foamy macrophages and mycobacterial cords, are reproduced in the model. This biomaterial system overcomes challenges associated with traditional platforms by modulating immune cells and closely mimicking in vivo infection conditions, including showing efficacy with clinically relevant concentrations of anti-TB drug pyrazinamide, not seen in any other in vitro infection model, making it reliable and readily adoptable for tuberculosis studies and drug screening. © 2024 Wiley-VCH GmbH.

Item Type:	Journal Article
Publication:	Advanced Healthcare Materials
Publisher:	John Wiley and Sons Inc
Additional Information:	The copyright for this article belongs to John Wiley and Sons Inc.
Keywords:	Diagnosis; Gene expression; Hydrogels; Macrophages; Mammals; Stiffness matrix, Collagen hydrogel; Condition; Cord formation; Culture systems; Foamy macrophages; Genes expression; In-vitro; In-vivo; Infection models; Pyrazinamide, Collagen
Department/Centre:	Division of Electrical Sciences > Electrical Communication Engineering
Date Deposited:	24 May 2024 05:25
Last Modified:	24 May 2024 05:25
URI:	https://eprints.iisc.ac.in/id/eprint/85046

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