IISc Develops Advanced 3D Hydrogel Culture System to Study Tuberculosis Infection

This breakthrough allows for a detailed study of Mycobacterium tuberculosis (Mtb), the bacteria responsible for tuberculosis (TB).

Researchers at the Indian Institute of Science (IISc), Bengaluru, have created a 3D hydrogel culture system. This breakthrough allows for a detailed study of Mycobacterium tuberculosis (Mtb), the bacteria responsible for tuberculosis (TB).

Additionally, by mimicking the mammalian lung environment, this system offers a new method for investigating TB infection and assessing the efficacy of TB treatments.

How does this 3D Hydrogel Culture System Work?

Current models for studying Mtb infection have significant limitations. Typically, these models use monolayer culture plates that fail to replicate the complex 3D structure of lung tissue.

The extracellular matrix (ECM) surrounding lung cells is much more intricate, affecting how cells interact with the environment and pathogens.

However, the IISc team developed a hydrogel culture using collagen, a significant component of the lung's ECM, which is water-soluble at a slightly acidic pH.

When the pH increases, collagen forms fibrils that cross-link into a gel-like 3D structure. By incorporating human macrophages—immune cells that fight infections—along with Mtb during the gelling process, the researchers could simulate the infection environment more accurately. This method trapped macrophages and bacteria in the collagen, enabling the team to monitor the infection process.

One of the study's significant findings was the effectiveness of pyrazinamide, a common TB drug, within the 3D hydrogel culture. Even at a low concentration of 10 µg/ml, pyrazinamide successfully eliminated Mtb in the culture.

Furthermore, this result underscores the hydrogel system's potential to test TB drugs in conditions that closely resemble the human lung environment.

Previous Developments: BFI Collaboration

Previously, Blockchain For Impact (BFI), a healthcare fund established during the second wave of the COVID-19 pandemic in India, joined forces with IISc to propel biomedical research and innovation in India.

BFI invested $1 million over three years in the BFI-Biome Virtual Network Programme. This initiative supports collaborative projects that translate research outcomes into tangible healthcare solutions.

The BFI-Biome, formed in partnership with IISc, supports selected life sciences research projects led by IISc faculty, with an annual expectation of assisting two to three projects.

Future Directions

Looking ahead, the researchers aim to create models of granulomas, which are clusters of infected white blood cells often found in TB patients.

This aspect of the study could provide insights into why some individuals develop latent TB while others exhibit severe symptoms. Understanding the mechanism of action of pyrazinamide in this context could also help discover new, effective TB treatments.