A trick to trick the sugary immune system: Therapeutic strategy to heal diabetic wounds

Work done in the lab of Dr. Siddharth Jhunjhunwala at the Centre for BioSystems Science and Engineering, Indian Institute of Science, Bengaluru

About author

Jayashree is a graduate student at the Centre for BioSystems Science and Engineering at the Indian Institute of Science, Bengaluru. She is pursuing a Ph.D. in Bioengineering under Dr. Siddharth Jhunjhunwala at the Immunoengineering laboratory. Her fundamental research interests include immunoengineering, human immunology, and data sciences. Her doctoral thesis aims to understand why few diabetic individuals’ foot ulcers heal while many fail to despite standard treatment practices. She uses both in-vivo and ex-vivo approaches to address this question and implements statistical techniques to identify biomarkers associated with poor healing.

Besides research, she enjoys many activities, including running, playing snooker, gaming, painting, and occasional reading. Gardening has been her favorite hobby, with a particular interest in experimenting with plant propagation. If not in the lab, she can be found in campus cafeterias catching up with friends over coffee or lost in her mini balcony garden working with her little plants.

Interview

How would you explain your research outcomes to the non-scientific community?

Our study aimed to develop drug-releasing bandages that could improve the healing of diabetic foot ulcers. To study this, we used an animal model for diabetes that closely mimics the condition of type 2 diabetes observed in humans. In this system, we first characterized the state of circulatory immune cells in diabetic animals to determine if drugs that target dysfunctional immune cells could be used. We observed that specific immune cells were present in abnormally high numbers in circulation. We also observed these immune cells to poorly respond to bacteria-like stimuli suggesting that such alterations may contribute to poor healing of wounds. Hence, we developed a bandage that could release an immunomodulatory drug, and tested its effect on healing of wounds in diabetic animals. Our data showed that the drug-loaded bandage did indeed accelerate healing in diabetic animals, showing promise for clinical translation.

Purple panel (left) shows the identified features of chronic systemic inflammation in diabetic mice through the current study, highlighting the dysregulations of immune cells, specifically neutrophils, and monocytes involved in wound healing. The orange panel (right) indicates our approach to correct the dysregulated healing by applying a drug-loaded patch on surgically induced wounds in diabetic mice, which showed accelerated healing.

How do these findings contribute to your research area?

This research leads to a better understanding of the phenotype and function of monocytes and neutrophils in the context of diabetes. Researchers have long suspected that immune cells have aberrant activity in individuals with hyperglycemia. Our data confirm this suspicion and enable researchers to focus on the consequences of such changes.

The research also presents an approach to correct dysregulated healing through immunomodulation using a previously approved drug. Following further testing for the safety of this drug-loaded bandage and analysis in a larger preclinical animal model, we believe that this approach can be used in the clinic.

“Our research presents an approach to correct dysregulated healing through immunomodulation using a previously approved drug.”

What was the exciting moment during your research?

After several optimization attempts and breaks in experiments due to covid-associated lockdowns, I was very excited to see faster wound healing in diabetic animals when treated with drug-releasing bandages. Double joy when statistics also agreed with our experimental observation.

What do you hope to do next?

I plan to pursue post-doctoral studies in immuno-engineering and systems immunology. I’m specifically interested in exploring quantitative approaches for analyzing large immunological datasets to answer clinically relevant questions for improving patient outcomes.

Where do you seek scientific inspiration from?

I have always been fascinated by how organisms have evolved and managed to thrive by constantly fighting biological extinction threats, including the current one, COVID-19. Learning that it is the immune system’s powerful defense mechanism that allows all organisms to fight threats inspired me to learn more about this system and exploit it to benefit humankind. Nature’s complex design of such a robust system to purely function based on logic is awe-inspiring, which interests me to modulate and engineer this system to solve emerging clinical problems.

How do you intend to help Indian science improve?

Science outreach has been one of my key interests in addition to research. An opportunity to pursue the same during doctoral studies via Science for Rural India (SFRI – student outreach group at IISc) has helped me realize the need for science education and awareness of careers in science amongst students, especially in rural India. Through a few existing platforms and potential future connections, I hope to continue contributing virtually to such activities, particularly encouraging female students to pursue careers in science to increase women’s representation in STEM.

Academically, I’m interested in returning to India after post-doctoral studies to work on clinically relevant immunological questions to advance Indian clinical science and ultimately translate the findings or technologies to the clinic to improve patient care in India.

Reference

Jayashree Vijaya Raghavan, Vinod Kumar Dorai, Shruthi Ksheera Sagar, Archana Sivaraman, Kalpana S R, and Siddharth Jhunjhunwala. Immunomodulatory Bandage for Accelerated Healing of Diabetic Wounds. ACS Bio Med Chem Au 2022, 2, 4, 409–418. https://pubs.acs.org/doi/10.1021/acsbiomedchemau.1c00063

Copy Editor

Kshipra S. Kapoor

Ph.D. candidate at Rice University

Kshipra has completed Bachelor’s in Biomedical engineering from University of Mumbai where she was the recipient of institute gold medal and university bronze medal for obtaining the highest GPA in her cohort. She received her master’s degree in Electrical and Computer Engineering at Rice University. She is currently a Ph.D. candidate at Rice University, where she is working with Prof. Raghu Kalluri in the field of exosomes. Specifically she is interested in dissecting the exosome heterogeneity between healthy and cancer cells-derived nanovesicles and advancing the understanding of exosomes classes in cancer. In her spare time, Kshipra enjoys keeping fit, cooking, calligraphy and family & friends.

Kshipra is also involved in various professional development programs and as a first generation-PhD student is helping amplify the voices and stories of minorities in her field via the global organization she is part of snevresearch where she manages the events.

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