Department of Biomedical Engineering

Indian Institute of Technology Hyderabad (IITH) is a premier institute of science and technology established in 2008. IITH has been consistently ranked in the&nbsp;<a href="https://iith.ac.in/reports/" rel="noopener noreferrer">top 10 institutes</a>&nbsp;in India for Engineering&nbsp;<a href="https://www.nirfindia.org/2021/EngineeringRanking.html" rel="noopener noreferrer" target="_blank">according to NIRF</a>&nbsp;making it one of the most coveted schools for science and technology in the country.

IITH offers&nbsp;<a href="https://iith.ac.in/academics/under-graduate/">undergraduate programs</a>&nbsp;in all the classical engineering disciplines, applied sciences, design, as well as several modern interdisciplinary areas. Students are given a flexibility to explore a broad set of areas, and potentially pursue a minor or double major in a discipline that is not their own. Students who wish to seek a deeper understanding of their own discipline are strongly encouraged to get involved in cutting-edge research with the help of a faculty to mentor them, and earn an Honors in their own field.

The very foundation of IIT Hyderabad is based on&nbsp;<a href="https://iith.ac.in/research/">research and innovation</a>. The vibrant research culture is evident from the number of patents and publications that IITH produces consistently every year. IITH offers&nbsp;<a href="https://iith.ac.in/academics/programmes-offered/">graduate programs</a>&nbsp;at both a masters, and a doctoral level, in several diverse areas. There are separate programs for technology, design, science, and liberal arts. The&nbsp;<a href="https://iith.ac.in/academics/post-graduate/">MTech program</a>&nbsp;is offered in various modes and durations to cater to the ever-growing need of postgraduate level professionals in the country.

IITH encourages and supports&nbsp;<a href="https://iic-iith.netlify.app/index.html" rel="noopener noreferrer" target="_blank">innovation and entrepreneurship</a>&nbsp;at every stage. The minor program in entrepreneurship is open to all students of IITH, and many of the courses are offered by industrialists who are entrepreneurs themselves. There are various&nbsp;<a href="https://iith.ac.in/research/centres-incubators/">innovation centers and incubators</a>&nbsp;that promote entrepreneurship and help mentor young innovators. IITH has been very successful in building tie-ups with leading academic institutions around the globe.

IITH enjoys a very special relationship with Japanese universities and industries that goes beyond academic and research collaborations. In fact, some of the iconic buildings in IITH campus will carry the signature of Japanese architecture.

IITH creates a unique holistic ecosystem for education that offers interactive learning, a very flexible academic structure, cutting-edge research, strong industry collaboration, and entrepreneurship. This is an environment which enables students and faculty to translate their dreams into realities.

IIT Hyderabad

RNA interference (RNAi) has increased the possibility of restoring RNA drug targets for cancer treatment. Small interfering RNA (siRNA) is a promising therapeutic RNAi tool that targets the defective gene by inhibiting its mRNA expression and stopping its translation. However, siRNAs have flaws like poor intracellular trafficking, RNase degradation, rapid kidney filtration, off-targeting, and toxicity, which limit their therapeutic efficiency. Nanocarriers (NCs) have been designed to overcome such flaws and increase antitumor activity. Combining siRNA and anticancer drugs can give synergistic effects in cancer cells, making them a significant gene-modification tool in cancer therapy. Our discussion of NCs-mediated siRNA delivery in this review includes their mechanism, limitations, and advantages in comparison with naked siRNA delivery. We will also discuss organic NCs (polymers and lipids) and inorganic NCs (quantum dots, carbon nanotubes, and gold) that have been reported for extensive delivery of therapeutic siRNA to tumor sites. Finally, we will conclude by discussing the studies based on organic and inorganic NCs-mediated siRNA drug delivery systems conducted in the years 2020 and 2021. © 2022 American Chemical Society.

World University root node

Molecular Pharmaceutics

Recent Advancements in the Design of Nanodelivery Systems of siRNA for Cancer Therapy

Objective. In this study we explored the utility of post-prandial vascular stiffness as a surrogate measure for estimating insulin resistance, which is a pre-diabetic condition. Approach. A cohort of 51 healthy young adults with varying body mass index (BMI) values was studied using fasting plasma values of insulin and glucose, fasting and post-meal finger photoplethysmography (PPG) and electrocardiogram (ECG). Insulin resistance was estimated by homeostatic model assessment for insulin resistance 2 (HOMA-IR2) using fasting plasma insulin and glucose. Vascular stiffness was estimated by reciprocal of pulse arrival time (rPAT) from ECG and finger PPG at five time points from fasting to 2 h post-oral glucose ingestion. We examined if insulin resistance correlates with meal-induced vascular stiffness changes, supporting the feasibility of using finger PPG to estimate insulin resistance. Main results. HOMA-IR2 was positively correlated with an early rise (0 to 30 min post-meal) and delayed fall (30 to 120 min post-meal) of rPAT. Correlation persisted even after the effect of BMI has been partialled out in subgroup analysis. We conclude that finger PPG-based pulse waveform and single-lead ECG has the potential to be used as a non-invasive method for the assessment of insulin resistance. Significance. As both signals, namely ECG and PPG, can be easily acquired using wearable and other low-cost sensing systems, the present study can serve as a pointer to develop accessible strategies for monitoring and longitudinal tracking of insulin resistance in health and pathophysiological states. © 2022 Institute of Physics and Engineering in Medicine.

Physiological Measurement

Feasibility of home-based tracking of insulin resistance from vascular stiffness estimated from the photoplethysmographic finger pulse waveform

The tumor microenvironment (TME) typically comprises cancer cells, tumor vasculature, stromal components like fibroblasts, and host immune cells that assemble to support tumorigenesis. However, preexisting classic cancer models like 2D cell culture methods, 3D cancer spheroids, and tumor organoids seem to lack essential TME components. 3D bioprinting offers enormous advantages for developing in vitro tumor models by allowing user-controlled deposition of multiple biomaterials, cells, and biomolecules in a predefined architecture. This review highlights the recent developments in 3D cancer modeling using different bioprinting techniques to recreate the TME. 3D bioprinters enable the fabrication of high-resolution microstructures to reproduce TME intricacies. Furthermore, 3D bioprinted models can be applied as a preclinical model for versatile research applications in the tumor biology and pharmaceutical industries. These models provide an opportunity to develop high-throughput drug screening platforms and can further be developed to suit individual patient requirements hence giving a boost to the field of personalized anti-cancer therapeutics. We underlined the various ways the existing studies have tried to mimic the TME, mimic the hallmark events of cancer growth and metastasis within the 3D bioprinted models and showcase the 3D drug-tumor interaction and further utilization of such models to develop personalized medicine. © 2022 IOP Publishing Ltd.

Fulltext

Biofabrication

Mimicking tumor microenvironment by 3D bioprinting: 3D cancer modeling

Topography and roughness are key features that can direct the behavior of cells. Here, we have developed a surface pattern comparable to the features and roughness present in the native liver tissue by virtue of the liver extracellular matrix. This study used polydimethylsiloxane to get an imprint of the topographical pattern of the native liver and used this imprint as a template to guide the differentiation of adipose-derived mesenchymal stem cells. The results showed a similar gene and protein expression profile to that of hepatocytes, showing potential in the field of scaffold development for tissue engineering applications. © 2022, Indian National Science Academy.

Proceedings of the Indian National Science Academy

Hepatogenic differentiation of adipose-derived mesenchymal stem cells directed by topographical cues: a proof of concept study

Objective: Fabrication and analyses of mucoadhesive patches made from chitosan oligosaccharide for the purpose of oromucosal drug delivery. Significance: The mucosal epithelium in the oral cavity, consisting of buccal and sublingual epithelium, has gained significant attention in the last decade as an alternative anatomical site for systemic drug delivery that could potentially minimize the challenges of solid oral dosage and parenteral delivery. In this study, we have fabricated and tested drug-loaded chitosan oligosaccharide-based patches for the oromucosal drug delivery. Methods: The chitosan oligosaccharide (with and without alginate) based patches were fabricated using the conventional solvent casting method and were analyzed for their swelling capacity, hydrophilicity, anti-cancer activity, in vitro drug release, and in vivo drug release activity. The in-house developed artificial saliva was used for the swelling study. Results: Alginate-containing patches showed lesser swelling ability compared to the bare chitosan oligosaccharide-based patches. The former was also found to be more hydrophobic compared to the latter one. Both the unloaded patches restricted the growth of epithelial cancer cells indicating their anti-cancer behavior. In vitro drug release indicated a super case II release pattern while in vivo study demonstrated the release of drug from the patch into the plasma indicating the purpose of the fabricated patch. Conclusions: The chitosan oligosaccharide-based mucoadhesive hydrogel patch fabricated in this study can be highly suitable for possible translational purposes. © 2022 Informa UK Limited, trading as Taylor & Francis Group.

Drug Development and Industrial Pharmacy

Fabrication and analysis of chitosan oligosaccharide based mucoadhesive patch for oromucosal drug delivery

The performance of the human visual system is very efficient in many visual tasks such as identifying visual scenes, anticipating future actions based on the past observations, assessing the quality of visual stimuli, etc. A significant amount of effort has been directed towards finding quality aware representations of natural videos to solve the quality prediction task. In this work we present a novel no reference video quality assessment (NR-VQA) algorithm based on the functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) signal prediction with voxel-wise encoding models of the human brain. The voxel encoding models are learnt using deep features extracted from the AlexNet model to predict the fMRI response to natural video stimuli. We show that the curvature in the predicted voxel response time series provides good quality discriminability, and forms an important feature for quality prediction. Further, we show that the proposed curvature features in combination with the spatial index, temporal index and NIQE features deliver acceptable performance on the Video Quality Assessment (VQA) task on both synthetic and authentic distortion data-sets. © 2021 IEEE.

Department of Electrical Engineering

IEEE Signal Processing Letters

No-Reference Video Quality Assessment Using Voxel-Wise fMRI Models of the Visual Cortex

Background and Objectives: Virtual patients and physiologies allow experimentation, design, and early-stage clinical trials in-silico. Virtual patient technology for human movement systems that encompasses musculoskeleton and its neural control are few and far in between. Our major goal is to create a neuro- musculoskeletal upper limb in-silico model, which is modular in architecture and generates movement as an emergent phenomenon out of a multiscale co-simulation of spinal cord neural control and musculoskeletal dynamics. Methods: The model is developed on the NEUROiD movement simulation platform that enables a co-simulation of popular neural simulator NEURON and the musculoskeletal simulator OpenSim. We further characterized and demonstrated the use of this model in generating a range of commonly observed upper limb movements by means of a spatio-temporal stimulation pattern delivered to the cervical spinal cord. Results: We were able to characterize the model based on proprioception (Ia, Ib and II fibers), afferent conduction delay and inital postures of the musculoskeletal system. A smooth movement was achieved in all the considered experiments. The generated movements in all degrees of freedom were reproduced in accordance with the previous experimental studies. Conclusion: In this work, design and development of the upper limb model was described in a modular fashion, while reusing existing models and modules. We believe this work enables a first and small step towards an in-silico paradigms for understanding upper limb movement, disease pathology, medication, and rehabilitation. © 2022

Computer Methods and Programs in Biomedicine

In-silico neuro musculoskeletal model reproduces the movement types obtained by spinal micro stimulation

Presently on a global scale, one of the major concerns is to find effective strategies to manage the agricultural waste to protect the environment. One strategy that has been drawing attention among the researchers is the development of biocompatible materials from agricultural waste. This strategy implies successful conversion of agricultural waste products (e.g.: cellulose, eggshell etc.) into building blocks for biomaterial development. Some of these wastes contain even bioactive compounds having biomedical applications. The replacement and augmentation of human tissue with biomaterials as alternative to traditional method not only bypasses immune-rejection, donor scarcity, and maintenance; but also provides long term solution to damaged or malfunctioning organs. Biomaterials development as one of the key challenges in tissue engineering approach, resourced from natural origin imparts better biocompatibility due to closely mimicking composition with cellular microenvironment. The “Garbage In, Biomaterials Out (GIBO)” concept, not only recycles the agricultural wastes, but also adds to biomaterial raw products for further product development in tissue regeneration. This paper reviews the conversion of garbage agricultural by-products to the biocompatible materials for various biomedical applications. Graphical abstract: The agro-waste biomass processed, purified, modified, and further utilized for the fabrication of biomaterials-based support system for tissue engineering applications to grow living body parts in vitro or in vivo. [Figure not available: see fulltext.] © 2022, The Author(s), under exclusive licence to Tehran University of Medical Sciences.

Journal of Environmental Health Science and Engineering

Advancement in “Garbage In Biomaterials Out (GIBO)” concept to develop biomaterials from agricultural waste for tissue engineering and biomedical applications

Breast cancer with unpredictable metastatic recurrence is the leading cause of cancer-related mortality. Early cancer detection and optimized therapy are the principal determining factors for increased survival rate. Worldwide, researchers and clinicians are in search of efficient strategies for the timely management of cancer progression. Efficient preclinical models provide information on cancer initiation, malignancy progression, relapse, and drug efficacy. The distinct histopathological features and clinical heterogeneity allows no single model to mimic breast tumor. However, engineering three-dimensional (3D) in vitro models incorporating cells and biophysical cues using a combination of organoid culture, 3D printing, and microfluidic technology could recapitulate the tumor microenvironment. These models serve to be preferable predictive models bridging the translational research gap in drug development. Microfluidic device is a cost-effective advanced in vitro model for cancer research, diagnosis, and drug assay under physiologically relevant conditions. Integrating a biosensor with microfluidics allows rapid real-time analytical validation to provide highly sensitive, specific, reproducible, and reliable outcomes. In this manner, the multi-system approach in identifying biomarkers associated with cancer facilitates early detection, therapeutic window optimization, and post-treatment evaluation. This chapter showcases the advancements related to in vitro breast cancer metastasis models focusing on microfluidic devices. The chapter aims to provide an overview of microfluidic biosensor-based devices for cancer detection and high-throughput chemotherapeutic drug screening. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Advances in Experimental Medicine and Biology

Microfluidic Biosensor-Based Devices for Rapid Diagnosis and Effective Anti-cancer Therapeutic Monitoring for Breast Cancer Metastasis

Studies have shown that in cancer cells, there is an increased T-type calcium channel (TTCC) expression compared to healthy cells. Therefore, the studies targeting TTCC for cancer therapy have shown many positive outcomes. Here, we have used TTA-A2- a potent TTCC inhibitor as a test drug, and paclitaxel (PTX)- a tubule-binding anti-cancer agent as a positive control. Blocking TTCC has shown to overcome resistance in cancer cells towards anti-cancer drugs by reducing calcium influx, and some studies have shown that PTX treatment also reduces the intracellular calcium signaling in cells. So, there is a possibility that PTX might be interacting with calcium channels. Since, drug-drug interaction can cause severe side-effects, or alter the actions of each other; we aim to study the interactions among TTA-A2, PTX, and TTCC. In this study, we have used computational analysis to test the binding of TTA-A2 and PTX with TTCC. To confirm the in-silico result, we further tested these drugs in a 3D spheroid model of A549, a lung adenocarcinoma cell line. The in-silico result showed that both the drugs, TTA-A2 and PTX, could interact at the same site of TTCC to form a higher stable complex as compared to the TTCC-native. The in vitro result showed the antagonistic interaction between the drugs when they are used at the same time. By using the sequential treatment, the spheroids were sensitized by TTA-A2, before treating with PTX. The result indicated that sequential treatment could help to overcome the antagonistic interaction between the two drugs. Communicated by Ramaswamy H. Sarma. © 2020 Informa UK Limited, trading as Taylor & Francis Group.