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.

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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.

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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

Three-dimensional (3D) tissue printing is the approach to printing millimeter- to centimeter-sized biological constructs that include several cell types and biomaterials simultaneously. Biomimetic 3D tissue printing relies on mimicking key features of the extracellular matrix (ECM), either physically or chemically, for successful tissue regeneration. In native tissue, the ECM provides cells with a variety of physical, chemical, and biological cues that affect cell growth and function. Numerous methods are being developed to create 3D tissue scaffolds with control over their physical and mechanical properties, cell adhesion, and the spatiotemporal release of growth factors to mimic the physicochemical attributes of the ECM.We herein present an overview of a variety of 3D tissue printing methods that are currently used to produce 3D tissue for implantation, modify their surfaces with biochemical ligands, incorporate growth factors, and control their nano- and microscale geometry to create biomimetic scaffolds. Furthermore, various innovative attempts in biomimetic 3D tissue printing based on either physical or chemical approaches for production of tissue or organs are discussed.A basic understanding of the entire spectrum of biomimetic 3D tissue printing provides a pragmatic insight into how it can potentially be used in diverse tissue engineering applications and regenerative medicine. © 2014 by World Scientific Publishing Co. Pte. Ltd.

World University root node

Handbook of Biomimetics and Bioinspiration: Biologically-driven Engineering of Materials, Processes, Devices, and Systems (In 3 Volumes)

Biomimetic 3D Tissue Printing

Converging evidence from transgenic animal models of amyotrophic lateral sclerosis (ALS) and human studies suggest alterations in excitability of the motor neurons in ALS. Specifically, in studies on human subjects with ALS the motor cortex was reported to be hyperexcitable. The present study was designed to test the hypothesis that infusion of cerebrospinal fluid from patients with sporadic ALS (ALS-CSF) into the rat brain ventricle can induce hyperexcitability and structural changes in the motor cortex leading to motor dysfunction. A robust model of sporadic ALS was developed experimentally by infusing ALS-CSF into the rat ventricle. The effects of ALS-CSF at the single neuron level were examined by recording extracellular single unit activity from the motor cortex while rats were performing a reach to grasp task. We observed an increase in the firing rate of the neurons of the motor cortex in rats infused with ALS-CSF compared to control groups. This was associated with impairment in a specific component of reach with alterations in the morphological characteristics of the motor cortex. It is likely that the increased cortical excitability observed in the present study could be the result of changes in the intrinsic properties of motor cortical neurons, a dysfunctional inhibitory mechanism and/or an underlying structural change culminating in a behavioral deficit. © 2013 Springer-Verlag Wien.

Journal of Neural Transmission

Reach task-associated excitatory overdrive of motor cortical neurons following infusion with ALS-CSF

We propose a label-free biosensor platform to investigate the binding kinetics using antigen-antibody interaction via electrochemical and surface plasmon resonance (SPR) techniques. The l-cysteine in situ capped cadmium sulfide (CdS; size &lt; 7 nm) quantum dots (QDs) self-assembled on gold (Au) coated glass electrode have been covalently functionalized with apolipoprotein B-100 antibodies (AAB). This protein conjugated QDs-based electrode (AAB/CysCdS/Au) has been used to detect lipid (low density lipoprotein, LDL) biomolecules. The electrochemical impedimetric response of the AAB/CysCdS/Au biosensor shows higher sensitivity (32.8 kΩ μM-1/cm 2) in the detection range, 5-120 mg/dL. Besides this, efforts have been made to investigate the kinetics of antigen-antibody interactions at the CysCdS surface. The label-free SPR response of AAB/CysCdS/Au biosensor exhibits highly specific interaction to protein (LDL) with association constant of 33.4 kM-1 s-1 indicating higher affinity toward LDL biomolecules and a dissociation constant of 0.896 ms-1. The results of these studies prove the efficacy of the CysCdS-Au platform as a high throughput compact biosensing device for investigating biomolecular interactions. © 2014 American Chemical Society.

Analytical Chemistry

Protein-conjugated quantum dots interface: Binding kinetics and label-free lipid detection

Planar Cell Polarity (PCP) is an evolutionarily conserved characteristic of animal tissues marked by coordinated polarization of cells or structures in the plane of a tissue. In insect wing epithelium, for instance, PCP is characterized by en masse orientation of hairs orthogonal to its apical-basal axis and pointing along the proximal-distal axis of the organ. Directional cue for PCP has been proposed to be generated by complex sets of interactions amongst three proteins - Fat (Ft), Dachsous (Ds) and Four-jointed (Fj). Ft and Ds are two atypical cadherins, which are phosphorylated by Fj, a Golgi kinase. Ft and Ds from adjacent cells bind heterophilically via their tandem cadherin repeats, and their binding affinities are regulated by Fj. Further, in the wing epithelium, sub-cellular levels of Ft-Ds heterodimers are seen to be elevated at the distal edges of individual cells, prefiguring their PCP. Mechanisms generating this sub-cellular asymmetry of Ft-Ds heterodimer in proximal and distal edges of cells, however, have not been resolved yet. Using a mathematical modeling approach, here we provide a framework for generation of this sub-cellular asymmetry of Ft-Ds heterodimer. First, we explain how the known interactions within Ft-Ds-Fj system translate into sub-cellular asymmetry of Ft-Ds heterodimer. Second, we show that this asymmetric localization of Ft-Ds heterodimer is lost when tissue-level gradient of Fj is flattened, or when phosphorylation of Ft by Fj is abolished, but not when tissue-level gradient of Ds is flattened or when phosphorylation of Ds is abrogated. Finally, we show that distal enrichment of Ds also amplifies Ft-Ds asymmetry. These observations reveal that gradient of Fj expression, phosphorylation of Ft by Fj and sub-cellular distal accumulation of Ds are three critical elements required for generating sub-cellular asymmetry of Ft-Ds heterodimer. Our model integrates the known experimental data and presents testable predictions for future studies. © 2014 Jolly et al.

Fulltext

PLoS ONE

Mathematical modeling of sub-cellular asymmetry of fat-dachsous heterodimer for generation of planar cell polarity

A label-free biosensor based on antiapolipoprotein B 100 functionalized-aminated reduced graphene oxide interface has been fabricated for detection of low density lipoprotein (LDL or lipid) cholesterol. The aminated reduced graphene oxide (NH2-rGO) based electrode surface is covalently functionalized with antiapolipoprotein B 100 (AAB or lipid) using EDC/NHS coupling chemistry. The lipid-lipid interactions at the NH 2-rGO electrode surface have been investigated using electrochemical impedance spectroscopic technique. The structural and morphological investigations of NH2-rGO based immunosensor have been accomplished via transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, UV-visible, and electrochemical techniques. The impedimetric response of the proposed immunosensor shows excellent sensitivity (612 Ω mg-1 dL cm-2), a response time of 250 s, and a low detection limit of 5 mg/dL of LDL molecules. The association, dissociation, and equilibrium rate constants for this immunoelectrode are found to be 1.66 M-1 s-1, 0.6 s-1, and 2.77 M -1, respectively. The long-term stability and excellent reproducibility of the proposed immunosensor indicates a suitable platform for detection of LDL or lipid molecules. This immunosensor provides an efficient platform for analysis of the antigen-antibody interactions of lipid molecules. © 2014 American Chemical Society.

Langmuir

Lipid-lipid interactions in aminated reduced graphene oxide interface for biosensing application

Addition of staining and contrast agents to living cells to improve the contrast, are not applicable to live cell image as they are toxic. We demonstrate a quantitative phase imaging of live yeast cells without any staining agents using digital holographic microscope. © OSA 2014.

International Conference on Fibre Optics and Photonics, 2014

Quantitative phase imaging of live yeast cells using digital holographic microscopyc

We demonstrate a digital holographic microscope platform for phase imaging of micron scale samples. A method for quantitative phase visualization and compensation of the aberrations in coherence microscopic imaging is proposed. Preliminary results are presented as proof of concept for aberration corrections. © 2013 IEEE.

WRAP 2013 - Workshop on Recent Advances in Photonics

Quantitative phase visualization and aberration correction using digital holographic microscope

we demonstrate a digital holographic microscope with a synthetic aperture for improvement in resolution. An aperture was synthesized by moving the camera at 9 different positions. Experiment results of imaging E.coli are presented. © OSA 2014.

3D reconstruction of E.Coli bacteria using synthetic aperture digital holographic microscopy

Bioactive glass (BG) scaffolds are being investigated for bone tissue engineering applications because of their osteoconductive and angiogenic nature. However, to increase the in vivo performance of the scaffold, including enhancing the angiogenetic growth into the scaffolds, some researchers use different modifications of the scaffold including addition of inorganic ionic components to the basic BG composition. In this study, we investigated the in vitro biocompatibility and bioactivity of Cu2+-doped BG derived scaffolds in either BMSC (bone-marrow derived mesenchymal stem cells)-only culture or co-culture of BMSC and human dermal microvascular endothelial cells (HDMEC). In BMSC-only culture, cells were seeded either directly on the scaffolds (3D or direct culture) or were exposed to ionic dissolution products of the BG scaffolds, kept in permeable cell culture inserts (2D or indirect culture). Though we did not observe any direct osteoinduction of BMSCs by alkaline phosphatase (ALP) assay or by PCR, there was increased vascular endothelial growth factor (VEGF) expression, observed by PCR and ELISA assays. Additionally, the scaffolds showed no toxicity to BMSCs and there were healthy live cells found throughout the scaffold. To analyze further the reasons behind the increased VEGF expression and to exploit the benefits of the finding, we used the indirect method with HDMECs in culture plastic and Cu2+-doped BG scaffolds with or without BMSCs in cell culture inserts. There was clear observation of increased endothelial markers by both FACS analysis and acetylated LDL (acLDL) uptake assay. Only in presence of Cu2+-doped BG scaffolds with BMSCs, a high VEGF secretion was demonstrated by ELISA; and typical tubular structures were observed in culture plastics. We conclude that Cu2+-doped BG scaffolds release Cu2+, which in turn act on BMSCs to secrete VEGF. This result is of significance for the application of BG scaffolds in bone tissue engineering approaches. © 2014 Rath et al.

Bioactive copper-doped glass scaffolds can stimulate endothelial cells in co-culture in combination with mesenchymal stem cells

Bone tissue engineering strategies mainly depend on porous scaffold materials. In this study, novel biphasic calcium phosphate (BCP) matrices were generated by 3D-printing. High porosity was achieved by starch consolidation. This study aimed to characterise the porous BCP-scaffold properties and interactions of osteogenic cells and growth factors under in vivo conditions. Five differently treated constructs were implanted subcutaneously in syngeneic rats: plain BCP constructs (group A), constructs pre-treated with BMP-2 (group B; 1.6μg BMP-2 per scaffold), seeded with primary osteoblasts (OB) (group C), seeded with OB and BMP-2 (group D) and constructs seeded with OB and pre-cultivated in a flow bioreactor for 6weeks (group E). After 2, 4 and 6weeks, specimens were explanted and subjected to histological and molecular biological analyses. Explanted scaffolds were invaded by fibrovascular tissue without significant foreign body reactions. Morphometric analysis demonstrated significantly increased bone formation in samples from group D (OB+BMP-2) compared to all other groups. Samples from groups B-E displayed significant mRNA expression of bone-specific genes after 6weeks. Pre-cultivation in the flow bioreactor (group E) induced bone formation comparable with group B. In this study, differences in bone distribution between samples with BMP-2 or osteoblasts could be observed. In conclusion, combination of osteoblasts and BMP-2 synergistically enhanced bone formation in novel ceramic scaffolds. These results provide the basis for further experiments in orthotopic defect models with a focus on future applications in orthopaedic and reconstructive surgery. © 2012 John Wiley & Sons, Ltd.