Vellore Institute of Technology (VIT) is a private university located in&nbsp;Tamil Nadu, India. Founded in 1984, as Vellore Engineering College, the institution offers 20 undergraduate, 34 postgraduate, four integrated and four research programs. It has campuses in Vellore, Amravati, Bhopal and Chennai.

VIT is one of the top ranked private universities in India according to NIRF, THE and QS Rankings.&nbsp;Govt. of India has recognized&nbsp;VIT, Vellore as an&nbsp;Institution of Eminence. This has allowed VIT to take independent quality initiatives and move up in world ranking.

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VIT University

Centre for Biomaterials, Cellular and Molecular Theranostics

In this chapter, we investigate the impact of induced pluripotent stem cells (iPSCs) in scaffold-based tissue engineering and its potential for tissue regenerative medicine. Scaffold-based tissue engineering aims to develop functionalized tissues/organs for repair and regeneration of damaged or diseased body parts by employing engineered matrices called scaffolds cultured with cells and bioactive molecules. iPSCs are adult cells that have been genetically reprogrammed into an embryonic-cell-like state. Owing to their unique regenerative capacity, iPSCs have attracted the attention of the biomedical community and demonstrated their capability as an invaluable cell source for cell therapy and for scaffold-based tissue engineering. However, the underlying mechanism of the interaction of iPSCs with three-dimensional (3D) scaffolds is unclear, which is very essential to realize the full potential of iPSCs in engineering functional tissues and organs. In this chapter, we therefore review the impact of iPSCs in scaffold-based tissue engineering and its potential for tissue regenerative medicine. The techniques employed for the culture of iPSCs into 3D scaffolds, the effect of the 3D microenvironment in controlling iPSCs' fate and function, and the potential applications of iPSCs in tissue engineering are discussed with illustrated examples. The chapter is expected to be useful for readers to gain insight into the impact of iPSCs in various 3D scaffold-based tissue engineering fields such as bone, cartilage, cardiac, skin, and neural tissue engineering. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA.

World University root node

VIT Unitversity

Vellore Campus

Tissue Engineering for Artificial Organs

Induced Pluripotent Stem Cells in Scaffold-Based Tissue Engineering

Organ transplantation is an effective treatment for chronic organ dysfunctioning conditions. However, a dearth of available donor organs for transplantation leads to the death of numerous patients waiting for a suitable organ donor. The potential of decellularized scaffolds, derived from native tissues or organs in the form of scaffolds has been evolved as a promising approach in tissue-regenerative medicine for translating functional organ replacements. In recent years, donor organs, such as heart, liver, lung and kidneys, have been reported to provide acellular extracellular matrix (ECM)-based scaffolds through the process called ‘decellularization’ and proved to show the potential of recellularization with selected cell populations, particularly with stem cells. In fact, decellularized stem cell matrix (DSCM) has also emerged as a potent biological scaffold for controlling stem cell fate and function during tissue organization. Despite the proven potential of decellularized scaffolds in tissue engineering, the molecular mechanism responsible for stem cell interactions with decellularized scaffolds is still unclear. Stem cells interact with, and respond to, various signals/cues emanating from their ECM. The ability to harness the regenerative potential of stem cells via decellularized ECM-based scaffolds has promising implications for tissue-regenerative medicine. Keeping these points in view, this article reviews the current status of decellularized scaffolds for stem cells, with particular focus on: (a) concept and various methods of decellularization; (b) interaction of stem cells with decellularized scaffolds; (c) current recellularization strategies, with associated challenges; and (iv) applications of the decellularized scaffolds in stem cell-driven tissue engineering and regenerative medicine. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Journal of Tissue Engineering and Regenerative Medicine

Development of decellularized scaffolds for stem cell-driven tissue engineering

In this study, we present the preparation of graphene quantum dots (GQDs) and graphene oxide quantum dots (GOQDs). GQDs/GOQDs are prepared by an easy electrochemical exfoliation method, in which two graphite rods are used as electrodes. The electrolyte used is a combination of citric acid and alkali hydroxide in water. Four types of quantum dots, GQD1-GQD4, are prepared by varying alkali hydroxide concentration in the electrolyte, while keeping the citric acid concentration fixed. Variation of alkali hydroxide concentration in the electrolyte results in the production of GOQDs. Balanced reaction of citric acid and alkali hydroxide results in the production of GQDs (GQD3). However, three variations in alkali hydroxide concentration result in GOQDs (GQD1, GQD2, and GQD4). GOQDs show tunable oxygen functional groups, which are confirmed by X-ray photoelectron spectroscopy. GQDs/GOQDs show absorption in the UV region and show excitation-dependent photoluminescence behavior. The obtained average size is 2-3 nm, as revealed by transmission electron microscopy. X-ray diffraction peak at around 10° and broad D band peak at 1350 cm-1 in Raman spectra confirm the presence of oxygen-rich functional groups on the surface of GOQDs. These GQDs and GOQDs show blue to green luminescence under 365 nm UV irradiation. © 2017 American Chemical Society.

Fulltext

ACS Omega

Electrochemical Method to Prepare Graphene Quantum Dots and Graphene Oxide Quantum Dots

In the field of drug delivery, consistent efforts are under progress targeting upgraded human healthcare and improving current drug therapeutics. Most of the drugs introduced into the body by conventional methods, using oral tablets and intravenous injections, encounter problems including poor solubility, undesirable biodistribution, burst release kinetics, tissue damage during extravasation, cytotoxicity, and many more objectionable side effects. To overcome these limitations, advanced drug delivery systems (DDS) aim at maximum therapeutics efficiency, enhanced bioavailability, targeted drug release, extended drug release profile, minimum toxicity, and reduced dosage frequency to encourage patient compliance. Nanofiber scaffolds are the most modern and competent drug delivery carriers, revolutionizing the field of nanomedicines due to their high surface-to-volume ratio, increased loading efficiency, and enhanced permeation and retention effects. Nanofiber composites exploit the synergism of two or more materials to achieve desired therapeutic objective, e.g., targeted drug delivery, stimulus-sensitive drug release, dual drug release with independent release kinetics, adjustable control release, on-off switchable drug release, etc. In this chapter, we present different types of nanofiber composites fabricated in the context of drug delivery, with their distinctive implications. The applications of different nanocomposites in the fields of advanced pharmaceuticals, wound dressings, tissue engineering, and cancer therapeutics have also been demonstrated for their future prospects. © 2017 Elsevier Ltd. All rights reserved.

Department of Multimedia

School of Design

Nanofiber Composites for Biomedical Applications

Nanofiber composites in gene delivery

MicroRNAs are small RNAs that negatively regulate gene expression posttranscriptionally. Because changes in microRNA expression can promote or maintain disease states, microRNA-based therapeutics are being evaluated extensively. Unfortunately, the therapeutic potential of microRNA replacement is limited by deficient delivery vehicles. In this work, microRNAs are delivered in the absence of a protective vehicle. The method relies on direct attachment of microRNAs to folate (FolamiR), which mediates delivery of the conjugated microRNA into cells that overexpress the folate receptor. We show that the tumor-suppressive FolamiR, FolamiR-34a, is quickly taken up both by triple-negative breast cancer cells in vitro and in vivo and by tumors in an autochthonous model of lung cancer and slows their progression. This method delivers microRNAs directly to tumors in vivo without the use of toxic vehicles, representing an advance in the development of nontoxic, cancer-targeted therapeutics. Copyright © 2017 The Authors.

Science Translational Medicine

FolamiRs: Ligand-targeted, vehicle-free delivery of microRNAs for the treatment of cancer

Two water soluble Ru(ii)-arene complexes of the type [Ru(η6-arene)(met)Cl]Cl 1 and 2, where the arene is either p-cymene (1) or benzene (2) and met is metformin (antidiabetic drug) have been isolated and characterized by analytical and spectral methods. The X-ray crystal structure of 1 reveals that the coordination geometry around Ru(ii) is described as the familiar pseudo-octahedral "piano-stool" structure. Absorption and emission spectral studies reveal that the complexes interact with calf thymus DNA through hydrophobic and hydrogen bonding interactions of coordinated ligands with the DNA base pairs. Molecular docking studies show that complex 1 effectively docks in the major groove of DNA. The decrease in viscosities of CT DNA upon binding to 1 and 2 suggest the covalent mode of DNA binding of complexes. Further, the covalent mode of binding is validated by the retardation of the mobility of supercoiled (SC) plasmid DNA by the formation of covalent adducts observed in gel electrophoretic mobility studies. The protein binding affinity of the complexes depends upon the arene ligand and follows the order of p-cymene (1) &gt; benzene (2), which is the same as that for DNA binding affinity. Docking studies with BSA and transferrin show that the complex-protein interaction is stabilized by hydrophobic as well as hydrogen bonding interactions. The α-amylase inhibition assay of 1 and 2 indicates that they have the potency to exhibit the antidiabetic activity in vitro. A study of cytotoxicity of 1 and 2 against human breast carcinoma (MDA-MB-231), human lung carcinoma (A549), human ovarian carcinoma (A2780) cell lines and non-tumorigenic human embryonic kidney (HEK293) cells reveals that they are specifically toxic to cancerous cells and non-toxic to normal cells. Remarkably, complexes 1 and 2 exhibit cytotoxicity with potency more than the metformin suggesting that the incorporation of antidiabetic drug with the organometallic Ru-arene frameworks is potential approach to develop effective anticancer drugs. The morphological changes observed by employing AO/EB and Hoechst 33258 staining methods reveal that the complexes 1 and 2 induce an apoptotic mode of cell death in breast cancer cells. © 2017 The Royal Society of Chemistry.

RSC Advances

Water soluble Ru(II)-arene complexes of the antidiabetic drug metformin: DNA and protein binding, molecular docking, cytotoxicity and apoptosis-inducing activity

The main objective of this study was to fabricate poly (ε-caprolactone) (PCL)-based auxetic nanofiber membranes and characterize them for their mechanical and physicochemical properties. As a first step, the PCL nanofibers were fabricated by electrospinning with two different thicknesses of 40 μm (called PCL thin membrane) and 180 μm (called PCL thick membrane). In the second step, they were tailored into auxetic patterns using femtosecond laser cut technique. The physicochemical and mechanical properties of the auxetic nanofiber membranes were studied and compared with the conventional electrospun PCL nanofibers (non-auxetic nanofiber membranes) as a control. The results showed that there were no significant changes observed among them in terms of their chemical functionality and thermal property. However, there was a notable difference observed in the mechanical properties. For instance, the thin auxetic nanofiber membrane showed the magnitude of elongation almost ten times higher than the control, which clearly demonstrates the high flexibility of auxetic nanofiber membranes. This is because that the auxetic nanofiber membranes have lesser rigidity than the control nanofibers under the same load which could be due to the rotational motion of the auxetic structures. The major finding of this study is that the auxetic PCL nanofiber membranes are highly flexible (10-fold higher elongation capacity than the conventional PCL nanofibers) and have tunable mechanical properties. Therefore, the auxetic PCL nanofiber membranes may serve as a potent material in various biomedical applications, in particular, tissue engineering where scaffolds with mechanical cues play a major role. © 2017

Materials Science and Engineering C

Design and fabrication of auxetic PCL nanofiber membranes for biomedical applications

Stem cell plays a significant role in tissue engineering and regenerative medicine. However, one of the major limitations in translation of stem cell technologies for clinical applications is limited cell survival and growth upon implantation. To address this limitation, authors have made an attempt to design polyacrylamide/alginate (PAAm/Algi) based tough hydrogel substrates and studied their impact on the survival and proliferation of human bone marrow-derived mesenchymal stem cells (hBMSCs). The PAAm/Algi hydrogel substrates have been prepared by initiator-induced free radical polymerization with mechanical properties quite similar to human soft tissues. To evaluate the efficacy of hydrogel substrates in support of cellular functions, hBMSCs were cultured on the PAAm/Algi hydrogel substrate (Gel system) and conventional tissue culture plate (TcP system) under defined conditions. The results of this study demonstrated that the cells cultured on the Gel and TcP systems showed 80–90% of cell viability throughout the period of study. The cells cultured on the Gel system showed 25% increase in proliferation after 7 days of culture, whereas the TcP system showed only an increase of 10%. These results confirm the cellular compatibility and enhanced cell proliferative nature of the hydrogel substrates, due the fact that the hydrogel substrates provided necessary microenvironmental cues to the cells as compared the conventional TcP system. The overall results suggest that the PAAm/Algi based hydrogels could be used as a potential substrate for hBMSCs culture and expansion. © 2017 Elsevier B.V.

Enhanced proliferation of human bone marrow derived mesenchymal stem cells on tough hydrogel substrates

Zirconia is the preferred material used in many applications including biomedical implant. The zirconia in its sintered form is the most preferred one to manufacture a near net shaped implant material with minimal work. But it is very difficult to shape as the material chip away during the machining or grinding process. Hence zirconia in a pre-sintered form is used to achieve the required shape and size for a specific application. Then it is sintered and used. In this work, the grindability of the presintered zirconia was evaluated using a dense vitreous bond silicon carbide wheel. The grinding parameters such as wheel speed, radial depth of cut and feed rate are varied to investigate its grindability in terms of force ratio, specific energy, surface finish, G-ratio and ground surface under both wet and MQL cooling conditions. The forces produced during the grinding of pre-sintered zirconia was observed lower in the MQL (Minimum Quantity Lubrication) technique due to the reduction of friction, when compared to the wet cooling condition. The calculated specific energy was less in MQL cooling condition, due to the reduction in heat generation and friction. The surface finish of the workpiece obtained from the wet cooling condition was better due to the reduction in wheel loading. The percentage difference of the G-ratio between both the wet and MQL cooling conditions was observed to be 24 percent. This was due to the active participation of grains and less wheel loading in wet grinding condition. The ground surfaces obtained from the wet cooling condition were smooth and regular, compared to the MQL grinding condition. © 2017 The Authors

Procedia Manufacturing

Investigation on Grindability of Medical Implant Material Using a Silicon Carbide Wheel with Different Cooling Conditions

Nanofiber Composite Materials for Biomedical Applications presents new developments and recent advances in nanofiber-reinforced composite materials and their use in biomedical applications, including biomaterial developments, drug delivery, tissue engineering, and regenerative medicine. Unlike more conventional titles on composite materials, this book covers the most innovative new developments in nanofiber-based composites, including polymers, ceramics, and metals, with particular emphasis on their preparation and characterization methodology. Selected case studies illustrate new developments in clinical and preclinical use, making the information critical for the development of new medical materials and systems for use in human health care, and for the exploration of new design spaces based on these nanofibers. This book is essential reading for those working in biomedical science and engineering, materials science, nanoscience, biomedical nanotechnology, and biotechnology. Covers innovative new developments in nanofiber composites, including polymers, ceramics, and metals with particular emphasis on their preparation and characterization methodology. Deals with biomedical applications, including biomaterials developments, drug delivery, tissue engineering, and regenerative medicine. Presents selected case studies on nanofiber composite materials in both clinical and preclinical use. © 2017 Elsevier Ltd. All rights reserved.