Qualification: 
Ph.D
ullas19351@aims.amrita.edu

Dr. Mony received his Ph.D (Haematology) from The University of Nottingham, UK. He worked on targeting of minimal residual disease in Acute Myeloid Leukemia. He developed a 'niche-like' condition for testing the chemosensitivity of leukemic stem and progenitor cells. Dr. Mony had identified multiple signaling pathways involved in the survival of leukemic stem and progenitor cells. He received prestigious awards such as Overseas Research Scholarship and Developing Solutions Scholarship (University of Nottingham, UK). He was also a recipient of the British Association of Cancer Research student award during his Ph.D time. He had his postdoctoral training as a senior fellow in a collaborative research programme at Memorial Sloan-Kettering Cancer Centre, USA, and Broad Institute of MIT and Harvard, USA. His expertise and training includes hemato-oncology, tumor microenvironment, preclinical drug discovery (small molecules), pre-clinical mice model development of cancers, and induced pluripotent stem cells (iPSC). He is trained and certified in rodent major surgical procedures from Cornell University, USA, and Memorial Sloan-Kettering Cancer Center, USA. He got trained in iPSC generation and differentiation from The University of Queensland and Monash University, Australia. 

Dr. Mony joined Amrita Center for Nanosciences and Molecular Medicine as Assistant Professor in April 2009. Dr. Mony's Stem cell and translational lab is focused mainly in two areas. Firstly in finding out the molecular heterogeneity and identification of novel targets in AML cells treated with various therapeutic agents, and secondly, in the generation and differentiation of iPS cells for drug screening and disease modeling applications. He is also heading the advanced immunohematology and flowcytometry facility of the center for disease diagnosis and research. His publications are in major international journals of repute such as Leukemia, Blood, Haematologica, Molecular Oncology etc.

His research interest includes Leukemic Stem Cells/Acute Myeloid Leukemia and targeting, Tumor microenvironment, Immunotherapy, Pre-clinical mice model development, proteomics and iPSC.

Publications

Publication Type: Journal Article

Year of Publication Publication Type Title

2018

Journal Article

S. Vignesh, Gopalakrishnan, A., Poorna, M. R., Shantikumar V Nair, Dr. Jayakumar Rangasamy, and Dr. Ullas Mony, “Fabrication of micropatterned alginate-gelatin and k-carrageenan hydrogels of defined shapes using simple wax mould method as a platform for stem cell/induced Pluripotent Stem Cells (iPSC) culture”, International Journal of Biological Macromolecules, 2018.[Abstract]


Micropatterning techniques involve soft lithography, which is laborious, expensive and restricted to a narrow spectrum of biomaterials. In this work we report, first time employment of patterned wax moulds for generation of micropatterned alginate-gelatin and κ-carrageenan (κ-CRG) hydrogel systems by a novel, simple and cost effective method. We generated and characterized uniform and reproducible micropatterned hydrogels of varying sizes and shapes such as square projections, square grooves, and circular grids and crisscrossed hillocks. The rheological analysis showed that κ-carrageenan hydrogels had higher gel strength when compared to alginate-gelatin hydrogels. Human Mesenchymal stem cells (hMSCs) and Human Induced Pluripotent Stem Cells (hiPSCs) were found to be cytocompatible with these hydrogels. This micropatterned hydrogel system may have potential application in tissue engineering and also in understanding the basic biology behind the stem cell/iPSC fate.

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2018

Journal Article

K. T. Shalumon, Anjana, J., Dr. Ullas Mony, Jayakumar, R., and Chen, J. - P., “Process Study, Development and Degradation Behavior of Different Size Scale Electrospun Poly(caprolactone) and Poly(lactic acid) Fibers”, Journal of Polymer Research, vol. 25, 2018.[Abstract]


This study describes the preparation of electrospun poly(caprolactone) (PCL) and poly(lactic acid) (PLA) fibrous scaffolds with and without nano-hydroxyapatite (nHAp) having nanoscale, microscale and combined micro/nano (multiscale) architecture. Processing parameters such as polymer concentration, voltage, flow rate and solvent compositions were varied in wide range to display the effect of each one in determining the diameter and morphology of fibers. The effect of each regulating parameter on fiber morphology and diameter was evaluated and characterized using scanning electron microscope (SEM). Degradability of the selected fibrous scaffolds was verified by phosphate buffered saline immersion and its morphology was analyzed through SEM, after 5 and 12 months. Quantitative measurement in degradation was further evaluated through pH analysis of the medium. Both studies revealed that PLA had faster degradation compared to PCL irrespective of the size scale nature of fibers. Structural stability evaluation of the degraded fibers in comparison with pristine fibers by thermogravimetric analysis further confirmed faster degradability of PLA compared to PCL fibers. The results indicate that PLA showed faster degradation than PCL irrespective of the size-scale nature of fibrous scaffolds, and therefore, could be applied in a variety of biomedical applications including tissue engineering. © 2018, Springer Science+Business Media B.V., part of Springer Nature

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2017

Journal Article

S. Sowmya, Dr. Ullas Mony, P., J., Reshma, S., R Kumar, A., Arzate, H., Shantikumar V Nair, and Jayakumar, R., “Tri-Layered Nanocomposite Hydrogel Scaffold for the Concurrent Regeneration of Cementum, Periodontal Ligament, and Alveolar Bone.”, Adv Healthc Mater, 2017.[Abstract]


A tri-layered scaffolding approach is adopted for the complete and concurrent regeneration of hard tissues-cementum and alveolar bone-and soft tissue-the periodontal ligament (PDL)-at a periodontal defect site. The porous tri-layered nanocomposite hydrogel scaffold is composed of chitin-poly(lactic-co-glycolic acid) (PLGA)/nanobioactive glass ceramic (nBGC)/cementum protein 1 as the cementum layer, chitin-PLGA/fibroblast growth factor 2 as the PDL layer, and chitin-PLGA/nBGC/platelet-rich plasma derived growth factors as the alveolar bone layer. The tri-layered nanocomposite hydrogel scaffold is cytocompatible and favored cementogenic, fibrogenic, and osteogenic differentiation of human dental follicle stem cells. In vivo, tri-layered nanocomposite hydrogel scaffold with/without growth factors is implanted into rabbit maxillary periodontal defects and compared with the controls at 1 and 3 months postoperatively. The tri-layered nanocomposite hydrogel scaffold with growth factors demonstrates complete defect closure and healing with new cancellous-like tissue formation on microcomputed tomography analysis. Histological and immunohistochemical analyses further confirm the formation of new cementum, fibrous PDL, and alveolar bone with well-defined bony trabeculae in comparison to the other three groups. In conclusion, the tri-layered nanocomposite hydrogel scaffold with growth factors can serve as an alternative regenerative approach to achieve simultaneous and complete periodontal regeneration. More »»

2017

Journal Article

M. Kumaran Sa Kumar, Nair, S., Dr. Ullas Mony, Kalingavarman, S., Venkat, R., Sivanarayanan, T. Balakrishn, Unni, A. Kodakara K., Rajeshkannan, R., Anandakuttan, A., Radhakrishnan, S., and Menon, K. N., “Significance of elevated Prohibitin 1 levels in Multiple Sclerosis patients lymphocytes towards the assessment of subclinical disease activity and its role in the central nervous system pathology of disease.”, International Journal of Biological Macromolecules, 2017.[Abstract]


Multiple Sclerosis (MS) is an autoimmune-neurodegenerative disorder managed therapeutically by modulating lymphocytes activity which has potential in disease management. Prohibitin 1(PHB) that controls the reactive oxygen species (ROS) and present on the activated lymphocytes have significance in the therapy of MS as esters of fumaric acid that regulates ROS is in phase II/III clinical trials. Thus, we evaluated the expression levels of PHB1 in experimental autoimmune encephalomyelitis (EAE), the animal model of MS and on MS patient's lymphocytes. PHB levels in brain tissue of EAE animals were determined by immunoblotting and on blood lymphocytes from MS relapse, Remission, Optic Neuritis, Neurological controls and Healthy volunteers by FACS using anti-PHB and anti-CD45 antibodies. We observed significant elevation of PHB in EAE brains (91.0 ± 17.59%) vs controls (29.8 ± 12.9%) (p = 0.01) and on lymphocytes of MS patients in acute (73.5 ± 11.20%) or relapsing (69.3 ± 17.33%) phase compared to remission (45.9 ± 8.08%) [p = 0.034 acute vs remission; p = 0.004 relapse vs remission]. Up regulation of PHB in relapsing vs remission MS patients imply the potential use of PHB to clinically evaluate subclinical disease status towards prognosis of an oncoming relapse. Elevated PHB levels in EAE brains signify the role of PHB in regulating ROS and implies PHB's role in oxidative stress.

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2015

Journal Article

A. Anitha, Maya, S., Sivaram, A. J., Dr. Ullas Mony, and Dr. Jayakumar Rangasamy, “Combinatorial nanomedicines for colon cancer therapy”, Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 2015.[Abstract]


<p>Colon cancer is one of the major causes of cancer deaths worldwide. Even after surgical resection and aggressive chemotherapy, 50% of colorectal carcinoma patients develop recurrent disease. Thus, the rationale of developing new therapeutic approaches to improve the current chemotherapeutic regimen would be highly recommended. There are reports on the effectiveness of combination chemotherapy in colon cancer and it has been practiced in clinics for long time. These approaches are associated with toxic side effects. Later, the drug delivery research had shown the potential of nanoencapsulation techniques and active targeting as an effective method to improve the effectiveness of chemotherapy with less toxicity. This current focus article provides a brief analysis of the ongoing research in the colon cancer area using the combinatorial nanomedicines and its outcome. © 2015 Wiley Periodicals, Inc.</p>

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2015

Journal Article

S. Narayanan, Dr. Ullas Mony, Vijaykumar, D. K., Dr. Manzoor K., Dr. Bindhu Paul, and Dr. Deepthy Menon, “Sequential release of epigallocatechin gallate and paclitaxel from PLGA-casein core/shell nanoparticles sensitizes drug-resistant breast cancer cells”, Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 11, pp. 1399-1406, 2015.[Abstract]


Nanomedicines consisting of combinations of cytotoxic drugs and molecular targeted therapeutics which inhibit specific downstream signals are evolving as a novel paradigm for breast cancer therapy. This research addresses one such combination of Paclitaxel (Ptx), having several adversities related to the activation of NF-κB pathway, with Epigallocatechin gallate (EGCG), a multiple signaling inhibitor, encapsulated within a targeted core/shell PLGA-Casein nanoparticle. The sequential release of EGCG followed by Ptx from this core/shell nanocarrier sensitized Ptx resistant MDA-MB-231 cells to Ptx, induced their apoptosis, inhibited NF-κB activation and downregulated the key genes associated with angiogenesis, tumor metastasis and survival. More importantly, Ptx-induced expression of P-glycoprotein was repressed by the nanocombination both at the protein and gene levels. This combination also offered significant cytotoxic response on breast cancer primary cells, indicating its translational value. From the Clinical Editor: Breast cancer is the most common cancer in women worldwide. As well as surgery, chemotherapy plays a major role in the treatment of breast cancer. The authors investigated in this article the combination use of a chemotherapeutic agent, Paclitaxel (Ptx), and an inhibitor of NF-?B pathway, packaged in a targeted nano-based delivery platform. The positive results provided a new pathway for future clinical use of combination chemotherapy in breast cancer. © 2015 Elsevier Inc.

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2015

Journal Article

M. G. Sangeet Nair, Dr. Ullas Mony, Dr. Deepthy Menon, Dr. Manzoor K., Sidharthan, N., Pavithran, K., Shantikumar V Nair, and Krishnakumar N. Menon, “Development and molecular characterization of polymeric micro-nanofibrous scaffold of a defined 3-D niche for in vitro chemosensitivity analysis against acute myeloid leukemia cells”, International journal of nanomedicine, 2015.[Abstract]


Standard in vitro drug testing employs 2-D tissue culture plate systems to test anti-leukemic drugs against cell adhesion-mediated drug-resistant leukemic cells that harbor in 3-D bone marrow microenvironments. This drawback necessitates the fabrication of 3-D scaffolds that have cell adhesion-mediated drug-resistant properties similar to in vivo niches. We therefore aimed at exploiting the known property of polyurethane (PU)/poly-L-lactic acid (PLLA) in forming a micro-nanofibrous structure to fabricate unique, not presented before, as far as we are aware, 3-D micro-nanofibrous scaffold composites using a thermally induced phase separation technique. Among the different combinations of PU/PLLA composites generated, the unique PU/PLLA 60:40 composite displayed micro-nanofibrous morphology similar to decellularized bone marrow with increased protein and fibronectin adsorption. Culturing of acute myeloid leukemia (AML) KG1a cells in FN-coated PU/PLLA 60:40 shows increased cell adhesion and cell adhesion-mediated drug resistance to the drugs cytarabine and daunorubicin without changing the original CD34(+)/CD38(-)/CD33(-) phenotype for 168 hours compared to fibronectin tissue culture plate systems. Molecularly, as seen in vivo, increased chemoresistance is associated with the upregulation of anti-apoptotic Bcl2 and the cell cycle regulatory protein p27(Kip1) leading to cell growth arrest. Abrogation of Bcl2 activity by the Bcl2-specific inhibitor ABT 737 led to cell death in the presence of both cytarabine and daunorubicin, demonstrating that the cell adhesion-mediated drug resistance induced by Bcl2 and p27(Kip1) in the scaffold was similar to that seen in vivo. These results thus show the utility of a platform technology, wherein drug testing can be performed before administering to patients without the necessity for stromal cells.

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2015

Journal Article

S. BN, Dr. Ullas Mony, Dr. Deepthy Menon, VK, B., AG, M., and Shantikumar V Nair, “Bone Tissue Engineering with Multilayered Scaffolds-Part I: An Approach for Vascularizing Engineered Constructs In Vivo.”, Tissue Eng Part A., pp. 19-20, 2015.[Abstract]


Obtaining functional capillaries through the bulk has been identified as a major challenge in tissue engineering, particularly for critical-sized defects. In the present study, a multilayered scaffold system was developed for bone tissue regeneration, designed for through-the-thickness vascularization of the construct. The basic principle of this approach was to alternately layer mesenchymal stem cell-seeded nanofibers (osteogenic layer) with microfibers or porous ceramics (osteoconductive layer), with an intercalating angiogenic zone between the two and with each individual layer in the microscale dimension (100-400 μm). Such a design can create a scaffold system potentially capable of spatially distributed vascularization in the overall bulk tissue. In the cellular approach, the angiogenic zone consisted of collagen/fibronectin gel with endothelial cells and pericytes, while in the acellular approach, cells were omitted from the zone without altering the gel composition. The cells incorporated into the construct were analyzed for viability, distribution, and organization of cells on the layers and vessel development in vitro. Furthermore, the layered constructs were implanted in the subcutaneous space of nude mice and the processes of vascularization and bone tissue regeneration were followed by histological and energy-dispersive X-ray spectroscopy (EDS) analysis. The results indicated that the microenvironment in the angiogenic zone, microscale size of the layers, and the continuously channeled architecture at the interface were adequate for infiltrating host vessels through the bulk and vascularizing the construct. Through-the-thickness vascularization and mineralization were accomplished in the construct, suggesting that a suitably bioengineered layered construct may be a useful design for regeneration of large bone defects.

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2013

Journal Article

N. S. Binulal, Natarajan, A., Dr. Deepthy Menon, Bhaskaran, V. K., Dr. Ullas Mony, and Shantikumar V Nair, “PCL-gelatin composite nanofibers electrospun using diluted acetic acid-ethyl acetate solvent system for stem cell-based bone tissue engineering”, Journal of Biomaterials Science, Polymer Edition, vol. 25, no. 4, 2013.[Abstract]


Composite nanofibrous scaffolds with various poly(ε-caprolactone) (PCL)/gelatin ratios (90:10, 80:20, 70:30, 60:40, 50:50 wt.%) were successfully electrospun using diluted acetic and ethyl acetate mixture. The effects of this solvent system on the solution properties of the composites and its electrospinning properties were investigated. Viscosity and conductivity of the solutions, with the addition of gelatin, allowed for the electrospinning of uniform nanofibers with increasing hydrophilicity and degradation. Composite nanofibers containing 30 and 40 wt.% gelatin showed an optimum combination of hydrophilicity and degradability and also maintained the structural integrity of the scaffold. Human mesenchymal stem cells (hMSCs) showed favorable interaction with and proliferation on, the composite scaffolds. hMSC proliferation was highest in the 30 and 40 wt.% gelatin containing composites. Our experimental data suggested that PCL-gelatin composite nanofibers containing 30-40 wt.% of gelatin and electrospun in diluted acetic acid-ethyl acetate mixture produced nanofiber scaffolds with optimum hydrophilicity, degradability, and bio-functionality for stem cell-based bone tissue engineering.

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2013

Journal Article

R. Nadesh, Narayanan, D., P.r., S., Vadakumpully, S., Dr. Ullas Mony, Koyakkutty, M., Shantikumar V Nair, and Dr. Deepthy Menon, “Hematotoxicological analysis of surface-modified and -unmodified chitosan nanoparticles”, Journal of Biomedical Materials Research - Part A, vol. 101, pp. 2957-2966, 2013.[Abstract]


The increasing interest in using chitosan nanoparticles for controlled drug delivery is hampered by its blood incompatibility, especially for intravenous applications. This study investigated the effects of processing solvents (acetic acid/lactic acid), dispersing media (acidic medium/saline), and surface modifiers (polyethylene glycol, polyvinyl alcohol, and ethylenediaminetetraacetatic acid) on the hemocompatibility of chitosan. Blood compatibility of chitosan nanoparticles prepared by ionotropic gelation with altered surface chemistry was evaluated by assessing their hemolytic activity, platelet aggregation, coagulation, and cytokine induction. It was observed that nanoparticles prepared in lactic acid and dispersed in saline did not show hemolysis, platelet aggregation, or coagulation, whereas nanoparticles prepared in acetic acid showed strong hemolysis. Surface modifiers were not observed to significantly affect blood compatibility, with the exception of EDTA, which delayed blood clotting times. Thus, chitosan nanoparticles prepared in lactic acid and dispersed in saline may be an ideal nanocarrier for parenteral applications. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A:2957-2966, 2013. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

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2012

Journal Article

N. S. Binulal, Natarajan, A., Menon, D., Bhaskaran, V. K., Dr. Ullas Mony, and Nair, S. V., “Gelatin nanoparticles loaded poly(€-caprolactone) nanofibrous semi-synthetic scaffolds for bone tissue engineering”, Biomedical Materials (Bristol), vol. 7, 2012.[Abstract]


Nanofibrous semi-synthetic polymeric nanocomposite scaffolds were engineered by incorporating a maximum of 15 wt% biopolymeric gelatin nanoparticles (nGs) into the synthetic polymer poly(€-caprolactone) (PCL) prior to electrospinning. The effect of nGs in altering the physico-chemical properties, cell material interaction and biodegradability of the scaffolds was evaluated. Experimental results showed that the inherent hydrophobicity of PCL scaffolds remained unaltered even after the incorporation of hydrophilic nGs. However, breakdown of the continuous nanofibers into lengths less than 7 νm occurred within four to eight weeks in the presence of nGs in contrast with the greater than two year time frame for the degradation of PCL fibers alone that is known from the literature. In terms of cell-material interaction, human mesenchymal stem cells (hMSCs) were found to attach and spread better and faster on PCL-nG scaffolds compared to PCL scaffolds. However, there was no difference in hMSC proliferation and differentiation into osteogenic lineage between the scaffolds. These results indicate that PCL-nG nanofibrous nanocomposite scaffolds are an improvement over PCL scaffolds for bone tissue engineering applications in that the PCL-nG scaffolds provide improved cell interaction and are able to degrade and resorb more efficiently. © 2012 IOP Publishing Ltd.

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2012

Journal Article

N. Ganesh, Dr. Jayakumar Rangasamy, Koyakutty, M., Dr. Ullas Mony, and Nair, S. V., “Embedded silica nanoparticles in poly(caprolactone) nanofibrous scaffolds enhanced osteogenic potential for bone tissue engineering”, Tissue Engineering - Part A, vol. 18, pp. 1867-1881, 2012.[Abstract]


Poly(caprolactone) (PCL) has been frequently considered for bone tissue engineering because of its excellent biocompatibility. A drawback, however, of PCL is its inadequate mechanical strength for bone tissue engineering and its inadequate bioactivity to promote bone tissue regeneration from mesenchymal stem cells. To correct this deficiency, this work investigates the addition of nanoparticles of silica (nSiO2) to the scaffold to take advantage of the known bioactivity of silica as an osteogenic material and also to improve the mechanical properties through nanoscale reinforcement of the PCL fibers. The nanocomposite scaffolds and the pristine PCL scaffolds were evaluated physicochemically, mechanically, and biologically in the presence of human mesenchymal stem cells (hMSCs). The results indicated that, when the nanoparticles of size approximately 10 nm (concentrations of 0.5% and 1% w/v) were embedded within, or attached to, the PCL nanofibers, there was a substantial increase in scaffold strength, protein adsorption, and osteogenic differentiation of hMSCs. These nSiO2 nanoparticles, when directly added to the cells evidently pointed to ingestion of these particles by the cells followed by cell death. The polymer nanofibers appeared to protect the cells by preventing ingestion of the silica nanoparticles, while at the same time adequately exposing them on fiber surfaces for their desired bioactivity. © Copyright 2012, Mary Ann Liebert, Inc.

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2012

Journal Article

G. Nitya, Nair, G. T., Dr. Ullas Mony, Chennazhi, K. P., and Nair, S. V., “In vitro evaluation of electrospun PCL/nanoclay composite scaffold for bone tissue engineering”, Journal of Materials Science: Materials in Medicine, vol. 23, pp. 1749-1761, 2012.[Abstract]


Polycaprolactone (PCL) is a widely accepted synthetic biodegradable polymer for tissue engineering, however its use in hard tissue engineering is limited because of its inadequate mechanical strength and low bioactivity. In this study, we used halloysite nanoclay (NC) as an inorganic filler material to prepare PCL/NC fibrous scaffolds via electrospinning technique after intercalating NC within PCL by solution intercalation method. The obtained nanofibrous mat was found to be mechanically superior to PCL fibrous scaffolds. These scaffolds allowed greater protein adsorption and enhanced mineralization when incubated in simulated body fluid. Moreover, our results indicated that human mesenchymal stem cells (hMSCs) seeded on these scaffolds were viable and could proliferate faster than in PCL scaffolds as confirmed by fluorescence and scanning electron microscopic observations. Further, osteogenic differentiation of hMSCs on nanoclay embedded scaffolds was demonstrated by an increase in alkaline phosphatase activity when compared to PCL scaffold without nanoclay. All of these results suggest the potential of PCL/NC scaffolds for bone tissue engineering. © Springer Science+Business Media, LLC 2012.

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2012

Journal Article

S. Narayanan, Sathy, B. N., Dr. Ullas Mony, Koyakutty, M., Nair, S. V., and Menon, D., “Biocompatible magnetite/gold nanohybrid contrast agents via green chemistry for MRI and CT bioimaging”, ACS Applied Materials and Interfaces, vol. 4, pp. 251-260, 2012.[Abstract]


Magnetite/gold (Fe 3O 4/Au) hybrid nanoparticles were synthesized from a single iron precursor (ferric chloride) through a green chemistry route using grape seed proanthocyanidin as the reducing agent. Structural and physicochemical characterization proved the nanohybrid to be crystalline, with spherical morphology and size ∼35 nm. Magnetic resonance imaging and magnetization studies revealed that the Fe 3O 4 component of the hybrid provided superparamagnetism, with dark T 2 contrast and high relaxivity (124.2 ± 3.02 mM -1 s -1). Phantom computed tomographic imaging demonstrated good X-ray contrast, which can be attributed to the presence of the nanogold component in the hybrid. Considering the potential application of this bimodal nanoconstruct for stem cell tracking and imaging, we have conducted compatibility studies on human Mesenchymal Stem Cells (hMSCs), wherein cell viability, apoptosis, and intracellular reactive oxygen species (ROS) generation due to the particle-cell interaction were asessed. It was noted that the material showed good biocompatibility even for high concentrations of 500 μg/mL and up to 48 h incubation, with no apoptotic signals or ROS generation. Cellular uptake of the nanomaterial was visualized using confocal microscopy and prussian blue staining. The presence of the nanohybrids were clearly visualized in the intracytoplasmic region of the cell, which is desirable for efficient imaging of stem cells in addition to the cytocompatible nature of the hybrids. Our work is a good demonstrative example of the use of green aqueous chemistry through the employment of phytochemicals for the room temperature synthesis of complex hybrid nanomaterials with multimodal functionalities. © 2011 American Chemical Society.

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2012

Journal Article

S. L, Z, Y., and Dr. Ullas Mony, “Biomaterials for periodontal regeneration: a review of ceramics and polymers”, Biomatter., vol. 2, no. 4, pp. 271-7, 2012.[Abstract]


Periodontal disease is characterized by the destruction of periodontal tissues. Various methods of regenerative periodontal therapy, including the use of barrier membranes, bone replacement grafts, growth factors and the combination of these procedures have been investigated. The development of biomaterials for tissue engineering has considerably improved the available treatment options above. They fall into two broad classes: ceramics and polymers. The available ceramic-based materials include calcium phosphate (eg, tricalcium phosphate and hydroxyapatite), calcium sulfate and bioactive glass. The bioactive glass bonds to the bone with the formation of a layer of carbonated hydroxyapatite in situ. The natural polymers include modified polysaccharides (eg, chitosan,) and polypeptides (collagen and gelatin). Synthetic polymers [eg, poly(glycolic acid), poly(L-lactic acid)] provide a platform for exhibiting the biomechanical properties of scaffolds in tissue engineering. The materials usually work as osteogenic, osteoconductive and osteoinductive scaffolds. Polymers are more widely used as a barrier material in guided tissue regeneration (GTR). They are shown to exclude epithelial downgrowth and allow periodontal ligament and alveolar bone cells to repopulate the defect. An attempt to overcome the problems related to a collapse of the barrier membrane in GTR or epithelial downgrowth is the use of a combination of barrier membranes and grafting materials. This article reviews various biomaterials including scaffolds and membranes used for periodontal treatment and their impacts on the experimental or clinical management of periodontal defect.

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2011

Journal Article

A. Retnakumari, Jayasimhan, J., Chandran, P., Menon, D., Nair, S., Dr. Ullas Mony, and Koyakutty, M., “CD33 monoclonal antibody conjugated Au cluster nano-bioprobe for targeted flow-cytometric detection of acute myeloid leukaemia”, Nanotechnology, vol. 22, 2011.[Abstract]


Protein stabilized gold nanoclusters (Au-NCs) are biocompatible, near-infrared (NIR) emitting nanosystems having a wide range of biomedical applications. Here, we report the development of a Au-NC based targeted fluorescent nano-bioprobe for the flow-cytometric detection of acute myeloid leukaemia (AML) cells. Au-NCs with ∼ 25-28 atoms showing bright red-NIR fluorescence (600-750nm) and average size of ∼ 0.8nm were prepared by bovine serum albumin assisted reduction-cum-stabilization in aqueous phase. The protein protected clusters were conjugated with monoclonal antibody against CD33 myeloid antigen, which is overexpressed in ∼ 99.2% of the primitive population of AML cells, as confirmed by immunophenotyping using flow cytometry. Au-NC-CD33 conjugates having average size of ∼ 12nm retained bright fluorescence over an extended duration of ∼ a year, as the albumin protein protects Au-NCs against degradation. Nanotoxicity studies revealed excellent biocompatibility of Au-NC conjugates, as they showed no adverse effect on the cell viability and inflammatory response. Target specificity of the conjugates for detecting CD33 expressing AML cells (KG1a) in flow cytometry showed specific staining of ∼ 95.4% of leukaemia cells within 1-2h compared to a non-specific uptake of ∼ 8.2% in human peripheral blood cells (PBMCs) which are CD33low. The confocal imaging also demonstrated the targeted uptake of CD33 conjugated Au-NCs by leukaemia cells, thus confirming the flow cytometry results. This study demonstrates that novel nano-bioprobes can be developed using protein protected fluorescent nanoclusters of Au for the molecular receptor targeted flow cytometry based detection and imaging of cancer cells. © 2011 IOP Publishing Ltd. More »»

2010

Journal Article

S. Narayanan, Binulal, N. S., Dr. Ullas Mony, Manzoor, K., Nair, S., and Menon, D., “Folate targeted polymeric 'green' nanotherapy for cancer”, Nanotechnology, vol. 21, 2010.[Abstract]


The concept of 'green' chemotherapy by employing targeted nanoparticle mediated delivery to enhance the efficacy of phytomedicines is reported. Poly (lactide-co-glycolide) (PLGA) nanoparticles encapsulating a well known nutraceutical namely, grape seed extract (GSE) - 'NanoGSE' - was prepared by a nanoprecipitation technique. The drug-loaded nanoparticles of size ∼ 100nm exhibited high colloidal stability at physiological pH. Molecular receptor targeting of this nanophytomedicine against folate receptor over-expressing cancers was demonstrated invitro by conjugation with a potential cancer targeting ligand, folic acid (FA). Fluorescence microscopy and flow cytometry data showed highly specific cellular uptake of FA conjugated NanoGSE on folate receptor positive cancer cells. Studies were also conducted to investigate the efficiency of targeted (FA conjugated) versus non-targeted (non-FA conjugated) nanoformulations in causing cancer cell death. The IC50 values were lowered by a factor of ∼ 3for FA-NanoGSE compared to the free drug, indicating substantially enhanced bioavailability to the tumor cells, sparing the normal ones. Receptor targeting of FA-NanoGSE resulted in a significant increase in apoptotic index, which was also quantified by flow cytometry and fluorescence microscopy. This invitro study provides a basis for the use of nanoparticle mediated delivery of anticancer nutraceuticals to enhance bioavailability and effectively target cancer by a 'green' approach. © 2010 IOP Publishing Ltd. More »»

2010

Journal Article

N. S. Binulal, Deepthy, M., Selvamurugan, N., Shalumon, K. T., Suja, S., Dr. Ullas Mony, Dr. Jayakumar Rangasamy, and Nair, S. V., “Role of nanofibrous poly(caprolactone) scaffolds in human mesenchymal stem cell attachment and spreading for in vitro bone tissue engineering-response to osteogenic regulators”, Tissue Engineering - Part A, vol. 16, pp. 393-404, 2010.[Abstract]


In this study, we evaluated the role of fiber size scale in the adhesion and spreading potential of human mesenchymal stem cells (hMSCs) on electrospun poly(caprolactone) (PCL) nanofibrous and microfibrous scaffolds. The effect of in vivo regulators in inducing osteogenic differentiation of hMSCs on PCL nanofibrous scaffolds was investigated using osteogenic differentiation marker gene expression and matrix mineralization. Here, we report for the first time the influence of in vivo regulators in an in vitro setting with hMSCs for bone tissue engineering on PCL nanofibrous matrices. Our results indicated that hMSCs attached and spread rapidly on nanofibrous scaffolds in comparison to microfibrous PCL. Further, hMSCs proliferated well on the nanofibrous scaffolds. The cells on the nanofibrous PCL were found to differentiate into the osteoblast lineage and subsequently mineralize upon addition of in vivo osteogenic regulators. The attachment and spreading of hMSCs were more effective on the nanofibers compared with the microfibers despite the lower protein surface coverage (total adsorbed protein per unit fiber surface area) on nanofibers. Copyright 2010, Mary Ann Liebert, Inc. More »»

2009

Journal Article

C. M. Girish, Binulal, N. S., Anitha, V. C., Nair, S., Dr. Ullas Mony, and Prasanth, R., “Atomic force microscopic study of folate receptors in live cells with functionalized tips”, Applied Physics Letters, vol. 95, 2009.[Abstract]


Membrane associated folate receptors (FR) is gaining importance in cancer research. Understanding the FR density, distribution, and the strength of its interaction with ligands is crucial in cancer diagnostics and therapeutics. Here we reported the enhanced phase contrast image of FR by scanning with properly functionalized atomic force microscope (AFM) tips over live cell lines. The choice of the ligand was made for better interaction of tip with FR, expressed in the cell lines. The selectively enhanced force of interaction at the receptor molecule produced a considerable enhancement in the phase contrast between a receptor site and a nonreceptor site. © 2009 American Institute of Physics. More »»

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