Browsing by Author "Mohan, N"
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Item A 3D biodegradable protein based matrix for cartilage tissue engineering and stem cell differentiation to cartilage(JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, 2009) Mohan, N; Nair, PD; Tabata, YA protein based 3D porous scaffold is fabricated by blending gelatin and albumin. The biomimetic biodegradable gelatin, promoted good cell adhesion and its hydrophilic nature enabled absorption of culture media. Albumin is proposed to serve as a nontoxic foaming agent and also helped to attain a hydrophobic-hydrophilic balance. The hydrophobic-hydrophilic balance and appropriate crosslinking of the scaffold avoided extensive swelling, as well as retained the stability of scaffold in culture medium for long period. The scaffold is found to be highly porous with open interconnected pores. The adequate swelling and mechanical property of the scaffold helped to withstand the loads imparted by the cells during in vitro culture. The scaffold served as a nontoxic material to monolayer of fibroblast cells and is found to be cell compatible. The suitability of scaffold for chondrocyte culture and stem cell differentiation to chondrocytes is further explored in this work. The scaffold provided appropriate environment for chondrocyte culture, resulting in deposition of cartilage specific matrix molecules that completely masked the pores of the porous scaffold. The scaffold promoted the proliferation and differentiation of mesenchymal stem cells to chondrocytes in presence of growth factors. The transforming growth factor, TGF beta 3 promoted better chondrogenic differentiation than its isoform TGF beta 1 in this scaffold.Item A 3D biodegradable protein based matrix for cartilage tissue engineering and stem cell differentiation to cartilage (vol 20, pg 49, 2009)(JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, 2014) Mohan, N; Nair, PD; Tabata, YItem Biomimetic fiber assembled gradient hydrogel to engineer glycosaminoglycan enriched and mineralized cartilage: An in vitro study(JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 2015) Mohan, N; Wilson, JJ; Joseph, D; Vaikkath, D; Nair, PDThe study investigated the potential of electrospun fiber assembled hydrogel, with physical gradients of chondroitin sulfate (CS) and sol-gel-derived bioactive glass (BG), to engineer hyaline and mineralized cartilage in a single 3D system. Electrospun poly(caprolactone) (PCL) fibers incorporated with 0.1% w/w of CS (CSL) and 0.5% w/w of CS (CSH), 2.4% w/w of BG (BGL) and 12.5% w/w of BG (BGH) were fabricated. The CS showed a sustained release up to 3 days from CSL and 14 days from CSH fibers. Chondrocytes secreted hyaline like matrix with higher sulfated glycosaminoglycans (sGAG), collagen type II and aggrecan on CSL and CSH fibers. Mineralization was observed on BGL and BGH fibers when incubated in simulated body fluid for 14 days. Chondrocytes cultured on these fibers secreted a mineralized matrix that consisted of sGAG, hypertrophic proteins, collagen type X, and osteocalcin. The CS and BG incorporated PCL fiber mats were assembled in an agarose-gelatin hydrogel to generate a 3D hybrid scaffold. The signals in the fibers diffused and generated continuous opposing gradients of CS (chondrogenic signal) and BG (mineralization) in the hydrogel. The chondrocytes were encapsulated in hybrid scaffolds; live dead assay at 48 h showed viable cells. Cells maintained their phenotype and secreted specific extracellular matrix (ECM) in response to signals within the hydrogel. Continuous opposing gradients of sGAG enriched and mineralized ECM were observed surrounding each cell clusters on gradient hydrogel after 14 days of culture in response to the physical gradients of raw materials CS and BG. A construct with gradient mineralization might accelerate integration to subchondral bone during in vivo regeneration. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3896-3906, 2015.Item Copper(ii) salen-based complexes as potential anticancer agents(New Journal of Chemistry, 2022-05) Mohan, N; Vidya, CV; Vasudevan, S; Jimna, MA; Kasoju, N; Mohanan, PV; Sreejith, SS; Prathapachandra Kurup, MRIn this work, we have systematically designed and synthesized four Cu(II) salen compounds (1–4), which have been characterized using various spectroscopic and analytical techniques. Single-crystal XRD studies were carried out on three of the compounds (1, 2 and 4), which revealed that all of them have a water molecule encapsulated/pseudo-encapsulated in the N2O4 cavity. The binding affinity of the complexes with calf thymus DNA (CT-DNA) was explored using UV-visible and fluorescence techniques. The compounds exhibit excellent DNA binding and cleavage activities. The binding mechanism was probed by molecular docking studies. These results display high binding-constant values owing to the intercalative type of binding. In addition, the binding affinity of the compounds with proteins was also studied via an in silico molecular-docking method using human serum albumin as the receptor. The in vitro cytotoxic effect of the complexes was evaluated in the HeLa cell line, derived from cervical cancer cells. The cleavage of DNA strands was investigated using gel electrophoresis. All of the tested compounds show a high binding-constant value with both DNA and protein and exhibit cytotoxic effects towards cancerous cells. The observed toxicity of these compounds towards a normal cell line could be minimized via interaction of the metal centre with the detoxifier glutathione, and detoxification studies were also conducted. The synthesized compounds were found to be potential candidates for the pharmaceutical industry. Considering the results and compared with existing reports, we propose a promising candidate (compound 4) for the development of efficient therapeutic drugs.Item Hybrid scaffold bearing polymer-siloxane Schiff base linkage for bone tissue engineering(MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS, 2015) Nair, BP; Gangadharan, D; Mohan, N; Sumathi, B; Nair, PDScaffolds that can provide the requisite biological cues for the fast regeneration of bone are highly relevant to the advances in tissue engineering and regenerative medicine. In the present article, we report the fabrication of a chitosan-gelatin-siloxane scaffold bearing interpolymer-siloxane Schiff base linkage, through a single-step dialdehyde cross-linking and freeze-drying method using 3-aminopropyltriethoxysilane as the siloxane precursor. Swelling of the scaffolds in phosphate buffered saline indicates enhancement with increase in siloxane concentration, whereas compressive moduli of the wet scaffolds reveal inverse dependence, owing to the presence of siloxane, rich in silanol groups. It is suggested that through the strategy of dialdehyde cross-linking, a limiting siloxane loading of 20 wt.% into a chitosan -gelatin matrix should be considered ideal for bone tissue engineering, because the scaffold made with 30 wt.% siloxane loading degrades by 48 wt.%, in 21 days. The hybrid scaffolds bearing Schiff base linkage between the polymer and siloxane, unlike the stable linkages in earlier reports, are expected to give a faster release of siloxanes and enhancement in osteogenesis. This is verified by the in vitro evaluation of the hybrid scaffolds using rabbit adipose mesenchymal stem cells, which revealed osteogenic cell-clusters on a polymer-siloxane scaffold, enhanced alkaline phosphatase activity and the expression of bone-specific genes, whereas the control scaffold without siloxane supported more of cell-proliferation than differentiation. A siloxane concentration dependent enhancement in osteogenic differentiation is also observed. (C) 2015 Elsevier B.V. All rights reserved.Item Hydroxyapatite scaffolds constituting highly oriented crystals derived from synthetic precursors by hydrothermal reactions(CERAMICS INTERNATIONAL, 2016) Mohan, N; Palangadan, R; Varma, HA series of hydroxyapatite scaffolds having oriented crystal morphologies were fabricated through hydrothermal exchange reactions of tri calcium phosphate porous precursors in different solutions by the regulation of reaction parameters. The newly developed scaffolds have unique crystal morphologies and a preferred orientation with hybrid micro and nano dimensional structures such as fibres, rods, tubes and flowers. These crystals of apatite grow in the a(b)-plane of the hydroxyapatite lattice with orientation along the c-axis. The developed scaffolds were subjected to in vitro bioactivity evaluation in simulated body fluid (SBF). Physicochemical characterisation of the materials were performed by scanning electron microscopy, X-ray diffraction and fourier transform infra-red spectroscopy. This study shows the transformation of a lower calcium phosphate material to a fast resorbing hydroxyapatite scaffold with a preferred orientation along the c-axis and a higher aspect ratio of crystals which is intended for use in the field of dentistry and orthopaedics as a scaffold for tissue regeneration. (C) 2016 Elsevier Ltd and Techna Group S.r.l. All rights reserved.Item Material characterization of microsphere-based scaffolds with encapsulated raw materials(MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS, 2016) Sridharan, B; Mohan, N; Berkland, CJ; Detamore, MSRaw materials, or materials capable of serving both as building blocks and as signals, which are often but not always natural materials, are taking center stage in biomaterials for contemporary regenerative medicine. In osteochondral tissue engineering, a field leveraging the underlying bone to facilitate cartilage regeneration, common raw materials include chondroitin sulfate (CS) for cartilage and p-tricalcium phosphate (TCP) for bone. Building on our previous work with gradient scaffolds based on microspheres, here we delved deeper into the characterization of individual components. In the current study, the release of CS and TCP from poly(D,L-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds was evaluated over a time period of 4 weeks. Raw material encapsulated groups were compared to 'blank' groups and evaluated for surface topology, molecular weight, and mechanical performance as a function of time. The CS group may have led to increased surface porosity, and the addition of CS improved the mechanical performance of the scaffold. The finding that CS was completely released into the surrounding media by 4 weeks has a significant impact on future in vivo studies, given rapid bioavailability. The addition of TCP seemed to contribute to the rough external appearance of the scaffold. The current study provides an introduction to degradation patterns of homogenous raw material encapsulated scaffolds, providing characterization data to advance the field of microsphere-based scaffolds in tissue engineering. (C) 2016 Elsevier B.V. All rights reserved.Item Microsphere-based gradient implants for osteochondral regeneration: a long-term study in sheep(REGENERATIVE MEDICINE, 2015) Mohan, N; Gupta, V; Sridharan, BP; Mellott, AJ; Easley, JT; Palmer, RH; Galbraith, RA; Key, VH; Berkland, CJ; Detamore, MSBackground: The microfracture technique for cartilage repair has limited ability to regenerate hyaline cartilage. Aim: The current study made a direct comparison between microfracture and an osteochondral approach with microsphere-based gradient plugs. Materials & methods: The PLGA-based scaffolds had opposing gradients of chondroitin sulfate and beta-tricalcium phosphate. A 1-year repair study in sheep was conducted. Results: The repair tissues in the microfracture were mostly fibrous and had scattered fissures with degenerative changes. Cartilage regenerated with the gradient plugs had equal or superior mechanical properties; had lacunated cells and stable matrix as in hyaline cartilage. Conclusion: This first report of gradient scaffolds in a long-term, large animal, osteochondral defect demonstrated potential for equal or better cartilage repair than microfracture.Item The potential of encapsulating “raw materials” in 3D osteochondral gradient scaffolds.(Biotechnology Bioengineering. 2013,, 2013-12) Mohan, N; Gupta, V; Sridharan, BP; Sutherland, A; Detamore, MSItem Pulsed laser deposition of hydroxyapatite on nanostructured titanium towards drug eluting implants(Materials Science and Engineering: C. 2013, 2013-04) Rajesh, P; Mohan, N; Yokogawa, Y; Varma, HKItem The Potential of Encapsulating "Raw Materials'' in 3D Osteochondral Gradient Scaffolds(BIOTECHNOLOGY AND BIOENGINEERING, 2014) Mohan, N; Gupta, V; Sridharan, B; Sutherland, A; Detamore, MSScaffolds with continuous gradients in material composition and bioactive signals enable a smooth transition of properties at the interface. Components like chondroitin sulfate (CS) and bioactive glass (BG) in 3D scaffolds may serve as raw materials for synthesis of new extracellular matrix (ECM), and may have the potential to completely or partially replace expensive growth factors. We hypothesized that scaffolds with gradients of ECM components would enable superior performance of engineered constructs. Raw material encapsulation altered the appearance, structure, porosity, and degradation of the scaffolds. They allowed the scaffolds to better retain their 3D structure during culture and provided a buffering effect to the cells in culture. Following seeding of rat mesenchymal stem cells, there were several instances where glycosaminoglycan (GAG), collagen, or calcium contents were higher with the scaffolds containing raw materials (CS or BG) than with those containing transforming growth factor (TGF)-3 or bone morphogenetic protein (BMP)-2. It was also noteworthy that a combination of both CS and TGF-3 increased the secretion of collagen type II. Moreover, cells seeded in scaffolds containing opposing gradients of CS/TGF-3 and BG/BMP-2 produced clear regional variations in the secretion of tissue-specific ECM. The study demonstrated raw materials have the potential to create a favorable microenvironment for cells; they can significantly enhance the synthesis of certain extracellular matrix (ECM) components when compared to expensive growth factors; either alone or in combination with growth factors they can enhance the secretion of tissue specific matrix proteins. Raw materials are promising candidates that can be used to either replace or be used in combination with growth factors. Success with raw materials in lieu of growth factors could have profound implications in terms of lower cost and faster regulatory approval for more rapid translation of regenerative medicine products to the clinic. Biotechnol. Bioeng. 2014;111: 829-841. (c) 2013 Wiley Periodicals, Inc.