Browsing by Author "Varma, HK"

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    A functional hydrogel for regeneration of nucleus pulposus
    (JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, 2014) Roudmiane, MM; Babu, S; Varma, HK; John, A
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    An in vitro study on the interaction of hydroxyapatite nanoparticles and bone marrow mesenchymal stem cells for assessing the toxicological behaviour
    (COLLOIDS AND SURFACES B-BIOINTERFACES, 2014) Remya, NS; Syama, S; Gayathri, V; Varma, HK; Mohanan, PV
    Mesenchymal stem cells or multipotent progenitor cells isolated from bone marrow presents close resemblance to the natural in vivo milieu and hence preferred more than the conventional cell culture systems to predict the toxicological behavior of bio-nano interaction. The objective of the present study is to evaluate the molecular toxicity of hydroxyapatite nanoparticles (HANPs) using mouse bone marrow mesenchymal stem cells (BMSCs). In-house synthesized HANPs (50 nm) were used to study the cytotoxicity, nano particle uptake, effect on cyto skeletal arrangement, oxidative stress response and apoptotic behavior with the confluent BMSCs as per standard protocols. The results of the MIT assay indicated that HANPs does not induce cytotoxicity up to 800 mu g/mL. It was also observed that oxidative stress related apoptosis and reactive oxygen species (ROS) production following nanoparticle treatment was similar to that of control (cells without treatment). Hence it can be concluded that the in-house synthesized HANPs are non-toxic/safe at the molecular level suggesting that the HANPs are compatible to BMSCs. Further, the in vitro BMSCs cell culture can be used as a model for evaluating the preliminary toxicity of nanomaterials. (C) 2014 Elsevier B.V. All rights reserved.
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    An aqueous method for the controlled manganese (Mn2+) substitution in superparamagnetic iron oxide nanoparticle for contrast enhancement in MRI
    (Physical Chemistry Chemical Physics., 2015-01) Beerana, AE; Nazeerb, SS; Fernandezc, FB; Muvvala, KS; Wunderlich, W; Anil, S; Vellappally, S; Rao, R; John A, A; Jayasree, RS; Varma, HK
    Despite the success in the use of superparamagnetic iron oxide nanoparticles (SPION) for various scientific applications, its potential in biomedical fields has not been exploited to its full potential. In this context, an in situ substitution of Mn2+ was performed in SPION and a series of ferrite particles, MnxFe1−xFe2O4 with a varying molar ratio of Mn2+ : Fe2+ where ‘x’ varies from 0–0.75. The ferrite particles obtained were further studied in MRI contrast applications and showed appreciable enhancement in their MRI contrast properties. Manganese substituted ferrite nanocrystals (MnIOs) were synthesized using a novel, one-step aqueous co-precipitation method based on the use of a combination of sodium hydroxide and trisodium citrate (TSC). This approach yielded the formation of highly crystalline, superparamagnetic MnIOs with good control over their size and bivalent Mn ion crystal substitution. The presence of a TSC hydrophilic layer on the surface facilitated easy dispersion of the materials in an aqueous media. Primary characterizations such as structural, chemical and magnetic properties demonstrated the successful formation of manganese substituted ferrite. More significantly, the MRI relaxivity of the MnIOs improved fourfold when compared to SPION crystals imparting high potential for use as an MRI contrast agent. Further, the cytocompatibility and blood compatibility evaluations demonstrated excellent cell morphological integrity even at high concentrations of nanoparticles supporting the non-toxic nature of nanoparticles. These results open new horizons for the design of biocompatible water dispersible ferrite nanoparticles with good relaxivity properties via a versatile and easily scalable co-precipitation route.
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    Assessment of hydroxyapatite nanoparticles induced oxidative stress- An in vitro study.
    (J Free Rad Antioxidants, 2014) Syama, S; Reshma, SC; Gayathri, V; Varma, HK; Mohanan, PV
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    Attenuation of Cisplatin Induced Toxicity by Melatonin, Loaded on a Dextran Modified Iron Oxide Nanoparticles: An In Vitro Study
    (J Forensic Toxicol Pharmacol, 2015-06) Shyma, MS; Ansar, EB; Gayathri, V; Varma, HK; Mohanan, PV
    Conjugation drug therapy of melatonin has emerged as a promising modality for reducing cisplatin (cis-diammine di chloro platinum (II) or cis-DDP or CDDP) induced toxicity. The objective of the present study is to determine the attenuation of cisplatin induced toxicity by Melatonin loaded on a Dextran modified Iron Oxide nanoparticles (DIO-M). The DIO-M was developed, characterized and analyzed. Loading of melatonin was confirmed by Fouriertransform infrared spectroscopy (FTIR). Particle size analysis was carried out using Dynamic Light Scattering (DLS) and Transmission Electron Microcope (TEM) techniques. Phase purity of crystals was determined by X-ray diffraction analysis (XRD) and the magnetic property of particle material was characterized by Vibrational sample magnetometry (VSM). Cytotoxicity studies using by MTT assay in L929 cell lines confirmed the melatonin nanoparticles to be nontoxic. The protective effect of DIO-M against cisplatin induced toxicity was confirmed by antioxidant parameters such as reduced glutathione, superoxide dismutase, and glutathione peroxidase and glutathione reductase. Free radical mediated cell damage was quantitatively determined by the measurement of malondialdehyde level. It was found that the inhibitory effect of malondialdehyde levels by DIO-M could be attributed to the increased activities of antioxidant enzymes (p<0.005). Splenocyte proliferation demonstrated that DIO-M has the ability to influence the spleen cells. Splenocytes when treated with cisplantin and DIO-M was able to overcome the antiproliferative property of cisplatin. Hence, these findings contribute with important insight that DIO-M can be useful for management of toxicity induced by anti-cancer drug cisplatin.
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    Biodegradation and cytocompatibility studies of a triphasic ceramic coated porous hydroxyapatite for bone substitute applications
    (International Journal of Applied Ceramic Technology, 2008) John, A; Nair, MB; Varma, HK; Bernhardt, A; Gelinsky, M
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    Biodegradation and cytocompatibility studies of a triphasic ceramic-coated porous hydroxyapatite for bone substitute applications
    (INTERNATIONAL JOURNAL OF APPLIED CERAMIC TECHNOLOGY, 2008) John, A; Nair, MB; Varma, HK; Bernhardt, A; Gelinsky, M
    Bone defects due to trauma or disease have led to the need for biomaterials as substitutes for tissue regeneration and repair. Herein, we introduce a porous triphasic ceramic-coated hydroxyapatite scaffold (HASi) for such applications. Interestingly, in the degradation experiments with isotonic buffer, HASi showed a significant release of silica with the disappearance of the tricalcium phosphate phase. Furthermore, the material also exhibited cytocompatibility with cultured bone marrow-derived mesenchymal stem cells of human origin. The material chemistry, together with the favorable cellular characteristics, indicates HASi as a promising candidate for critical-size bony defects, which still remains a formidable clinical challenge in the orthopedic scenario.
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    Biomimetic approaches with smart interfaces for bone regeneration
    (JOURNAL OF BIOMEDICAL SCIENCE, 2016) Sailaja, GS; Ramesh, P; Vellappally, S; Anil, S; Varma, HK
    A 'smart tissue interface' is a host tissue-biomaterial interface capable of triggering favourable biochemical events inspired by stimuli responsive mechanisms. In other words, biomaterial surface is instrumental in dictating the interface functionality. This review aims to investigate the fundamental and favourable requirements of a 'smart tissue interface' that can positively influence the degree of healing and promote bone tissue regeneration. A biomaterial surface when interacts synergistically with the dynamic extracellular matrix, the healing process become accelerated through development of a smart interface. The interface functionality relies equally on bound functional groups and conjugated molecules belonging to the biomaterial and the biological milieu it interacts with. The essential conditions for such a special biomimetic environment are discussed. We highlight the impending prospects of smart interfaces and trying to relate the design approaches as well as critical factors that determine species-specific functionality with special reference to bone tissue regeneration.
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    Biomimetic deposition of hydroxyapatite on titanium with help of sol-gel grown calcium pyrophosphate prelayer
    (MATERIALS RESEARCH INNOVATIONS, 2011) Sureshbabu, S; Komath, M; Shibli, SMA; Varma, HK
    The biomimetic method is a cost effective, low temperature route for coating hydroxyapatite on titanium bone implants so as to provide an osteointegrating interface. However, biomimetic coatings have the limitations of poor adhesion and lower growth rates. This work investigates the role of a prelayer of calcium pyrophosphate made through sol-gel technique in growing adherent and thick layer of biomimetic hydroxyapatite over titanium surface. Cleaned titanium substrates were dip coated in a calcium-phosphate-citrate sol and calcined at 650 degrees C to form an adherent calcium phosphate layer. These were then subjected to biomimetic processing in 1.5 simulated body fluid for 7-14 days. The prelayer and the biomimetic layer were analysed for micromorphology (using SEM) and chemical phase (using X-ray diffraction, Fourier transform infrared spectroscopy and energy dispersive X-ray spectroscopy). Thickness measurements were performed on an optical profilometer and the adhesion was assessed through a microcombi scratch tester. The prelayer showed petal-like morphology, whereas globular particles were seen in the biomimetic growth. The prelayer had a thickness of 3.6 mu m and was found to contain calcium pyrophosphate, with calcium titanate at the interface. The phase in the biomimetic layer was identified to be hydroxyapatite, with a growth rate of 5.3 mu m/day. The scratch test gave the delamination load for this layer to be 6.23 N. Results show that it is possible to obtain adherent hydroxyapatite layer on the titanium surface at a faster rate by combining the sol-gel coating and the biomimetic growth technique.
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    Bone growth response with porous hydroxyapatite granules in a critical sized lapine tibial-defect model
    (Bulletin of Materials Science., 2002) John, A; Abiraman, S; Varma, HK; Kumar, TV; Umashankar, PR
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    Can Iliac Crest Reconstruction Reduce Donor Site Morbidity? A Study Using Degradable Hydroxyapatite-bioactive Glass Ceramic Composite
    (JOURNAL OF SPINAL DISORDERS & TECHNIQUES, 2010) Acharya, NK; Mahajan, CV; Kumar, RJ; Varma, HK; Menon, VK
    Study Design: Prospective study. Objective: To prospectively validate the hypothesis that iliac crest donor site morbidity may be a structural issue and by reconstructing the crest its incidence might be reduced. The study also evaluates the efficacy of Chitra hydroxyapatite-bioactive glass ceramic composite (Chitra-HABG) as a material for reconstructing the iliac crest. Summary of Background Data: Tricortical iliac crest bone graft harvesting is associated with significant donor site morbidity, varying from 3% to 61%. Reconstruction of the defect has been shown to reduce this morbidity, but the only materials which have been shown to be useful and readily available are bioactive apatite-wollastonite glass ceramic and morcellized beta-tricalcium phosphate. Methods: Twenty-six patients in whom tricortical graft was harvested from the iliac crest and defect reconstructed with an indigenously developed and tested graft substitute-Chitra HABG-were followed up to duration of 1 year. Outcome measures were donor site morbidity as assessed clinically and radiologic assessment for ceramic incorporation, dissolution, fragmentation, and migration. Results: At the end of 1 year from surgery, 25 of the 26 patients (96.15%) had no pain at the donor site, which had been reconstructed. Radiologic evaluation showed that in 21 cases the ceramic incorporation was complete, partial in 3, and absent in 2. Partial dissolution of ceramic was noticed in 3 patients and migration in 1. Conclusions: This study validates our hypothesis that the donor site morbidity after tricortical iliac crest graft harvesting is probably a structural issue and it can be reduced by reconstruction of the defect. It also highlights the fact that the Chitra-HABG block is an excellent material for reconstruction of the iliac crest defect, as it gets incorporated into the surrounding bone without adverse effects.
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    Cell interaction studies with novel Bioglass coated Hydroxyapatite porous blocks
    (Trends in Biomaterials & Artificial Organs., 2006) Nair, MB; Varma, HK; Kumary, TV; Babu, SS; John, A
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    Cell patch seeding and functional analysis of cellularized scaffolds for tissue engineering
    (BIOMEDICAL MATERIALS, 2007) Kumar, PRA; Varma, HK; Kumary, TV
    Cell seeding has a direct impact on the final structure and function of tissue constructs, especially for applications like tissue engineering and regeneration. In this study seeding cell patches retrieved from the thermoresponsive poly(N-isopropylacrylamide) surface were used to generate in vitro tissue constructs. Porous and dense bone substitute materials were cellularized using osteoblast cells by a patch transfer and a trypsin method. The function and proliferation of cells was analyzed after 7 days of culture. The relative cell growth rate was found to be higher in cellularized porous hydroxyapatite (PHA) than in dense hydroxyapatite. Live-dead staining confirmed viable cells inside the pores of PHA. Increased alkaline phosphatase activity of cells transferred by the cell patch over the trypsin method revealed the significance of cell patch seeding. This novel method of generating tissue constructs by cell patch seeding was successful in cellularizing scaffolds with intact cell function.
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    Cells-nano interactions and molecular toxicity after delayed hypersensitivity, in Guinea pigs on exposure to hydroxyapatite nanoparticles
    (COLLOIDS AND SURFACES B-BIOINTERFACES, 2013) Geetha, CS; Remya, NS; Leji, KB; Syama, S; Reshma, SC; Sreekanth, PJ; Varma, HK; Mohanan, PV
    The aim of the study was to evaluate the cells-nanoparticle interactions and molecular toxicity after delayed hypersensitivity in Guinea pigs, exposed to hydroxyapatite nanoparticles (HANP). The study focuses on synthesizing and characterizing HANPs and gaining an insight into the cytotoxicity, molecular toxicity, hypersensitivity and oxidative stress caused by them in vitro and in vivo. HANP was synthesized by chemical method and characterized by standard methods. Cytotoxicity was assessed on L929 cells by MTT assay and in vitro studies were carried out on rat liver homogenate. In vivo study was carried out by topical exposure of Guinea pigs with HANP, repeatedly, and evaluating the skin sensitization potential, blood parameters, oxidative stress in liver and brain and DNA damage (8-hydroxyl-2-deoxyguanosine: 8-OHdG) in liver. The results of the study indicated that there was no cytotoxicity (up to 600 mu g/mL) and oxidative damage (up to 100 mu g/mL), when exposed to HANPs. It was also evident that, there was no skin sensitization and oxidative damage when HANP were exposed to Guinea pigs. (C) 2013 Elsevier B.V. All rights reserved.
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    Cellular and sub-chronic toxicity of hydroxyapatite porous beads loaded with antibiotic in rabbits, indented for chronic osteomyelitis
    (International Journal of Pharmaceutics, 2022-02) Vandana, U; Akhil, V; Suresh Babu, S; Francis, B; Sabareeswaran, A; Varma, HK; Mohanan, PV
    Bioceramics have emerged as a hopeful remedy for site-specific drug delivery in orthopaedic complications, especially in chronic osteomyelitis. The bioresorbable nature of bioceramic materials shaped them into a versatile class of local antibiotic delivery systems in the treatment of chronic osteomyelitis. Hydroxyapatite (HA) based bioceramics with natural bone mimicking chemical composition are of particular interest due to their excellent biocompatibility, better osteoconductive and osteointegrative properties. Although HA has been widely recognized as an efficient tool for local delivery of antibiotics, information regarding its subchronic systemic toxicity have not been explored yet. Moreover, a detailed investigation of in vivo subchronic systemic toxicity of HA is critical for understanding its biocompatibility and futuristic clinical applications of these materials as novel therapeutic system in its long haul. Evaluation of biocompatibility and sub-chronic systemic toxicity are significant determinants in ensuring biomedical device’s long-term functionality and success. Sub-chronic systemic toxicity allows assessing the potential adverse effects caused by leachable and nanosized wear particles from the device materials under permissible human exposure to the distant organs that are not in direct contact with the devices. In this context, the present study evaluates the sub-chronic systemic toxicity of in-house developed Hydroxyapatite porous beads (HAPB), gentamicin-loaded HAPB (HAPB + G) and vancomycin- loaded HAPB (HAPB + V) through 4 and 26-week muscle implantation in New Zealand white rabbits, as per ISO 10993–6 and ISO 10993–11. Analysis of cellular responses of HAPB towards Human Osteosarcoma (HOS) cell line through MTT assay, direct contact cytotoxicity, live/dead assay based on Imaging Flow Cytometry (IFC) showed its non-cytotoxic behaviour. Histopathological analysis of muscle tissue, organs like heart, lungs, liver, kidney, spleen, adrenals, intestine, testes, ovaries, and uterus did not reveal any abnormal biological responses. Our study concludes that the HAPB, gentamicin-loaded HAPB (HAPB + G) and vancomycin-loaded HAPB (HAPB + V) are biocompatible and did not induce sub-chronic systemic toxicity and hence satisfies the criteria for regulatory approval of HAs as a plausible candidate for
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    Characterisation of novel bioactive glass coated hydroxyapatite granules in correlation with in vitro and in vivo studies
    (Trends in Biomaterials & Artificial Organs., 2006) Sandeep, G; Varma, HK; Kumary, TV; Babu, SS; John, A
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    Contact Guidance Mediated by Hybrid Thread Topography Enhances Osseointegration of As-machined Ti6Al4V Dental Implant.
    (Regenerative Engineering and Translational Medicine, 2023-03) Mishra, D; Neethu, RS; Shetty, V; Shenoy, SJ; Komath, M; Varma, HK; Sabareeswaran, A; Basu, B
    Purpose The main objective of this study is to investigate the key role of as-machined implant design features on the osseointegration. The bone regeneration ability of the newly developed Ti6Al4V hybrid threaded tapered implant without any surface modification has been validated and benchmarked against Straumann® implant (control) in the rabbit model for 12 weeks. Material and Methods The test and control implants were implanted in the femur medial condyle of twelve adult New Zealand white rabbits on the contralateral limbs; each femoral medial condyle received a test or control implant randomly. The bone formation and osseointegration around the implants were assessed qualitatively and quantitatively using histology, micro-computed tomography (Micro-CT), molecular gene studies, and histomorphometric analysis after 12 weeks of implantation. Results The overall assessment suggests homogenous and continuous neobone formation and osseointegration around the hybrid threads of the test implants. Superior bone-to-implant contact percentage (BIC) was observed in the case of hybrid threaded test implants with an average value of 80.8%, compared to 67.1% for the control implant. Upregulated expression of osteogenic (COL1A1, RUNX2, SPARC, and SPP1) and angiogenic (VEGF) genes in the case of test implant indicates better coupled osseointegrationa and angiogenesis. Conclusion It can be concluded that the extent of neobone formation and expression of the osteogenic/angiogenic genes is positively correlated with optimal design features of the implant, which leads to the contact guidance of the osteoblasts on the implant surface. The study also advocates that the novel tapered multithreaded implant design concept alone, without any surface modification, can facilitate osseointegration in a manner better than clinically used surface-modified implants. Lay Summary Dental implants are artificial tooth roots and are used to treat complete or partial toothlessness. The new implant design concept reported here is expected to support both soft tissue and hard tissue attachment and to improve primary stability. This study unraveled the effect of the novel external hybrid thread design on the implant integration with the surrounding bone. This aspect was validated in the rabbit model and benchmarked against the commercially available Straumann® implant. This study has unambiguously demonstrated the ability of as-machined Ti implants to facilitate better new bone and new blood vessels formation than the commercial implant.
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    Cytocompatibility Studies of a Novel Bioactive Glass Coated Porous Hydroxyapatite Bioceramic for Use as a Bone Substitute
    (Key Engineering Materials., 2005) John, A; Varma, HK; Kumari, TV; Nisha, VR; Narayanan, D
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    Dense hydroxy apatite ceramics through gel casting technique
    (MATERIALS LETTERS, 1996) Varma, HK; Sivakumar, R
    A simple gel casting process is described for the preparation of uniform green HAP (hydroxy apatite) ceramic bodies. Such green compacts were observed to sinter more uniformly compared to the compacts derived by the dry pressing technique. The samples were sintered at temperatures ranging between 1100 and 1250 degrees C for 2 h. The sintering characteristics of the compacts were assessed by density measurements, microhardness variations and scanning electron microscopy. The highest density was obtained for gel cast samples, i.e. > 99%, when they, were sintered at 1200 degrees C for 2 h. The microstructure of the above sample was highly uniform. The improved uniformity in structure and properties of the sintered gel cast samples would make them suitable for better dental and orthopaedic implants.