Browsing by Author "Sabareeswaran, A"

Now showing 1 - 20 of 46
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    A Novel Design of Wound Dressing Matrix with Electrospun Porous Fibers and Antibiotic Loaded Chitosan Microbeads
    (TISSUE ENGINEERING PART A, 2015) Kumar, PRA; Bhaskaran, A; Krishnan, VSH; Sabareeswaran, A; Haritha, VH; Anie, Y; Kumary, TV
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    Asialoglycoprotein receptor targeted optical and magnetic resonance imaging and therapy of liver fbrosis using pullulan stabilized multi-functional iron oxide nanoprobe
    (Scientific Reports., 2021-09) Saraswathy, A; Nazeer, SS; Nimi, N; Hema, S; Parvathy, RS; Jibin, K; Victor, M; Fernandez, FB; Sabareeswaran, A; Shenoy, SJ; Harikrishna Varma, PR; Jayasre, RS
    Early diagnosis and therapy of liver fibrosis is of utmost importance, especially considering the increased incidence of alcoholic and non-alcoholic liver syndromes. In this work, a systematic study is reported to develop a dual function and biocompatible nanoprobe for liver specific diagnostic and therapeutic applications. A polysaccharide polymer, pullulan stabilized iron oxide nanoparticle (P-SPIONs) enabled high liver specificity via asialogycoprotein receptor mediation. Longitudinal and transverse magnetic relaxation rates of 2.15 and 146.91 mM−1 s−1 respectively and a size of 12 nm, confirmed the T2 weighted magnetic resonance imaging (MRI) efficacy of P-SPIONs. A current of 400A on 5 mg/ml of P-SPIONs raised the temperature above 50 °C, to facilitate effective hyperthermia. Finally, a NIR dye conjugation facilitated targeted dual imaging in liver fibrosis models, in vivo, with favourable histopathological results and recommends its use in early stage diagnosis using MRI and optical imaging, and subsequent therapy using hyperthermia.
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    Biocompatibility of strontium incorporated ceramic coated titanium oxide implant indented for orthopaedic applications
    (Materials Science & Engineering B, 2021-02) Vandana, U; Nancy, D; Sabareeswaran, A; Remya, NS; Rajendran, N; Mohanan, PV
    Titanium and its alloys are the most commonly used materials for manufacturing orthopaedicimplants. Various surface modifications are done in titanium alloys to improve osseointegration as well as for long term success of endosseous implants. In the present study preclinical safety evaluation of two nanoporous mixed metal oxide bone implant materials, TiO2-Nb2O5 (TN) and Sr-HAP modified TN (TNS) were assessed by in vitro and in vivo methods. The surface morphological analysis of fabricated materials was done by XRD, IR and SEM. The biocompatibility evaluations performed were In vitro cytotoxicity tests using L929 cells, Assessment of hemolytic properties of materials and Test for local effects after implantation in bone as per international standards. The results of the study conclude that the materials, TN and TNS are non-cytotoxic, non-hemolytic and biocompatible and can be used safely for orthopaedic applications.
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    Biocompatibility property of 100% strontium-substituted SiO2-Al2O3-P2O5- CaO-CaF2 glass ceramics over 26 weeks implantation in rabbit model: Histology and micro-Computed Tomography analysis.
    (Journal of Biomedical Materials Research Part B: Applied Biomaterials., 2014-08) Basu, B; Sabareeswaran, A; Shenoy, SJ
    One of the desired properties for any new biomaterial composition is its long-term stability in a suitable animal model and such property cannot be appropriately assessed by performing short-term implantation studies. While hydroxyapatite (HA) or bioglass coated metallic biomaterials are being investigated for in vivo biocompatibility properties, such study is not extensively being pursued for bulk glass ceramics. In view of their inherent brittle nature, the implant stability as well as impact of long-term release of metallic ions on bone regeneration have been a major concern. In this perspective, the present article reports the results of the in vivo implantation experiments carried out using 100% strontium (Sr)-substituted glass ceramics with the nominal composition of 4.5 SiO2–3Al2O3–1.5P2O5–3SrO–2SrF2 for 26 weeks in cylindrical bone defects in rabbit model. The combination of histological and micro-computed tomography analysis provided a qualitative and quantitative understanding of the bone regeneration around the glass ceramic implants in comparison to the highly bioactive HA bioglass implants (control). The sequential polychrome labeling of bone during in vivo osseointegration using three fluorochromes followed by fluorescence microscopy observation confirmed homogeneous bone formation around the test implants. The results of the present study unequivocally confirm the long-term implant stability as well as osteoconductive property of 100% Sr-substituted glass ceramics, which is comparable to that of a known bioactive implant, that is, HA-based bioglass.
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    Biocompatibility property of 100% strontium-substituted SiO2-Al2O3-P2O5-CaO-CaF2 glass ceramics over 26 weeks implantation in rabbit model: Histology and micro-Computed Tomography analysis
    (JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS, 2015) Basu, B; Sabareeswaran, A; Shenoy, SJ
    One of the desired properties for any new biomaterial composition is its long-term stability in a suitable animal model and such property cannot be appropriately assessed by performing short-term implantation studies. While hydroxyapatite (HA) or bioglass coated metallic biomaterials are being investigated for in vivo biocompatibility properties, such study is not extensively being pursued for bulk glass ceramics. In view of their inherent brittle nature, the implant stability as well as impact of long-term release of metallic ions on bone regeneration have been a major concern. In this perspective, the present article reports the results of the in vivo implantation experiments carried out using 100% strontium (Sr)-substituted glass ceramics with the nominal composition of 4.5 SiO2-3Al(2)O(3)-1.5P(2)O(5)-3SrO-2SrF(2) for 26 weeks in cylindrical bone defects in rabbit model. The combination of histological and micro-computed tomography analysis provided a qualitative and quantitative understanding of the bone regeneration around the glass ceramic implants in comparison to the highly bioactive HA bioglass implants (control). The sequential polychrome labeling of bone during in vivo osseointegration using three fluorochromes followed by fluorescence microscopy observation confirmed homogeneous bone formation around the test implants. The results of the present study unequivocally confirm the long-term implant stability as well as osteoconductive property of 100% Sr-substituted glass ceramics, which is comparable to that of a known bioactive implant, that is, HA-based bioglass. (c) 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 1168-1179, 2015.
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    Biological evaluation of a new organically modified ceramic-based dental restorative resin
    (JOURNAL OF APPLIED POLYMER SCIENCE, 2012) Lizymol, PP; Mohanan, PV; Sabareeswaran, A; Krishnan, VK
    Material tissue interactions of a newly developed organically modified ceramic (ormocer)-based dental restorative composite based on a resin containing mixture of alkoxides of silicone and calcium with polymerizable methacrylate end groups are discussed in this study. Admira, a commercially available ormocer was used as control. A solgel process has been used to synthesize organically modified ceramic resins from liquid precursors, which allow one to produce inorganicorganic hybrid polymer materials, which can be functionalized to optimize their physical and chemical properties. Besides, the resulting material properties have been significantly modified by further technological processing such as photochemical curing of the materials by incorporating dimethacrylate groups as organically polymerizable units. Intracutaneous (intradermal) irritation test is found not to elicit any gross signs of tissue reaction. The results of maximization test for delayed hypersensitivity also did not show any adverse skin reaction during the induction or challenge period. Histological analysis after 1, 4, and 12 weeks of subcutaneous implantation of restorative composite resin on the dorsal surface on one side of the spinal column of Wister rats is also found not to reveal any inflammatory response after the implantation. Granuloma and material debris is found to be absent in all three periods of implantation in both test and control. No necrosis was observed around the implanted materials, which were found to be encapsulated by fibrous connective tissue consisting of predominantly fibroblasts and inflammatory cells. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
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    Biological Evaluation of Laser Rapid Manufactured Ti Porus Structures ( Project - 8092 )
    (SCTIMST, 2017-12-31) Sabareeswaran, A; Mohanan, PV; Paul, CP
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    Biphasic Hydroxyapatite based keratoprosthesis cvaluation in a rabbit modcl (proof of conccpt). ( Project - 6205 )
    (SCTIMST, 2015-05-17) Sabareeswaran, A; Vinay Sukumaran, Pillai; Hari Krishna, Varma; Sachin J, Shenoy; Vijayan, S
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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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    Combinatorial Application of Hyaluronic Acid and Curcumin-Albumin Conjugate for Cartilage Repair in TNF- α Induced Inflammation in Rabbit Knee Joint
    (Archives of Clinical and Biomedical Research, 2021-06) Sathee, D; Shenoy, SJ; Anil, A; Sabareeswaran, A; Krishnan, LK
    Osteoarthritis has emerged as a consequential disorder resulting from changing lifestyles, especially in the aged population. It is one of the most devastating degenerative joint diseases caused due to inflammation, wear and tear of articular cartilage leading to irreversible damage and physical trauma. Several intra-articular formulations are experimented with for restoring damaged cartilage. Many of them failed because of minimal effectiveness in establishing long-term therapeutic potential. We explored the cartilage regeneration potential of Hyaluronic acid (HA) on combining with dimethoxy curcumin-human serum albumin (DMCHSA) conjugate upon intra-articular administration. HA is known to possess immense lubrication property and is a well-recognized visco-supplement. The DMCHSA has the potential to suppress the action of inflammatory markers. So, a combinatorial approach anticipates an ideal therapeutic strategy to overcome the demerits of existing interventions. Intra-articular injection of Tumor Necrosis Factor-α (TNF-α), repeatedly at 7-day intervals disrupted the cartilage morphology and produced an inflammatory knee joint model to study the therapeutic potential of DMCHSA-HA combination. Into separate inflamed knee-joint cartilage HA, DMCHSA and DMCHSA-HA were administered periodically to highlight the advantage of mixing the latter with the former. Histopathology and gene expression analysis assessed the restoration potential of the treatment. We observed remarkable restoration of degenerated cartilage upon treatment with the DMCHSA-HA combination. The columnar arrangement of cells, regulated deposition of ECM components such as glycosaminoglycans (GAGs) & collagen, and synchronized expressions of inflammatory marker molecules suggested restoration of the treated defects. The treatments with DMCHSA, HA, or HSA alone seemed inferior to DMCHSA-HA combination therapy. The study confirmed that the combination therapy restored the damaged cartilage to normalcy.
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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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    Corneal Epithelial Cell Sheet Engineering: Validation and Pre-Clinical Evaluation ( Project - 8223 )
    (SCTIMST, 2023-01-20) Naresh, Kasoju; Anil Kumar, PR; Sachin J, Shenoy; Sabareeswaran, A; Chitra, Raghavan,
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    Determination of oxidative stress related toxicity on repeated dermal exposure of hydroxyapatite nanoparticles in rats
    (Intl. J. Biomaterials. 2014, 2015-02) Mohanan, PV; Syama, S; Sabareeswaran, A
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    Early osseointegration of a strontium containing glass ceramic in a rabbit model
    (Biomaterials, 2013-09) Sabareeswaran, A; Bikramjit, Basu; Sachin, J Shenoy; Zahira, Jaffer; Naresh, Saha; Artemis, Stamboulis
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    Effect of surface-modified superparamagnetic iron oxide nanoparticles (SPIONS) on mast cell infiltration: An acute in vivo study
    (Nanomedicine: Nanotechnology, Biology and Medicine., 2016-07) Sabareeswaran, A; Ansar, EB; Varma, PR; Mohanan, PV; Kumary, TV
    Extensive use of superparamagnetic iron oxide nanoparticles (SPIONS) in theranostics prompted us to investigate the acute changes in cell morphology and function following intravenous administration of surface-modified SPIONS in a rat model. Dextran-coated (DEX) and polyethylene glycol-coated (PEG) SPIONS were synthesized and characterized, and cytocompatibility was evaluated in vitro. Haematological, histopathological, ultrastructural and oxidative stress analyses were carried out 24 h post intravenous administration in vivo. In test groups, SGPT and SGOT enzymes were significantly altered when compared to saline-only controls. Anti-oxidant imbalance and lipid peroxidation were observed in all major organs. Histology revealed iron-laden Kupffer cells and macrophages in liver and lung respectively. Iron overload was observed in the convoluted tubules of the kidney. Mast cell infiltration and distribution were observed differentially in test groups. Although surface modification of SPIONS improved biocompatibility in vitro, they affected anti-oxidant and tissue nitrite levels, which greatly influenced mast cell infiltration in vivo.
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    Enriched adipose stem cell secretome as an effective therapeutic strategy for in vivo wound repair and angiogenesis.
    (3 Biotech, 2023-03) Ajit, A; Santhosh Kumar, TR; Harikrishnan, VS; Anil, A; Sabareeswaran, A; Krishnan, LK
    The therapeutic potential of adipose tissue-derived mesenchymal stem cells (ADMSCs) is well studied for use in non-healing wounds. However, concerns on the transplantable cell number requirement, cell expansion, cell viability, retained cell multipotency and the limited cell implantation time for efficient impact hinders cell therapy. Recent literature is much inclined to the superiority of the ADMSCs’ secretome, pre-dominating its paracrine-mediated therapeutic impact. In this context, the possibility of attaining accelerated wound angiogenesis through non-viral mediated enrichment of the ADMSCs secretome with pro-angiogenic growth factors (AGF) seems promising. Accordingly, this study aimed to explore the effect of AGF-enriched ADMSCs secretome for accelerating wound angiogenesis and repair in acute large area full thickness excision rabbit wound model, as adopted from Salgado et al. (Chir Buchar Rom 108:706–710, 1990). Using sub-dermal single-dose injections along the margin of the dorsal wound, native ADMSCs secretome, AGF-enriched ADMSC secretome, allogenic rabbit ADMSCs and a combination of AGF-enriched ADMSC secretome with allogenic rabbit ADMSCs were transplanted independently. Twenty-eight days (28 days) post-transplantation, histopathological analysis was performed to assess the effect. Hematoxylin and eosin (H&E) staining showed enhanced epithelization, notable granulation tissue and collagen fiber deposition in AGF-enriched secretome transplanted groups. This was confirmed by elevated CD31 detection, faster wound closure time and collagen organization. The use of single-dose AGF-enriched ADMSCs’ secretome for therapeutic angiogenesis and wound repair seems to be a promising cell-free therapeutic option. Further investigations using multiple doses on larger animal groups remains to be explored in order to ascertain the comparative potential of AGF-enriched ADMSCs’ secretome.
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    Exploring cadaver skin for standardization of rabbit and porcine burn models in research
    (Annals of Burn and Fire Disasters, 2020-12) Ajit, A; Krishnan, LK; Harikrishnan, VS; Varkey, P; Sabareeswaran, A
    Burn animal models provide substantial insights into burn pathophysiology. Choice of the apt model is important for determining the clinical efficacy of new medicines. Therefore, standardization of burn models is crucial for scientific research. Use of common techniques like hot water, electricity and incandescent instruments to generate animal burn models is widely reported. However, great discrepancy in employed temperature and exposure times demands user-dependent standardization of the animal model prior to research. Establishment of custom generated in vivo burn models giving consideration to reduced use, suffering and risk of the experimental animal is equally crucial. Accordingly, this pilot study demonstrates a novel approach using rabbit and porcine cadaver skin for standardization of burn parameters prior to use in live animal models. Using a custom-made soldering iron coupled to a 16cm2 surface area copper plate, burns at randomly chosen temperatures of 80˚C and 120˚C, with exposure times ranging from 60s to 180s, were produced on rabbit and porcine cadaver skins. On gross and histopathological analysis, parameters required to generate characteristic changes for deep partial and full thickness burn involvement were established. The identified temperature and exposure time parameters were further validated in live animal models. In vivo validation established the success of this approach, highlighting reduced animal use, ease, reproducibility and efficacy in burn model standardization. The findings of this study will hopefully encourage researchers to opt for cadaver skin to determine parameters required to generate a specific degree of burn prior to its use in live animals for burn research.
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    Extracellular matrix-based combination scaffold for guided regeneration of large-area full-thickness rabbit burn wounds upon a single application
    (Journal of Biomedical Material Research Part B Applied Biomaterials, 2021-11) Ramakrishnan, R; Harikrishnan, VS; Anil, A; Sabareeswaran, A; Krishnan, LK
    Regeneration of large acute and chronic wounds is a concern worldwide. The present study evaluates wound healing competence of a completely human-origin, extracellular matrix (ECM)-based skin substitute/graft. It comprises cell-less amniotic membrane (AM), clinical-grade fibrin (FIB), and hyaluronic acid (HA) termed as AMFIBHA. The use of large-area third-degree rabbit burn wounds evaluated the product efficiency. The AMFIBHA induces hemostasis and permits suture-less positioning on the wound bed. In wet wounds, the AMFIBHA degrades and release biologically active molecules and guide cell migration, proliferation, and regeneration. The study demonstrated the effectiveness of this wound care product in terms of epithelial-dermal regeneration with angiogenesis. The study assessed injury-associated inflammation and different wound healing markers after 28 days of experiment and compared with both positive and negative controls-treated wounds. The regeneration of mature epidermis and dermis with rete pegs and hair follicle-like structure was evident upon a single application. The active involvement of host cells resulted in supple tissue formation. The ECM organization of AMFIBHA-treated tissue resulted in re-gain of mechanical properties comparable to native skin after 56 days. These guided regenerative outcomes reveal a promising translational value of the novel AMFIBHA skin substitute as an off-the-shelf product for clinical use.