Browsing by Author "Joseph, J"

Now showing 1 - 10 of 10
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    Comparison of Risk Models to Predict In-Hospital Mortality for Patients With Acute Coronary Syndrome in India: The CSI-Kerala Risk Score
    (CIRCULATION, 2011) Huffman, MD; Mathew, R; Harikrishnan, S; Krishan, MN; Zachriah, G; Joseph, J; Prabhakaran, D; Faizal, A; Jayagopal, PB; Varghese, PK; Nambiar, A; Mohanan, PP
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    Contribution of fibroblasts to the mechanical stability of in vitro engineered dermal-like tissue through extra cellular matrix deposition
    (Bio Research Open Access, 2014-10) Nair, RP; Joseph, J; Harikrishnan, VS; Krishnan, VK; Krishnan, LK
    Tissue-engineered skin with mechanical and biological properties that match the native tissue could be a valuable graft to treat non-healing chronic wounds. Fibroblasts grown on a suitable biodegradable scaffold are a feasible strategy for the development of a dermal substitute above which epithelialization may occur naturally. Cell growth and phenotype maintenance are crucial to ensure the functional status of engineered tissue. In this study, an electrospun biodegradable polymer scaffold composed of a terpolymer PLGC [poly(lactide-glycolide- caprolactone)] with appropriate mechanical strength was used as a scaffold so that undesirable contraction of the wound could be prevented when it was implanted. To enhance cell growth, synthetic PLGC was incorporated with a fibrin-based biomimetic composite. The efficacy of the hybrid scaffold was evaluated by comparing it with bare PLGC in terms of fibroblast growth potential, extracellular matrix (ECM) deposition, polymer degradation, and mechanical strength. A significant increase was observed in fibroblast attachment, proliferation, and deposition of ECM proteins such as collagen and elastin in the hybrid scaffold. After growing fibroblasts for 20 d and 40 d, immunochemical staining of the decellularized scaffolds showed deposition of insoluble collagen and elastin on the hybrid scaffold but not on the bare scaffold. The loss of mechanical strength consequent to in vitro polymer degradation seemed to be balanced owing to the ECMdeposition. Thus, tensile strength and elongation were better when cells were grown on the hybrid scaffold rather than the bare samples immersed in culture medium. Similar patterns of in vivo and in vitro degradation were observed during subcutaneous implantation and fibroblast culture, respectively. We therefore postulate that a hybrid scaffold comprising PLGC and fibrin is a potential candidate for the engineering of dermal tissue to be used in the regeneration of chronic wounds.
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    Influence of curing agent on fibrosis around silicone implants
    (JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION, 2013) Joseph, J; Mohanty, M
    Severe capsular contracture around silicone expander breast implants leading to pain and failure is a major clinical problem. Even though earlier studies have implicated the immunogenicity of silicone, the role of physical and chemical properties of the silicone material in excessive collagen deposition and fibrosis has been less addressed. The present study investigates whether there is any correlation between the type of curing systems i.e. addition and free radical curing and the fibrosis around silicone elastomer. The experiment carried out uses commercially available silicone ventriculo-peritoneal shunt material elastomer cured by platinum and the results are compared with results obtained in a similar study carried out by the authors using commercially available silicone tissue expander material cured by peroxide. Ultra-high molecular weight poly-ethylene (UHMWPE), the standard reference for biocompatibility evaluation, was used as the control material. The materials were implanted in rat skeletal muscle for 30 and 90days. Inflammatory cells, myofibroblasts, cytokines, and collagen deposition at the material-tissue interface were identified by haematoxylin-eosin and Masson's Trichrome stains and semi-quantitated based on immunohistochemical studies. Results indicate that even though the cellular response in the initial phase of wound healing was similar in both platinum and peroxide-cured materials, the collagen deposition in the proliferative phase was more around peroxide-cured material in comparison to the platinum-cured silicone elastomer. There is a need to look into the molecular mechanisms of this interaction and the possibility of using curing systems other than free radical peroxide in the manufacture of silicone elastomer expanders for breast prosthesis.
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    Mechanically stable and functional dermal-like tissue generation on biodegradable PLGC-fibrin hybrid scaffold
    (BioResearch Open Access., 2015-01) Nair, RP; Joseph, J; Harikrishnan, VS; Kalliyanakrishnan, V; Krishnan, LK
    Tissue-engineered skin with mechanical and biological properties that match the native tissue could be a valuable graft to treat non-healing chronic wounds. Fibroblasts grown on a suitable biodegradable scaffold are a feasible strategy for the development of a dermal substitute above which epithelialization may occur naturally. Cell growth and phenotype maintenance are crucial to ensure the functional status of engineered tissue. In this study, an electrospun biodegradable polymer scaffold composed of a terpolymer PLGC [poly(lactide-glycolide-caprolactone)] with appropriate mechanical strength was used as a scaffold so that undesirable contraction of the wound could be prevented when it was implanted. To enhance cell growth, synthetic PLGC was incorporated with a fibrin-based biomimetic composite. The efficacy of the hybrid scaffold was evaluated by comparing it with bare PLGC in terms of fibroblast growth potential, extracellular matrix (ECM) deposition, polymer degradation, and mechanical strength. A significant increase was observed in fibroblast attachment, proliferation, and deposition of ECM proteins such as collagen and elastin in the hybrid scaffold. After growing fibroblasts for 20 d and 40 d, immunochemical staining of the decellularized scaffolds showed deposition of insoluble collagen and elastin on the hybrid scaffold but not on the bare scaffold. The loss of mechanical strength consequent to in vitro polymer degradation seemed to be balanced owing to the ECM deposition. Thus, tensile strength and elongation were better when cells were grown on the hybrid scaffold rather than the bare samples immersed in culture medium. Similar patterns of in vivo and in vitro degradation were observed during subcutaneous implantation and fibroblast culture, respectively. We therefore postulate that a hybrid scaffold comprising PLGC and fibrin is a potential candidate for the engineering of dermal tissue to be used in the regeneration of chronic wounds.
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    Mediatory role of interleukin-6 in alpha smooth muscle actin induction and myofibroblast formation around silicone tissue expander
    (JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 2013) Joseph, J; Variathu, KT; Mohanty, M
    Materials used for medical devices are usually tested for their biocompatibility, before use. However, it is known that long-term implantation in the body may lead to degradation of the material leading to an adverse tissue response. The failure of silicone breast implants due to excessive fibrosis and contracture has led to studies to delineate the cause of fibrosis around this material. To detect the biological moieties involved, conditioned media from RAW 264.7 macrophages seeded over commercially available silicone tissue expander material was added to L929 fibroblasts. Ultrahigh-molecular-weight polyethylene and tissue culture grade polystyrene served as the control materials. The gene expression of fibrogenic cytokines, interleukin-6 (IL-6), and transforming growth factor beta (TGF) in the RAW macrophages and myofibroblast marker alpha smooth muscle actin (SMA) in L929 cells were quantitated by real time polymerase chain reaction. Protein expression analysis of SMA was carried out by immunocytochemical staining and confocal microscopy. An in vitro degradation study of silicone expander material in pseudoextracellular fluid (PECF) and the SMA expression in fibroblasts incubated with the silicone extract containing PECF has revealed the role of silicone leachants in induction of myofibroblasts. This in vitro expression study revealed the additional profibrotic role of IL-6 in fibroblast to myofibroblast transition and the synergy between material aspects and biomolecules in regulating fibrosis around Silicone implants. These findings may help in targeting newer biological moieties in the profibrotic pathway and in devising better manufacturing processes aiding the life of millions of patients. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 2967-2973, 2013.
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    Nanohydroxyapatite Incorporated Electrospun Polycaprolactone/Polycaprolactone-Polyethyleneglycol-Polycaprolactone Blend Scaffold for Bone Tissue Engineering Applications
    (JOURNAL OF BIOMEDICAL NANOTECHNOLOGY, 2013) Remya, KR; Joseph, J; Mani, S; John, A; Varma, HK; Ramesh, P
    The present work is a comparative evaluation of physical and biological properties of electrospun biodegradable fibrous scaffolds based on polycaprolactone (PCL) and its blend with polycaprolactone-polyethyleneglycol-polycaprolactone (CEC) with and without nanohydroxyapatite (nHAP) particles. The fiber morphology, porosity, surface wettability, and mechanical properties of electrospun PCL were distinctly influenced by the presence of both copolymer CEC and nHAP. The degradation in hydrolytic media affected both morphological and mechanical properties of the scaffolds and the tensile strength decreased by 58% for PCL, 83% for PCL/CEC, 36% for PCL/nHAP and 75% for PCL/CEC/nHAP in 90 days of PBS ageing. MU assay using mouse fibroblast L929 cells proved all the scaffolds to be non-cytotoxic. An overall enhanced performance was shown by PCL/CEC/nHAP scaffold in cell viability (LDH) and proliferation (Picogreen). Simultaneously, ELF assay of ALP activity (bone marker) confirmed the presence of osteogenic-induced Rabbit adipose-derived mesenchymal stem cells (ADMSCs) on all the scaffolds. In comparison, the results reveal the potential of the cytocompatible PCL/CEC/nHAP scaffold for the fabrication of living bony constructs for tissue engineering applications.
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    Presentation, Management, and Outcomes of 25,748 Acute Coronary Syndrome Admissions in Kerala, India: Results from the Kerala ACS Registry
    (CIRCULATION, 2011) Mohanan, PP; Mathew, R; Harikrishnan, S; Krishan, MN; Zachriah, G; Joseph, J; Huffman, MD; Eapen, K; Abraham, M; Menon, J; Manoj, P; Jacob, S; Prabhakaran, D
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    Rural/Urban Differences in Hospital Characteristics, Patient Presentation, Process-of-Care Measures, and Outcomes of 25,748 Acute Coronary Syndrome Admissions in Kerala, India: Results From the Kerala ACS Registry
    (CIRCULATION, 2011) Mathew, R; Harikrishnan, S; Krishan, MN; Zachriah, G; Joseph, J; Huffman, MD; Prabhakaran, D; Cholakkal, M; Ponnouse, E; Govindannunni, U; Abraham, AK; Mohanan, PP
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    TLR-4 expression in corrosion metal debri induced hypoxic milieu around stainless steel fracture plates.
    (Biomedical Physics & Engineering Express, 2018-03) Ramanathan, V; Joseph, J; Prasanth, MJ; Mohanty, M; Sabareeswaran, A
    The release of corrosion debris from metallic implants leading to adverse tissue reactions and pain has jeopardized the lives of patients. This study attempts to observe if this holds true for widely used cost efficient stainless steel fracture plates and screws by studying the microenvironment in the peri prosthetic tissue of the retrieved implants. Fracture plates and nails along with adjacent tissues were collected in 10% neutral buffered formalin. Cellular response was qualitatively evaluated using HE staining and debris distribution was semi-quantitatively graded. Elemental composition of metallic debris was analysed by ESEM-EDAX of the tissue sections. The presence of macrophages, endothelial cells, TLR-4 and HIF-1αwere quantitated by Immunohistochemistry and histomorphometry. Analysis of TLR-4 gene expression was carried out by real time PCR and the presence of a hypoxic milieu was confirmed by PCR Array. This study demonstrates the corrosion debris initiated chronic inflammatory reaction to stainless steel fracture plates. Nickel and Chromium ions released from implants induce a hypoxic environment resulting in TLR-4 induction. These results emphasize the need for identification of potential biomarker that could serve as a deciding factor for removal of stainless steel fracture plates from patients prior to the onset of inflammation associated reaction and also suggest the use of better manufacturing techniques and newer bio resorbable implants.