Publications (13)46.98 Total impact
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Article: In vivo biocompatibility of two PEG/PAA interpenetrating polymer networks as corneal inlays following deep stromal pocket implantation.
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ABSTRACT: This study compared the effects of implanting two interpenetrating polymer networks (IPNs) into rabbit corneas. The first (Implant 1) was based on PEG-diacrylate, the second (Implant 2) was based on PEG-diacrylamide. There were inserted into deep stromal pockets created using a manual surgical technique for either 3 or 6 months. The implanted corneas were compared with normal and sham-operated corneas through slit lamp observation, anterior segment optical coherence tomography, in vivo confocal scanning and histological examination. Corneas with Implant 1 (based on PEG-diacrylate) developed diffuse haze, ulcers and opacities within 3 months, while corneas with Implant 2 (based on PEG-diacrylamide) remained clear at 6 months. They also exhibited normal numbers of epithelial cell layers, without any immune cell infiltration, inflammation, oedema or neovascularisation at post-operative 6 month. Morphological studies showed transient epithelial layer thinning over the hydrogel inserted area and elevated keratocyte activity at 3 months; however, the epithelium thickness and keratocyte morphology were improved at 6 months. Implant 2 exhibited superior in vivo biocompatibility and higher optical clarity than Implant 1. PEG-diacrylamide-based IPN hydrogel is therefore a potential candidate for corneal inlays to correct refractive error.Journal of Materials Science Materials in Medicine 01/2013; · 2.32 Impact Factor -
Article: Dual functionalization of titanium with vascular endothelial growth factor and β-defensin analog for potential application in keratoprosthesis.
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ABSTRACT: Functionalization of material surfaces can improve their biointegration and bactericidal effect. To expand the biomedical applications of titanium in artificial cornea implantation surgery, titanium alloy substrates were coated with polydopamine and dual bound with recombinant vascular endothelial growth factor (VEGF) and anti-microbial peptide (AMP), SESB2V. Successful chemical binding was assessed with attenuated total reflectance-Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. Coating thickness was assessed by atomic force microscopy. Cellular studies revealed that the functionalized substrates displayed the abilities to enhance primary human corneal fibroblast adhesion, proliferation, and viability. Angiogenesis assay with human mesenchymal stem cells was used to verify the biological functions of immobilized VEGF while bactericidal assay was evaluated for the anti-microbial activities of immobilized SESB2V peptide. We found that the titanium surface that was sequentially functionalized with VEGF and SESB2V had enhanced fibroblast proliferation and anti-microbial properties. The incorporation of such peptides into an artificial cornea implant is important for implant-tissue integration and wound healing. This may improve implant integration and reduce the risk of device infection following artificial cornea implantation. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.Journal of Biomedical Materials Research Part B Applied Biomaterials 07/2012; 100(8):2090-100. · 2.15 Impact Factor -
Article: In vitro effect of a corrosive hostile ocular surface on candidate biomaterials for keratoprosthesis skirt.
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ABSTRACT: Keratoprosthesis (KPro) devices are prone to long-term corrosion and microbiological assault. The authors aimed to compare the inflammatory response and material dissolution properties of two candidate KPro skirt materials, hydroxyapatite (HA) and titania (TiO(2)) in a simulated in vitro cornea inflammation environment. Lipopolysaccharide-stimulated cytokine secretions were evaluated with human corneal fibroblasts on both HA and TiO(2). Material specimens were subjected to electrochemical and long-term incubation test with artificial tear fluid (ATF) of various acidities. Topography and surface roughness of material discs were analysed by scanning electron microscopy and atomic force microscopy. There were less cytokines secreted from human corneal fibroblasts seeded on TiO(2) substrates as compared with HA. TiO(2) was more resistant to the corrosion effect caused by acidic ATF in contrast to HA. Moreover, the elemental composition of TiO(2) was more stable than HA after long-term incubation with ATF. TiO(2) is more resistant to inflammatory degradation and has a higher corrosion resistance as compared with HA, and in this regard may be a suitable material to replace HA as an osteo-odonto-keratoprosthesis skirt. This would reduce resorption rates for KPro surgery.The British journal of ophthalmology 07/2012; 96(9):1252-8. · 2.92 Impact Factor -
Article: In vivo evaluation of titanium oxide and hydroxyapatite as an artificial cornea skirt.
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ABSTRACT: Keratoprosthetic devices are subject to chronic inflammatory, pathological processes and the external environment that affect their stability and biocompatibility with the ocular surface and adjacent ocular tissues. We compared the corrosion resistance property and tissue-implant reaction of titanium oxide (TiO(2)) with hydroxyapatite (HA) in artificial tear fluid and a rabbit skin implantation model. The dissolution properties of the implant surfaces were evaluated with scanning electronic microscope (SEM) and atomic force microscope (AFM). Tissue inflammatory reactions were evaluated by Hematoxylin & Eosin staining, avidin biotin peroxidase complex (ABC) immunoassay and immunofluorescence. SEM and AFM images showed that there was less pitting corrosion on the surface of TiO(2) implants compared with HA. TiO(2) and HA exhibited a similar pattern of foreign body capsule formation and inflammatory cellular responses. The Collagen I/Collagen III ratio of the TiO(2) capsule was higher than that of the HA capsule. TiO(2) implants possess a high corrosion resistance property both in vitro and in vivo and the inflammatory cellular response to TiO(2) is similar to HA. With regards to corrosion resistance and inflammatory tissue responses, TiO(2) appears to be a promising material for keratoprosthetic skirt devices.Journal of Materials Science Materials in Medicine 03/2012; 23(4):1063-72. · 2.32 Impact Factor -
Article: Effect of fibrin glue on the biomechanical properties of human Descemet's membrane.
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ABSTRACT: Corneal transplantation has rapidly evolved from full-thickness penetrating keratoplasty (PK) to selective tissue corneal transplantation, where only the diseased portions of the patient's corneal tissue are replaced with healthy donor tissue. Descemet's membrane endothelial keratoplasty (DMEK) performed in patients with corneal endothelial dysfunction is one such example where only a single layer of endothelial cells with its basement membrane (10-15 µm in thickness), Descemet's membrane (DM) is replaced. It is challenging to replace this membrane due to its intrinsic property to roll in an aqueous environment. The main objective of this study was to determine the effects of fibrin glue (FG) on the biomechanical properties of DM using atomic force microscopy (AFM) and relates these properties to membrane folding propensity. Fibrin glue was sprayed using the EasySpray applicator system, and the biomechanical properties of human DM were determined by AFM. We studied the changes in the "rolling up" tendency of DM by examining the changes in the elasticity and flexural rigidity after the application of FG. Surface topography was assessed using scanning electron microscopy (SEM) and AFM imaging. Treatment with FG not only stabilized and stiffened DM but also led to a significant increase in hysteresis of the glue-treated membrane. In addition, flexural or bending rigidity values also increased in FG-treated membranes. Our results suggest that fibrin glue provides rigidity to the DM/endothelial cell complex that may aid in subsequent manipulation by maintaining tissue integrity.PLoS ONE 01/2012; 7(5):e37456. · 4.09 Impact Factor -
Article: Tafazzin regulates human conjunctiva epithelial cell proliferation via inhibiting TGFβ signaling pathway.
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ABSTRACT: To investigate the role of Tafazzin (TAZ) protein in regulating the proliferation of normal human conjunctiva epithelial cells and epithelial cells from pterygium tissue. Conjunctiva epithelial cells were cultured in keratinocytes growth medium and treated with transformation growth factor β (TGFβ) to analyze the expression and translocation of TAZ protein by immunostaining and BrdU analysis. Immortalized conjunctiva epithelial cells (NHC) were treated with TGFβ, targeting siRNA, TGFβ receptor antibody or TGFβ receptor inhibitor, to study the involvement of TAZ and TGFβ signaling pathway in conjunctiva cell proliferation by cell adhesion assay. Conjunctiva tissues from a normal human eye and an eye with pterygium disease were collected for histological analyses and western blot to evaluate the TAZ protein expression in vivo. TAZ expression was upregulated in mitotic conjunctiva epithelial cells, proliferating conjunctiva epithelial cells, TGFβ treated conjunctiva epithelial cells and human pterygium epithelium. TAZ siRNA induced less conjunctiva epithelial cell growth. Moreover, TGFβ receptor antibody and TGFβ receptor inhibitor rescued this anti-proliferative effect of TAZ siRNA. TAZ is involved in human conjunctiva epithelial cells proliferation via regulating TGFβ signaling pathway.Molecular vision 01/2012; 18:1402-10. · 2.20 Impact Factor -
Article: Osteo-odonto keratoprosthesis: systematic review of surgical outcomes and complication rates.
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ABSTRACT: Case series on osteo-odonto keratoprosthesis (OOKP) published in English from 1950-June 2010 were identified in Medline/PubMed. Indications for surgery, visual acuity, anatomical survival, complication and repeat surgery rates were compared among the different studies. Our own case series is a retrospective review of all OOKP surgeries performed in our center from February 2004-July 2011. Eight case series including our own were systematically reviewed. Sample sizes ranged from 4-181 eyes. The most common indications for surgery were severe cases of Stevens-Johnson syndrome and thermal and chemical burns that were unamenable to other forms of surgery or had had previous surgical failure. Anatomical survival rate in all the studies was 87.8% (range 67-100%) at 5 years, and three studies showed survival rates of 81.0% (range 65-98%) at 20 years. Visual acuity was more than 6/18 in 52% (range 46-72%) of the eyes with OOKP surgery. The most common intraoperative complication was vitreous hemorrhage (0-52%) and the most common long-term blinding complication was glaucoma (7-47%). Endophthalmitis rates ranged from 2-8%. The most common repeat surgical procedure was mucosal trimming due to mucosal overgrowth at the optical cylinder and mucosal grafting for extrusion of the OOKP or mucosal ulceration. Of the available biological and synthetic keratoprosthesis, OOKP appears to be an excellent option for the treatment of end-stage corneal diseases.The ocular surface 01/2012; 10(1):15-25. · 3.93 Impact Factor -
Article: Ex vivo expansion of conjunctival and limbal epithelial cells using cord blood serum-supplemented culture medium.
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ABSTRACT: Conventional cell culture methods use fetal bovine serum (FBS) as a growth supplement. The purpose of this study was to develop a xenobiotic-free culture system using umbilical cord blood serum (CBS) as an alternative growth supplement for the cultivation of human conjunctival and limbal epithelial cells. Human conjunctival and limbal epithelial cells were cultivated in varying concentrations of CBS-supplemented medium and compared with FBS-supplemented medium. Bromodeoxyuridine (BrdU) ELISA proliferation assay, colony-forming efficiency (CFE), and a number of cell generations were analyzed. Cytokeratin expression of cultured cells was evaluated (K3, K4, K12, K13, K14, K15, K19, and PanCK). The authors compared the cytokine and growth factor levels in CBS, FBS, and adult serum using antibody array assays. Conjunctival and limbal cells cultivated in 0.25% CBS- and 0.5% CBS-supplemented culture media demonstrated the highest proliferative capacity in terms of BrdU proliferation assay, CFE, and number of cell generations. These results were comparable to FBS-supplemented medium. Cultured epithelial cells retained their normal cytokeratin expression. Cytokines brain-derived neurotrophic factor, growth-related oncogene, and leptin and growth factors EGF, HGF, FGF-6, IGF-1, PDGF, and IGFBP were present in higher concentrations in CBS than in FBS and adult serum. CBS-supplemented culture medium supported the proliferation and differentiation of conjunctival and limbal epithelial cells. CBS contained a higher concentration of growth factors and cytokines than FBS and adult serum. CBS may be a viable and safer alternative to FBS as a growth supplement in the culture medium for culturing epithelial cells, which may have important clinical implications when bioengineering tissues for clinical use.Investigative ophthalmology & visual science 04/2011; 52(9):6138-47. · 3.43 Impact Factor -
Article: Cobalt chromium alloy with immobilized BMP peptide for enhanced bone growth.
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ABSTRACT: Cobalt chromium (CoCr) alloys are widely used in orthopedic practice, however, lack of integration into the bone for long-term survival often occurs, leading to implant failure. Revision surgery to address such a failure involves increased risks, complications, and costs. Advances to enhancement of bone-implant interactions would improve implant longevity and long-term results. Therefore, we investigated the effects of BMP peptide covalently grafted to CoCr alloy on osteogenesis. The BMP peptide was derived from the knuckle epitope of bone morphogenic protein-2 (BMP-2) and was conjugated via a cysteine amino acid at the N-terminus. X-ray photoelectron spectroscopy and o-phthaldialdehyde were used to verify successful grafting at various stages of surface functionalization. Surface topography was evaluated from the surface profile determined by atomic force microscopy. Osteoblastic cells (MC3T3-E1) were seeded on the substrates, and the effects of BMP peptide on osteogenic differentiation were evaluated by measuring alkaline phosphatase (ALP) activity and calcium mineral deposition. The functionalized surfaces showed a twofold increase in ALP activity after 2 weeks incubation and a fourfold increase in calcium content after 3 weeks incubation compared to the pristine substrate. These findings are potentially useful in the development of improved CoCr implants for use in orthopedic applications.Journal of Orthopaedic Research 03/2011; 29(9):1424-30. · 2.81 Impact Factor -
Article: Comparison of candidate materials for a synthetic osteo-odonto keratoprosthesis device.
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ABSTRACT: Osteo-odonto keratoprosthesis is one of the most successful forms of keratoprosthesis surgery for end-stage corneal and ocular surface disease. There is a lack of detailed comparison studies on the biocompatibilities of different materials used in keratoprosthesis. The aim of this investigation was to compare synthetic bioinert materials used for keratoprosthesis surgery with hydroxyapatite (HA) as a reference. Test materials were sintered titanium oxide (TiO(2)), aluminum oxide (Al(2)O(3)), and yttria-stabilized zirconia (YSZ) with density >95%. Bacterial adhesion on the substrates was evaluated using scanning electron microscopy and the spread plate method. Surface properties of the implant discs were scanned using optical microscopy. Human keratocyte attachment and proliferation rates were assessed by cell counting and MTT assay at different time points. Morphologic analysis and immunoblotting were used to evaluate focal adhesion formation, whereas cell adhesion force was measured with a multimode atomic force microscope. The authors found that bacterial adhesion on the TiO(2), Al(2)O(3), and YSZ surfaces were lower than that on HA substrates. TiO(2) significantly promoted keratocyte proliferation and viability compared with HA, Al(2)O(3,) and YSZ. Immunofluorescent imaging analyses, immunoblotting, and atomic force microscope measurement revealed that TiO(2) surfaces enhanced cell spreading and cell adhesion compared with HA and Al(2)O(3). TiO(2) is the most suitable replacement candidate for use as skirt material because it enhanced cell functions and reduced bacterial adhesion. This would, in turn, enhance tissue integration and reduce device failure rates during keratoprosthesis surgery.Investigative ophthalmology & visual science 01/2011; 52(1):21-9. · 3.43 Impact Factor -
Article: Cell migration from baby to mother.
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ABSTRACT: Fetal cells migrate into the mother during pregnancy. Fetomaternal transfer probably occurs in all pregnancies and in humans the fetal cells can persist for decades. Microchimeric fetal cells are found in various maternal tissues and organs including blood, bone marrow, skin and liver. In mice, fetal cells have also been found in the brain. The fetal cells also appear to target sites of injury. Fetomaternal microchimerism may have important implications for the immune status of women, influencing autoimmunity and tolerance to transplants. Further understanding of the ability of fetal cells to cross both the placental and blood-brain barriers, to migrate into diverse tissues, and to differentiate into multiple cell types may also advance strategies for intravenous transplantation of stem cells for cytotherapeutic repair. Here we discuss hypotheses for how fetal cells cross the placental and blood-brain barriers and the persistence and distribution of fetal cells in the mother.Cell adhesion & migration 02/2007; 1(1):19-27. · 1.82 Impact Factor -
Article: Fetal Microchimerism in the Maternal Mouse Brain: A Novel Population of Fetal Progenitor or Stem Cells Able to Cross the Blood–Brain Barrier?
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ABSTRACT: We investigated whether fetal cells can enter the maternal brain during pregnancy. Female wild-type C57BL/6 mice were crossed with transgenic Green Mice ubiquitously expressing enhanced green fluorescent protein (EGFP). Green Mouse fetal cells were found in the maternal brain. Quantitative real-time polymerase chain reaction (PCR) of genomic DNA for the EGFP gene showed that more fetal cells were present in the maternal brain 4 weeks postpartum than on the day of parturition. After an excitotoxic lesion to the brain, more fetal cells were detected in the injured region. The presence of fetal cells in the maternal brain was also confirmed by quantitative real-time PCR for the sex-determining region of the Y chromosome. Four weeks postpartum, EGFP-positive Green Mouse fetal cells in the maternal brain were found to adopt locations, morphologies, and expression of immunocytochemical markers indicative of perivascular macrophage-, neuron-, astrocyte-, and oligodendrocyte-like cell types. Expression of morphological and immunocytochemical characteristics of neuron- and astrocyte-like cell types was confirmed on identification of fetal cells in maternal brain by Y chromosome fluorescence in situ hybridization. Although further studies are required to determine whether such engraftment of the maternal brain has any physiological or pathophysiological functional significance, fetomaternal microchimerism provides a novel model for the experimental investigation of the properties of fetal progenitor or stem cells in the brain without prior in vitro manipulation. Characterization of the properties of these cells that allow them to cross both the placental and blood–brain barriers and to target injured brain may improve selection procedures for isolation of progenitor or stem cells for brain repair by intravenous infusion.Stem Cells 10/2005; 23(10):1443 - 1452. · 7.78 Impact Factor -
Article: Fetal microchimerism in the maternal mouse brain: a novel population of fetal progenitor or stem cells able to cross the blood-brain barrier?
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ABSTRACT: We investigated whether fetal cells can enter the maternal brain during pregnancy. Female wild-type C57BL/6 mice were crossed with transgenic Green Mice ubiquitously expressing enhanced green fluorescent protein (EGFP). Green Mouse fetal cells were found in the maternal brain. Quantitative real-time polymerase chain reaction (PCR) of genomic DNA for the EGFP gene showed that more fetal cells were present in the maternal brain 4 weeks postpartum than on the day of parturition. After an excitotoxic lesion to the brain, more fetal cells were detected in the injured region. The presence of fetal cells in the maternal brain was also confirmed by quantitative real-time PCR for the sex-determining region of the Y chromosome. Four weeks postpartum, EGFP-positive Green Mouse fetal cells in the maternal brain were found to adopt locations, morphologies, and expression of immunocytochemical markers indicative of perivascular macrophage-, neuron-, astrocyte-, and oligodendrocyte-like cell types. Expression of morphological and immunocytochemical characteristics of neuron- and astrocyte-like cell types was confirmed on identification of fetal cells in maternal brain by Y chromosome fluorescence in situ hybridization. Although further studies are required to determine whether such engraftment of the maternal brain has any physiological or pathophysiological functional significance, fetomaternal microchimerism provides a novel model for the experimental investigation of the properties of fetal progenitor or stem cells in the brain without prior in vitro manipulation. Characterization of the properties of these cells that allow them to cross both the placental and blood-brain barriers and to target injured brain may improve selection procedures for isolation of progenitor or stem cells for brain repair by intravenous infusion.Stem Cells 23(10):1443-52. · 7.78 Impact Factor
Top co-authors
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Institutions
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2011–2013
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Singapore Eye Research Institute
Singapore, Singapore
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2005–2012
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National University of Singapore
- • Singapore Eye Research Institute
- • Department of Pharmacology
Singapore, Singapore
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