Port-of-Spain, Trinidad and Tobago
Port-of-Spain, Trinidad and Tobago

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Lopez R.,University of Aarhus | Belibasakis G.N.,Institute of Oral Biology
Virulence | Year: 2015

The current understanding on the role of microbiology on periodontitis causation is reviewed. An appraisal of the literature reveals several issues that have limited the attempts to investigate candidate periodontal pathogens as causes of periodontitis and confirms that only limited epidemiological evidence is available. Several aspects of the contemporary understanding on causal inference are discussed with examples for periodontitis. © 2015 Taylor & Francis Group, LLC.


Ahadian S.,Tohoku University | Ramon-Azcon J.,Tohoku University | Estili M.,Japan National Institute of Materials Science | Liang X.,Tohoku University | And 14 more authors.
Scientific Reports | Year: 2014

Biological scaffolds with tunable electrical and mechanical properties are of great interest in many different fields, such as regenerative medicine, biorobotics, and biosensing. In this study, dielectrophoresis (DEP) was used to vertically align carbon nanotubes (CNTs) within methacrylated gelatin (GelMA) hydrogels in a robust, simple, and rapid manner. GelMA-aligned CNT hydrogels showed anisotropic electrical conductivity and superior mechanical properties compared with pristine GelMA hydrogels and GelMA hydrogels containing randomly distributed CNTs. Skeletal muscle cells grown on vertically aligned CNTs in GelMA hydrogels yielded a higher number of functional myofibers than cells that were cultured on hydrogels with randomly distributed CNTs and horizontally aligned CNTs, as confirmed by the expression of myogenic genes and proteins. In addition, the myogenic gene and protein expression increased more profoundly after applying electrical stimulation along the direction of the aligned CNTs due to the anisotropic conductivity of the hybrid GelMA-vertically aligned CNT hydrogels. We believe that platform could attract great attention in other biomedical applications, such as biosensing, bioelectronics, and creating functional biomedical devices.


Li Y.,Tsinghua University | Li Y.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases | Liu W.,Tsinghua University | Liu F.,Tsinghua University | And 15 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

The promise of cell therapy for repair and restoration of damaged tissues or organs relies on administration of large dose of cells whose healing benefits are still limited and sometimes irreproducible due to uncontrollable cell loss and death at lesion sites. Using a large amount of therapeutic cells increases the costs for cell processing and the risks of side effects. Optimal cell delivery strategies are therefore in urgent need to enhance the specificity, efficacy, and reproducibility of cell therapy leading to minimized cell dosage and side effects. Here, we addressed this unmet need by developing injectable 3D microscale cellular niches (microniches) based on biodegradable gelatin microcryogels (GMs). The microniches are constituted by in vitro priming human adipose-derived mesenchymal stem cells (hMSCs) seeded within GMs resulting in tissue-like ensembles with enriched extracellular matrices and enhanced cell-cell interactions. The primed 3D microniches facilitated cell protection from mechanical insults during injection and in vivo cell retention, survival, and ultimate therapeutic functions in treatment of critical limb ischemia (CLI) in mouse models compared with free cell-based therapy. In particular, 3D microniche-based therapy with 105hMSCs realized better ischemic limb salvage than treatment with 106free-injected hMSCs, the minimum dosage with therapeutic effects for treating CLI in literature. To the best of our knowledge, this is the first convincing demonstration of injectable and primed cell delivery strategy realizing superior therapeutic efficacy for treating CLI with the lowest cell dosage in mouse models. This study offers a widely applicable cell delivery platform technology to boost the healing power of cell regenerative therapy.


Lee M.-H.,Korea Institute of Ceramic Engineering And Technology | Oh N.,Inha University | Lee S.-W.,East-West Center | Leesungbok R.,East-West Center | And 3 more authors.
Biomaterials | Year: 2010

In this study, we demonstrate surfaces with various dimensions of microgrooves fabricated by photolithography and subsequent acid etching that enhance various characteristics of titanium. Microgrooves with truncated V-shape in cross-section from 15 to 90 μm widths enabled us to report their exclusive effects on altering the surface chemistry and on enhancing the surface hydrophilicity, serum protein adsorption and osteoblast maturation on titanium substrata in a microgroove dimension-dependent manner. Further, acid etching and measurement direction separately affected the surface hydrophilicity results. By multiple correlation and regression analyses, surface chemistry, surface hydrophilicity and serum protein adsorption were determined to be the significant influential factors on osteoblast maturation. Within the limitations of this study, we conclude that combined submicron- and microtopography with relevant micro-dimension and structure enhance various characteristics of titanium, including surface hydrophilicity, which act as the essential factors influencing the osteoblast maturation on microgrooved titanium substrata. © 2010 Elsevier Ltd. All rights reserved.


Bao K.,Institute of Oral Biology | Papadimitropoulos A.,Cellec Biotek AG | Akgul B.,University of Cologne | Belibasakis G.N.,Institute of Oral Biology | Bostanci N.,Institute of Oral Biology
Virulence | Year: 2015

Periodontal infection involves a complex interplay between oral biofilms, gingival tissues and cells of the immune system in a dynamic microenvironment. A humanized in vitro model that reduces the need for experimental animal models, while recapitulating key biological events in a periodontal pocket, would constitute a technical advancement in the study of periodontal disease. The aim of this study was to use a dynamic perfusion bioreactor in order to develop a gingival epithelial-fibroblast-monocyte organotypic co-culture on collagen sponges. An 11 species subgingival biofilm was used to challenge the generated tissue in the bioreactor for a period of 24 h. The histological and scanning electron microscopy analysis displayed an epithelial-like layer on the surface of the collagen sponge, supported by the underlying ingrowth of gingival fibroblasts, while monocytic cells were also found within the sponge mass. Bacterial quantification of the biofilm showed that in the presence of the organotypic tissue, the growth of selected biofilm species, especially Campylobacter rectus, Actinomyces oris, Streptococcus anginosus, Veillonella dispar, and Porphyromonas gingivalis, was suppressed, indicating a potential antimicrobial effect by the tissue. Multiplex immunoassay analysis of cytokine secretion showed that interleukin (IL)-1 β, IL-2, IL-4, and tumor necrosis factor (TNF)-α levels in cell culture supernatants were significantly up-regulated in presence of the biofilm, indicating a positive inflammatory response of the organotypic tissue to the biofilm challenge. In conclusion, this novel host-biofilm interaction organotypic model might resemble the periodontal pocket and have an important impact on the study of periodontal infections, by minimizing the need for the use of experimental animal models. © 2015 Kai Bao, Adam Papadimitropoulos, Baki Akgül, Georgios N Belibasakis, and Nagihan Bostanci.


Lee H.J.,Institute of Oral Biology | Koo A.N.,Institute of Oral Biology | Lee S.W.,Kyung Hee University | Lee M.H.,Korea Institute of Ceramic Engineering And Technology | Lee S.C.,Institute of Oral Biology
Journal of Controlled Release | Year: 2013

We report on a novel surface functionalization approach to equip the titanium (Ti) surfaces with osteogenic properties. A key feature of the approach is the treatment of the Ti surfaces with Ti-adhesive nanoparticles that can stably load and controllably release bone morphogenetic protein-2 (BMP-2). Ti-adhesive nano-particles were prepared by self-assembly of a catechol-functionalized poly(amino acid) diblock copolymer, catechol-poly(L- aspartic acid)-b-poly(L-phenylalanine) (Cat-PAsp-PPhe). The nanoparticles consist of Ti-adhesive peripheral catechol groups, anionic PAsp shells, and PPhe inner cores. Field-emission scanning electron microscopy (Fe-SEM) images showed that the Ti-adhesive nanoparticles could be uniformly immobilized on Ti surfaces. X-ray photoelectron spectroscopy (XPS) confirmed the successful anchoring of nanoparticles onto Ti surfaces. After surface immobilization of the nanoparticles, the static water contact angle of the Ti substrate decreased from 75.3° to 50.0° or 36.4°, depending on the surface nanoparticle. Fluorescence microscopic analysis showed that BMP-2 could be effectively incorporated onto the Ti surface with adhesive nanoparticles. BMP-2 was controllably released for up to 40 days. The Ti substrate functionalized with BMP-2-incorporated nanoparticles significantly promoted attachment, proliferation, spreading, and alkaline phosphatase (ALP) activity of human adipose-derived stem cell (hADSC). The catechol-functionalized adhesive nanoparticles may be applied to various medical devices to create surfaces for improved performance. © 2013 Elsevier B.V. All rights reserved.


Charalampakis G.,Gothenburg University | Belibasakis G.N.,Institute of Oral Biology
Virulence | Year: 2015

Osseointegrated dental implants are now a wellestablished treatment option in the armament of restorative dentistry. These technologically advanced devices are designed to functionally and esthetically replace missing teeth. Despite the revolutionary advances that implants have incurred, they have also provided the oral cavity with new artificial surfaces prone to the formation of oral biofilms, similarly to the hard tissue surfaces of natural teeth. Biofilm formation on the implant surface can trigger the inflammatory destruction of the peri-implant tissue, in what is known as peri-implantitis. The mixed microbial flora of periimplant infections resembles that of periodontal infections, with some notable differences. These are likely to expand with the ever increasing application of metagenomics and metatrascriptomics in the analysis of oral ecology. This review presents the wealth of knowledge we have gained from microbiological methods used in the characterization of periimplant microflora and sheds light over potential new benefits, as well as limitations, of the new sequencing technology in our understanding of peri-implant disease pathogenesis. © 2015 Taylor & Francis Group, LLC.


Kang S.,Institute of Oral Biology | Yoon I.,Institute of Oral Biology | Lee H.,Kyung Hee University | Cho J.,Institute of Oral Biology
Oral Diseases | Year: 2011

Objectives: Dental caries is greatly influenced disease by environmental factors, but recently there are increasing evidences for a genetic component in caries susceptibility. AMELX is the gene coding amelogenin, which is the most important factor for normal enamel development. The aim of this study was to examine the relationship between dental caries and single nucleotide polymorphisms (SNPs) in AMELX. Subjects and methods: For this study, we used DNA samples collected from 120 unrelated individuals older than 12years of age. All of them were examined for their oral and dental status under the WHO recommended criteria, and clinical information such as DMFT and DMFS were evaluated. Individuals whose DMFT and DMFS index lower than 2 were designated 'very low caries experience' and higher than 3 were designated 'higher caries experience'. Genomic DNA was extracted from hair samples, and single nucleotide polymorphisms of AMELX were genotyped. Genotyping of three SNPs (rs17878486, rs5933871, rs5934997, intron) in AMELX gene was determined by direct sequencing and analyzed with SNPStats. Results: There were significant associations between rs5933871 and rs5934997 SNP and caries susceptibility in the water fluoridation group. Conclusions: These results suggest that SNPs of AMELX might be associated with dental caries susceptibility in Korean population. © 2010 John Wiley & Sons A/S.


Thurnheer T.,Institute of Oral Biology | Belibasakis G.N.,Institute of Oral Biology
Virulence | Year: 2015

Biofilms are polymicrobial communities that grow on surfaces in nature. Oral bacteria can spontaneously form biofilms on the surface of teeth, which may compromise the health of the teeth, or their surrounding (periodontal) tissues. While the oral bacteria exhibit high tropism for their specialized ecological niche, it is not clear if bacteria that are not part of the normal oral microbiota can efficiently colonize and grow within oral biofilms. By using an in vitro “supragingival” biofilm model of 6 oral species, this study aimed to investigate if 3 individual bacterial species that are not part of the normal oral microbiota (Eschericia coli, Staphylococcus aureus, Enterococcus faecails) and one not previously tested oral species (Aggregatibacter actinomycetemcomitans) can be incorporated into this established supragingival biofilm model. Staphylococcus aureus and A. actinomycetemcomitans were able to grow efficiently in the biofilm, without disrupting the growth of the remaining species. They localized in sparse small aggregates within the biofilm mass. Enterococcus faecalis and E. coli were both able to populate the biofilm at high numbers, and suppressed the growth of A. oris and S. mutants. Enterococcus faecalis was arranged in a chain-like conformation, whereas E. coli was densely and evenly spread throughout the biofilm mass. In conclusion, it is possible for selected species that are not part of the normal oral microbiota to be introduced into an oral biofilm, under the given experimental microenvironmental conditions. Moreover, the equilibrated incorporation of A. actinomycetemcomitans and S. aureus in this oral biofilm model could be a useful tool in the study of aggressive periodontitis and peri-implantitis, in which these organisms are involved, respectively. © 2015 Taylor & Francis Group, LLC.


Kim E.-C.,Institute of Oral Biology | Leesungbok R.,Kyung Hee University | Lee S.-W.,Kyung Hee University | Lee H.-W.,Institute of Oral Biology | And 3 more authors.
Bioelectromagnetics | Year: 2015

This study aimed to explore effects of static magnetic fields (SMFs) of moderate intensity (3-50mT) as biophysical stimulators of proliferation and osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells (MSCs). MSCs were exposed to SMFs of three intensities: 3, 15, and 50mT. Proliferation was assessed by cell counting and bromodeoxyuridine incorporation, and differentiation by measuring alkaline phosphatase (ALP) activity, calcium content, mineralized nodule formation, and transcripts of osteogenic markers. Moderate intensity SMFs increased cell proliferation, ALP activity, calcium release, and mineralized nodule formation in a dose- and time-dependent manner, which peaked at 15mT. In the same manner, they upregulated expression of osteogenic marker genes such as ALP, bone sialoprotein 2 (BSP2), collagen1a1 (COL1a1), osteocalcin (OCN), osteonectin (ON), osteopontin (OPN), osterix (OSX), and runt-related transcription factor 2 (RUNX2) with peak at 15mT after 14 or 21 days of exposure. Results demonstrate that moderate intensity SMFs promote proliferation and osteoblastic differentiation of MSCs. This effect could help to improve MSC responses during osseointegration between a dental implant and surrounding bone. © 2015 Wiley Periodicals, Inc.

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