Personalized scaffolding technologies for alveolar bone regenerative medicine

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149271/1/ocr12275.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149271/2/ocr12275_am.pd

Osteoinduction of Human Mesenchymal Stem Cells by Bioactive Composite Scaffolds without Supplemental Osteogenic Growth Factors

The development of a new family of implantable bioinspired materials is a focal point of bone tissue engineering. Implant surfaces that better mimic the natural bone extracellular matrix, a naturally nano-composite tissue, can stimulate stem cell differentiation towards osteogenic lineages in the absence of specific chemical treatments. Herein we describe a bioactive composite nanofibrous scaffold, composed of poly-caprolactone (PCL) and nano-sized hydroxyapatite (HA) or beta-tricalcium phosphate (TCP), which was able to support the growth of human bone marrow mesenchymal stem cells (hMSCs) and guide their osteogenic differentiation at the same time. Morphological and physical/chemical investigations were carried out by scanning, transmission electron microscopy, Fourier-transform infrared (FTIR) spectroscopy, mechanical and wettability analysis. Upon culturing hMSCs on composite nanofibers, we found that the incorporation of either HA or TCP into the PCL nanofibers did not affect cell viability, meanwhile the presence of the mineral phase increases the activity of alkaline phosphatase (ALP), an early marker of bone formation, and mRNA expression levels of osteoblast-related genes, such as the Runt-related transcription factor 2 (Runx-2) and bone sialoprotein (BSP), in total absence of osteogenic supplements. These results suggest that both the nanofibrous structure and the chemical composition of the scaffolds play a role in regulating the osteogenic differentiation of hMSCs

Malocclusion, psycho-social impacts and treatment need: A cross-sectional study of Tanzanian primary school-children

<p>Abstract</p> <p>Background</p> <p>studies on the relationship between children's malocclusion and its psycho-social impacts are so far largely unexplored in low-income countries. This study aimed to assess the prevalence of malocclusion, reported dental problems and dissatisfaction with dental appearance among primary school children in Tanzania. The relationship of dissatisfaction with socio-demographic characteristics, clinically defined malocclusion and psychosocial impacts of dental anomalies was investigated. Orthodontic treatment need was estimated using an integrated socio-dental approach.</p> <p>Method</p> <p>One thousand six hundred and one children (mean age 13 yr) attending primary schools in the districts of Kinondoni and Temeke completed face to face interviews and a full mouth clinical examination. The survey instrument was designed to measure a Kiswahili translated and culturally adapted Child Oral Impact on Daily Performance (Child-OIDP) frequency score, reported dental problems, dissatisfaction with dental appearance/function and socio-demographic characteristics.</p> <p>Results</p> <p>The prevalence of malocclusion varied from 0.9% (deep bite) to 22.5% (midline shift) with a total of 63.8% having at least one type of anomaly. Moderate proportions of children admitted dental problems; ranging from 7% (space position) to 20% (pain). The odds ratio of having problems with teeth position, spaces, pain and swallowing if having any malocclusion were, respectively 6.7, 3.9, 1.4 and 6.8. A total of 23.3% children were dissatisfied with dental appearance/function. Children dissatisfied with their dental appearance were less likely to be Temeke residents (OR = 0.5) and having parents of higher education (OR = 0.6) and more likely to reporting problem with teeth position (OR = 4.3) and having oral impacts (OR = 2.7). The socio-dental treatment need of 12% was five times lower than the normative need assessment of 63.8%.</p> <p>Conclusion</p> <p>Compared to the high prevalence of malocclusion, psycho social impacts and dissatisfaction with appearance/function was not frequent among Tanzanian schoolchildren. Subjects with malocclusion reported problems most frequently and malocclusion together with other psycho-social impact scores determined children's satisfaction with teeth appearance- and function.</p

Scaffolds with a standardized macro-architecture fabricated from several calcium phosphate ceramics using an indirect rapid prototyping technique

Calcium phosphate ceramics, commonly applied as bone graft substitutes, are a natural choice of scaffolding material for bone tissue engineering. Evidence shows that the chemical composition, macroporosity and microporosity of these ceramics influences their behavior as bone graft substitutes and bone tissue engineering scaffolds but little has been done to optimize these parameters. One method of optimization is to place focus on a particular parameter by normalizing the influence, as much as possible, of confounding parameters. This is difficult to accomplish with traditional fabrication techniques. In this study we describe a design based rapid prototyping method of manufacturing scaffolds with virtually identical macroporous architectures from different calcium phosphate ceramic compositions. Beta-tricalcium phosphate, hydroxyapatite (at two sintering temperatures) and biphasic calcium phosphate scaffolds were manufactured. The macro- and micro-architectures of the scaffolds were characterized as well as the influence of the manufacturing method on the chemistries of the calcium phosphate compositions. The structural characteristics of the resulting scaffolds were remarkably similar. The manufacturing process had little influence on the composition of the materials except for the consistent but small addition of, or increase in, a beta-tricalcium phosphate phase. Among other applications, scaffolds produced by the method described provide a means of examining the influence of different calcium phosphate compositions while confidently excluding the influence of the macroporous structure of the scaffolds

Factors influencing gastrointestinal tract and microbiota immune interaction in preterm infants

The role of microbial colonization is indispensable for keeping a balanced immune response in life. However, the events that regulate the establishment of the microbiota, their timing, and the way in which they interact with the host are not yet fully understood. Factors such as gestational age, mode of delivery, environment, hygienic measures, and diet influence the establishment of microbiota in the perinatal period. Environmental microbes constitute the most important group of exogenous stimuli in this critical time frame. However, the settlement of a stable gut microbiota in preterm infants is delayed compared to term infants. Preterm infants have an immature gastrointestinal tract and immune system which predisposes to infectious morbidity. Neonatal microbial dynamics and alterations in early gut microbiota may precede and/or predispose to diseases such as necrotizing enterocolitis (NEC), late-onset sepsis or others. During this critical period, nutrition is the principal contributor for immunological and metabolic development, and microbiological programming. Breast milk is a known source of molecules that act synergistically to protect the gut barrier and enhance the maturation of the gut-related immune response. Host-microbe interactions in preterm infants and the protective role of diet focused on breast milk impact are beginning to be unveiled.M.C. acknowledges a “Rio Hortega” Research Fellowship Grant (CM13/0017) and M.V. acknowledges grants PI11/0313 and RD12/0026/0012 (Red SAMID) from the Instituto Carlos III (Spanish Ministry of Economy and Competitivity). M.C.C. and G.P-M. were supported by the grant AGL2013-47420-R from the Spanish Ministry of Science and Innovation.Peer reviewe

Reducing Alaska Native paediatric oral health disparities: a systematic review of oral health interventions and a case study on multilevel strategies to reduce sugar-sweetened beverage intake

Background. Tooth decay is the most common paediatric disease and there is a serious paediatric tooth decay epidemic in Alaska Native communities. When untreated, tooth decay can lead to pain, infection, systemic health problems, hospitalisations and in rare cases death, as well as school absenteeism, poor grades and low quality-of-life. The extent to which population-based oral health interventions have been conducted in Alaska Native paediatric populations is unknown. Objective. To conduct a systematic review of oral health interventions aimed at Alaska Native children below age 18 and to present a case study and conceptual model on multilevel intervention strategies aimed at reducing sugar-sweetened beverage (SSB) intake among Alaska Native children. Design. Based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Statement, the terms &#x201C;Alaska Native&#x201D;, &#x201C;children&#x201D; and &#x201C;oral health&#x201D; were used to search Medline, Embase, Web of Science, GoogleScholar and health foundation websites (1970&#x2013;2012) for relevant clinical trials and evaluation studies. Results. Eighty-five studies were found in Medline, Embase and Web of Science databases and there were 663 hits in GoogleScholar. A total of 9 publications were included in the qualitative review. These publications describe 3 interventions that focused on: reducing paediatric tooth decay by educating families and communities; providing dental chemotherapeutics to pregnant women; and training mid-level dental care providers. While these approaches have the potential to improve the oral health of Alaska Native children, there are unique challenges regarding intervention acceptability, reach and sustainability. A case study and conceptual model are presented on multilevel strategies to reduce SSB intake among Alaska Native children. Conclusions. Few oral health interventions have been tested within Alaska Native communities. Community-centred multilevel interventions are promising approaches to improve the oral and systemic health of Alaska Native children. Future investigators should evaluate the feasibility of implementing multilevel interventions and policies within Alaska Native communities as a way to reduce children&#x0027;s health disparities

Assessing the complex sponge microbiota: core, variable and species-specific bacterial communities in marine sponges

Marine sponges are well known for their associations with highly diverse, yet very specific and often highly similar microbiota. The aim of this study was to identify potential bacterial sub-populations in relation to sponge phylogeny and sampling sites and to define the core bacterial community. 16S ribosomal RNA gene amplicon pyrosequencing was applied to 32 sponge species from eight locations around the world's oceans, thereby generating 2567 operational taxonomic units (OTUs at the 97% sequence similarity level) in total and up to 364 different OTUs per sponge species. The taxonomic richness detected in this study comprised 25 bacterial phyla with Proteobacteria, Chloroflexi and Poribacteria being most diverse in sponges. Among these phyla were nine candidate phyla, six of them found for the first time in sponges. Similarity comparison of bacterial communities revealed no correlation with host phylogeny but a tropical sub-population in that tropical sponges have more similar bacterial communities to each other than to subtropical sponges. A minimal core bacterial community consisting of very few OTUs (97%, 95% and 90%) was found. These microbes have a global distribution and are probably acquired via environmental transmission. In contrast, a large species-specific bacterial community was detected, which is represented by OTUs present in only a single sponge species. The species-specific bacterial community is probably mainly vertically transmitted. It is proposed that different sponges contain different bacterial species, however, these bacteria are still closely related to each other explaining the observed similarity of bacterial communities in sponges in this and previous studies. This global analysis represents the most comprehensive study of bacterial symbionts in sponges to date and provides novel insights into the complex structure of these unique associations

Transcriptomic profiling of host-parasite interactions in the microsporidian <i>Trachipleistophora hominis</i>

BACKGROUND: Trachipleistophora hominis was isolated from an HIV/AIDS patient and is a member of a highly successful group of obligate intracellular parasites. METHODS: Here we have investigated the evolution of the parasite and the interplay between host and parasite gene expression using transcriptomics of T. hominis-infected rabbit kidney cells. RESULTS: T. hominis has about 30 % more genes than small-genome microsporidians. Highly expressed genes include those involved in growth, replication, defence against oxidative stress, and a large fraction of uncharacterised genes. Chaperones are also highly expressed and may buffer the deleterious effects of the large number of non-synonymous mutations observed in essential T. hominis genes. Host expression suggests a general cellular shutdown upon infection, but ATP, amino sugar and nucleotide sugar production appear enhanced, potentially providing the parasite with substrates it cannot make itself. Expression divergence of duplicated genes, including transporters used to acquire host metabolites, demonstrates ongoing functional diversification during microsporidian evolution. We identified overlapping transcription at more than 100 loci in the sparse T. hominis genome, demonstrating that this feature is not caused by genome compaction. The detection of additional transposons of insect origin strongly suggests that the natural host for T. hominis is an insect. CONCLUSIONS: Our results reveal that the evolution of contemporary microsporidian genomes is highly dynamic and innovative. Moreover, highly expressed T. hominis genes of unknown function include a cohort that are shared among all microsporidians, indicating that some strongly conserved features of the biology of these enormously successful parasites remain uncharacterised. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1989-z) contains supplementary material, which is available to authorized users

Associations between the gut microbiota and host immune markers in pediatric multiple sclerosis and controls

BACKGROUND: As little is known of association(s) between gut microbiota profiles and host immunological markers, we explored these in children with and without multiple sclerosis (MS). METHODS: Children ≤18 years provided stool and blood. MS cases were within 2-years of onset. Fecal 16S rRNA gene profiles were generated on an Illumina Miseq platform. Peripheral blood mononuclear cells were isolated, and Treg (CD4(+)CD25(hi)CD127(low)FoxP3(+)) frequency and CD4(+) T-cell intracellular cytokine production evaluated by flow cytometry. Associations between microbiota diversity, phylum-level abundances and immune markers were explored using Pearson’s correlation and adjusted linear regression. RESULTS: Twenty-four children (15 relapsing-remitting, nine controls), averaging 12.6 years were included. Seven were on a disease-modifying drug (DMD) at sample collection. Although immune markers (e.g. Th2, Th17, Tregs) did not differ between cases and controls (p > 0.05), divergent gut microbiota associations occurred; richness correlated positively with Th17 for cases (r = +0.665, p = 0.018), not controls (r = −0.644, p = 0.061). Bacteroidetes inversely associated with Th17 for cases (r = −0.719, p = 0.008), not controls (r = +0.320, p = 0.401). Fusobacteria correlated with Tregs for controls (r = +0.829, p = 0.006), not cases (r = −0.069, p = 0.808). CONCLUSIONS: Our observations motivate further exploration to understand disruption of the microbiota-immune balance so early in the MS course. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12883-016-0703-3) contains supplementary material, which is available to authorized users