Jacob Dairaghi, Claudia Benito Alston, Rachel Cadle, Dan Rogozea, Luis Solorio, Clark T. Barco, N. Moldovan
{"title":"A dual osteoconductive-osteoprotective implantable device for vertical alveolar ridge augmentation","authors":"Jacob Dairaghi, Claudia Benito Alston, Rachel Cadle, Dan Rogozea, Luis Solorio, Clark T. Barco, N. Moldovan","doi":"10.3389/fdmed.2022.1066501","DOIUrl":"https://doi.org/10.3389/fdmed.2022.1066501","url":null,"abstract":"Repair of large oral bone defects such as vertical alveolar ridge augmentation could benefit from the rapidly developing additive manufacturing technology used to create personalized osteoconductive devices made from porous tricalcium phosphate/hydroxyapatite (TCP/HA)-based bioceramics. These devices can be also used as hydrogel carriers to improve their osteogenic potential. However, the TCP/HA constructs are prone to brittle fracture, therefore their use in clinical situations is difficult. As a solution, we propose the protection of this osteoconductive multi-material (herein called “core”) with a shape-matched “cover” made from biocompatible poly-ɛ-caprolactone (PCL), which is a ductile, and thus more resistant polymeric material. In this report, we present a workflow starting from patient-specific medical scan in Digital Imaging and Communications in Medicine (DICOM) format files, up to the design and 3D printing of a hydrogel-loaded porous TCP/HA core and of its corresponding PCL cover. This cover could also facilitate the anchoring of the device to the patient's defect site via fixing screws. The large, linearly aligned pores in the TCP/HA bioceramic core, their sizes, and their filling with an alginate hydrogel were analyzed by micro-CT. Moreover, we created a finite element analysis (FEA) model of this dual-function device, which permits the simulation of its mechanical behavior in various anticipated clinical situations, as well as optimization before surgery. In conclusion, we designed and 3D-printed a novel, structurally complex multi-material osteoconductive-osteoprotective device with anticipated mechanical properties suitable for large-defect oral bone regeneration.","PeriodicalId":73077,"journal":{"name":"Frontiers in dental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47360460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alissa Villhauer, Min Zhu, Wei Shi, Xian Jin Xie, Pamella Hughes, Amy Lesch, Karin Weber-Gasparoni, Justine Kolker, David Drake, Jeffrey A Banas
{"title":"Role of mutans streptococci, acid tolerant bacteria and oral <i>Candida</i> species in predicting the onset of early childhood caries.","authors":"Alissa Villhauer, Min Zhu, Wei Shi, Xian Jin Xie, Pamella Hughes, Amy Lesch, Karin Weber-Gasparoni, Justine Kolker, David Drake, Jeffrey A Banas","doi":"10.3389/fdmed.2023.991746","DOIUrl":"10.3389/fdmed.2023.991746","url":null,"abstract":"<p><strong>Aim: </strong>Early childhood caries is the most common chronic infectious disease in children in the United States. This study, which is part of a larger, longitudinal study exploring oral microbiological components of caries development in children, reports on the impact of total mutans streptococci (MS), total acid tolerant bacteria and <i>Candida</i> species on the development of dental caries in a subset of these children. Of particular interest was the relationship between caries development and co-colonization of mutans streptococci and <i>Candida</i> species.</p><p><strong>Methods: </strong>Children between the ages of 12 and 47 months displaying no evidence of dental caries were recruited for a longitudinal study (<i>n</i> = 130). Twelve age- and gender-matched pairs were selected. In each pair, one child developed caries during the study, and one did not. Whole mouth plaque samples were collected by swab at baseline and every 6 months thereafter for a duration of 18 months and spiral plated for microbial counts (CFU/ml). Cut-offs based on percent of total cultivable flora were designated for all microbial measures. A scoring system designated the Plaque Microbial Index (PMI) was developed for use in statistical analyses to assess potential predictive factors for caries risk assessment.</p><p><strong>Results: </strong>Children who developed caries were significantly more likely to harbor higher percentages of acid tolerant bacteria (<i>p</i> = 0.003), MS (<i>p</i> < 0.001) and have <i>Candida</i> species present (<i>p</i> < 0.001) at ≥1 visit leading up to caries onset. Mean PMI scores derived from the aforementioned microbial measures, were higher for caries active children than caries free children (<i>p</i> = 0.000147). Co-colonization of MS and <i>Candida</i> species was significantly associated with caries development (<i>p</i> < 0.001) and detection of both at the same visit had a 100% positive predictive value and 60% negative predictive value for caries development.</p><p><strong>Conclusion: </strong>In children who developed caries, there was a statistically significant association with the percent of total flora that was acid tolerant, the percent of MS, the presence of <i>Candida</i> and co-colonization of MS and <i>Candida</i> species. Combining these microbial measures into PMI scores further delineated children who developed caries from those who remained caries-free. These microbiological measures show potential as predictive factors and risk assessment tools for caries development.</p>","PeriodicalId":73077,"journal":{"name":"Frontiers in dental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10768932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43901167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A L Petrin, E Zeng, M A Thomas, D Moretti-Ferreira, M L Marazita, X J Xie, J C Murray, L M Moreno-Uribe
{"title":"DNA methylation differences in monozygotic twins with Van der Woude syndrome.","authors":"A L Petrin, E Zeng, M A Thomas, D Moretti-Ferreira, M L Marazita, X J Xie, J C Murray, L M Moreno-Uribe","doi":"10.3389/fdmed.2023.1120948","DOIUrl":"10.3389/fdmed.2023.1120948","url":null,"abstract":"<p><strong>Introduction: </strong>Van der Woude Syndrome (VWS) is an autosomal dominant disorder responsible for 2% of all syndromic orofacial clefts (OFCs) with <i>IRF6</i> being the primary causal gene (70%). Cases may present with lip pits and either cleft lip, cleft lip with cleft palate, or cleft palate, with marked phenotypic discordance even among individuals carrying the same mutation. This suggests that genetic or epigenetic modifiers may play additional roles in the syndrome's etiology and variability in expression. We report the first DNA methylation profiling of 2 pairs of monozygotic twins with VWS. Our goal is to explore epigenetic contributions to VWS etiology and variable phenotypic expressivity by comparing DNAm profiles in both twin pairs. While the mutations that cause VWS in these twins are known, the additional mechanism behind their phenotypic risk and variability in expression remains unclear.</p><p><strong>Methods: </strong>We generated whole genome DNAm data for both twin pairs. Differentially methylated positions (DMPs) were selected based on: (1) a coefficient of variation in DNAm levels in unaffected individuals < 20%, and (2) intra-twin pair absolute difference in DNAm levels >5% (delta beta > | 0.05|). We then divided the DMPs in two subgroups for each twin pair for further analysis: (1) higher methylation levels in twin A (Twin A > Twin B); and (2) higher methylation levels in twin B (Twin B >Twin A).</p><p><strong>Results and discussion: </strong>Gene ontology analysis revealed a list of enriched genes that showed significant differential DNAm, including clef-associated genes. Among the cleft-associated genes, <i>TP63</i> was the most significant hit (p=7.82E-12). Both twin pairs presented differential DNAm levels in CpG sites in/near <i>TP63</i> (Twin 1A > Twin 1B and Twin 2A < Twin 2B). The genes <i>TP63</i> and <i>IRF6</i> function in a biological regulatory loop to coordinate epithelial proliferation and differentiation in a process that is critical for palatal fusion. The effects of the causal mutations in <i>IRF6</i> can be further impacted by epigenetic dysregulation of <i>IRF6</i> itself, or genes in its pathway. Our data shows evidence that changes in DNAm is a plausible mechanism that can lead to markedly distinct phenotypes, even among individuals carrying the same mutation.</p>","PeriodicalId":73077,"journal":{"name":"Frontiers in dental medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9149861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sesha Hanson-Drury, Anjali P Patni, Deborah L Lee, Ammar Alghadeer, Yan Ting Zhao, Devon Duron Ehnes, Vivian N Vo, Sydney Y Kim, Druthi Jithendra, Ashish Phal, Natasha I Edman, Thomas Schlichthaerle, David Baker, Jessica E Young, Julie Mathieu, Hannele Ruohola-Baker
{"title":"Single Cell RNA Sequencing Reveals Human Tooth Type Identity and Guides <i>In Vitro</i> hiPSC Derived Odontoblast Differentiation (iOB).","authors":"Sesha Hanson-Drury, Anjali P Patni, Deborah L Lee, Ammar Alghadeer, Yan Ting Zhao, Devon Duron Ehnes, Vivian N Vo, Sydney Y Kim, Druthi Jithendra, Ashish Phal, Natasha I Edman, Thomas Schlichthaerle, David Baker, Jessica E Young, Julie Mathieu, Hannele Ruohola-Baker","doi":"10.3389/fdmed.2023.1209503","DOIUrl":"10.3389/fdmed.2023.1209503","url":null,"abstract":"<p><p>Over 90% of the U.S. adult population suffers from tooth structure loss due to caries. Most of the mineralized tooth structure is composed of dentin, a material produced and mineralized by ectomesenchyme derived cells known as odontoblasts. Clinicians, scientists, and the general public share the desire to regenerate this missing tooth structure. To bioengineer missing dentin, increased understanding of human tooth development is required. Here we interrogate at the single cell level the signaling interactions that guide human odontoblast and ameloblast development and which determine incisor or molar tooth germ type identity. During human odontoblast development, computational analysis predicts that early FGF and BMP activation followed by later HH signaling is crucial. Application of this sci-RNA-seq analysis generates a differentiation protocol to produce mature hiPSC derived odontoblasts <i>in vitro</i> (iOB). Further, we elucidate the critical role of FGF signaling in odontoblast maturation and its biomineralization capacity using the <i>de novo</i> designed FGFR1/2c isoform specific minibinder scaffolded as a C6 oligomer that acts as a pathway agonist. We find that FGFR1c is upregulated in functional odontoblasts and specifically plays a crucial role in driving odontoblast maturity. Using computational tools, we show on a molecular level how human molar development is delayed compared to incisors. We reveal that enamel knot development is guided by FGF and WNT in incisors and BMP and ROBO in the molars, and that incisor and molar ameloblast development is guided by FGF, EGF and BMP signaling, with tooth type specific intensity of signaling interactions. Dental ectomesenchyme derived cells are the primary source of signaling ligands responsible for both enamel knot and ameloblast development.</p>","PeriodicalId":73077,"journal":{"name":"Frontiers in dental medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46491582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Discoidin domain receptors; an ancient family of collagen receptors has major roles in bone development, regeneration and metabolism.","authors":"Renny T Franceschi, Shawn A Hallett, Chunxi Ge","doi":"10.3389/fdmed.2023.1181817","DOIUrl":"10.3389/fdmed.2023.1181817","url":null,"abstract":"<p><p>The extracellular matrix (ECM) niche plays a critical role in determining cellular behavior during bone development including the differentiation and lineage allocation of skeletal progenitor cells to chondrocytes, osteoblasts, or marrow adipocytes. As the major ECM component in mineralized tissues, collagen has instructive as well as structural roles during bone development and is required for bone cell differentiation. Cells sense their extracellular environment using specific cell surface receptors. For many years, specific β1 integrins were considered the main collagen receptors in bone, but, more recently, the important role of a second, more primordial collagen receptor family, the discoidin domain receptors, has become apparent. This review will specifically focus on the roles of discoidin domain receptors in mineralized tissue development as well as related functions in abnormal bone formation, regeneration and metabolism.</p>","PeriodicalId":73077,"journal":{"name":"Frontiers in dental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10785288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41341288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The dynamic interplay of dietary acid pH and concentration during early-stage human enamel and dentine erosion","authors":"J. Pattem, J. Field, P. Waterhouse, M. German","doi":"10.3389/fdmed.2022.1040565","DOIUrl":"https://doi.org/10.3389/fdmed.2022.1040565","url":null,"abstract":"Dental erosion continues to be a significant global health concern affecting nearly 30% of adults world-wide. With increasing soft drink consumption predominantly driving its prevalence, strategies for prevention and control are often implemented when erosion is severe, or rates are high in the populace. While factors affecting dental erosion such as pH on enamel has received much attention, the effect of dietary acid concentration when factored out to a commercially available pH has yet to be determined. Furthermore, understanding these effects on dentine, which is known to be more susceptible to erosion than enamel can unravel structure property relationships between acid characteristics and hard tissue types. This study aimed to develop structure-property relationships between dietary acid concentration, and pH, on the nano-textural and nano-mechanical properties of human enamel and dentine during short-term simulated drinking. To achieve this, a novel sample preparation methodology and analysis approach was developed by applying atomic force microscopy (AFM) in quantitative imaging mode. This enabled simultaneous measurement of enamel and dentine morphology and mechanical properties. Flow-cells were used to simulate drinking, exposing polished and smear layer free human enamel and dentine to 30 s repeated cycles of unbuffered citric acid 6% (pH = 1.88) and 1% (w/v) (pH = 2.55) and commercially available buffered pH = 3.8 states, for up to 180 s. The same 50 µm × 50 µm area of specimen morphology was analysed using in-house developed nanotextural analysis using the bearing area curve (BAC) with a focus on roughness (Ra), normalised peak (PA) and valley areas (VA). Mechanical properties were simultaneously measured for stiffness (N/m) after each 30 s. While all studies agree pH is a major factor in the erosion of enamel, here its dominance over the treatment time varied, with concentration surpassing the importance of pH after initial acid contact. Conversely, dentine erosion showed concentration-dependent changes in morpho-mechanical properties only. These results not only highlight the dynamic process of erosion, but how the interplay between acid characteristics and dental tissue type impact the progression of very early-stage erosion.","PeriodicalId":73077,"journal":{"name":"Frontiers in dental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47336725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Konstantinos Valamvanos, Theodoros-Filippos Valamvanos, Spyridon Toumazou, E. Gartzouni
{"title":"The combined use of photobiomodulation therapy and platelet-rich fibrin for the management of two MRONJ stage II cases: An alternative approach","authors":"Konstantinos Valamvanos, Theodoros-Filippos Valamvanos, Spyridon Toumazou, E. Gartzouni","doi":"10.3389/fdmed.2022.973738","DOIUrl":"https://doi.org/10.3389/fdmed.2022.973738","url":null,"abstract":"Medication-related osteonecrosis of the jaws (MRONJ) is a relatively rare but serious adverse drug reaction in patients under bone-targeting or antiangiogenic medication for malignant or osteometabolic diseases. The pathogenesis of MRONJ is multifactorial with the inhibition of osteoclasts and angiogenesis considered to play a keyrole in an individually susceptible environment, thus its prevalence is highly differentiated according to each study. Even though MRONJ has been reported since 2003 and the literature is expanding rapidly about possible risk factors, prevention and treatment options, the successful management with no recurrence is still under controversy. The conservative non-surgical (optimal oral hygiene, systemic antibiotic therapy) and surgical procedures (debridement, sequestrectomy or bone resection) are considered the treatment of choice especially at the early stages. Adjuvant therapies have been proposed to further stimulate bone and tissue healing such as teriparatide, bone morphogenic proteins, platelet concentrates, hyperbaric oxygen, ozone therapy, photodynamic therapy and lasers with promising results. The need to develop minimally invasive treatment protocols using novel technologies in particular for those patients with severe medical history has been highlighted in the literature. The clinical protocol that has been developed in our dental department, which is effectively contributing to MRONJ management and associates Photobiomodulation therapy (PBMT) with platelet-rich fibrin (A-PRF), will be presented in this article.","PeriodicalId":73077,"journal":{"name":"Frontiers in dental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42287781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetic aspects of dental caries","authors":"D. Çoğulu, Ceren Sağlam","doi":"10.3389/fdmed.2022.1060177","DOIUrl":"https://doi.org/10.3389/fdmed.2022.1060177","url":null,"abstract":"Dental caries is a common chronic disease affecting humans in all age groups. Various factors can affect the formation of caries including demineralization and remineralization processes with oral flora; dietary and oral hygiene habits; salivary composition, flow rate, pH and buffering capacity; morphological features of the teeth; fluoride exposures, environmental and socioeconomic factors. One of the most important factors causing inter-individual variations in caries susceptibility is the host genetics. Several genes affect individual caries susceptibility. Genes play a role in immune response, development of saliva and tooth enamel. The present review aims to overview the literature focusing on the genetic features of dental caries.","PeriodicalId":73077,"journal":{"name":"Frontiers in dental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41628595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Jing, Mingyi Zhang, T. Guo, Fei Pei, Yuchen Yang, Y. Chai
{"title":"Rodent incisor as a model to study mesenchymal stem cells in tissue homeostasis and repair","authors":"J. Jing, Mingyi Zhang, T. Guo, Fei Pei, Yuchen Yang, Y. Chai","doi":"10.3389/fdmed.2022.1068494","DOIUrl":"https://doi.org/10.3389/fdmed.2022.1068494","url":null,"abstract":"The homeostasis of adult tissues, such as skin, hair, blood, and bone, requires continuous generation of differentiated progeny of stem cells. The rodent incisor undergoes constant renewal and can provide an extraordinary model for studying stem cells and their progeny in adult tissue homeostasis, cell differentiation and injury-induced regeneration. Meanwhile, cellular heterogeneity in the mouse incisor also provides an opportunity to study cell-cell communication between different cell types, including interactions between stem cells and their niche environment. More importantly, the molecular and cellular regulatory mechanisms revealed by the mouse incisor have broad implications for other organs. Here we review recent findings and advances using the mouse incisor as a model, including perspectives on the heterogeneity of cells in the mesenchyme, the niche environment, and signaling networks that regulate stem cell behavior. The progress from this field will not only expand the knowledge of stem cells and organogenesis, but also bridge a gap between animal models and tissue regeneration.","PeriodicalId":73077,"journal":{"name":"Frontiers in dental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45556891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}