Topic Editors

Prof. Dr. Gianrico Spagnuolo
Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples “Federico II”, 80131 Naples, Italy
Prof. Dr. Marco Tatullo
1. Department of Translational Biomedicine and Neuroscience (DiBraiN), University of Bari “Aldo Moro”, 70121 Bari, Italy
2. Honorary Senior Clinical Lecturer, University of Dundee, Dundee DD1 4HR, UK
3. Founding Member of MIRROR—Medical Institute for Regeneration and Repairing and Organ Replacement, Interdepartmental Center, University of Bari “Aldo Moro”, 70124 Bari, Italy

Advances in Dental Biomaterials and Oral Tissues Engineering

Abstract submission deadline
closed (31 December 2021)
Manuscript submission deadline
closed (31 March 2022)
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Topic Information

Dear Colleagues,

Novel and advanced dental biomaterials are rapidly improving the quality of clinical applications within the main branches of dentistry. Oral tissues engineering (OTE) belongs to the wider field of regenerative medicine, a miscellaneous area that embraces interdisciplinary fields of research with interesting clinical applications. OTE is mainly focused on reparation and substitution, as well as the regeneration of oral tissues and organs, aiming at their rehabilitation, restoring both function and anatomy. The healing of damaged tissues is commonly induced by physiological processes that successfully merge biomaterials, 3D scaffolds, growth factors, and stem cells together. Functional biomaterials represent the latest development of bioactive materials: they have been investigated and improved, especially in dental applications, demonstrating promising results on oral tissues healing and rehabilitation. Oral tissues engineering plays a pivotal role in the continuous development of novel biomaterials: the future challenges are based on the discovery of smart biomaterials, able not only to replace and/or restore dental tissues, but also to mimic their biological features, thus ensuring successful treatments in several dental applications.

The aim of this Topic is to provide an updated and highly impacting overview of the current best performers and on the future perspectives related to dental biomaterials. Debates on the role of scaffolds in bone regeneration, composites materials for dental restorations and biomaterials for oral tissues rehabilitation are highly welcome. The papers should also cover the current developments in biomaterials design, materials-to-tissues interaction, and tissue self-repairing. Authors are invited to focus their attention on bioactive materials, nanotechnologies and interdisciplinary research.

Potential topics include, but are not limited to:

- Regenerative dentistry

- Oral tissue engineering

- Bone substitute materials

- Newly developed composites materials

- Bioactive materials

- Advances in oral rehabilitation

- New diagnostic tools

- Biomaterial/tissue interactions

Prof. Dr. Gianrico Spagnuolo
Prof. Dr. Marco Tatullo
Topic Editors

Keywords

  • dental materials
  • dentistry biomaterials
  • tissue engineering, regenerative dentistry

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Applied Sciences
applsci
2.838 3.7 2011 17.4 Days 2300 CHF
Journal of Clinical Medicine
jcm
4.964 4.4 2012 20.6 Days 2400 CHF
Dentistry Journal
dentistry
- 3.5 2013 23.6 Days 1600 CHF
International Journal of Molecular Sciences
ijms
6.208 6.9 2000 15.9 Days 2300 CHF
Methods and Protocols
mps
- 3.0 2018 22.8 Days 1600 CHF

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Published Papers (23 papers)

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Article
Preparation of Calcium Phosphate Compounds on Zirconia Surfaces for Dental Implant Applications
Int. J. Mol. Sci. 2022, 23(12), 6675; https://doi.org/10.3390/ijms23126675 - 15 Jun 2022
Viewed by 800
Abstract
Titanium is widely used in medical implants despite the release of heavy metal ions over long-term use. Zirconia is very close to the color of teeth; however, its biological inertness hinders bonding with bone tissue. Alkaline treatment and coatings of calcium phosphate can [...] Read more.
Titanium is widely used in medical implants despite the release of heavy metal ions over long-term use. Zirconia is very close to the color of teeth; however, its biological inertness hinders bonding with bone tissue. Alkaline treatment and coatings of calcium phosphate can be used to enhance bone regeneration adjacent to dental implants. This study examined the effects of alkaline treatment, calcium phosphate coatings, and sintering, on the physical properties of implant material. Our analysis confirmed that the calcium phosphate species were octacalcium phosphate (OCP). The sintering of calcium phosphate was shown to create B-type HAP, which is highly conducive toward the differentiation of mesenchymal stem cells (MSCs) into osteoblasts for the facilitation of bone integration. Conclusions: This study demonstrated the room-temperature fabrication of dental implants with superhydrophilic surfaces to enhance biocompatibility. Full article
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Article
Blood Clots versus PRF: Activating TGF-β Signaling and Inhibiting Inflammation In Vitro
Int. J. Mol. Sci. 2022, 23(11), 5897; https://doi.org/10.3390/ijms23115897 - 24 May 2022
Viewed by 1052
Abstract
The preparation of platelet-rich fibrin (PRF) requires blood centrifugation to separate the yellow plasma from the red erythrocyte fraction. PRF membranes prepared from coagulated yellow plasma are then transferred to the defect sites to support tissue regeneration. During natural wound healing, however, it [...] Read more.
The preparation of platelet-rich fibrin (PRF) requires blood centrifugation to separate the yellow plasma from the red erythrocyte fraction. PRF membranes prepared from coagulated yellow plasma are then transferred to the defect sites to support tissue regeneration. During natural wound healing, however, it is the unfractionated blood clot (UBC) that fills the defect site. It is unclear whether centrifugation is necessary to prepare a blood-derived matrix that supports tissue regeneration. The aim of the present study was to compare lysates prepared from PRF and UBC based on bioassays and degradation of the respective membranes. We report here that lysates prepared from PRF and UBC membranes similarly activate TGF-β signaling, as indicated by the expression of interleukin 11 (IL-11), NADPH oxidase 4 (NOX-4) and proteoglycan 4 (PRG4) in gingival fibroblasts. Consistently, PRF and UBC lysates stimulated the phosphorylation and nuclear translocation of Smad3 in gingival fibroblasts. We further observed that PRF and UBC lysates have comparable anti-inflammatory activity, as shown by the reduction in lipopolysaccharide (LPS)-induced IL-6, inducible nitric oxidase synthase (iNOS) and cyclooxygenase 2 (COX-2) expression in RAW264.7 cells. Moreover, inflammation induced by Poly (1:C) HMW and FSL-1, which are agonists of Toll-like receptor (TLR) 3 and 2/6, respectively, was reduced by both PRF and UBC. PRF and UBC lysates reduced the nuclear translocation of p65 in LPS-induced RAW264.7 cells. In contrast to the similar activity observed in the bioassays, UBC membranes lack the structural integrity of PRF membranes, as indicated by the rapid and spontaneous disintegration of UBC membranes. We show here that the lysates prepared from PRF and UBC possess robust TGF-β and anti-inflammatory activity. However, visual inspection of the PRF and UBC membranes confirmed the negative impact of erythrocytes on the structural integrity of membranes prepared from whole blood. The data from the present study suggest that although both UBC and PRF have potent TGF-β and anti-inflammatory activity, UBC does not have the strength properties required to be used clinically to prepare applicable membranes. Thus, centrifugation is necessary to generate durable and clinically applicable blood-derived membranes. Full article
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Article
Differential Nanoscale Topography Dedicates Osteocyte-Manipulated Osteogenesis via Regulation of the TGF-β Signaling Pathway
Int. J. Mol. Sci. 2022, 23(8), 4212; https://doi.org/10.3390/ijms23084212 - 11 Apr 2022
Viewed by 888
Abstract
Osteocytes function as the master orchestrator of bone remodeling activity in the telophase of osseointegration. However, most contemporary studies focus on the manipulation of osteoblast and/or osteoclast functionality via implant surface engineering, which neglects the pivotal role of osteocytes in de novo bone [...] Read more.
Osteocytes function as the master orchestrator of bone remodeling activity in the telophase of osseointegration. However, most contemporary studies focus on the manipulation of osteoblast and/or osteoclast functionality via implant surface engineering, which neglects the pivotal role of osteocytes in de novo bone formation. It is confirmative that osteocyte processes extend directly to the implant surface, but whether the surface physicochemical properties can affect the functionality of osteocytes and determine the fate of the osseointegration in the final remodeling stage remains to be determined. Titania nanotube arrays (NTAs) with distinct diameters were fabricated to investigate the relationship between the nanoscale topography and the functionality of osteocytes. In vitro results pinpointed that NTA with a diameter of 15 nm (NTA-15) significantly promote osteogenesis of osteocytes via the enhancement of spreading, proliferation, and mineralization. The osteocyte transcriptome of each group further revealed that the TGF-β signaling pathway plays a pivotal role in osteocyte-mediated osteogenesis. The in vivo study definitely mirrored the aforementioned results, that NTA-15 significantly promotes bone formation around the implant. Consequently, nanoscaled topography-induced osteocyte functionality is important in late osseointegration. This suggests that surface designs targeting osteocytes may, therefore, be a potential approach to solving the aseptic loosening of the implant, and thus strengthen osseointegration. Full article
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Review
Sinus Lift Associated with Leucocyte-Platelet-Rich Fibrin (Second Generation) for Bone Gain: A Systematic Review
J. Clin. Med. 2022, 11(7), 1888; https://doi.org/10.3390/jcm11071888 - 28 Mar 2022
Viewed by 1123
Abstract
The purpose of this systematic review was to analyze sinus lifting procedures and to compare the efficiency of this treatment associated with the second generation of platelet-rich fibrin related to its effects on bone gain and to clarify the regenerative efficacy in sinus [...] Read more.
The purpose of this systematic review was to analyze sinus lifting procedures and to compare the efficiency of this treatment associated with the second generation of platelet-rich fibrin related to its effects on bone gain and to clarify the regenerative efficacy in sinus lift procedure, whether alone or as a coadjutant to other bone graft materials. The PICOT question was, “In clinical studies with patients needing a maxillary sinus lift (P), does the use of PRF either alone (I) or in conjunction with other biomaterials (C) improve the clinical outcome associated with bone gain and density (O), with at least three months of follow-up (T)?” An electronic search was conducted in the MEDLINE (PubMed), Science Direct, and Scopus databases through a search strategy. A total of 443 articles were obtained from the electronic database search. Sixteen articles met all criteria and were included in this review. Within the limitation of this study and interpreting the results carefully, it was suggested that a higher risk for implant failure after a sinus elevation might be seen in patients with residual bone ≤4 mm, and PRF application was effective, suggesting reducing the time needed for new bone formation. Full article
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Article
Adhesion of Oral Bacteria to Commercial d-PTFE Membranes: Polymer Microstructure Makes a Difference
Int. J. Mol. Sci. 2022, 23(6), 2983; https://doi.org/10.3390/ijms23062983 - 10 Mar 2022
Cited by 2 | Viewed by 1192
Abstract
Bacterial contamination of the membranes used during guided bone regeneration directly influences the outcome of this procedure. In this study, we analyzed the early stages of bacterial adhesion on two commercial dense polytetrafluoroethylene (d-PTFE) membranes in order to identify microstructural features that led [...] Read more.
Bacterial contamination of the membranes used during guided bone regeneration directly influences the outcome of this procedure. In this study, we analyzed the early stages of bacterial adhesion on two commercial dense polytetrafluoroethylene (d-PTFE) membranes in order to identify microstructural features that led to different adhesion strengths. The microstructure was investigated by X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR). The surface properties were analyzed by atomic force microscopy (AFM), scanning electron microscopy (SEM), and surface free energy (SFE) measurements. Bacterial properties were determined using the microbial adhesion to solvents (MATS) assay, and bacterial surface free energy (SFE) was measured spectrophotometrically. The adhesion of four species of oral bacteria (Streptococcus mutans, Streptococcus oralis, Aggregatibacter actinomycetemcomitas, and Veilonella parvula) was studied on surfaces with or without the artificial saliva coating. The results indicated that the degree of crystallinity (78.6% vs. 34.2%, with average crystallite size 50.54 nm vs. 32.86 nm) is the principal feature promoting the adhesion strength, through lower nanoscale roughness and possibly higher surface stiffness. The spherical crystallites (“warts”), observed on the surface of the highly crystalline sample, were also identified as a contributor. All bacterial species adhered better to a highly crystalline membrane (around 1 log10CFU/mL difference), both with and without artificial saliva coating. Our results show that the changes in polymer microstructure result in different antimicrobial properties even for chemically identical PTFE membranes. Full article
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Article
In Vitro Analysis of Organic Ester Functional Groups in Carious Dentine
Appl. Sci. 2022, 12(3), 1088; https://doi.org/10.3390/app12031088 - 20 Jan 2022
Viewed by 756
Abstract
Background: With the implementation of minimally invasive selective caries removal protocols to treat cavitated, deep carious dentine lesions, there is a need to investigate specific biochemical moiety distributions to help characterise and distinguish between infected (contaminated) and affected (demineralised) zones within the dentine [...] Read more.
Background: With the implementation of minimally invasive selective caries removal protocols to treat cavitated, deep carious dentine lesions, there is a need to investigate specific biochemical moiety distributions to help characterise and distinguish between infected (contaminated) and affected (demineralised) zones within the dentine lesion. The present in vitro investigation aimed to compare the distribution of ester functional groups (1740 cm−1) within carious dentine tissue (infected and affected dentine). The null hypothesis stipulated that there are no differences in ester function intensity/distribution within carious dentine lesions. Materials and Methods: From a total of five extracted human molar teeth with carious dentine lesions, 246 points from 10 sections of carious dentine were examined using high-resolution Raman spectroscopy and characterised into infected, affected and sound dentine. The peak intensity of the characteristic vibration mode of the ester function was calculated from sample scans. Results: Analyses indicated a statistically significant difference in the spectroscopic vibration bands of esters between the infected and affected dentine zones. Conclusion: The ester functional group is higher in intensity in the caries-infected dentine zone compared to the affected tissue. This finding could be used to develop an objective indicator for the selective operative management of carious dentine. Full article
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Article
Effects of a Novel Cold Atmospheric Plasma Treatment of Titanium on the Proliferation and Adhesion Behavior of Fibroblasts
Int. J. Mol. Sci. 2022, 23(1), 420; https://doi.org/10.3390/ijms23010420 - 31 Dec 2021
Cited by 3 | Viewed by 792
Abstract
Cold plasma treatment increases the hydrophilicity of the surfaces of implants and may enhance their integration with the surrounding tissues. The implaPrep prototype device from Relyon Plasma generates cold atmospheric plasma via dielectric barrier discharge (DBD). In this study, titanium surfaces were treated [...] Read more.
Cold plasma treatment increases the hydrophilicity of the surfaces of implants and may enhance their integration with the surrounding tissues. The implaPrep prototype device from Relyon Plasma generates cold atmospheric plasma via dielectric barrier discharge (DBD). In this study, titanium surfaces were treated with the implaPrep device for 20 s and assessed as a cell culture surface for fibroblasts. One day after seeding, significantly more cells were counted on the surfaces treated with cold plasma than on the untreated control titanium surface. Additionally, the viability assay revealed significantly higher viability on the treated surfaces. Morphological observation of the cells showed certain differences between the treated and untreated titanium surfaces. While conventional plasma devices require compressed gas, such as oxygen or argon, the implaPrep device uses atmospheric air as the gas source. It is, therefore, compact in size and simple to handle, and may provide a safe and convenient tool for treating the surfaces of dental implants, which may further improve the implantation outcome. Full article
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Article
Novel Bioactive Adhesive Monomer CMET Promotes Odontogenic Differentiation and Dentin Regeneration
Int. J. Mol. Sci. 2021, 22(23), 12728; https://doi.org/10.3390/ijms222312728 - 25 Nov 2021
Cited by 1 | Viewed by 1036
Abstract
This study aimed to evaluate the in vitro effect of the novel bioactive adhesive monomer CMET, a calcium salt of 4-methacryloxyethyl trimellitate acid (4-MET), on human dental pulp stem cells (hDPSCs) and its capacity to induce tertiary dentin formation in a rat pulp [...] Read more.
This study aimed to evaluate the in vitro effect of the novel bioactive adhesive monomer CMET, a calcium salt of 4-methacryloxyethyl trimellitate acid (4-MET), on human dental pulp stem cells (hDPSCs) and its capacity to induce tertiary dentin formation in a rat pulp injury model. Aqueous solutions of four tested materials [4-MET, CMET, Ca(OH)2, and mineral trioxide aggregate (MTA)] were added to the culture medium upon confluence, and solvent (dH2O) was used as a control. Cell proliferation was assessed using the Cell Counting Kit-8 assay, and cell differentiation was evaluated by real-time quantitative reverse transcription-polymerase chain reaction. The mineralization-inducing capacity was evaluated using alizarin red S staining and an alkaline phosphatase activity assay. For an in vivo experiment, a mechanical pulp exposure model was prepared on Wistar rats; damaged pulp was capped with Ca(OH)2 or CMET. Cavities were sealed with composite resin, and specimens were assessed after 14 and 28 days. The in vitro results showed that CMET exhibited the lowest cytotoxicity and highest odontogenic differentiation capacity among all tested materials. The favorable outcome on cell mineralization after treatment with CMET involved p38 and c-Jun N-terminal kinases signaling. The nuclear factor kappa B pathway was involved in the CMET-induced mRNA expression of odontogenic markers. Similar to Ca(OH)2, CMET produced a continuous hard tissue bridge at the pulp exposure site, but treatment with only CMET produced a regular dentinal tubule pattern. The findings suggest that (1) the evaluated novel bioactive adhesive monomer provides favorable biocompatibility and odontogenic induction capacity and that (2) CMET might be a very promising adjunctive for pulp-capping materials. Full article
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Article
3D Visualization of Dynamic Cellular Reaction of Pulpal CD11c+ Dendritic Cells against Pulpitis in Whole Murine Tooth
Int. J. Mol. Sci. 2021, 22(23), 12683; https://doi.org/10.3390/ijms222312683 - 24 Nov 2021
Viewed by 1009
Abstract
In dental pulp, diverse types of cells mediate the dental pulp immunity in a highly complex and dynamic manner. Yet, 3D spatiotemporal changes of various pulpal immune cells dynamically reacting against foreign pathogens during immune response have not been well characterized. It is [...] Read more.
In dental pulp, diverse types of cells mediate the dental pulp immunity in a highly complex and dynamic manner. Yet, 3D spatiotemporal changes of various pulpal immune cells dynamically reacting against foreign pathogens during immune response have not been well characterized. It is partly due to the technical difficulty in detailed 3D comprehensive cellular-level observation of dental pulp in whole intact tooth beyond the conventional histological analysis using thin tooth slices. In this work, we validated the optical clearing technique based on modified Murray’s clear as a valuable tool for a comprehensive cellular-level analysis of dental pulp. Utilizing the optical clearing, we successfully achieved a 3D visualization of CD11c+ dendritic cells in the dentin-pulp complex of a whole intact murine tooth. Notably, a small population of unique CD11c+ dendritic cells extending long cytoplasmic processes into the dentinal tubule while located at the dentin-pulp interface like odontoblasts were clearly visualized. 3D visualization of whole murine tooth enabled a reliable observation of these rarely existing cells with a total number less than a couple of tens in one tooth. These CD11c+ dendritic cells with processes in the dentinal tubule were significantly increased in the dental pulpitis model induced by mechanical and chemical irritation. Additionally, the 3D visualization revealed a distinct spatial 3D arrangement of pulpal CD11c+ cells in the pulp into a front-line barrier-like formation in the pulp within 12 h after the irritation. Collectively, these observations demonstrated the unique capability of optical clearing-based comprehensive 3D cellular-level visualization of the whole tooth as an efficient method to analyze 3D spatiotemporal changes of various pulpal cells in normal and pathological conditions. Full article
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Article
Regenerative Healing of Chitosan Scaffold Impregnated with Simvastatin in Repairing Furcal Perforation
Appl. Sci. 2021, 11(19), 8992; https://doi.org/10.3390/app11198992 - 27 Sep 2021
Viewed by 969
Abstract
This study aimed to evaluate the healing of furcation when repaired with Chitosan (CS) scaffold impregnated or not with Simvastatin (SIM) compared with CollaCote (CL) in goat premolar teeth. Root canal treatment was performed in 52 mandibular premolars followed by furcal perforation induction. [...] Read more.
This study aimed to evaluate the healing of furcation when repaired with Chitosan (CS) scaffold impregnated or not with Simvastatin (SIM) compared with CollaCote (CL) in goat premolar teeth. Root canal treatment was performed in 52 mandibular premolars followed by furcal perforation induction. The perforation was repaired with CL, CS, or CS with SIM after leaving it untreated for 4 weeks. White mineral trioxide aggregate was carried into the furcal site followed by a 2–3 mm resin-modified glass ionomer. The perforation was left untreated, and the access cavity was left open without coronal filling in the control group. The animals were sacrificed after one and three months. Block sections of the premolars were prepared and examined histologically to evaluate the inflammation and type of healing. Hard tissue formation was found in CL, CS, and CS/SIM groups in both periods. At one month, no significant differences were detected among the experimental groups, whereas at three months, CS without SIM showed significantly better performance compared to CL and CS/SIM groups (p = 0.040). Therefore, repairing furcal perforation with CS scaffolds shows desirable biological responses and healing characteristics in favor of bone regeneration at three months. Full article
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Article
Bacterial Biofilm Growth on Various Dental Stabilization Systems for Avulsed and Luxated Teeth
Appl. Sci. 2021, 11(19), 8982; https://doi.org/10.3390/app11198982 - 27 Sep 2021
Viewed by 981
Abstract
With the increased incidence of traumatic injuries and the advanced understanding of the periodontal and alveolar healing process, teeth splinting has become a common practice for stabilizing traumatized teeth. Consequently, several splinting materials and techniques have been introduced in the past few years. [...] Read more.
With the increased incidence of traumatic injuries and the advanced understanding of the periodontal and alveolar healing process, teeth splinting has become a common practice for stabilizing traumatized teeth. Consequently, several splinting materials and techniques have been introduced in the past few years. Despite the detrimental role of bacterial biofilm on healing, the level of biofilm development on these material surfaces has not been well investigated. Bacterial biofilms are severely detrimental for periodontal healing of avulsed and luxated teeth. Thus, biofilm growth becomes a critical factor in selecting the material of choice for dental splints. In this study, we aim to assess the level of oral biofilm growth on four different splinting systems: Ribbond©, orthodontic NiTi wire, monofilament fishing line, and Titanium Trauma Splint. A total of 72 extracted anterior teeth were divided into four groups. We splinted six rows of three teeth each per group. The teeth selected were caries-free and periodontitis-free at the time of extraction. To assess biofilm growth, a supragingival dental plaque sample was cultured and directly inoculated into all groups. After 7 days, bacterial growth was quantified by live/dead fluorescent microscopy assay and colony forming unit counts (CFU). Using one-way ANOVA and Bonferroni’s post hoc tests, we demonstrated that all splint systems allowed for bacterial growth. However, the Titanium Trauma Splint (TTS) allowed for the least amount of biofilm growth compared to other splint systems. Full article
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Article
Estimation of Distances in 3D by Orthodontists Using Digital Models
Appl. Sci. 2021, 11(18), 8285; https://doi.org/10.3390/app11188285 - 07 Sep 2021
Cited by 1 | Viewed by 781
Abstract
In the field of orthodontics, digital dental arch models are increasingly replacing plaster models in orthodontic diagnostics. This change in interface from physical plaster models to digital image-based models raises the question of how orthodontists interpret intra- and inter-arch relationships from an image [...] Read more.
In the field of orthodontics, digital dental arch models are increasingly replacing plaster models in orthodontic diagnostics. This change in interface from physical plaster models to digital image-based models raises the question of how orthodontists interpret intra- and inter-arch relationships from an image on a screen. In particular, the issue of the accuracy of the distances estimated on numerical models is crucial since the estimation of distances is the basis of the therapeutic decision-making process. Studies have shown that distances were well estimated on plaster models, but no study has verified this point on numerical models. This is the question that our study addresses. The experimental protocol consisted of collecting estimates of measurements made by orthodontists using digital models. The reliability of these measurements was then assessed by comparing them to the actual physical distances. We asked 31 orthodontists (19 women and 12 men; an average age of 37 years) to generate 3D model-based measurements of seven different elements: mandibular congestion, the maxillary intermolar distance, Spee’s curve, 16/26 symmetry, the right canine class, overbite, and overjet. These values were then compared to the actual measurements calculated using Insignia® software (ORMCO Corporation: Brea, CA, USA), using single sample t-tests. This test makes it possible to compare a distance estimated by the participants with a reference value, which corresponds here to the real distance. The results indicate that, overall, the distance estimates made on the 3D models differ significantly from the actual distances measured using the Insignia® software. This was particularly so for mandibular crowding (test value = 0; t (30) = 10.74; p ≤ 0.01), test value = 1; t (30) = 6.23; p ≤ 0.01). Although no study has focused on distance estimation on numerical models in the field of orthodontics, our results agree with the conclusions of studies showing that distances are not estimated in the same way in real environments and virtual environments. Additional studies will make it possible to identify more clearly the parameters (individual factors, equipment, etc.), which make it possible to improve the estimation of distances in the practice of orthodontics. In any case, these studies are necessary to improve the training of future practitioners in the use of virtual models for decision-making and to support them in the digital transition. Full article
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Article
Comparison of Osteogenic Potentials of Dental Pulp and Bone Marrow Mesenchymal Stem Cells Using the New Cell Transplantation Platform, CellSaic, in a Rat Congenital Cleft-Jaw Model
Int. J. Mol. Sci. 2021, 22(17), 9478; https://doi.org/10.3390/ijms22179478 - 31 Aug 2021
Cited by 4 | Viewed by 1889
Abstract
Scaffolds stimulate cell proliferation and differentiation and play major roles in providing growth and nutrition factors in the repair of bone defects. We used the recombinant peptide Cellnest™ to prepare the three-dimensional stem cell complex, CellSaic, and evaluated whether CellSaic containing rat dental [...] Read more.
Scaffolds stimulate cell proliferation and differentiation and play major roles in providing growth and nutrition factors in the repair of bone defects. We used the recombinant peptide Cellnest™ to prepare the three-dimensional stem cell complex, CellSaic, and evaluated whether CellSaic containing rat dental pulp stem cells (rDPSCs) was better than that containing rat bone marrow stem cells (rBMSCs). rDPSC-CellSaic or rBMSC-CellSaic, cultured with or without osteogenic induction medium, formed the experimental and control groups, respectively. Osteoblast differentiation was evaluated in vitro and transplanted into a rat model with a congenital jaw fracture. Specimens were collected and evaluated by microradiology and histological analysis. In the experimental group, the amount of calcium deposits, expression levels of bone-related genes (RUNX2, ALP, BSP, and COL1), and volume of mineralized tissue, were significantly higher than those in the control group (p < 0.05). Both differentiated and undifferentiated rDPSC-CellSaic and only the differentiated rBMSC-CellSaic could induce the formation of new bone tissue. Overall, rBMSC-CellSaic and rDPSC-CellSaic made with Cellnest™ as a scaffold, provide excellent support for promoting bone regeneration in rat mandibular congenital defects. Additionally, rDPSC-CellSaic seems a better source for craniofacial bone defect repair than rBMSC-CellSaic, suggesting the possibility of using DPSCs in bone tissue regenerative therapy. Full article
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Article
Early Bone Healing on Hydroxyapatite-Coated and Chemically-Modified Hydrophilic Implant Surfaces in an Ovine Model
Int. J. Mol. Sci. 2021, 22(17), 9361; https://doi.org/10.3390/ijms22179361 - 28 Aug 2021
Cited by 2 | Viewed by 1056
Abstract
Implant topography affects early peri-implant bone healing by changing the osteoconduction rate in the surrounding biological environment. Implant surfaces have been designed to promote faster and stronger bone formation for rapid and stable prosthesis loading. Early peri-implant bone healing has been observed with [...] Read more.
Implant topography affects early peri-implant bone healing by changing the osteoconduction rate in the surrounding biological environment. Implant surfaces have been designed to promote faster and stronger bone formation for rapid and stable prosthesis loading. Early peri-implant bone healing has been observed with a sandblasted, acid-etched implant that was chemically modified to be hydrophilic (cmSLA). The present study investigates whether early peri-implant bone healing extends to a rough surface implant with a high crystalline hydroxyapatite surface (TSV MP-1 HA). Three implants were randomly placed in porous trabecular bone within both medial femoral condyles of 10 sheep. Early peri-implant bone stability was measured at 3- and 6-weeks healing time following implant insertion. Results indicated a similar implant stability quotient between the implants at insertion and over time. The significant increase over time of reverse torque values with respect to insertion torque (p < 0.001) did not differ between the implants. However, the bone-to-implant contact of TSV MP-1 HA was significantly higher than that of cmSLA implants at 6 weeks (p < 0.01). These data validate previous findings of a hydrophilic implant surface and extend the observation of early osseointegration to a rough surface implant in porous trabecular bone. Full article
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Article
Melanoma Inhibitory Activity and Melanoma Inhibitory Activity 2 as Novel Immunohistochemical Markers of Oral Epithelial Dysplasia
J. Clin. Med. 2021, 10(16), 3661; https://doi.org/10.3390/jcm10163661 - 18 Aug 2021
Cited by 2 | Viewed by 898
Abstract
Oral potentially malignant disorders are associated with the development of oral squamous cell carcinoma (OSCC). Most OSCCs are diagnosed via histopathology as oral epithelial dysplasia (OED), but the histologic diagnostic criteria remain non-uniform. Accordingly, the establishment of a diagnostic marker to assist in [...] Read more.
Oral potentially malignant disorders are associated with the development of oral squamous cell carcinoma (OSCC). Most OSCCs are diagnosed via histopathology as oral epithelial dysplasia (OED), but the histologic diagnostic criteria remain non-uniform. Accordingly, the establishment of a diagnostic marker to assist in diagnosis could contribute towards cancer prevention. Melanoma inhibitory activity (MIA) and MIA2 are involved in tumor growth, invasion, and lymph node metastasis in various malignancies. The purpose of this study was to clarify the usefulness of MIA and MIA2 as diagnostic markers of oral mucosal lesions. The expression of MIA and MIA2 was analyzed immunohistochemically in 100 specimens (10 specimens with normal oral mucosa (NOM) and 30 specimens each with low-grade epithelial dysplasia (LED), high-grade epithelial dysplasia (HED), and OSCC). Immunohistochemical results were evaluated based on the Allred scoring system. Cytoplasmic expression of MIA and MIA2 increased in the order of LED, HED, and OSCC. All NOM specimens were negative for cytoplasmic expression. Significant differences were observed between the groups (NOM vs. HED, p < 0.05, NOM vs. OSCC, p < 0.001). These results demonstrate that MIA and MIA2 are expressed in the oral mucosa within early neoplastic lesions and suggest that MIA and MIA2 are useful novel immunohistochemical markers for discriminating between normal tissue and OED. Full article
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Review
Insights into the Cellular and Molecular Mechanisms That Govern the Fracture-Healing Process: A Narrative Review
J. Clin. Med. 2021, 10(16), 3554; https://doi.org/10.3390/jcm10163554 - 12 Aug 2021
Cited by 3 | Viewed by 1873
Abstract
Fracture-healing is a complex multi-stage process that usually progresses flawlessly, resulting in restoration of bone architecture and function. Regrettably, however, a considerable number of fractures fail to heal, resulting in delayed unions or non-unions. This may significantly impact several aspects of a patient’s [...] Read more.
Fracture-healing is a complex multi-stage process that usually progresses flawlessly, resulting in restoration of bone architecture and function. Regrettably, however, a considerable number of fractures fail to heal, resulting in delayed unions or non-unions. This may significantly impact several aspects of a patient’s life. Not surprisingly, in the past few years, a substantial amount of research and number of clinical studies have been designed, aiming at shedding light into the cellular and molecular mechanisms that regulate fracture-healing. Herein, we present the current knowledge on the pathobiology of the fracture-healing process. In addition, the role of skeletal cells and the impact of marrow adipose tissue on bone repair is discussed. Unveiling the pathogenetic mechanisms that govern the fracture-healing process may lead to the development of novel, smarter, and more effective therapeutic strategies for the treatment of fractures, especially of those with large bone defects. Full article
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Article
Uptake of Nanotitania by Gingival Epithelial Cells Promotes Inflammatory Response and Is Accelerated by Porphyromonas gingivalis Lipopolysaccharide: An In Vitro Study
Int. J. Mol. Sci. 2021, 22(15), 8084; https://doi.org/10.3390/ijms22158084 - 28 Jul 2021
Cited by 1 | Viewed by 963
Abstract
Titanium is often used in the medical field and in dental implants due to its biocompatibility, but it has a high rate of leading to peri-implantitis, which progresses faster than periodontitis. Therefore, in the present study, the expression of cytokines from gingival epithelial [...] Read more.
Titanium is often used in the medical field and in dental implants due to its biocompatibility, but it has a high rate of leading to peri-implantitis, which progresses faster than periodontitis. Therefore, in the present study, the expression of cytokines from gingival epithelial cells by nanotitania was investigated, which is derived from titanium in the oral cavity, and the additional effect of Porphyromonasgingivalis (periodontopathic bacteria) lipopolysaccharide (PgLPS) was investigated. Ca9-22 cells were used as a gingival epithelial cell model and were cultured with nanotitania alone or with PgLPS. Cytokine expression was examined by reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. In addition, cellular uptake of nanotitania was observed in scanning electron microscopy images. The expression of interleukin (IL)-6 and IL-8 significantly increased in Ca9-22 cells by nanotitania treatment alone, and the expression was further increased by the presence of PgLPS. Nanotitania was observed to phagocytose Ca9-22 cells in a dose- and time-dependent manner. Furthermore, when the expression of IL-11, related to bone resorption, was investigated, a significant increase was confirmed by stimulation with nanotitania alone. Therefore, nanotitania could be associated with the onset and exacerbation of peri-implantitis, and the presence of periodontal pathogens may worsen the condition. Further clinical reports are needed to confirm these preliminary results. Full article
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Article
Comparison of Implant Stability between Regenerated and Non-Regenerated Bone. A Prospective Cohort Study
J. Clin. Med. 2021, 10(15), 3220; https://doi.org/10.3390/jcm10153220 - 21 Jul 2021
Cited by 1 | Viewed by 954
Abstract
Implant stability is one of the main indicators of successful osseointegration. Although it has been measured in numerous studies, there has been little research on implant stability in regenerated bone. The study compares primary and secondary stability between implants placed in regenerated versus [...] Read more.
Implant stability is one of the main indicators of successful osseointegration. Although it has been measured in numerous studies, there has been little research on implant stability in regenerated bone. The study compares primary and secondary stability between implants placed in regenerated versus native bone and evaluates the influence of bone quality on the results. Sixty implants were placed in 31 patients: 30 implants inserted in native bone (non-regenerated) after a healing period of at least 6 months post-exodontia and 30 inserted in regenerated bone at 6 months after grafting with xenograft. Resonance frequency analysis (RFA) was used to obtain implant stability quotient (ISQ) values at baseline (implant placement), 8 weeks, and 12 weeks. Statistically significant differences were found between implants placed in regenerated bone and those placed in native bone at all measurement time points (p < 0.05). ISQ values were significantly influenced by bone quality at baseline (p < 0.05) but not at 8 or 12 weeks. Greater stability was obtained in implants placed in native bone; however, those placed in regenerated bone showed adequate primary and secondary stability for prosthetic loading. Bone quality influences the primary but not secondary stability of the implants in both native and regenerated bone. Full article
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Article
Effect of Different Titanium Dental Implant Surfaces on Human Adipose Mesenchymal Stem Cell Behavior. An In Vitro Comparative Study
Appl. Sci. 2021, 11(14), 6353; https://doi.org/10.3390/app11146353 - 09 Jul 2021
Cited by 1 | Viewed by 895
Abstract
Background: The aim of this research was to evaluate the effects of three different titanium (Ti) implant surfaces on the viability and secretory functions of mesenchymal stem cells isolated from a Bichat fat pad (BFP-MSCs). Methods: Four different Ti disks were used as [...] Read more.
Background: The aim of this research was to evaluate the effects of three different titanium (Ti) implant surfaces on the viability and secretory functions of mesenchymal stem cells isolated from a Bichat fat pad (BFP-MSCs). Methods: Four different Ti disks were used as substrate: (I) D1: smooth Ti, as control; (II) D2: chemically etched, resembling the Kontact S surface; (III) D3: sandblasted, resembling the Kontact surface; (IV) D4: blasted/etched, resembling the Kontact N surface. BFP-MSCs were plated on Ti disks for 72 h. Cell viability, adhesion on disks and release of a panel of cytokines, chemokines and growth factor were evaluated. Results: BFP-MSCs plated in wells with Ti surface showed a viability rate (~90%) and proliferative rate comparable to cells plated without disks and to cells plated on D1 disks. D2 and D4 showed the highest adhesive ability. All the Ti surfaces did not interfere with the release of cytokines, chemokines and growth factors by BFP-MSCs. However, BFP-MSCs cultured on D4 surface released a significantly higher amount of Granulocyte Colony-Stimulating Factor (G-CSF) compared either to cells plated without disks and to cells plated on D1 and D2. Conclusions: The implant surfaces examined do not impair the BFP-MSCs cell viability and preserve their secretion of cytokines and chemokines. Further in vitro and in vivo studies are necessary to define the implant surface parameters able to assure the chemokines’ optimal release for a real improvement of dental implant osseointegration. Full article
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Article
Effect of Water Storage on Hardness and Interfacial Strength of Resin Composite Luting Agents Bonded to Surface-Treated Monolithic Zirconia
Dent. J. 2021, 9(7), 78; https://doi.org/10.3390/dj9070078 - 04 Jul 2021
Cited by 2 | Viewed by 1679
Abstract
Background: Durable bonding between resin composite luting agents (CLA) and zirconia is still a matter of controversy. The purpose of this study was to evaluate the effect of water storage on hardness and interfacial strength of three CLA, a non-adhesive (Multilink Automix/ML), an [...] Read more.
Background: Durable bonding between resin composite luting agents (CLA) and zirconia is still a matter of controversy. The purpose of this study was to evaluate the effect of water storage on hardness and interfacial strength of three CLA, a non-adhesive (Multilink Automix/ML), an adhesive (Panavia F 2.0/PF) and a self-adhesive (PermaCem 2.0/PC), bonded to polished (CL) and grit-blasted (AL: 50 μm alumina, SJ: Sil-Jet + Monobond Plus silane) monolithic zirconia surfaces. Methods: CLA specimens (n = 5/cement, condition) were prepared, stored under dry conditions or immersed in water, and Vickers hardness (VH) measurements were obtained at 1 h, 24 h, 1 week and 3 weeks intervals. Optical profilometry was used to determine the roughness parameters (Sa, Sz, Sdr, Sci) of zirconia surfaces (n = 5/treatment). A shear strength test (SBS, n = 10 × 2/cement) was performed to assess the strength and fractography of the cements bonded to zirconia after isothermal water storage and thermal-cycling (TC). Results: PF demonstrated significantly lower VHN after water storage at all time intervals, PC at 1 w, 3 w and ML at 3 w. SJ and AL showed significantly higher values from CL in all roughness parameters. Weibull analysis revealed the following significance in σο ranking within the same material: AL, SJ, ALTC > SJTC, CL > CLTC (PF); SJ, SJTC, AL, ALTC > CL, CLTC (PC) and SJ, SJTC > AL > ALTC > CL, CLTC (ML). Within the same surface treatment subgroups, the significance in σo ranking was PC, ML > PF (before/after TC) for SJ; PC > PF > ML (before TC), PC, PF > ML (after TC) for AL, and PC > PF > ML (before/after TC) for CL. For the m ranking, the only significant difference within each material group was found in PC (AL > ALTC) and for the same surface treatment in AL (PC > ML). Conclusion: There are significant differences in the water plasticization susceptibility of the CLA tested; the materials with adhesive monomers were the most affected. Tribo-chemical silica coating combined with a silane coupling agent was the most efficient bonding treatment for the non-adhesive and the self-adhesive materials. The adhesive CLA performed better on alumina-blasted than on tribo-chemically coated surfaces. Full article
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Article
Stage-Specific Role of Amelx Activation in Stepwise Ameloblast Induction from Mouse Induced Pluripotent Stem Cells
Int. J. Mol. Sci. 2021, 22(13), 7195; https://doi.org/10.3390/ijms22137195 - 03 Jul 2021
Cited by 2 | Viewed by 2100
Abstract
Amelogenin comprises ~90% of enamel proteins; however, the involvement of Amelx transcriptional activation in regulating ameloblast differentiation from induced pluripotent stem cells (iPSCs) remains unknown. In this study, we generated doxycycline-inducible Amelx-expressing mouse iPSCs (Amelx-iPSCs). We then established a three-stage ameloblast induction [...] Read more.
Amelogenin comprises ~90% of enamel proteins; however, the involvement of Amelx transcriptional activation in regulating ameloblast differentiation from induced pluripotent stem cells (iPSCs) remains unknown. In this study, we generated doxycycline-inducible Amelx-expressing mouse iPSCs (Amelx-iPSCs). We then established a three-stage ameloblast induction strategy from Amelx-iPSCs, including induction of surface ectoderm (stage 1), dental epithelial cells (DECs; stage 2), and ameloblast lineage (stage 3) in sequence, by manipulating several signaling molecules. We found that adjunctive use of lithium chloride (LiCl) in addition to bone morphogenetic protein 4 and retinoic acid promoted concentration-dependent differentiation of DECs. The resulting cells had a cobblestone appearance and keratin14 positivity. Attenuation of LiCl at stage 3 together with transforming growth factor β1 and epidermal growth factor resulted in an ameloblast lineage with elongated cell morphology, positivity for ameloblast markers, and calcium deposition. Although stage-specific activation of Amelx did not produce noticeable phenotypic changes in ameloblast differentiation, Amelx activation at stage 3 significantly enhanced cell adhesion as well as decreased proliferation and migration. These results suggest that the combination of inducible Amelx transcription and stage-specific ameloblast induction for iPSCs represents a powerful tool to highlight underlying mechanisms in ameloblast differentiation and function in association with Amelx expression. Full article
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Article
Engineering of a Biomimetic Interface between a Native Dental Tissue and Restorative Composite and Its Study Using Synchrotron FTIR Microscopic Mapping
Int. J. Mol. Sci. 2021, 22(12), 6510; https://doi.org/10.3390/ijms22126510 - 17 Jun 2021
Cited by 8 | Viewed by 2564
Abstract
The aim of this work is to develop a biomimetic interface between the natural tooth tissue and the restorative composite and to study it on the basis of synchrotron micro-FTIR mapping and multidimensional processing of the spectral data array. Using hierarchical cluster analysis [...] Read more.
The aim of this work is to develop a biomimetic interface between the natural tooth tissue and the restorative composite and to study it on the basis of synchrotron micro-FTIR mapping and multidimensional processing of the spectral data array. Using hierarchical cluster analysis of 3D FTIR data revealed marked improvements in the formation of the dentine/adhesive/dental hybrid interface using a biomimetic approach. The use of a biomimetic strategy (application of an amino acid–modified primer, alkaline calcium and a nano-c-HAp–modified adhesive) allowed the formation of a matrix that can be structurally integrated with natural dentine and dental composite. The biomimetic hybrid layer was characterised by homogeneous chemical composition and a higher degree of conversion of the adhesive during polymerisation, which should provide optimal integration of the dental composite with the dentine. Full article
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Article
Effect of a Simvastatin-Impregnated Chitosan Scaffold on Cell Growth and Osteoblastic Differentiation
Appl. Sci. 2021, 11(12), 5346; https://doi.org/10.3390/app11125346 - 09 Jun 2021
Cited by 2 | Viewed by 1308
Abstract
This study aims to evaluate the effect of chitosan (CS) scaffold, alone, and the potential synergistic effect when impregnated with simvastatin (SIM), on immortalized human bone-marrow mesenchymal stem cells (hbMMSCs) compared to CollaCote (CL). CS scaffolds were fabricated and seeded with immortalized hBMMSCs. [...] Read more.
This study aims to evaluate the effect of chitosan (CS) scaffold, alone, and the potential synergistic effect when impregnated with simvastatin (SIM), on immortalized human bone-marrow mesenchymal stem cells (hbMMSCs) compared to CollaCote (CL). CS scaffolds were fabricated and seeded with immortalized hBMMSCs. Samples were divided into control groups (negative with no added material and positive with CL added) and four experimental groups: CS alone, CS/SIM 0.01, 0.03, and 0.05 mg, respectively. Cell viability, osteoblastic differentiation and calcium deposition were investigated via AlamarBlue, alkaline phosphate activity assays and alizarin red S staining at 1 and 14 days, respectively. At day one, no significant difference was noted between the groups regarding cell viability. However, all CS/SIM groups showed significant cutback at day 14 in cell proliferation compared to CS alone and CL groups (p < 0.001). All groups supported osteoblastic differentiation with no significant difference. Alkaline phosphate activity increased in both time periods in the CS/SIM 0.05 mg group compared to the other SIM groups, with no significant difference among the experimental groups. Chitosan scaffold is a bioactive compatible material capable of regenerative potential of hBMMSCs and a promising material to be used for perforation repair. Full article
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