Micro-computed tomography analysis of early stage bone healing using micro-porous titanium mesh for guided bone regeneration: preliminary experiment in a canine model.

The aim of this study was to evaluate the amount of bone formation beneath a defect area after treatment with titanium mesh membranes with different thicknesses and pore sizes alone or in combination with bone graft to induce bone formation during the early stage of healing time. The mandibular premolars were extracted bilaterally from three adult beagle dogs, and 8-mm-diameter bone defects were created on the buccal site of the premolar regions. Hydroxyapatite bone graft substitute was applied in the defect site unilaterally, and other site was left empty. Then, a novel micro-porous mesh (50 µm in pore diameter) or commercially available macro-porous titanium mesh (1700 µm in pore diameter) was placed on the defect and secured with screws. After 4 weeks, the mandibles were harvested, imaged using micro-computed tomography, and prepared for histological and morphometric evaluation. Higher new bone volumes (mm3), percentage of new bone volumes in the total defect volumes (bone ratio: %), and new bone area (mm2) through morphometric evaluation were found on the novel membranes with 50-µm-diameter pores compared to the commercial titanium mesh. Moreover, experiment sites without bone graft were observed with higher new bone volume and bone ratio compared with sites with bone graft. However, bone mineral density of novel mesh was observed to be lower compared with other experimental sites. Under the experimental condition, the result of this study suggests that titanium meshes with 50-µm-diameter pores were effective for guided bone regeneration in the early stage of healing.

Fibroblast attachment onto novel titanium mesh membranes for guided bone regeneration.

Titanium mesh is used in orthopedic surgery as a barrier membrane, as it offers suitable characteristics, which allow mechanical support during the formation of new bone. An ideal membrane would facilitate cell attachment onto its surface, thereby helping to stabilize the blood clot and integrate the membrane into the tissue. However, currently available titanium mesh has millimeter-level pore sizes, which lead to soft tissue ingrowth through the pores. Therefore, the aim of this study was to investigate the fibroblast attachment and migration on different designs of novel titanium mesh with micrometer pore size for guided bone regeneration treatment. Six types of novel titanium mesh membrane and three groups of commercially available membranes were used in this study. Fibroblasts were isolated from 4-day-old green fluorescence protein rats and seeded onto membrane surfaces. At 24 h, the cells attached to the membrane surfaces were fixed and stained with DAPI. The blue-stained nuclei on membrane surfaces, and both upper and lower sides were counted. It was shown that different membrane materials, structure and design differ considerably in their capacity for cell attachment to the membrane surface. The novel membranes, especially mesh with 12 pores compared with mesh with multi-pores, allowed the fibroblast attachment on the membrane surface, but hindered the fibroblast migration through the pores into the lower side of the membrane, which is associated with the defect area in the clinical condition.

Bacterial adhesion affinities of various implant abutment materials.

OBJECTIVES: To investigate bacterial adhesion to various abutment materials. MATERIAL AND METHODS: Thirty volunteers participated in this study. Resin splints were fabricated, and five types of disks were fabricated from pure titanium, gold-platinum alloy, zirconia, alumina, and hydroxyapatite with uniform surface roughness and attached to the buccal surface of each splint. After 4 days of use by the subjects, the plaque accumulated on the disk surfaces was analyzed. The bacterial community structure was evaluated using 16S rRNA gene profiling with terminal restriction fragment length polymorphism analysis. The total bacterial count on each disk was estimated using quantitative polymerase chain reaction. RESULTS: Terminal restriction fragment length polymorphism profiles were more similar between tested materials than between subjects, suggesting that the bacterial community structures on the abutment material were influenced more by the individuals than by the type of material. However, the total number of bacteria attached to a disk was significantly different among five materials (P < 0.001, Brunner-Langer test for longitudinal data). Fewer bacteria were attached to the gold-platinum alloy than to the other materials. CONCLUSIONS: Gold-platinum alloy appears to be useful material for abutments when considering the accumulation of plaque. However, alternative properties of the abutment material, such as effects on soft tissue healing, should also be taken into consideration when choosing an abutment material.

Trueness of the Combined Intra- and Extraoral Scanning Technique for Transferring Subgingival Contours from Provisional Restorations to Definitive Restorations

PURPOSE: To compare the morphologic trueness of provisional and definitive restorations constructed with conventional custom impression techniques to those constructed with intra- and extraoral scanning (IEOS), which can digitally transfer the subgingival morphology of the provisional restoration to the definitive restoration. MATERIALS AND METHODS: Provisional restorations were fabricated on typodonts in which implants were placed. In the conventional method, a customized impression coping was produced by using polymethyl methacrylate resin to transfer the subgingival contour of the provisional restoration. Impressions were taken with silicone impression material, and definitive restorations were made by CAM. The IEOS technique was performed as previously reported. In brief, three individually scanned stereolithography (STL) files were superimposed in CAD software to transfer the morphology of the provisional restoration to the definitive restoration. Definitive restorations were then made by CAM. The provisional and definitive restorations were both scanned by IOS. Scanned data files were superimposed with morphometry software, and the distortions were measured. Student t test was used for statistical analysis. RESULTS: The subgingival morphologies of definitive restorations prepared by the conventional method showed significant negative distortions compared to definitive restorations prepared by the IEOS technique. CONCLUSION: The IEOS technique can more accurately transfer the subgingival contour of provisional restorations to definitive restorations compared to the conventional customized impression coping technique.

The difference of fibroblast behavior on titanium substrata with different surface characteristics.

Connective tissue, one of the main components of peri-implant soft tissue, is key to the formation of the peri-implant mucosal seal and helping to prevent epithelial ingrowth. Rough surfaces (Rs), machined surfaces (Ms) or microgrooved surface (MG) are used in the neck area of commercially available titanium implants. In this paper, we aimed to evaluate the influence of surface topography of titanium substratum on connective tissue fibroblasts to gain a better understanding of this effect. Fibroblasts were cultured on titanium plates with Rs, Ms and MG. Adhesion cell number at day 3 was compared and protein distribution of both F-actin and vinculin was determined to observe cellular structure and adhesion. Cell adhesion strength was compared on each surface. At day 3, the number of fibroblasts attached on each substratum was in the order of MG ≈ Ms > Rs. Fibroblasts strongly expressed vinculin in the peripheral area on Ms and MG, and showed strong F-actin architecture. Decreased expression of vinculin and weaker continuity of F-actin were observed on Rs. Fibroblasts on MG were aligned along the grooves, with a significantly higher cell density, whereas cells on Ms and Rs had no clear orientation. The cell adhesion strength was significantly lower on Rs, and no significant difference was seen between MG and Ms. Both MG and Ms showed greater adhesion cell numbers and adhesion strength of fibroblasts when compared with Rs at day 3. The cell density on MG was greater than those on other substrata.

Titanium membrane layered between fluvastatin-loaded poly (lactic-co-glycolic) acid for guided bone regeneration.

The aim of this study was to investigate titanium membranes (TMs) layered between poly (lactic-co-glycolic acid) (PLGA) containing fluvastatin (FS) for use in guided bone regeneration. Membranes consisting of PLGA, FS-containing PLGA (PLGA-FS), TM layered between PLGA (TM-PLGA) and TM layered between FS-containing PLGA (TM-PLGA-FS) were prepared, and their mechanical and chemical properties were evaluated. The TM groups showed statistically significant differences, in terms of tensile strength and elastic modulus, when compared to the PLGA groups. The release of FS was demonstrated to be higher in the TM-PLGA-FS group than the PLGA-FS group after Day 14. The effect of membrane implantation on the calvaria of Wistar rats was measured using micro-computed tomography (micro-CT) and morphometrical analyses, as well as histological observations. At 4 weeks, the TM-PLGA-FS and TM-PLGA groups were found to have lower bone mineral density but higher bone formation, when compared to the control and PLGA groups. At 8 weeks, the use of TM-PLGA-FS membranes significantly enhanced bone formation in the calvaria model, compared to the other groups. These results suggest that a TM layered between PLGA containing FS potentially enhances bone formation, thus showing good potential as a GBR membrane.

Effects of Autoclave Sterilization and Multiple Use on Implant Scanbody Deformation In Vitro.

In the intraoral scanner (IOS) impression technique for dental implants, a scanbody (SB) is connected to the implant and scanned. Poly(ether-ether-ketone) (PEEK) is a widely used material for SBs and it is recommended for single use. However, from the perspective of the Sustainable Development Goals, it is desirable to use these products multiple times. As SBs are used in patients' mouths, proper sterilization is necessary for multiple uses. In the present study, the effect of autoclave treatment and connection/disconnection on SB deformation was investigated. The SB was connected to the implant and stereolithography (STL) data were obtained. Then, the SB was disconnected and underwent autoclave treatment, or was connected and disconnected multiple times, or underwent a combination of both processes. The results showed that there were significant differences in the distance and angle when comparing SBs before and after the autoclave treatment, but repeated connections with or without autoclave treatment had no significant impact on the measured values. The surface texture, observed with scanning electron microscopy, showed that a groove was observed on the surface of the SB, but the groove did not show major changes after 10 connection/autoclave processes. These results indicate that autoclave sterilization has some impact on SB deformation but connection/disconnection itself may not have a huge impact on SB deformation.

Therapeutic effect of fluvastatin on medication-related osteonecrosis of the jaw.

BACKGROUND: Refractory jaw osteonecrosis that occurs in osteoporotic or cancer patients treated with bisphosphonates is called medication-related osteonecrosis of the jaw but its underlying mechanism is unclear. Statins, therapeutic agents for dyslipidemia, lower blood low-density lipoprotein cholesterol. Fluvastatin promotes the healing of tooth extraction sockets and reduces the risk of developing medication-related osteonecrosis of the jaw-like lesions. We used a rat model to investigate whether injecting fluvastatin at extraction sites promoted the healing of medication-related osteonecrosis of the jaw-like lesions. METHODS: Upper first molars of rats administered zoledronate and dexamethasone for 2 weeks were extracted. Two weeks after tooth extraction, rats with medication-related osteonecrosis of the jaw-like lesions (bone exposure) were included in this study. A single injection of fluvastatin was administered in the vicinity of the medication-related osteonecrosis of the jaw-like onset site in rats. RESULTS: The distance between the edges of the epithelia, the length of the necrotic bone exposed toward the oral cavity, the area of the necrotic bone, and the necrotic bone ratio were significantly smaller in the fluvastatin-administered group compared with the saline group. A single application of fluvastatin near the site of medication-related osteonecrosis of the jaw onset showed a tendency to close the epithelium, reduce necrotic bone, and form new bone, even when symptoms had already developed. CONCLUSION: This study suggests that a single topical administration of fluvastatin may be a novel treatment for medication-related osteonecrosis of the jaw.

Therapeutic Effect of Benidipine on Medication-Related Osteonecrosis of the Jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is an intractable disease that is typically observed in patients with osteoporosis or tumors that have been treated with either bisphosphonate (BP) or antiangiogenic medicine. The mechanism of MRONJ pathogenesis remains unclear, and no effective definitive treatment modalities have been reported to date. Previous reports have indicated that a single injection of benidipine, an antihypertensive calcium channel blocker, in the vicinity of a tooth extraction socket promotes wound healing in healthy rats. The present study was conducted to elucidate the possibility of using benidipine to promote the healing of MRONJ-like lesions. In this study, benidipine was administered near the site of MRONJ symptom onset in a model rat, which was then sacrificed two weeks after benidipine injection, and analyzed using histological sections and CT images. The analysis showed that in the benidipine groups, necrotic bone was reduced, and soft tissue continuity was recovered. Furthermore, the distance between epithelial edges, length of necrotic bone exposed in the oral cavity, necrotic bone area, and necrotic bone ratio were significantly smaller in the benidipine group. These results suggest that a single injection of benidipine in the vicinity of MRONJ-like lesions can promote osteonecrotic extraction socket healing.

Soft Tissue Interface with Various Kinds of Implant Abutment Materials.

Various materials, such as titanium, zirconia and platinum-gold (Pt-Au) alloy, have been utilized for dental implant trans-mucosal parts. However, biological understanding of soft tissue reaction toward these materials is limited. The aim of this study was to compare the response of cell lines and soft tissue to titanium, zirconia and Pt-Au substrata. The surface hydroxyl groups and protein adsorption capacities of the substrata were measured. Next, gingival epithelial-like cells (Sa3) and fibroblastic cells (NIH3T3) were cultured on the materials, and initial cell attachment was measured. Immuno-fluorescent staining of cell adhesion molecules and cytoskeletal proteins was also performed. In the rat model, experimental implants constructed from various materials were inserted into the maxillary tooth extraction socket and the soft tissue was examined histologically and immunohistochemically. No significant differences among the materials were observed regarding the amount of surface hydroxyl groups and protein adsorption capacity. Significantly fewer cells of Sa3 and NIH3T3 adhered to the Pt-Au alloy compared to the other materials. The expression of cell adhesion molecules and a well-developed cytoskeleton was observed, both Sa3 and NIH3T3 on each material. In an animal model, soft tissue with supracrestal tissue attachment was observed around each material. Laminin-5 immuno-reactivity was seen in epithelia on both titanium and zirconia, but only in the bottom of epithelia on Pt-Au alloy. In conclusion, both titanium and zirconia, but not Pt-Au alloy, displayed excellent cell adhesion properties.

Accuracy of the Intra- and Extra-Oral Scanning Technique for Transferring the Intaglio Surface of a Pontic of Provisional Restorations to Definitive Restorations.

When taking the final impression for a three-unit fixed partial denture (FPD), the intaglio surface of the pontic of provisional restoration cannot be transferred accurately to that of definitive restoration. The intra- and extra-oral scanning (IEOS) technique, a method for accurately reproducing the submucosal morphology of the superstructure of an implant, has been reported using an intraoral scanner. In the present study, we evaluated the difference between the conventional impression method using impression material and the IEOS technique in reproducing the morphology of the surface of the pontic of a definitive FPD. There was a significant difference in the trueness of the intaglio surface morphology of the pontic between the conventional method and the IEOS technique; however, no significant difference in precision was observed. As a result, the intaglio surface of the pontic of the three-unit FPD could be transferred to definitive restorations more accurately with the IEOS technique than with the conventional method. These results suggest that the IEOS technique can duplicate the intaglio surface of the pontic more reproducibly to the definitive restorations compared with the conventional method.

Preventive effect of fluvastatin on the development of medication-related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) occurs in patients undergoing oral surgery while medicated with bisphosphonate, denosumab or anti-angiogenic agents. We employed a MRONJ-like rat model to investigate whether injecting fluvastatin at extraction sites prevents MRONJ-like lesion. A MRONJ-like model was created by treating rats with zoledronate and dexamethasone, extracting teeth, and immediately injecting fluvastatin at the extraction site. The experimental group comprised three subgroups treated with low (0.1 mg/kg; FS-L), medium (1.0 mg/kg; FS-M) and high concentrations (10 mg/kg; FS-H) of fluvastatin. Necrotic bone exposure was significantly lower in the FS-M (p = 0.028) and FS-H (p = 0.041) groups than in the MRONJ group. The distance between the edges of the epithelial surfaces was significantly shorter in the FS-M (p = 0.042) and FS-H (p = 0.041) groups. The area of necrotic bone and the necrotic bone ratio were significantly smaller in the FS-H group (p = 0.041 and p = 0.042 respectively). Bone volume fraction calculated on µ-CT images was significantly larger in the FS-H group than in the MRONJ group (p = 0.021). Our findings suggest that a single local injection of fluvastatin following tooth extraction can potentially reduce the chance of developing MRONJ-like lesion in rats.

Long Term Retention of Gingival Sealing around Titanium Implants with CaCl2 Hydrothermal Treatment: A Rodent Study.

We previously reported that CaCl2 hydrothermal-treated (Ca-HT) titanium (Ti) implants induced a tight sealing at the interface between the implant and peri-implant epithelium (PIE) after implantation. However, it is not clear how long this improved epithelium sealing can be maintained. We subsequently investigated whether the positive effect of Ca-HT to promote sealing between the PIE and implant was sustained longer term. Maxillary molars were extracted from rats and replaced with either Ca-HT implants (Ca-HT group), distilled water-HT implants (DW-HT group) or non-treated implants (control group). After 16 weeks, the majority of implants in the Ca-HT group remained at the maxillary with no apical extension of the PIE. Conversely, half the number of control implants was lost following down-growth of the PIE. The effect of Ca-HT on migration and proliferation of rat oral epithelial cells (OECs) was also investigated. In OECs cultured on Ca-HT Ti plates, protein expression in relation to cell migration decreased, and proliferation was higher than other groups. Surface analysis indicated HT enhanced the formation of surface TiO2 layer without altering surface topography. Consequently, Ca-HT of Ti reduced PIE down-growth via tight epithelial attachment to the surface, which may enhance implant capability for a longer time post-implantation.

Epithelial and Connective Tissue Sealing around Titanium Implants with Various Typical Surface Finishes.

Soft tissue barrier around a dental implant plays a crucial role in the success of dental implants because it protects underlying hard tissue structures. A number of surface alteration procedures of implants have been introduced to improve bone-implant contact, but there has been little research on the peri-implant soft tissue (PIS) seal. The present study focuses on the "biologic width" of epithelial and connective tissue seals around implants with various typical surface finishes by testing surfaces that have been machined (Ms), roughened by sandblasting and acid etching (Rs), treated hydrothermally with CaCl2 (Cs), or anodized (As). Ms, Rs, and As techniques are commonly used to finish surfaces of commercially available dental implants. The Cs technique was reported to produce strong epithelial cell-titanium adhesion. For culture study, rat oral epithelial cells (OECs) and fibroblasts were cultured on Ms, Rs, Cs, and As titanium plates. There was less cell adherence of OECs and more collagen expression when cultured on Rs and As plates than when cultured on Ms and Cs plates. For the in vivo study, implants with Ms, Rs, Cs, and As surfaces were placed in the rats' oral cavity. Although the PIS structure was similar to that around natural teeth, a horseradish peroxide assay revealed that the sealing ability around the Ms and Rs implants was weaker than that around Cs implants. After 16 weeks, Rs implants exhibited peri-implant epithelial apical down-growth and had lost bone support. Thus, although a smooth surface (Ms and Cs) showed better epithelial attachment, rough surfaces (Rs and As) are more suitable for binding to the connective tissue. Strong epithelium-implant attachment seems to be a fundamental defense against foreign body penetration. Selecting suitable surfaces to ensure strong sealing is important for implant success.

Epithelial sealing effectiveness against titanium or zirconia implants surface.

The aims of implant treatment now involve not only restoration of mastication function, but also recovery of esthetics. Currently, zirconia is widely used as an esthetic material for implant abutment. Therefore, it is very important to understand the efficacy of zirconia for epithelial sealing as an implant material. We compared the effects of materials on the sealing of the peri-implant epithelium (PIE) to titanium (Ti) or zirconia (Zr) implants, for application to clinical work. Maxillary first molars were extracted from rats and replaced with Ti or Zr implants. The sealing of the PIE to the implants was evaluated with immunohistochemistry observation and HRP analysis. The morphological and functional changes in rat oral epithelial cells (OECs) cultured on Ti or Zr plates were also evaluated. After 4 weeks, the PIE on the Ti and Zr implants showed similar structures. The Zr implants appeared to form a weak epithelial seal at the tissue-implant interface, and exhibited markedly less adhesive structures than the Ti implants under electron microscopic observation. In the in vitro experiments, decreased expression levels of adhesion proteins were observed in OECs cultured on Zr plates compared with those cultured on Ti plates. In addition, the cell adherence on Zr plates was reduced, while the cell migration was low on Ti plates. Zr is a better choice for an esthetic implant material, but needs further improvement for integration with the epithelial wound healing process around a dental implant. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.

Effect of Hydrothermal Treatment with Distilled Water on Titanium Alloy for Epithelial Cellular Attachment.

The enhancement of oral epithelial adhesion to the trans-mucosal material of dental implants may improve their long-term stability. The aim of this study is to investigate whether hydrothermal treatment with distilled water (HT-DW) applied to a Ti-6Al-4V (Ti64) alloy could improve epithelial cellular attachment. We hypothesized that this treatment would enhance the adsorption of proteins and the adhesion of gingival epithelial GE1 cells. This treatment changed the surface crystal structure into an anatase type of titanium oxide without an apparent change of surface roughness or topography. Nitrogen was not detected on the HT-DW-treated Ti64, which indicates decontamination. HT-DW-treated Ti64 exhibited a hydrophilic surface with a less than 10° angle of water contact. Adsorption of laminin-332 to the HT-DW-treated Ti64 was significantly greater than that of the untreated Ti64 plates (64). The number of GE1 cells on the HT-DW-treated Ti64 at 1 and 3 days was significantly lower than that on 64; however, cell adhesion strength on HT-DW was greater, with a higher expression of integrin ß4, compared with 64. This indicates that the HT-DW treatment of Ti64 improves the integration of GE1 cells, which might facilitate the development of a soft tissue barrier around the implant.

Effect of a Single Injection of Benidipine-Impregnated Biodegradable Microcarriers on Bone and Gingival Healing at the Tooth Extraction Socket.

Objective: A dihydropyridine-type calcium channel blocker, benidipine (BD), is extensively used in hypertension therapy. In vitro study reported BD promoting bone metabolism. We evaluated the effect of sustained release of BD-loaded poly(lactic-co-glycolic acid) (PLGA) microcarriers on the promotion of bone and gingival healing at an extraction socket in vivo. In addition, the effect of BD on osteoblasts, osteocytes, fibroblasts, and epithelial cells was evaluated in vitro. Approach: The maxillary first molar of rats was extracted. Next, PLGA microcarriers containing BD were directly injected into the gingivobuccal fold as a single dose. After injection, bone and soft-tissue healing was histologically evaluated. Effect of BD on proliferation, migration, and gene expression of gingival and bone cell was also examined in vitro. Results: After tooth extraction, BD significantly augmented bone volume and density, and also epithelial wound healing. During in vitro studies, BD promoted significant proliferation and migration of fibroblasts and epithelial cells. Real-time RT-PCR revealed that BD upregulated messenger RNA expression of Ahsg (alpha 2-HS glycoprotein) and Csf2 (colony-stimulating factor 2) in osteoblasts. Innovation: The prevention of bone and soft-tissue reduction associated with tooth extraction has been eagerly anticipated in the field of dentistry. This study first reported the effect of BD on extraction socket healing. Conclusion: A single dose of topically administered BD-loaded PLGA microcarriers promoted bone and soft-tissue healing at the extraction site of tooth.

Carbonate Apatite Containing Statin Enhances Bone Formation in Healing Incisal Extraction Sockets in Rats.

The purpose of this study was to evaluate the feasibility of using apatite blocks fabricated by a dissolution⁻precipitation reaction of preset gypsum, with or without statin, to enhance bone formation during socket healing after tooth extraction. Preset gypsum blocks were immersed in a Na3PO4 aqueous solution to make hydroxyapatite (HA) low crystalline and HA containing statin (HAFS), or in a mixed solution of Na2HPO4 and NaHCO3 to make carbonate apatite (CO) and CO containing statin (COFS). The right mandibular incisors of four-week-old male Wistar rats were extracted and the sockets were filled with one of the bone substitutes or left untreated as a control (C). The animals were sacrificed at two and four weeks. Areas in the healing socket were evaluated by micro-computed tomography (micro-CT) and histological analyses. The bone volume, trabecular thickness, and trabecular separation were greatest in the COFS group, followed by the CO, HAFS, HA, and C groups. The bone mineral density of the COFS group was greater than that of the other groups when evaluated in the vertical plane. The results of this study suggest that COFS not only allowed, but also promoted, bone healing in the socket. This finding could be applicable for alveolar bone preservation after tooth extraction.

Neural Progenitor-Like Cells Induced from Human Gingiva-Derived Mesenchymal Stem Cells Regulate Myelination of Schwann Cells in Rat Sciatic Nerve Regeneration.

Regeneration of peripheral nerve injury remains a major clinical challenge. Recently, mesenchymal stem cells (MSCs) have been considered as potential candidates for peripheral nerve regeneration; however, the underlying mechanisms remain elusive. Here, we show that human gingiva-derived MSCs (GMSCs) could be directly induced into multipotent NPCs (iNPCs) under minimally manipulated conditions without the introduction of exogenous genes. Using a crush-injury model of rat sciatic nerve, we demonstrate that GMSCs transplanted to the injury site could differentiate into neuronal cells, whereas iNPCs could differentiate into both neuronal and Schwann cells. After crush injury, iNPCs, compared with GMSCs, displayed superior therapeutic effects on axonal regeneration at both the injury site and the distal segment of the injured sciatic nerve. Mechanistically, transplantation of GMSCs, especially iNPCs, significantly attenuated injury-triggered increase in the expression of c-Jun, a transcription factor that functions as a major negative regulator of myelination and plays a central role in dedifferentiation/reprogramming of Schwann cells into a progenitor-like state. Meanwhile, our results also demonstrate that transplantation of GMSCs and iNPCs consistently increased the expression of Krox-20/EGR2, a transcription factor that governs the expression of myelin proteins and facilitates myelination. Altogether, our findings suggest that transplantation of GMSCs and iNPCs promotes peripheral nerve repair/regeneration, possibly by promoting remyelination of Schwann cells mediated via the regulation of the antagonistic myelination regulators, c-Jun and Krox-20/EGR2. Stem Cells Translational Medicine 2017;6:458-470.

Soft tissue sealing around dental implants based on histological interpretation.

PURPOSE: The aim of this study was to provide an overview on the biology and soft tissue sealing around dental implants and teeth. STUDY SELECTION: This is a narrative review performed through scientific articles published between 1977 and 2014, indexed in MEDLINE and PubMed databases. The study selected articles that focused on epithelial sealing around dental implant or teeth with cell biology and histology of soft tissue. RESULTS: Implant therapy has been widely applied in dental rehabilitation for many years, with predictable long-term results. The longevity and functionality of dental implants is dependent on both osseointegration around the implant body and the establishment of a soft tissue barrier that protects the underlying hard tissue structures and the implant itself. The health and stability of the peri-implant mucosa also affects the esthetics of the implant. The healing and maintenance of the epithelial and connective tissues around implants are increasingly recognized as being fundamental to implant success. However, there has been little research into the function or formation of the soft tissue seal around dental implants, and the roles of this unique mucosal interface remain unclear. CONCLUSIONS: This narrative review explores the extent of the current knowledge of soft tissue barriers around implants from both a basic and clinical perspective, and aims to consolidate this knowledge and highlight the most pertinent questions relating to this area of research.