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Keywords = mucosae sealing

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25 pages, 3319 KiB  
Review
Peri-Implant Soft Tissue in Contact with Zirconium/Titanium Abutments from Histological and Biological Perspectives: A Concise Review
by Fatma A. N. Abouel Maaty, Mai A. Ragab, Yasmin M. El-Ghazawy, Fatma I. Elfaiedi, Marwa M. S. Abbass, Israa Ahmed Radwan, Dina Rady, Sara El Moshy, Nahed Sedky Korany, Geraldine M. Ahmed, Christof E. Dörfer and Karim M. Fawzy El-Sayed
Cells 2025, 14(2), 129; https://doi.org/10.3390/cells14020129 - 17 Jan 2025
Cited by 1 | Viewed by 2437
Abstract
Dental implants are crucial in contemporary oral rehabilitation, necessitating optimal integration with the surrounding soft tissues for durable success. The attachment between the implant surface and peri-implant mucosa should establish a secure seal to prevent bacterial infiltration and subsequent tissue inflammation. This concise [...] Read more.
Dental implants are crucial in contemporary oral rehabilitation, necessitating optimal integration with the surrounding soft tissues for durable success. The attachment between the implant surface and peri-implant mucosa should establish a secure seal to prevent bacterial infiltration and subsequent tissue inflammation. This concise review examines the histological and biological perspectives of peri-implant soft tissue reactions to zirconium and titanium abutments, shedding light on their respective advantages and limitations. While titanium has been the gold standard, zirconia has gained attention due to its biocompatibility and aesthetic appeal. Histological studies show comparable soft tissue attachment and inflammatory responses between the two materials. Further research is needed to explore surface treatments and optimize outcomes in dental implant rehabilitation. Full article
(This article belongs to the Special Issue Recent Advances in Regenerative Dentistry—Second Edition)
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20 pages, 1856 KiB  
Review
Bioengineering the Junctional Epithelium in 3D Oral Mucosa Models
by Marianna Gavriiloglou, Mira Hammad, Jordan M. Iliopoulos, Pierre Layrolle and Danae A. Apatzidou
J. Funct. Biomater. 2024, 15(11), 330; https://doi.org/10.3390/jfb15110330 - 6 Nov 2024
Cited by 1 | Viewed by 3208
Abstract
Two-dimensional (2D) culture models and animal experiments have been widely used to study the pathogenesis of periodontal and peri-implant diseases and to test new treatment approaches. However, neither of them can reproduce the complexity of human periodontal tissues, making the development of a [...] Read more.
Two-dimensional (2D) culture models and animal experiments have been widely used to study the pathogenesis of periodontal and peri-implant diseases and to test new treatment approaches. However, neither of them can reproduce the complexity of human periodontal tissues, making the development of a successful 3D oral mucosal model a necessity. The soft-tissue attachment formed around a tooth or an implant function like a biologic seal, protecting the deeper tissues from bacterial infection. The aim of this review is to explore the advancements made so far in the biofabrication of a junctional epithelium around a tooth-like or an implant insert in vitro. This review focuses on the origin of cells and the variety of extracellular components and biomaterials that have been used for the biofabrication of 3D oral mucosa models. The existing 3D models recapitulate soft-tissue attachment around implant abutments and hydroxyapatite discs. Hereby, the qualitative and quantitative assessments performed for evidencing the soft-tissue attachment are critically reviewed. In perspective, the design of sophisticated 3D models should work together for oral immunology and microbiology biofilms to accurately reproduce periodontal and peri-implant diseases. Full article
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21 pages, 7872 KiB  
Article
Biological Response of the Peri-Implant Mucosa to Different Definitive Implant Rehabilitation Materials
by María Baus-Domínguez, Elena Oliva-Ferrusola, Serafín Maza-Solano, Gonzalo Ruiz-de-León, María-Ángeles Serrera-Figallo, José-Luis Gutiérrez-Perez, Daniel Torres-Lagares and Laura Macías-García
Polymers 2024, 16(11), 1534; https://doi.org/10.3390/polym16111534 - 29 May 2024
Cited by 2 | Viewed by 1960
Abstract
Background: Sealing the peri-implant tissue is a determining factor for long-term implant survival. In the transmucosal region, the cervical fraction of the prosthetic crown is in contact with these tissues, so mucointegration will also be influenced by the biomaterial used for the prosthetic [...] Read more.
Background: Sealing the peri-implant tissue is a determining factor for long-term implant survival. In the transmucosal region, the cervical fraction of the prosthetic crown is in contact with these tissues, so mucointegration will also be influenced by the biomaterial used for the prosthetic restoration. This study aims to compare the tissue response generated by definitive restorative materials and polymeric materials from a histological point of view. Methods: This study performed an observational prospective cohort study in which biopsies of the peri-implant mucosa were taken after placement of implant-supported prosthetic restorations made of different materials (zirconium oxide, lithium disilicate, and PMMA). Results: A statistically significant difference was observed in the increase in the thickness of the non-keratinized epithelium when comparing the definitive materials (zirconium oxide/lithium disilicate) vs. the provisional material (PMMA) and in the number of collagen fibers when comparing zirconium oxide and lithium disilicate. Conclusions: This study found that zirconia is the material that presents the most adequate biological response of peri-implant tissues. It shows a lower intensity of inflammatory cellular content, a total normality in the number of collagen fibers (the arrangement of the fibers is normal in 90% of the cases), and vascular proliferation of connective tissue in 83% of the cases. These parameters make it a material with a predictable response. Similarly, only the following slight statistically significant differences between the definitive and provisional materials are observed, indicating that the biological response generated by the provisional material (PMMA) is not very different from that obtained with the placement of the definitive restoration. Full article
(This article belongs to the Special Issue Advances in Polymeric Dental Materials)
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12 pages, 748 KiB  
Systematic Review
Accuracy of Intraoral Scanner for Recording Completely Edentulous Arches—A Systematic Review
by Gunjan Srivastava, Subrat Kumar Padhiary, Neeta Mohanty, Pedro Molinero-Mourelle and Najla Chebib
Dent. J. 2023, 11(10), 241; https://doi.org/10.3390/dj11100241 - 18 Oct 2023
Cited by 28 | Viewed by 5901
Abstract
Scanning edentulous arches during complete denture fabrication is a crucial step; however, the quality of the resulting digital scan is still questionable. The purpose of this study is to systematically review studies (both clinical and in vitro) and determine whether intraoral scanners have [...] Read more.
Scanning edentulous arches during complete denture fabrication is a crucial step; however, the quality of the resulting digital scan is still questionable. The purpose of this study is to systematically review studies (both clinical and in vitro) and determine whether intraoral scanners have clinically acceptable accuracy when recording completely edentulous arches for the fabrication of removable complete dentures. An electronic search in medical databases like PubMed, Scopus, and Web of Science (WOS), using a combination of relevant keywords, retrieved 334 articles. After full-text evaluation, twelve articles fulfilled the inclusion criteria for this review (eight clinical studies and four in vitro studies). A quality analysis of the included studies was carried out using the QUADAS-2 tool. The accuracy values varied between different intraoral scanners. Different regions of the edentulous arches showed differences in trueness and precision values in both in vitro and clinical studies. Peripheral borders, the inner seal, and poorly traceable structures like the soft palate showed maximum discrepancies. The accuracy of intraoral scanners in recording clear anatomic landmarks like hard tissues with attached mucosa was comparable to conventional edentulous arch impressions. However, higher discrepancies were recorded when digitizing mobile and poorly traceable structures. Intraoral scanners can be used to digitize denture-bearing areas, but the interpretation of the peripheral border and the soft palate should be carefully carried out. Full article
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13 pages, 1778 KiB  
Article
Behaviour of the Peri-Implant Soft Tissue with Different Rehabilitation Materials on Implants
by María Baus-Domínguez, Serafín Maza-Solano, Celia Vázquez-Pachón, Marta Flores-Cerero, Daniel Torres-Lagares, María-Ángeles Serrera-Figallo and Laura Macías-García
Polymers 2023, 15(15), 3321; https://doi.org/10.3390/polym15153321 - 7 Aug 2023
Cited by 5 | Viewed by 2633
Abstract
(1) Background: Mucointegration seems to gain interest when talking about success in the maintenance of dental implants. As we well know, collagen fibres cannot be inserted due to the lack of root structure on the implant surface, so the structural integration of peri-implant [...] Read more.
(1) Background: Mucointegration seems to gain interest when talking about success in the maintenance of dental implants. As we well know, collagen fibres cannot be inserted due to the lack of root structure on the implant surface, so the structural integration of peri-implant tissues that provide a firm seal around implants seems to be of interest when it comes to ensuring the survival of dental implants. To achieve a good epithelial barrier, the physicochemical characteristics of the surfaces of the restorative materials are of vital importance; therefore, the objective of this study is to analyse the histological behaviour of the peri-implant soft tissues in three different restorative materials. (2) Methods: Histological analysis of biopsied peri-implant keratinised mucosa, inflammatory epithelium and connective tissue in contact with a reinforced composite (BRILLIANT Crios), a cross-linked polymethylmethacrylate (TELIO CAD), and a hybrid ceramic (Vita Enamic), restored on a customised Atlantis-type abutment (Dentsply Sirona) between 60 and 180 days after restoration. (3) Results: A greater number of cells per mm2 of keratinised epithelium is observed in the reinforced composite, which could indicate greater surface roughness with greater inflammatory response. In this way, the greater number of lymphocytes and the lateral cellular composition of the inflammatory cells confirm the greater inflammatory activity towards that material. The best material to rehabilitate was hybrid ceramic, as it shows a better cellular response. (4) Conclusions: Knowing the limitations of the proposed study, despite the fact that greater inflammation is observed in the reinforced composite relative to the other materials studied, no statistically significant differences were found. Full article
(This article belongs to the Special Issue Advances in Polymeric Dental Materials)
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19 pages, 6828 KiB  
Article
Spanlastics as a Potential Approach for Enhancing the Nose-To-Brain Delivery of Piperine: In Vitro Prospect and In Vivo Therapeutic Efficacy for the Management of Epilepsy
by Isha Gupta, Syeda Nashvia Adin, Md Abdur Rashid, Yahya Alhamhoom, Mohd. Aqil and Mohd. Mujeeb
Pharmaceutics 2023, 15(2), 641; https://doi.org/10.3390/pharmaceutics15020641 - 14 Feb 2023
Cited by 34 | Viewed by 5342
Abstract
The present study delineates the preparation of piperine-loaded spanlastics (PIP-SPL) to improve piperine (PIP) solubility, bioavailability, and permeation through nasal mucosa for intranasal delivery. PIP-SPL was formulated using the thin-film hydration method and optimization was performed using Box–Behnken design (BBD). PIP-SPL optimized formulation [...] Read more.
The present study delineates the preparation of piperine-loaded spanlastics (PIP-SPL) to improve piperine (PIP) solubility, bioavailability, and permeation through nasal mucosa for intranasal delivery. PIP-SPL was formulated using the thin-film hydration method and optimization was performed using Box–Behnken design (BBD). PIP-SPL optimized formulation (PIP-SPLopt) was characterized for polydispersity index (PDI), vesicle size, entrapment efficiency, zeta potential, and in vitro PIP release. For further evaluation, blood–brain distribution study, transmission electron microscopy (TEM), nasal permeation study, and confocal scanning laser microscopy (CLSM) were performed withal. The PIP-SPLopt presented spherical and sealed shape vesicles with a small vesicle size of 152.4 nm, entrapment efficiency of 72.93%, PDI of 0.1118, and in vitro release of 82.32%. The CLSM study unveiled that the developed formulation has greater permeation of PIP across the nasal mucosa in comparison with the PIP suspension. The blood–brain distribution study demonstrated higher Cmax and AUC0–24h of PIP-SPL via the intranasal route in comparison to PIP-SPL via oral administration. The in vivo study revealed that the PIP-SPL has good antiepileptic potential in comparison with the standard diazepam, which was evinced by seizure activity, neuromuscular coordination by rotarod test, biochemical estimation of oxidative stress markers, and histopathological studies. Furthermore, nasal toxicity study confirm that the developed PIP-SPL formulation is safer for intranasal application. The current investigation corroborated that the prepared spanlastic vesicle formulation is a treasured carrier for the PIP intranasal delivery for the management of epilepsy. Full article
(This article belongs to the Special Issue Novel Drug Delivery Systems of Phytomedicines)
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17 pages, 2668 KiB  
Article
Ultraviolet Treatment of Titanium to Enhance Adhesion and Retention of Oral Mucosa Connective Tissue and Fibroblasts
by Takayuki Ikeda, Takeshi Ueno, Juri Saruta, Makoto Hirota, Wonhee Park and Takahiro Ogawa
Int. J. Mol. Sci. 2021, 22(22), 12396; https://doi.org/10.3390/ijms222212396 - 17 Nov 2021
Cited by 25 | Viewed by 3378
Abstract
Peri-implantitis is an unsolved but critical problem with dental implants. It is postulated that creating a seal of gingival soft tissue around the implant neck is key to preventing peri-implantitis. The objective of this study was to determine the effect of UV surface [...] Read more.
Peri-implantitis is an unsolved but critical problem with dental implants. It is postulated that creating a seal of gingival soft tissue around the implant neck is key to preventing peri-implantitis. The objective of this study was to determine the effect of UV surface treatment of titanium disks on the adhesion strength and retention time of oral connective tissues as well as on the adherence of mucosal fibroblasts. Titanium disks with a smooth machined surface were prepared and treated with UV light for 15 min. Keratinized mucosal tissue sections (3 × 3 mm) from rat palates were incubated for 24 h on the titanium disks. The adhered tissue sections were then mechanically detached by agitating the culture dishes. The tissue sections remained adherent for significantly longer (15.5 h) on the UV-treated disks than on the untreated control disks (7.5 h). A total of 94% of the tissue sections were adherent for 5 h or longer on the UV-treated disks, whereas only 50% of the sections remained on the control disks for 5 h. The adhesion strength of the tissue sections to the titanium disks, as measured by tensile testing, was six times greater after UV treatment. In the culture studies, mucosal fibroblasts extracted from rat palates were attached to titanium disks by incubating for 24, 48, or 96 h. The number of attached cells was consistently 15–30% greater on the UV-treated disks than on the control disks. The cells were then subjected to mechanical or chemical (trypsinization) detachment. After mechanical detachment, the residual cell rates on the UV-treated surfaces after 24 and 48 h of incubation were 35% and 25% higher, respectively, than those on the control surfaces. The remaining rate after chemical detachment was 74% on the control surface and 88% on the UV-treated surface for the cells cultured for 48 h. These trends were also confirmed in mouse embryonic fibroblasts, with an intense expression of vinculin, a focal adhesion protein, on the UV-treated disks even after detachment. The UV-treated titanium was superhydrophilic, whereas the control titanium was hydrophobic. X-ray photoelectron spectroscopy (XPS) chemical analysis revealed that the amount of carbon at the surface was significantly reduced after UV treatment, while the amount of TiOH molecules was increased. These ex vivo and in vitro results indicate that the UV treatment of titanium increases the adhesion and retention of oral mucosa connective tissue as a result of increased resistance of constituent fibroblasts against exogenous detachment, both mechanically and chemically, as well as UV-induced physicochemical changes of the titanium surface. Full article
(This article belongs to the Special Issue Implant and Graft Interactions with Hard and Soft Tissues)
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14 pages, 2084 KiB  
Article
Epidermal Growth Factor Is Associated with Loss of Mucosae Sealing and Peri-Implant Mucositis: A Pilot Study
by José Jorge Schoichet, Carlos Fernando de Almeida Barros Mourão, Edgard de Mello Fonseca, Carlos Ramirez, Ricardo Villas-Boas, Juliana Prazeres, Valquiria Quinelato, Telma Regina Aguiar, Marina Prado, Angelo Cardarelli, Rafael Mello-Machado and Priscila Casado
Healthcare 2021, 9(10), 1277; https://doi.org/10.3390/healthcare9101277 - 27 Sep 2021
Cited by 2 | Viewed by 2616
Abstract
This study aimed to evaluate the correlation between epidermal growth factor (EGF) and receptor (EGFR) levels in different clinical stages of dental implant rehabilitation and trace mucositis development’s biological profile. Thirty-six participants from the Specialization in Implant Dentistry, Universidade Federal Fluminense, Brazil, were [...] Read more.
This study aimed to evaluate the correlation between epidermal growth factor (EGF) and receptor (EGFR) levels in different clinical stages of dental implant rehabilitation and trace mucositis development’s biological profile. Thirty-six participants from the Specialization in Implant Dentistry, Universidade Federal Fluminense, Brazil, were included in the study and underwent sample collection: inside the alveolar socket, immediately before implant placement (Group 1, n = 10); at the peri-implant crevicular fluid (PICF) during reopening (Group 2, n = 10); PICF from healthy peri-implant in function (Group 3, n = 8); and PICF from mucositis sites (Group 4, n = 18). Quantitative polymerase chain reaction (PCR) evaluated EGF/EGFR gene expression using the SYBR Green Master Mix detection system. The results showed that EGF expression in the peri-implant crevicular fluid was statistically different. There was a higher EGF expression for group C (peri-implant health) (p = 0.04) than for the other groups. Regarding EGFR, there was no statistical difference among the groups (p = 0.56). It was concluded that low levels of EGF gene expression in the peri-implant crevicular fluid are related to the development of peri-implant mucositis and the absence of mucosae sealing. There was no correlation between EGFR gene expression with health or mucositis. Full article
(This article belongs to the Collection Dentistry, Oral Health and Maxillofacial Surgery)
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11 pages, 3899 KiB  
Article
Assessment of the Soft-Tissue Seal at the Interface between the Base of the Fixed Denture Pontic and the Oral Mucosa
by Ikiru Atsuta, Ikue Narimatsu, Taichiro Morimoto, Chi-Hsiang Cheng, Kiyoshi Koyano and Yasunori Ayukawa
Materials 2021, 14(14), 3997; https://doi.org/10.3390/ma14143997 - 16 Jul 2021
Cited by 4 | Viewed by 3185
Abstract
Fixed dentures (bridges) are often selected as a treatment option for a defective prosthesis. In this study, we assess the contact condition between the base of the pontic and oral mucosa, and examine the effect of prosthetic preparation and material biocompatibility. The molars [...] Read more.
Fixed dentures (bridges) are often selected as a treatment option for a defective prosthesis. In this study, we assess the contact condition between the base of the pontic and oral mucosa, and examine the effect of prosthetic preparation and material biocompatibility. The molars were removed and replaced with experimental implants with a free-end type bridge superstructure after one week. In Experiment 1, we assessed different types of prosthetic pre-treatment: (1) the untreated control group (Con: mucosa recovering from the tooth extraction); (2) the laser irradiation group (Las: mucosa recovering after the damage caused by a CO2 laser); and (3) the tooth extraction group (Ext: mucosa recovering immediately after the teeth extraction). In Experiment 2, five materials (titanium, zirconia, porcelain, gold-platinum alloy, and self-curing resin) were placed at the base of the bridge pontic. Four weeks after the placement of the bridge, the mucosa adjacent to the pontic base was histologically analyzed. In Experiment 1, the Con and Las groups exhibited no formation of an epithelial sealing structure on the pontic base. In the Ext group, adherent epithelium was observed. In Experiment 2, the sealing properties at the pontic interface were superior for titanium and the zirconia compared with those made of porcelain or gold-platinum alloy. In the resin group, a clear delay in epithelial healing was observed. Full article
(This article belongs to the Special Issue Surface Treatment of Implant Materials)
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13 pages, 2232 KiB  
Article
Titanium Functionalized with Polylysine Homopolymers: In Vitro Enhancement of Cells Growth
by Maria Contaldo, Alfredo De Rosa, Ludovica Nucci, Andrea Ballini, Davide Malacrinò, Marcella La Noce, Francesco Inchingolo, Edit Xhajanka, Kenan Ferati, Arberesha Bexheti-Ferati, Antonia Feola and Marina Di Domenico
Materials 2021, 14(13), 3735; https://doi.org/10.3390/ma14133735 - 3 Jul 2021
Cited by 13 | Viewed by 3086
Abstract
In oral implantology, the success and persistence of dental implants over time are guaranteed by the bone formation around the implant fixture and by the integrity of the peri-implant mucosa seal, which adheres to the abutment and becomes a barrier that hinders bacterial [...] Read more.
In oral implantology, the success and persistence of dental implants over time are guaranteed by the bone formation around the implant fixture and by the integrity of the peri-implant mucosa seal, which adheres to the abutment and becomes a barrier that hinders bacterial penetration and colonization close to the outer parts of the implant. Research is constantly engaged in looking for substances to coat the titanium surface that guarantees the formation and persistence of the peri-implant bone, as well as the integrity of the mucous perimeter surrounding the implant crown. The present study aimed to evaluate in vitro the effects of a titanium surface coated with polylysine homopolymers on the cell growth of dental pulp stem cells and keratinocytes to establish the potential clinical application. The results reported an increase in cell growth for both cellular types cultured with polylysine-coated titanium compared to cultures without titanium and those without coating. These preliminary data suggest the usefulness of polylysine coating not only for enhancing osteoinduction but also to speed the post-surgery mucosal healings, guarantee appropriate peri-implant epithelial seals, and protect the fixture against bacterial penetration, which is responsible for compromising the implant survival. Full article
(This article belongs to the Special Issue Design of Materials for Bone Tissue Scaffolds)
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16 pages, 9706 KiB  
Article
An In-Vitro Analysis of Peri-Implant Mucosal Seal Following Photofunctionalization of Zirconia Abutment Materials
by Masfueh Razali, Wei Cheong Ngeow, Ros Anita Omar and Wen Lin Chai
Biomedicines 2021, 9(1), 78; https://doi.org/10.3390/biomedicines9010078 - 15 Jan 2021
Cited by 17 | Viewed by 3636
Abstract
The presence of epithelial and connective tissue attachment at the peri-implant–soft tissue region has been demonstrated to provide a biological barrier of the alveolar bone from the oral environment. This barrier can be improved via surface modification of implant abutment materials. The effect [...] Read more.
The presence of epithelial and connective tissue attachment at the peri-implant–soft tissue region has been demonstrated to provide a biological barrier of the alveolar bone from the oral environment. This barrier can be improved via surface modification of implant abutment materials. The effect of photofunctionalization on creating a bioactive surface for the enhancement of the epithelial and connective tissue attachment of zirconia implant abutment’s peri-implant mucosal interface using organotypic model has not been investigated. Therefore, this study aimed to evaluate the soft tissue seal around peri-implant mucosa and to understand the effect of photofunctionalization on the abutment materials. Three types of abutment materials were used in this study; yttria-stabilized zirconia (YSZ), alumina-toughened zirconia, and grade 2 commercially pure titanium (CPTi) which were divided into nontreated (N-Tx) and photofunctionalized group (UV-Tx). The three-dimensional peri-implant mucosal model was constructed using primary human gingival keratinocytes and fibroblasts co-cultured on the acellular dermal membrane. The biological seal was determined through the concentration of tritiated water permeating the material–soft tissue interface. The biological seal formed by the soft tissue in the N-Tx group was significantly reduced compared to the UV-treated group (p < 0.001), with YSZ exhibiting the lowest permeability among all materials. Photofunctionalization of implant abutment materials improved the biological seal of the surrounding soft tissue peri-implant interface. Full article
(This article belongs to the Special Issue Bioengineered In Vitro Models for Biomedical Applications)
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13 pages, 2976 KiB  
Article
Load Transfer during Magnetic Mucoperiosteal Distraction in Newborns with Complete Unilateral and Bilateral Orofacial Clefts: A Three-Dimensional Finite Element Analysis
by Prasad Nalabothu, Carlalberta Verna, Benito K. Benitez, Michel Dalstra and Andreas A. Mueller
Appl. Sci. 2020, 10(21), 7728; https://doi.org/10.3390/app10217728 - 31 Oct 2020
Cited by 2 | Viewed by 2570
Abstract
The primary correction of congenital complete unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP) is challenging due to inherent lack of palatal tissue and small extent of the palatal shelves at birth. The tissue deficiency affects the nasal [...] Read more.
The primary correction of congenital complete unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP) is challenging due to inherent lack of palatal tissue and small extent of the palatal shelves at birth. The tissue deficiency affects the nasal mucosa, maxillary bone and palatal mucosa. This condition has driven the evolution of several surgical and non-surgical techniques for mitigating the inherent problem of anatomical deficits. These techniques share the common principle of altering the neighboring tissues around the defect area in order to form a functional seal between the oral and nasal cavity. However, there is currently no option for rectifying the tissue deficiency itself. Investigations have repeatedly shown that despite the structural tissue deficiency of the cleft, craniofacial growth proceeds normal if the clefts remain untreated, but the cleft remains wide. Conversely, craniofacial growth is reduced after surgical repair and the related alteration of the tissues. Therefore, numerous attempts have been made to change the surgical technique and timing so as to reduce the effects of surgical repairs on craniofacial growth, but they have been only minimally effective so far. We have determined whether the intrinsic structural soft and hard tissue deficiency can be ameliorated before surgical repair using the principles of periosteal distraction by means of magnetic traction. Two three-dimensional maxillary finite element models, with cleft patterns of UCLP and BCLP, respectively, were created from computed tomography slice data using dedicated image analysis software. A virtual dental magnet was positioned on either side of the cleft at the mucoperiosteal borders, and an incremental magnetic attraction force of up to 5 N was applied to simulate periosteal distraction. The stresses and strains in the periosteal tissue induced by the magnet were calculated using finite element analysis. For a 1 N attraction force the maximum strains did not exceed 1500 µstrain suggesting that adaptive remodeling will not take place for attraction forces lower than 1 N. At 5 N the regions subject to remodeling differed between the UCLP and BCLP models. Stresses and strains at the periosteum of the palatal shelf ridges in the absence of compressive forces at the alveolar borders were greater in the UCLP model than the BCLP model. The findings suggest that in newborns with UCLP and BCLP, periosteal distraction by means of a magnetic 5 N attraction force can promote the generation of soft and hard tissues along the cleft edges and rectify the tissue deficiency associated with the malformation. Full article
(This article belongs to the Special Issue Applied Biomaterials in Oral Surgery and Personalized Dentistry)
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16 pages, 2423 KiB  
Article
In Vitro Effects of Streptococcus oralis Biofilm on Peri-Implant Soft Tissue Cells
by Alexandra Ingendoh-Tsakmakidis, Jörg Eberhard, Christine S. Falk, Meike Stiesch and Andreas Winkel
Cells 2020, 9(5), 1226; https://doi.org/10.3390/cells9051226 - 15 May 2020
Cited by 21 | Viewed by 5234
Abstract
Human gingival epithelial cells (HGEps) and fibroblasts (HGFs) are the main cell types in peri-implant soft tissue. HGEps are constantly exposed to bacteria, but HGFs are protected by connective tissue as long as the mucosa–implant seal is intact. Streptococcus oralis is one of [...] Read more.
Human gingival epithelial cells (HGEps) and fibroblasts (HGFs) are the main cell types in peri-implant soft tissue. HGEps are constantly exposed to bacteria, but HGFs are protected by connective tissue as long as the mucosa–implant seal is intact. Streptococcus oralis is one of the commensal bacteria, is highly abundant at healthy implant sites, and might modulate soft tissue cells—as has been described for other streptococci. We have therefore investigated the effects of the S. oralis biofilm on HGEps and HGFs. HGEps or HGFs were grown separately on titanium disks and responded to challenge with S. oralis biofilm. HGFs were severely damaged after 4 h, exhibiting transcriptional inflammatory and stress responses. In contrast, challenge with S. oralis only induced a mild transcriptional inflammatory response in HGEps, without cellular damage. HGFs were more susceptible to the S. oralis biofilm than HGEps. The pro-inflammatory interleukin 6 (IL-6) was attenuated in HGFs, as was interleukin 8 (CXCL8) in HGEps. This indicates that S. oralis can actively protect tissue. In conclusion, commensal biofilms can promote homeostatic tissue protection, but only if the implant–mucosa interface is intact and HGFs are not directly exposed. Full article
(This article belongs to the Special Issue Immunomodulatory Factors in Host Defense)
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18 pages, 2729 KiB  
Article
Enhanced CXCR4 Expression Associates with Increased Gene Body 5-Hydroxymethylcytosine Modification but not Decreased Promoter Methylation in Colorectal Cancer
by Alexei J. Stuckel, Wei Zhang, Xu Zhang, Shuai Zeng, Urszula Dougherty, Reba Mustafi, Qiong Zhang, Elsa Perreand, Tripti Khare, Trupti Joshi, Diana C. West-Szymanski, Marc Bissonnette and Sharad Khare
Cancers 2020, 12(3), 539; https://doi.org/10.3390/cancers12030539 - 26 Feb 2020
Cited by 15 | Viewed by 4463 | Correction
Abstract
In colorectal cancer (CRC), upregulation of the C-X-C motif chemokine receptor 4 (CXCR4) is correlated with metastasis and poor prognosis, highlighting the need to further elucidate CXCR4’s regulation in CRC. For the first time, DNA methylation and 5-hydroxymethylcytosine aberrations were investigated to [...] Read more.
In colorectal cancer (CRC), upregulation of the C-X-C motif chemokine receptor 4 (CXCR4) is correlated with metastasis and poor prognosis, highlighting the need to further elucidate CXCR4’s regulation in CRC. For the first time, DNA methylation and 5-hydroxymethylcytosine aberrations were investigated to better understand the epigenetic regulation of CXCR4 in CRC. CXCR4 expression levels were measured using qPCR and immunoblotting in normal colon tissues, primary colon cancer tissues and CRC cell lines. Publicly available RNA-seq and methylation data from The Cancer Genome Atlas (TCGA) were extracted from tumors from CRC patients. The DNA methylation status spanning CXCR4 gene was evaluated using combined bisulfite restriction analysis (COBRA). The methylation status in the CXCR4 gene body was analyzed using previously performed nano-hmC-seal data from colon cancers and adjacent normal colonic mucosa. CXCR4 expression levels were significantly increased in tumor stromal cells and in tumor colonocytes, compared to matched cell types from adjacent normal-appearing mucosa. CXCR4 promoter methylation was detected in a minority of colorectal tumors in the TCGA. The CpG island of the CXCR4 promoter showed increased methylation in three of four CRC cell lines. CXCR4 protein expression differences were also notable between microsatellite stable (MSS) and microsatellite instable (MSI) tumor cell lines. While differential methylation was not detected in CXCR4, enrichment of 5-hydroxymethylcytosine (5hmC) in CXCR4 gene bodies in CRC was observed compared to adjacent mucosa. Full article
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17 pages, 1902 KiB  
Review
Potential for Tight Junction Protein–Directed Drug Development Using Claudin Binders and Angubindin-1
by Yosuke Hashimoto, Keisuke Tachibana, Susanne M. Krug, Jun Kunisawa, Michael Fromm and Masuo Kondoh
Int. J. Mol. Sci. 2019, 20(16), 4016; https://doi.org/10.3390/ijms20164016 - 17 Aug 2019
Cited by 38 | Viewed by 7126
Abstract
The tight junction (TJ) is an intercellular sealing component found in epithelial and endothelial tissues that regulates the passage of solutes across the paracellular space. Research examining the biology of TJs has revealed that they are complex biochemical structures constructed from a range [...] Read more.
The tight junction (TJ) is an intercellular sealing component found in epithelial and endothelial tissues that regulates the passage of solutes across the paracellular space. Research examining the biology of TJs has revealed that they are complex biochemical structures constructed from a range of proteins including claudins, occludin, tricellulin, angulins and junctional adhesion molecules. The transient disruption of the barrier function of TJs to open the paracellular space is one means of enhancing mucosal and transdermal drug absorption and to deliver drugs across the blood–brain barrier. However, the disruption of TJs can also open the paracellular space to harmful xenobiotics and pathogens. To address this issue, the strategies targeting TJ proteins have been developed to loosen TJs in a size- or tissue-dependent manner rather than to disrupt them. As several TJ proteins are overexpressed in malignant tumors and in the inflamed intestinal tract, and are present in cells and epithelia conjoined with the mucosa-associated lymphoid immune tissue, these TJ-protein-targeted strategies may also provide platforms for the development of novel therapies and vaccines. Here, this paper reviews two TJ-protein-targeted technologies, claudin binders and an angulin binder, and their applications in drug development. Full article
(This article belongs to the Special Issue The Tight Junction and Its Proteins: More Than Just a Barrier)
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