Abstract

Oral cavity stem cells (OCSCs) have been the focus of intense scientific efforts due to their accessibility and stem cell properties. The present work aims to compare the different characteristics of 6 types of dental stem cells derived from the oral cavity: dental pulp stem cells (DPSC), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSC), stem cells from the apical papilla (SCAP), bone marrow mesenchymal stem cells (BMSC), and gingival mesenchymal stem cells (GMSC). Using immunofluorescence and real-time polymerase chain reaction techniques, we analysed the cells for stem cell, differentiation, adhesion, and extracellular matrix markers; the ability to proliferate in vitro; and multilineage differentiation potential. Markers such as vimentin, CD44, alkaline phosphatase, CD146, CD271, CD49f, Oct 3/4, Sox 9, FGF7, nestin, and BMP4 showed significant differences in expression levels, highlighting the heterogeneity and unique characteristics of each cell type. At the same time, we confirmed that all cell types successfully differentiated into osteogenic, chondrogenic, or adipose lineages, with different readiness. In conclusion, our study reveals the distinct properties and potential applications of various dental-derived stem cells. These findings contribute to a deeper understanding of OCSCs and their significance in future clinical applications.

Introduction

Bone marrow mesenchymal stem cells (BMSCs) exhibit high proliferation ability and multilineage differentiation potential. They were the first mesenchymal stem cells (MSCs) to be described, isolated from adults’ bone marrow aspirate.1 They have been extensively researched in human and animal model systems using in vivo and in vitro cell cultures. Further, they have bridged the divide and are integrated into various trials for clinical applications, with mixed success.2,3 BMSCs are not easily accessible, and an invasive procedure is required. Therefore, further research in the field, aiming at identifying alternative stem cell sources, has led to the discovery of oral cavity stem cells (OCSCs).

Currently, several different types of OCSCs are well known, including dental pulp stem cells (DPSC), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSC), stem cells from the apical papilla (SCAP), dental follicle stem cells (DFSC), and gingival mesenchymal stem cells (GMSC).

Conclusions

This analysis of oral cavity–derived stem cells has exposed distinct and specific expression patterns of surface markers, ECM components, ECM remodelling enzymes, collagen genes, integrins, and differentiation potential. These findings may provide insights into the functional properties of these cell populations. Оur study aims to uncover the nuanced characteristics specific to each distinct cell type. Through experimentation and analysis, we anticipate to not only understand their individual functionalities but also gain deeper insights into their collective behaviour. Understanding both their shared characteristics and distinct attributes is an important step in using their regenerative potential in various tissue repair and regeneration contexts, thereby advancing the field of regenerative medicine and tissue engineering. By contributing meaningfully to the advancement of knowledge in regenerative medicine and tissue engineering, we aspire to pave the way for transformative breakthroughs in health care.

Highlights

Abstract

Keywords

1. Introduction

2. Materials and methods

3. Results

4. Discussion

5. Conclusions

Declaration of Competing Interest

Acknowledgement

References

Abstract

The objective of this research is to study the feasibility using nanomaterials to prevent and/or repair wear of teeth. Canine teeth have thin enamel prone to dental wear, causing pain, tooth loss, and infection. This research developed a new teeth repair agent based on the tribochemically active nanoparticles. The presence and properties of synthesized repair agents were evaluated after applying the repair agents by rubbing (simulated chewing) between extracted dog teeth. Polyether modified alpha‑zirconium phosphate (α-ZrP) nanoparticles form a strong and durable protective layer on a canine tooth’s enamel surface through chewing. The effectiveness of this protective film generation was enhanced by adding hydroxyapatite (HAp) nanoparticles into the repair agent. This protective film is up to 2 μm thick and has a hardness comparable to the enamel substrate. These results show that by chewing with the repair agent, the teeth are protected. The tomography result shows this repair agent also has the potential to mend cracks on the enamel surface. This research reports a novel approach to protect the wear of teeth. Nanoparticles promoted the generation of a protective film in situ during the chewing process. This nanomaterial can be the base of novel dental protective devices such as chewing toys or gums that preventing or reversing tooth wear and reducing the stress and cost of dental restoration operations.

1. Introduction
Tooth enamel is the hardest and most dense structure in the mammalian body. It serves to protect the interior of the tooth from the normal flora of the oral cavity and other harmful substances [1,2]. Although it is the hardest tissue in humans and animals [3–6], it can suffer damage from mechanical forces [7–12] and acidic solutions [13–16]. In dogs, the enamel layer is significantly thinner than in humans [17] and more prone to excessive wear and damage. This type of wear can result in dentin and pulp exposure causing significant oral pain, tooth loss, or periarticular and pulpal infections [18,19], leading to deterioration in quality of life and, in extreme cases, to be life threatening [13,20,21]. Recently, remineralization of damaged tooth enamel was presented as an alternative method to traditional dental operations [22–24]. These researchers utilized the bio-mineralization process that naturally presented in the dental environment [25–27]. Precursors to the nanoparticle hydroxyapatite were used to form the hard enamel tissue in vitro or in vivo [23,27]. Some examples of the precursors are casein phosphopeptide-stabilized amorphous calcium phosphate [28–30]; amelogenin with fluoride [31], and polydopamine with hydroxyapatite (HAP) [23]. Unlike traditional dental treatments, this method repaired teeth with materials that were almost identical to the teeth themselves. However, like the natural biomineralization process, using the remineralization method required significant time (>24 h) to take effect [22,23,27]. This is a major limitation to the clinical application of this approach.

1- Introduction

2- Development of periodontal tissue

3- Periodontal tissue regeneration with somatic NCCs and MSCs

4- Tissue engineering for periodontal tissue regeneration

5- Periodontal tissue regeneration using pluripotent stem cells

6- Discussion

References

Abstract

Periodontitis is commonly observed and is an important concern in dental health. It is characterized by a multifactorial etiology, including imbalance of oral microbiota, mechanical stress, and systemic diseases such as diabetes mellitus. The current standard treatments for periodontitis include elimination of the microbial pathogen and application of biomaterials for treating bone defects. However, the periodontal tissue regeneration via a process consistent with the natural tissue formation process has not yet been achieved. Developmental biology studies state that periodontal tissue is composed of neural crest-derived ectomesenchyme. To elucidate the process of periodontal regeneration, it is essential to understand the developmental background and intercellular cross-talk. Several recent studies have reported the efficacy of transplantation of mesenchymal stem cells for periodontal tissue regeneration. In this review, we discuss the basic knowledge of periodontal tissue regeneration using mesenchymal stem cells and highlight the potential of stem cell-based periodontal regenerative medicine.

Introduction

Periodontal tissues include soft tissues such as gingiva and periodontal ligaments (PDLs) and hard tissues such as the alveolar bones. Periodontitis is usually defined as bone resorption and periodontal tissue destruction due to acute (sometimes aggressive) or chronic inflammation. And periodontitis is very important concerns not only in dental health but also systemic health. The primary treatments for periodontal tissue inflammation include scaling and root planing and periodontal surgery for periodontal tissue reconstruction. Periodontal tissue regeneration using guided tissue regeneration and enamel matrix derivatives are being used for 2e3-wall alveolar bone defects [1,2]. These methods depend on mesenchymal stem cells (MSCs) residing in the periodontal tissues, space provision for the differentiation of MSCs, and the availability of growth factors.

Abstract

The aim of this study was to compare the 5-year outcome of full-arch mandibular fixed prosthetic rehabilitation using the All-on-4 concept in smoking and nonsmoking patients. This retrospective cohort study included 200 patients (n = 100 smokers, n = 100 nonsmokers), 119 women and 81 men, with an average age of 53.7 years, rehabilitated in immediate function with 800 implants. Implant cumulative survival rate estimation (Kaplan-Meier with log-rank test) and marginal bone resorption (MBR) at 5 years (Mann-Whitney test) were compared between both groups. Multivariable analysis was used to investigate potential risk indicators for MBR ≥ 2.8 mm at 5 years. Nine patients (4.5%) were lost to follow-up. Four patients lost eight implants, specifically one nonsmoking patient (n = 1 implant) and three smoking patients (n = 7 implants), resulting in a cumulative survival rate estimation of 99.0% and 96.9% for nonsmokers and smokers, respectively (P = 0.296). The average (standard deviation) MBR at 5 years was 1.68 mm (0.76 mm) and 1.98 mm (1.02 mm) for nonsmokers and smokers, respectively (P = 0.045). Smoking (odds ratio = 2.92) was the only risk indicator significantly associated with MBR ≥ 2.8 mm in multivariable analysis. Smoking should not be an absolute contraindication for rehabilitation of the edentulous mandible through the All-on-4 concept; however, smoking habits were significantly associated with MBR ≥ 2.8 mm.

Introduction

Smoking has long been causally associated with several cancers, heart disease, and chronic obstructive pulmonary disease and represents the leading cause of premature death and morbidity in the Western world (U.S. Department of Health and Human Services. The health consequences of smoking: a report of the surgeon general. 2004; 1). Cigarette smoking was previously reported to have a detrimental effect on early bone tissue response around dental implants, with marginal bone loss, gaps, and fibrous tissue surrounding the implants retrieved from smokers, together with a significant decrease in bone to implant contact percentage compared to nonsmokers (2).

Purpose. This study sought to assess the clinical outcome and survival rate of oral implants placed in individuals with ectodermal dysplasia (ED), based on previously published studies. Methods. An electronic search without time restrictions was undertaken in 5 databases (PubMed/Medline, Web of Science, ScienceDirect, J-Stage, Lilacs). Descriptive statistics, Kaplan Meier estimator and implant failure probability were calculated. Results. 90 publications were included, reporting 228 ED patients that received 1472 implants (1392 conventional, 47 zygomatic, 33 mini-implants). Mean age of the patients was 20.2±6.8 years (2-56). Patients had a mean of 3.2±2.5 maxillary and 2.1±2.6 mandibular permanent teeth (min-max, 0-14). Patients received a mean of 8.2±3.8 implants (1-20). Most implants were placed in the third decade of life, 24.6% of the implants were placed in children (0-17 years of age). 1391 implants had information on follow-up (72 failures, 5.2%). The 20-year CSR was 84.6%. The probability of failure was 4.5% (95%CI 3.5%-5.6%, p<0.001). Additional treatments performed were Le Fort I (99 implants, 20 patients, 3.5% failed), grafting (497 implants, 77 patients, 5.2% failed), distraction osteogenesis (79 implants, 16 patients, 10.1% failed). Mean follow-up was 42.9±41.9 months (min-max, 2-240). Conclusions. Dental implants placed in ED patients, either infants or adults, present a high survival rate (20-year CSR 84.6%).

INTRODUCTION

Ectodermal dysplasia (ED) encompasses a number of genetic syndromes characterized by a congenital defect in two or more of the ectodermal structures of the body. The condition is estimated to occur in approximately 1 in 100,000 live births, and approximately 132 different hereditary syndromes related to ED have been identified (Clarke, 1987). The syndromes usually affect the hair, teeth, nails, sweat glands, craniofacial structures, digits, and occasionally mesodermal abnormalities (Clarke, 1987). The impact on the oral and maxillofacial region includes decreased growth of the mandible and maxilla, deficient development of the maxillary and mandibular alveolar ridges, significant reduction in salivary secretions, and malformations and anomalies of number and shape of primary and permanent teeth (Martin et al., 2005). As many of these patients present oligodontia (absence of 6 or more teeth) or anodontia (complete absence of teeth), a prosthetic rehabilitation is usually desirable. The degree of dentoalveolar tissue deficiency can make an implant-supported prosthesis an appropriate method of definitive occlusal restoration in these patients. However, as the absence of teeth is congenital, this raises the issue of placement of oral implants in growing children, mainly due to the influence of craniofacial growth on the implant’s behavior (Singer et al., 2012). The aim of the present review was to assess the clinical outcome and survival rate of oral implants used for the oral rehabilitation of ED patients.

In this paper we present the first results of a broad research line aiming a better understanding about dental implants as the number of procedures, successes and failures in Brazil and possible reasons of losses (from problems on diagnose to fabrication defects from different brands offered in the Brazilian market). One thing that is already evident is the lack of details of the performed elemental analysis of implants, not only in Brazil but also on the majority of reported analyses published on international journals dedicated to the field. There are already a significant number of reports about the composition of dental implants and its surfaces, but in general they have not performed tests enough to validate the results nor reported the procedure with sufficient details establishing their comprehensiveness, which is critical to enable a comparison between those results. One detected problem is the using of a non standard geometry in some equipment that require special shapes or dimension for the analysis. The other is the determination of the uncertainties to be associated to the results. Here we will perform a brief review of the dental implant history, of some problems found in the elemental analysis and will present two sets of measurements, one to investigate the consequences of using nonstandard geometries and another comparing elemental analyses made with different instruments.

INTRODUCTION

The first record of dental implants was 2000 BC, with the use of gold, platinum and porcelain. The Mayan civilization, among the many scientific advances it generated, was the first to use endosseous dental implants [1]. Over the years, various materials have been tested for dental implants, such as chromium-cobalt-molybdenum and iron-chromium-nickel alloys, stainless steel, and metals such as gold, platinum and silver. However, the clinical success obtained in the medium and long term for these materials was very low due to high peri-implant bone reabsorption [2]. The finding of the concept of osseointegration only occurred in 1965 by Brånemark in Sweden, leading a research group at the University of Gothenburg [3]. The original research of Brånemark was on the microcirculation of blood in rabbit tibias, with the assistance of a small titanium optical chamber, which was surgically inserted in the bone, to investigate the blood supply. After some time, when he tried to remove the chamber, Brånemark found it impossible because the chamber was integrated to the bone. It was thus evident that the integration between this metal and bone occurred perfectly, and there was no rejection [3]. The concept of osseointegration was then defined as the direct structural and functional connection between ordered, living bone and the surface of a loadcarrying implant. [4] Brånemark’s next step was to apply his discovery to oral rehabilitation, using titanium to built dental implants. Since then it was noticed that the clinical success of the implantology is directly related to the occurrence of the phenomenon of osseointegration and the type of material used [3].

Introduction: Companies selling dental implant guided systems mostly offer similar surgical guides. The purpose of this paper is to present an innovative-guided surgery system which originality lies in its guidance device, and to report the author’s experience in using this system for dental implant surgery. Technical protocol: Two parallel tubes on either side of the drilling axis guide the successive drills and the implant placement. As a result of the lateral guidance, there is no friction of the drills on the surgical guide, which would damage it or contaminate the drilling hole with particles torn out from the guide. No radiological guide is needed during the radiographic examination stage. No successive diameter reduction tubes are requested. This guide can be used for all brands of implants. Discussion: In our experience, 67 implants (31 titanium and 36 zircon implants) were placed in 35 patients with guided surgery system. Multiple clinical cases were treated with this system: ‘onestage’ or a ‘two-stage’ surgical protocol, with flap and flapless surgical techniques, and with delayed or immediate loading. Clinical cases treated revealed good implant placement with planning. The widely open design of this guide allows irrigation and practitioner’s sight control under conditions comparable to those of operations performed without surgical guide. Conclusion: This dental implant guided system appears to be a significant advance in the field of implant surgical guides.

Introduction

The use of guides in implant surgery is constantly increasing. This success is due to the service provided both to trainee practitioners (ensuring their surgical gesture) and to experienced clinicians (for whom guided surgery provides a reliable therapeutic solution in the case of complex implantations in which the accuracy of the implant positioning is crucial and may sometimes avoid pre-implant surgery). Of course, the use of these techniques is also interesting in the implant-supported rehabilitation by immediate ‘loading’. If the characteristics of the ideal guide had to be defined, first of all one would ask for precision: absence of defective manufactur ing, a perfect fit in the mouth, high stability during the operation and optimal drill guide for a perfect reproducibility of the planning. It is also necessary that the guide can be transported, stored and sterilized without any distortion or degradation. In addition, it is desirable that the design of the guide does not interfere with the visual inspection by the surgeon and with the drill irrigation. Finally, the use of this guide should not lead to a high increase in the cost of the operation. Companies selling dental implant guided systems offer surgical guides of similar design: they are dental, mucosa or bone supported, mostly made of resin, whereby drill  holes are prepared within the body of the guide itself. These drill holes usually receive metal sleeves of various diameters to guide successive drills. aving had the opportunity to test this innovative device, which differs significantly from the usual design, the authors wish to describe the system and the surgical protocol and to share their experience in their clinical cases (67 implants).

Objective. To determine the translucency acceptability and perceptibility thresholds for dental resin composites using CIEDE2000 and CIELAB color difference formulas. Methods. A 30-observer panel performed perceptibility and acceptability judgments on 50 pairs of resin composites discs (diameter: 10mm; thickness: 1mm). Disc pair differences for the Translucency Parameter (TP) were calculated using both color difference formulas (TP00 ranged from 0.11 to 7.98, and TPab ranged from 0.01 to 12.79). A Takagi–Sugeno–Kang (TSK) Fuzzy Approximation was used as fitting procedure. From the resultant fitting curves, the 95% confidence intervals were estimated and the 50:50% translucency perceptibility and acceptability thresholds (TPT and TAT) were calculated. Differences between thresholds were statistically analyzed using Student t tests (˛ = 0.05). Results. CIEDE2000 50:50% TPT was 0.62 and TAT was 2.62. Corresponding CIELAB values were 1.33 and 4.43, respectively. Translucency perceptibility and acceptability thresholds were significantly different using both color difference formulas (p = 0.01 for TPT and p = 0.005 for TAT). CIEDE2000 color difference formula provided a better data fit than CIELAB formula. Significance. The visual translucency difference thresholds determined with CIEDE2000 color difference formula can serve as reference values in the selection of resin composites and evaluation of its clinical performance.

Introduction

The increased demand of patients for highly esthetic restorations has driven the development of dental materials with suitable optical properties. Translucency is an important property of dental tissues and materials. Thus, an appropri- ate determination and communication of optical properties should include translucency, in addition to more popular parameters such as: lightness (L*), a* and b* (CIELAB coordinates), hue angle (h◦) and chroma (C*). Translucency describes the ability of a material to transmit light [1]. The translucency parameter [2] (TP) has been used to assess the translucency of dental materials [3–7]. TP is defined as the CIELAB color difference (E*ab) for a material, at a particular thickness, on optical contact with ideal black and white backings [2]. Aiming to improve correction between perceived and computed color differences of CIELAB formula, the Commission Internationale de l’Éclairage (CIE) [8] recommended the use of CIEDE2000 color difference formula. However, at the moment in the majority of translucency studies in dental literature, the TP is still quantified using the CIELAB color space and its associated color formula (E*ab). Thus, determination of TP has shown differences in translucency of different composite resins depending of its shade [9],thickness [10]; matrix composition [11]; filler particle size and content [12,13] and type and amount of the opacifiers used [14]. Perceptibility difference threshold represents the lower perceptual limit, and it is widely applicable, mainly, to develop new color notation systems and their color difference metrics, to study discernible colors by the human visual system [15] and to understand the mechanisms of color vision [16]. However, in many practical situations, differences above the threshold (supra-threshold) are used, passing from perceptibility thresholds or “just noticeable differences” to higher differences, named “acceptable differences” or “tolerances.” The industrial interest on these differences is justified, on one hand, by the high cost required to maintain the industrial production below the limits of the visual threshold (perceptible threshold) and, on the other hand, by the need of maintaining the differences under an admissible limit. The complete absence of control (monitoring) should involves a lack of similarity in the production outcome, with negative implications on the overall quality of the product.

Visualize an MRI scanner that is less expensive and designed to image a smaller field of view (FOV), like a knee, ankle, or wrist. Such anatomy-specific MRI scanners have been developed and are currently or soon to be available.1 Facilitating this development is an MRI design shift away from using larger and more expensive magnets with excellent field homogeneity and toward accepting smaller, less homogeneous (or less perfect) magnetic fields produced by cheaper and smaller magnets. Image formation can remain feasible by computationally correcting for magnet inhomogeneity and technological advances in pulse sequences and coil design, allowing for MRI scanners to become even cheaper to manufacture.1–3 Now, imagine optimizing these smaller FOV scanners to image teeth, the jaws, and face, and you have the design of an MRI scanner designed for dental use. The physics of producing an image with magnetic resonance are more complex and quite different from computed tomography (CT) or cone beam computed tomography (CBCT) using radiograph. Consequently, MRI has considerably more opportunity for producing useful depictions of human tissues. With the development of dental and face-specific MRI coils, plus the freedom found in sequence design and image processing, researchers can feasibly develop custom techniques to address any number of dental imaging indications: anatomic characterization of hard tissues including bone and teeth for “routine” dental indications like implant placement, caries detection, and fracture detection; anatomic and functional characterization of soft tissues, including periodontal/periapical inflammation, muscle and nerves to characterize neural and pain disorders, and pathologic tissue characterization to diagnose neoplasms and dysplasia without a surgical biopsy; blood flow imaging in both bulk and perfusion forms to assess tissue viability/inflammatory status; and finally, spectroscopy to provide molecular profiles of tissue. Related technological advances in pulse sequence design will likely lead us into uncharted knowledge about normal dental anatomy and physiology as well as pathology and pathophysiology. In this article, the authors provide a brief overview of the use of conventional MRI techniques applied to dental indications, discuss relevant MRI physics in the various steps of image formation, and highlight recent hardware and software technical developments that contribute to (1) the cost/size of MRI decreasing significantly, allowing use in the typical dental clinic, and (2) the facilitation of very specific dental imaging applications that will solve clinical problems.

Traumatic injuries, genetic diseases and external harmful agents such as bacteria and acids often compromise tooth integrity. There is an unmet medical need to develop alternative, innovative dental treatments that complement traditional restorative and surgery techniques. Stem cells have transformed the medical field during the last years. The combination of stem cells with bioactive scaffolds and nanostructured materials turn out to be increasingly beneficial in regenerative dental medicine. Stem cell-based regenerative approaches for the formation of dental tissues will significantly improve treatments and will have a major impact in dental practice. To date there is no established and reliable stem cell-based treatment translated into the dental clinics, however, the advances and improved technological knowledge are promising for successful dental therapies in the near future. Here, we review some of the contemporary challenges in dental medicine and describe the benefits and future possibilities of certain novel approaches in the emerging field of regenerative dentistry.

INTRODUCTION – TOOTH SPECIFICITY

Teeth exert fundamental roles in physiological functions, such as mastication and speech, and are a key feature of facial aesthetics. Tooth functioning relies on its unique combination of hard and soft tissues. Enamel is the hardest tissue of the human body with exceptional physical characteristics to withstand masticatory forces and to protect dental tissues from chemical and bacterial assaults (Figure 1A). 1 Ameloblasts synthesize the organic components of enamel, where hydroxyapatite prisms are formed, but these cells are lost upon tooth eruption, making human teeth incapable of regenerating enamel. Dentin forms a less mineralized matrix tightly interconnected with the enamel and dental pulp, a richly vascularized and innervated soft connective tissue that occupies the central portion of teeth (Figure 1A). Dentin is synthesized by pulp-derived odontoblasts and is characterized by the presence of dentinal tubules that contain the cytoplasmic extensions of odontoblasts as well as sensory nerve endings, thus making dentin highly sensitive to external stimuli and permeable to bacteria upon enamel destruction. Upon tooth injury, a newly formed dentin- or bone-like matrix (i.e., tertiary dentin) protects pulp vitality, but more important damage often leads to pulp necrosis. 1 Teeth are anchored to the alveolar bone by their roots that consist of dentin and cementum. The roots are connected to the bone via the periodontal ligament, a connective tissue that provides stability to the teeth and absorbs mechanical stresses during mastication. 2 Traumatic injuries, infections and genetic diseases, combined with age, often result in tooth loss. It is therefore necessary to develop innovative approaches for the repair/regeneration of damaged or missing dental and alveolar bone tissues.3 However, the unique characteristics of enamel and dentin make tooth regeneration particularly challenging. Technological advancements ranging from digitalization to nanotechnology have become an inherent aspect of many medical fields, and the same applies to dentistry. These progresses aim to offer improved, faster, painless and more effective treatments when compared to methods traditionally used in dental clinics.