Dental Regeneration Research Articles

In Vitro Characterization of Reversine-Treated Gingival Fibroblasts and Their Safety Evaluation after In Vivo Transplantation.

Reversine is a purine derivative that has been investigated with regard to its biological effects, such as its anticancer properties and, mostly, its ability to induce the dedifferentiation of adult cells, increasing their plasticity. The obtained dedifferentiated cells have a high potential for use in regenerative procedures, such as regenerative dentistry (RD). Instead of replacing the lost or damaged oral tissues with synthetic materials, RD uses stem cells combined with matrices and an appropriate microenvironment to achieve tissue regeneration. However, the currently available stem cell sources present limitations, thus restricting the potential of RD. Based on this problem, new sources of stem cells are fundamental. This work aims to characterize mouse gingival fibroblasts (GFs) after dedifferentiation with reversine. Different administration protocols were tested, and the cells obtained were evaluated regarding their cell metabolism, protein and DNA contents, cell cycle changes, morphology, cell death, genotoxicity, and acquisition of stem cell characteristics. Additionally, their teratoma potential was evaluated after in vivo transplantation. Reversine caused toxicity at higher concentrations, with decreased cell metabolic activity and protein content. The cells obtained displayed polyploidy, a cycle arrest in the G2/M phase, and showed an enlarged size. Additionally, apoptosis and genotoxicity were found at higher reversine concentrations. A subpopulation of the GFs possessed stem properties, as supported by the increased expression of CD90, CD105, and TERT, the existence of a CD106+ population, and their trilineage differentiation capacity. The dedifferentiated cells did not induce teratoma formation. The extensive characterization performed shows that significant functional, morphological, and genetic changes occur during the dedifferentiation process. The dedifferentiated cells have some stem-like characteristics, which are of interest for RD.

An online learning journey in regenerative dentistry.

An online learning journey in regenerative dentistry.

Aptamers in dentistry: diagnosis, therapeutics, and future perspectives.

Oral health is essential to general health. The diagnosis of dental diseases and treatment planning of dental care need to be straightforward and accurate. Recent studies have reported the use of aptamers in dentistry to achieve a simple diagnosis and facilitate therapy. Aptamers comprise nucleic acid sequences that possess a strong affinity for their target. Synthesized chemically, aptamers have several advantages, including smaller size, higher stability, and lower immunogenicity compared with monoclonal antibodies. They can be used to detect biomarkers in saliva and the presence of various pathogens, or can be used as a targeted drug delivery system for disease treatment. This review highlights current research on aptamers for dental care, especially the recent progress in oral disease diagnosis and therapeutics. The challenges and unresolved problems faced by the clinical use of aptamers are also discussed. In the future, the clinical applications of aptamers will be further extended to include, for example, dental indications and regenerative dentistry.

Pediatric endodontic considerations in the application of regenerative therapy for immature permanent teeth: a review article

For adult teeth with necrosis or apical periodontitis, regenerative endodontics provides a useful alternative to standard endodontic treatment. This review focuses on the pediatric endodontic considerations in the application of regenerative therapy for immature permanent teeth. A thorough literature search was conducted in the MEDLINE database using the keywords "pediatric, regenerative, therapy, endodontics, immature, permanent, and teeth" to find relevant publications published between 2017 and 2024. Additionally, Google Scholar was used to find and access pertinent scientific publications using the appropriate search terms. Various inclusion criteria were applied to select the articles for review. The selected articles were published between 2020 and 2024 and included discussions on several specific elements. Topics covered include the criteria for case selection for regenerative endodontics. Overall, the existing evidence indicates that using regenerative endodontic techniques to treat adult permanent teeth with apical periodontitis or necrosis may successfully lead to the resolution of apical translucencies and the absence of clinical signs and symptoms. With slight modifications to the clinical procedure, regenerative dentistry methods can be effectively applied to specific cases, such as those involving a small apical foramen, decreased blood supply, and a lack of growth factors. However, additional research is required to determine the optimal conditions for achieving successful treatment outcomes.

Challenges in optimizing 3D scaffold for dentin-pulp complex regeneration

Regenerating dentin-pulp complex (DPC) using tissue engineering offers a novel and promising therapeutic alternative for restoring teeth. A crucial component of such a therapy is the designing and fabrication of an appropriate 3D Scaffold. In this review, we set out to highlight some of the general challenges associated with optimizing the most suitable scaffold for DPC regeneration to develop "bio-mimetic" approaches that influence stem cell proliferation, differentiation, and angiogenesis. It is essential to comprehend the biology and physical features of the dentin-pulp complex with updated bionanotechnology to overcome the limitations of biomaterials to address the challenges in manufacturing the optimal scaffold. To date, current scaffolding models fail to regenerate a whole tooth. The success of regenerative dentistry relies on stem cells and scaffolds may shape the future of dental treatment.

Success in Tooth Bud Regeneration: A Short Communication

IntroductionTooth caries and loss are frequent clinical diseases in dentistry. Tissue engineering is a new therapeutic choice for the complete biological regeneration of pulpal and dental tissues in regenerative dentistry. The aim of this study was to establish a protocol for in situ regeneration of a dental bud in the extracted socket. MethodsThe current study examined tooth bud regeneration with dental pulp stem cells induced by a dentin derivative signal in a rabbit’s jaw. ResultA tooth bud was regenerated; the morphology and structure of it were typical, and it was post–Bell stage. ConclusionsIn our study, a real tooth bud was formed in the post–Bell stage with complete morphologic and biological features. However, the application of this method for tooth regeneration in humans necessitates further research.

Scaffolds for Dentin-Pulp Complex Regeneration.

Background and Objectives: Regenerative dentistry aims to regenerate the pulp-dentin complex and restore those of its functions that have become compromised by pulp injury and/or inflammation. Scaffold-based techniques are a regeneration strategy that replicate a biological environment by utilizing a suitable scaffold, which is considered crucial for the successful regeneration of dental pulp. The aim of the present review is to address the main characteristics of the different scaffolds, as well as their application in dentin-pulp complex regeneration. Materials and Methods: A narrative review was conducted by two independent reviewers to answer the research question: What type of scaffolds can be used in dentin-pulp complex regeneration? An electronic search of PubMed, EMBASE and Cochrane library databases was undertaken. Keywords including "pulp-dentin regeneration scaffold" and "pulp-dentin complex regeneration" were used. To locate additional reports, reference mining of the identified papers was undertaken. Results: A wide variety of biomaterials is already available for tissue engineering and can be broadly categorized into two groups: (i) natural, and (ii) synthetic, scaffolds. Natural scaffolds often contain bioactive molecules, growth factors, and signaling cues that can positively influence cell behavior. These signaling molecules can promote specific cellular responses, such as cell proliferation and differentiation, crucial for effective tissue regeneration. Synthetic scaffolds offer flexibility in design and can be tailored to meet specific requirements, such as size, shape, and mechanical properties. Moreover, they can be functionalized with bioactive molecules, growth factors, or signaling cues to enhance their biological properties and the manufacturing process can be standardized, ensuring consistent quality for widespread clinical use. Conclusions: There is still a lack of evidence to determine the optimal scaffold composition that meets the specific requirements and complexities needed for effectively promoting dental pulp tissue engineering and achieving successful clinical outcomes.

Trajtimi jo-kirurgjikal me mineral treoksid agregat i incizivit lateral maksillar me apeks të hapur në një seancë

Although dental trauma is difficult to manage by general dental practices, it is important to follow the appropriate steps to achieve optimal results. This case report describes the non-surgical management of a tooth with an open apex and necrotic pulp using MTA and CWC (continuous wave compaction) to achieve endodontic success. Although it is a controversial technique, if the right conditions are provided, the creation of an artificial barrier continues to preserve an adequately functional and healthy tooth in the arch while avoiding extensive surgical and prosthet- ic procedures to replace a potentially compressed tooth. This case report highlights the beneficial effects of MTA, which are very good in the field of apexification or even regenerative dentistry as a whole. The 29-year-old man presents post-traumatic necrosis of the maxillary lateral incisor (tooth 12) which has been closed in the apical part with MTA, artificial barriers have been created, achieving the disinfection of the root canal, the remission of apical periodontitis, and where after 7 months of follow-up we have a lot of progress. The importance of using biocompatible materials such as MTA is emphasized, which in this case resulted in satisfactory results. This report reviews the management of a lateral incisor with open apex and necrotic pulp with apical plug with the aid of MTA and CWC achieving a successful apical and canalicular system seal.

Efikasiteti i aplikimit të plazmës të pasuruar me trombocite (PRP) si graft autolog në procedurën kirurgjikale për ngritjen e fundit të sinusit maksilar për vendosjen e implanteve dentare

Placement of dental implants in the upper jaw can pose difficulties due to insufficient bone volume caused by si- nus pneumatization and physiological bone resorption. The aim of this study was to evaluate the impact of using autologous platelet-rich plasma as a graft material for si- nus lift procedures. The mean height of the alveolar bone between the floor of the maxillary sinus and the alveolar crest was 2.50 ± 0.73 mm preoperatively, 16.90 ± 1.93 mm post-surgical procedure, and 14.4 mm after 6 months (p < 0.05). There were statistically significant differences in the changes of the values of the most mesial and distal distances in the augmented region. The average dimen- sions of the placed dental implants were 10 mm in length and 3.98 mm in diameter, with 88% high primary stabili- ty in the placed implants and 100% implant survival after a 6-month period. The application of platelet-rich plasma in maxillary sinus floor elevation procedures yields good results in terms of new bone formation, implant osseointe- gration, and positive clinical outcomes. However, further research is needed over a longer time interval to better understand the role and potential of this autogenous graft material in regenerative dentistry.

Physiologic dentin regeneration: its past, present, and future perspectives.

Regenerative dentistry has rapidly progressed since the advancement of stem cell biology and material science. However, more emphasis has been placed on the success of tissue formation than on how well the newly generated tissue retains the original structure and function. Once dentin is lost, tertiary dentinogenesis can be induced by new odontoblastic differentiation or re-activation of existing odontoblasts. The characteristic morphology of odontoblasts generates the tubular nature of dentin, which is a reservoir of fluid, ions, and a number of growth factors, and protects the inner pulp tissue. Therefore, understanding the dynamic but delicate process of new dentin formation by odontoblasts, or odontoblast-like cells, following dentinal defects is crucial. In this regard, various efforts have been conducted to identify novel molecules and materials that can promote the regeneration of dentin with strength and longevity. In this review, we focus on recent progress in dentin regeneration research with biological molecules identified, and discuss its potential in future clinical applications.

Induced Pluripotent Stem Cells - A New Perspective toward Regenerative Dentistry and Prosthodontics: A Narrative Review Article

Aim: This study aims to review the unexplored area in regenerative prosthodontics using induced pluripotent stem (IPS) cells. Materials and Methods: A computer-based search was done from the year 1981 to 2020, but more specifically for IPS cells from 2006 and, the data were collected from various sources such as the National Center for Biotechnology Information (via PubMed), Medline semantic scholar, BioMed Central, Directory of Open Access Journals, Science Open, and Bielefeld Academic Search Engine using the keywords stem cells in dentistry, IPS cells, embryonic stem cells (ESCs), prosthodontic regeneration using induced pluripotent cells, stem cells from the periodontal ligament, dental pulp, deciduous tooth, and dental follicle. We have also systematically reviewed the method to generate IPS cells and their research in obtaining various organs that is of concern in dentistry and especially prosthodontics. Results: Based on the keywords and cross-referencing, 69 articles were valid and selected for review. The chosen articles are organized according to the subheadings in the order of their publication date. This literature is based on studies conducted on animals, and it does not include the transplantation of IPS cells in humans. In 2006, when Yamanaka and Takahashi discovered IPS cells, there was a spike rise in the study of these cells. The number of clinical trials for IPS cells was around 75%, whereas for ESCs was just 25%. Most of the clinical trials for IPS cells have been done in the USA (37%) whereas India accounts for only 1% of the study. Conclusion: This review article suggests the future of IPS cells in regenerative dentistry and prosthodontics. It gives information on the types of stem cells, why IPS cells have been chosen for the review, the source of IPS cells, the method of induction of IPS cells, and their use in prosthodontics and implantology.

Comparative evaluation of the effect of 2% graphene oxide and 5% hydroxyapatite nanoparticles in isolation and in combination on micro tensile bond strength of 5th generation adhesive

Graphene is the thinnest, strongest, and stiffest imaginable material. The biocompatible property of graphene oxide can initiate and facilitate cell adhesion, proliferation, and differentiation of periodontal ligament, osteogenic, and oral epithelial cells. Furthermore, the antibiofilm and anti-adhesion properties of graphene oxide in the prevention of dental biofilm infections, dental caries, and dental erosion as well as for implant surface modification and as an anti-quorum sensing agent. Composites are the most often utilized materials for restoration in the field of dentistry due to adhesive resins' improved mechanical and cosmetic properties. To safeguard the dentin and prevent dental cavities, dentin adhesives are utilized to affix hydrophobic resin composites to hydrophilic dentin tissue. Dental adhesives have a harder time adhering to dentin because it contains more water and is less mineralized than enamel. This makes the method more sensitive. As a result, it was chosen to assess and contrast the impact of 5% Hydroxyapatite nanoparticles and 2% Graphene oxide nanoparticles, both separately and together, on the Micro tensile bond strength of 5th generation adhesive. Graphene oxide is the most versatile form of Graphite in structural and functional configuration. Graphene oxide possesses extraordinary physical, chemical, optical, electrical and mechanical properties. Among the graphene family nanomaterials, the reduced form of Graphite adding the oxygenated functional group to the structure increases the surface area and therefore exhibits enviable excellent interaction ability with metal and ions as well as organic species. Graphene oxide in dentistry has provided outstanding results in antimicrobial action, regenerative dentistry, bone tissue engineering, drug delivery, physicochemical properties, enhancement of dental biomaterials and oral cancer treatment.

Gene-Activated Materials in Regenerative Dentistry: Narrative Review of Technology and Study Results.

Treatment of a wide variety of defects in the oral and maxillofacial regions requires the use of innovative approaches to achieve best outcomes. One of the promising directions is the use of gene-activated materials (GAMs) that represent a combination of tissue engineering and gene therapy. This approach implies that biocompatible materials will be enriched with gene-carrying vectors and implanted into the defect site resulting in transfection of the recipient's cells and secretion of encoded therapeutic protein in situ. GAMs may be presented in various designs depending on the type of material, encoded protein, vector, and way of connecting the vector and the material. Thus, it is possible to choose the most suitable GAM design for the treatment of a particular pathology. The use of plasmids for delivery of therapeutic genes is of particular interest. In the present review, we aimed to delineate the principle of work and various designs of plasmid-based GAMs and to highlight results of experimental and clinical studies devoted to the treatment of periodontitis, jaw bone defects, teeth avulsion, and other pathologies in the oral and maxillofacial regions.

Three-dimensional eco-friendly bacterial nanocellulose (BNC) scaffold for regenerative dentistry: Characterization, cytocompatibility and differentiation potential

ObjectiveRegenerative dentistry (RD) is an innovative strategy for treating necrotic teeth and regenerating damaged dental tissue. Biocompatible materials are pivotal for the advancement of RD, and the rising interest in environmental sustainability drives exploration of sustainable materials for dentistry. Bacterial nanocellulose (BNC) has emerged as a promising eco-friendly option and this study aims to assess BNC's suitability as scaffolds for regenerative dentistry applications. MethodsDifferent in vitro methods have been utilized to characterize the properties of BNC scaffolds in regenerative dentistry, such as scanning electron microscopy (SEM) to analyse surface property and porosity, as well as examining their absorption behaviour using phosphate-buffered saline and bovine serum. Dental pulp stem cell (DPSCs) attachment, viability, and proliferation were evaluated using SEM, live and dead, and tetrazolium reduction assays. The odontogenic potential of the scaffold was evaluated using Alizarin Red staining and qPCR (14 and 21 days). ResultsScanning electron microscopy (SEM) images and ethanol displacement method demonstrated the porous architecture of the BNC scaffold with an average porosity of 70.02 ± 4.74% and 50.26 ± 1.43% respectively. The scaffold absorbed 2846.54 ± 258.95 of BSA and 1648.63 ± 50.37% PBS after immersion in solution for 1 h, following pseudo first and second order kinetics. The biocompatibility assay indicated that cell density increased with time and that the scaffold was appropriate for cell adhesion and migration. Moreover, the BNC led to significantly higher mineralization and odontogenic expression compared to the control (BNC in conditioned media). SignificanceBNC showed fast adsorption of bovine serum, allowed DPSC attachment, migration, and odontogenic differentiation. This suggests its suitability as a biocompatible scaffold for triggering in situ mineralized tissue regeneration for regenerative dental applications.

Advancing Dentistry through Bioprinting: Personalization of Oral Tissues.

Despite significant advancements in dental tissue restoration and the use of prostheses for addressing tooth loss, the prevailing clinical approaches remain somewhat inadequate for replicating native dental tissue characteristics. The emergence of three-dimensional (3D) bioprinting offers a promising innovation within the fields of regenerative medicine and tissue engineering. This technology offers notable precision and efficiency, thereby introducing a fresh avenue for tissue regeneration. Unlike the traditional framework encompassing scaffolds, cells, and signaling factors, 3D bioprinting constitutes a contemporary addition to the arsenal of tissue engineering tools. The ongoing shift from conventional dentistry to a more personalized paradigm, principally under the guidance of bioprinting, is poised to exert a significant influence in the foreseeable future. This systematic review undertakes the task of aggregating and analyzing insights related to the application of bioprinting in the context of regenerative dentistry. Adhering to PRISMA guidelines, an exhaustive literature survey spanning the years 2019 to 2023 was performed across prominent databases including PubMed, Scopus, Google Scholar, and ScienceDirect. The landscape of regenerative dentistry has ushered in novel prospects for dentoalveolar treatments and personalized interventions. This review expounds on contemporary accomplishments and avenues for the regeneration of pulp-dentin, bone, periodontal tissues, and gingival tissues. The progressive strides achieved in the realm of bioprinting hold the potential to not only enhance the quality of life but also to catalyze transformative shifts within the domains of medical and dental practices.

Moringa oleifera Use in Maintaining Oral Health and Its Potential Use in Regenerative Dentistry.

Phytomedicine refers to the use of naturally derived products to cure and mitigate human conditions. Natural products have the advantages of causing minimum side effects, being biocompatible, available, and economical, with a wide array of biological activities. Reports have described the use of natural products with antimicrobial and anti-inflammatory properties to treat oral conditions and promote wound healing. Moringa oleifera, known as the "drumstick" or "horseradish" tree, is believed to have medicinal properties regarding a range of medical conditions, though there is limited information on its use in oral medicine. This narrative review focuses on the use of Moringa extracts in the management of oral conditions, including oral infections, inflammatory conditions, the remineralization of hard tissues, oral wound healing, and tissue regeneration, drawing from both in vitro and in vivo studies which indicate that the potential of Moringa extracts in supporting dentin-pulp regeneration after caries or trauma is worthy of more careful consideration.

Stem-Cell Therapy: Filling Gaps in Oro-Maxillofacial Region.

How do stem cells function? Why should we, as dentists, care about stem cells? How might dental procedures be substituted by stem cells? Are stem cells capable of regenerating a tooth or temporomandibular joint (TMJ)? Although the ability to regenerate a destroyed tissue has been known for a while, research into regenerative medicine and dentistry has made significant strides in molecular biology. A paradigm shift in the therapeutic toolbox for dental and oral diseases is likely to result from a growing understanding of biological concepts inthe regeneration of oral/dental tissues along with stem cell research, leading to an intense search for "biological solutions to biological problems." Among other tissues, orofacial tissues effectively separate stem cells from human tissues. Because they can self-renew and produce different cell types, stem cells offer novel techniques for regenerating damaged tissues and curing illnesses. A number of significant milestone successes have shown their practical applicability, traditional biomaterial-based treatments in regenerative dentistry as therapeutic alternatives that offer regeneration of damaged oral tissues rather than merely "filling the gaps." In order to use these innovative accomplishments for patient well-being, the ultimate goal of this ground-breaking technology, well-designed clinical studies must be implemented as a crucial next step. The review's objective is to briefly synthesize the literature on stem cells in terms of their traits, subtypes, and uses for dental stem cells. It has been highlighted that stem cell therapy has the ability to treat craniofacial abnormalities and regenerate teeth in the oral and maxillofacial regions.

Sol-Gel Technologies to Obtain Advanced Bioceramics for Dental Therapeutics.

The aim of this work is to review the application of bioceramic materials in the context of current regenerative dentistry therapies, focusing on the latest advances in the synthesis of advanced materials using the sol-gel methodology. Chemical synthesis, processing and therapeutic possibilities are discussed in a structured way, according to the three main types of ceramic materials used in regenerative dentistry: bioactive glasses and glass ceramics, calcium phosphates and calcium silicates. The morphology and chemical composition of these bioceramics play a crucial role in their biological properties and effectiveness in dental therapeutics. The goal is to understand their chemical, surface, mechanical and biological properties better and develop strategies to control their pore structure, shape, size and compositions. Over the past decades, bioceramic materials have provided excellent results in a wide variety of clinical applications related to hard tissue repair and regeneration. Characteristics, such as their similarity to the chemical composition of the mineral phase of bones and teeth, as well as the possibilities offered by the advances in nanotechnology, are driving the development of new biomimetic materials that are required in regenerative dentistry. The sol-gel technique is a method for producing synthetic bioceramics with high purity and homogeneity at the molecular scale and to control the surfaces, interfaces and porosity at the nanometric scale. The intrinsic nanoporosity of materials produced by the sol-gel technique correlates with the high specific surface area, reactivity and bioactivity of advanced bioceramics.

Single-cell census of human tooth development enables generation of human enamel.

Tooth enamel secreted by ameloblasts (AMs) is the hardest material in the human body, acting as a shield to protect the teeth. However, the enamel is gradually damaged or partially lost in over 90% of adults and cannot be regenerated due to a lack of ameloblasts in erupted teeth. Here, we use single-cell combinatorial indexing RNA sequencing (sci-RNA-seq) to establish a spatiotemporal single-cell census for the developing human tooth and identify regulatory mechanisms controlling the differentiation process of human ameloblasts. We identify key signaling pathways involved between the support cells and ameloblasts during fetal development and recapitulate those findings in human ameloblast invitro differentiation from induced pluripotent stem cells (iPSCs). We furthermore develop a disease model of amelogenesis imperfecta in a three-dimensional (3D) organoid system and show AM maturation to mineralized structure invivo. These studies pave the way for future regenerative dentistry.

Influence of Extracellular Matrix Components on the Differentiation of Periodontal Ligament Stem Cells in Collagen I Hydrogel.

Regeneration of periodontal tissues requires an integrated approach to the restoration of the periodontal ligament, cementum, and alveolar bone surrounding the teeth. Current strategies in endogenous regenerative dentistry widely use biomaterials, in particular the decellularized extracellular matrix (dECM), to facilitate the recruitment of populations of resident cells into damaged tissues and stimulate their proliferation and differentiation. The purpose of our study was to evaluate the effect of the exogenous components of the extracellular matrix (hyaluronic acid, laminin, fibronectin) on the differentiation of periodontal ligament stem cells (PDLSCs) cultured with dECM (combinations of decellularized tooth matrices and periodontal ligament) in a 3D collagen I hydrogel. The immunohistochemical expression of various markers in PDLSCs was assessed quantitatively and semi-quantitatively on paraffin sections. The results showed that PDLSCs cultured under these conditions for 14 days exhibited phenotypic characteristics consistent with osteoblast-like and odontoblast-like cells. This potential has been demonstrated by the expression of osteogenic differentiation markers (OC, OPN, ALP) and odontogenic markers (DSPP). This phenomenon corresponds to the in vivo state of the periodontal ligament, in which cells at the interface between bone and cementum tend to differentiate into osteoblasts or cementoblasts. The addition of fibronectin to the dECM most effectively induces the differentiation of PDLSCs into osteoblast-like and odontoblast-like cells under 3D culture conditions. Therefore, this bioengineered construct has a high potential for future use in periodontal tissue regeneration.