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The objective of this study was to create injectable photo-crosslinkable biomaterials, using gelatin methacryloyl (GelMA) hydrogel, combined with a decellularized bone matrix (BMdc) and a deproteinized (BMdp) bovine bone matrix. These were intended to serve as bioactive scaffolds for dentin regeneration. The parameters for GelMA hydrogel fabrication were initially selected, followed by the incorporation of BMdc and BMdp at a 1% (w/v) ratio. Nano-hydroxyapatite (nHA) was also included as a control. A physicochemical characterization was conducted, with FTIR analysis indicating that the mineral phase was complexed with GelMA, and BMdc was chemically bonded to the amide groups of gelatin. The porous structure was preserved post-BMdc incorporation, with bone particles incorporated alongside the pores. Conversely, the mineral phase was situated inside the pore opening, affecting the degree of porosity. The mineral phase did not modify the degradability of GelMA, even under conditions of type I collagenase-mediated enzymatic challenge, allowing hydrogel injection and increased mechanical strength. Subsequently, human dental pulp cells (HDPCs) were seeded onto the hydrogels. The cells remained viable and proliferative, irrespective of the GelMA composition. All mineral phases resulted in a significant increase in alkaline phosphatase activity and mineralized matrix deposition. However, GelMA-BMdc exhibited higher cell expression values, significantly surpassing those of all other formulations. In conclusion, our results showed that GelMA-BMdc produced a porous and stable hydrogel, capable of enhancing odontoblastic differentiation and mineral deposition when in contact with HDPCs, thereby showing potential for dentin regeneration., (© 2024 Wiley Periodicals LLC.)

Purpose: developing customized titanium specimens, with innovative surfaces, is a suitable strategy to overcome implant failure. Additionally, a faster and efficient osteogenic commitment assists tissue regeneration. To investigate the interplay between inflammation and differentiation upon implantation, Dental Pulp Stem Cells (DPSCs) were cultured on 3D-printed titanium owning an internal open cell form, administering osteogenic factors by a liposomal formulation (LipoMix) compared to traditional delivery of differentiation medium (DM)., Materials and Methods: osteogenic differentiation was evaluated by western blot, by measuring β1 integrin expression, and by and real-time RT-PCR, by measuring SP7 and Collagen I gene expression; while.angiogenesis was characterized by measuring VEGF secretion levels. Matrix mineralization was assessed by means of Alizarin Red Staining, cell adhesion and inflammation responses through western blot, enzymatic and ELISA assays evaluating Nrf2 expression, catalase activity and Prostaglandin E2 secretion, respectively., Results: LipoMix enhances cell proliferation and adhesion, as revealed by increased integrin β1 expression. Mineralized matrix deposition, SP7 gene expression, Collagen I release and Alkaline Phosphatase activity appear increased in LipoMix condition. Additionally, the redox-sensitive transcription factor Nrf2 is overexpressed at the earliest experimental times, triggering the catalase activity., Conclusions: data reported confirm that internal topography and post-production treatments on titanium surfaces dynamically and positively condition the DPSC progress towards the osteogenic phenotype, moreover, the combination with LipoMix fastens the positive modulation of inflammation under osteogenic conditions. Therefore, the development of customized surfaces along with the administration of differentiating factors enclosed in a liposomal delivery system, could represent a promising and innovative tool in regenerative dentistry.

Regenerative medicine in dentistry focuses on repairing damaged oral tissues using advanced tools like stem cells, biomaterials, and tissue engineering (TE). Mesenchymal stem cells (MSCs) from dental sources, such as dental pulp and periodontal ligament, show significant potential for tissue regeneration due to their proliferative and differentiative abilities. This systematic review, following PRISMA guidelines, evaluated fifteen studies and identified effective strategies for improving dental, periodontal, and bone tissue regeneration through scaffolds, secretomes, and bioengineering methods. Key advancements include the use of dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) to boost cell viability and manage inflammation. Additionally, pharmacological agents like matrine and surface modifications on biomaterials improve stem cell adhesion and promote osteogenic differentiation. By integrating these approaches, regenerative medicine and TE can optimize dental therapies and enhance patient outcomes. This review highlights the potential and challenges in this field, providing a critical assessment of current research and future directions.

Purpose: Ridge preservation is essential to restore alveolar ridge volume and to enhance esthetic and functional outcomes for dental implants. The addition of hyaluronic acid to allogeneic bone substitute materials might enhance these outcomes. This clinical study evaluated the efficacy of ridge preservation after tooth extraction using granular allografts with and without hyaluronic acid addition., Methods: In this retrospective study, 40 patients with compromised extraction sockets were enrolled. Among them, 19 received particulate allogeneic bone substitutes (Allo), 21 received allogeneic bone substitutes with hyaluronic acid (AlloHya). Vertical and horizontal graft stability, graft shrinkage rate, and bone mineral density were assessed using radiographic measurements on CBCT scans conducted before tooth extraction, directly after ridge preservation and after four months. Patients were followed up 12 months post-implantation., Results: Vertical height loss after 4 months was significantly greater in the Allo group (-0.82 ± 0.95 mm) compared to the AlloHya group (-0.19 ± 0.51 mm; p = 0.011). Graft shrinkage rate was 16.9 ± 11.5% (Allo) and 10.3 ± 7.7% (AlloHya) (p = 0.038). After four months, average bone density was significantly higher in the AlloHya compared to the Allo group (p = 0.004). Nearly all implants (39 out of 40) were classified as "Success" according to the ICOI scheme, with no differences in implant quality between the two study groups., Conclusions: Improved graft stability, reduced resorption, and increased bone density were observed in hyaluronic acid-enriched allografts compared to pure allografts. Adding hyaluronic acid to allogeneic bone grafts significantly enhanced outcomes in ridge preservation., (© 2024. The Author(s).)

The biomaterial of dentin has emerged as a promising candidate for the tissue engineering of dental hard tissues. In bone tissue engineering, it may serve as either a scaffold or a reservoir of growth factors. The physical and chemical similarities between the dentin structure and bone have sparked scientific interest in using its features for the development of a new bone transplant material. Dentin, unlike hard and fragile enamel, is viscoelastic, making it a very effective bone replacement. The regeneration of pulp tissue has proven challenging due to its encasement in dentin, which lacks collateral blood flow except from the apical end of the root. Yet, the emergence of contemporary tissue engineering and the identification of dental stem cells have enabled experimentation with the regeneration of both pulp and dentin. This review will explain the different types of dentin grafts, their biocompatibility, safety, and effectiveness, along with difficulties. Additionally, the paper covers several strategies for creating autogenous dentin grafts and gives evidence-based insights into their clinical effectiveness. Overall, dentin grafts appear as a potential alternative to standard graft materials, stimulating tissue regeneration and enhancing patient outcomes in regenerative dentistry operations., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Dixit et al.)

In recent years, the field of regenerative dentistry has garnered considerable attention for its focus on restoring and renewing damaged dental tissue. This narrative review explores the potential of bone morphogenetic protein 7 (BMP7) and its diverse applications in the regeneration of dental tissue. Recently, significant efforts have been made to understand BMP7's role in advancing regenerative dentistry. Amongst the various signalling molecules investigated for their regenerative capabilities, BMP7 emerges as a pivotal candidate, demonstrating the ability to stimulate the regeneration of dental pulp, periodontal, craniofacial, and alveolar bone tissues for dental implant placement. Whilst BMP7 exhibits significant promise as a therapeutic agent in regenerative dentistry, further research and clinical trials are necessary to fully unlock its potential and optimise its clinical effectiveness in addressing diverse dental and craniofacial conditions. This review highlights BMP7's substantial potential and emphasises the ongoing need for continued research to effectively harness its clinical utility in diverse dental and craniofacial contexts., Competing Interests: Conflict of interest None disclosed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Stem cells isolated from human exfoliated deciduous teeth or SHED possess high rate of proliferation along with high osteogenic as well as neurogenic differentiation when compared with dental pulpal stem cells. This stem cell population is an important source for therapeutic regeneration of tissues. Hence, the aim of present review article was to analyze the potential applications of SHED., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Zinc is known for its role in enhancing bone metabolism, cell proliferation, and tissue regeneration. Several studies proposed the incorporation of zinc into hydroxyapatite (HA) to produce biomaterials (ZnHA) that stimulate and accelerate bone healing. This systematic review aimed to understand the physicochemical characteristics of zinc-doped HA-based biomaterials and the evidence of their biological effects on osteoblastic cells. A comprehensive literature search was conducted from 2022 to 2024, covering all years of publications, in three databases (Web of Science, PUBMED, Scopus), retrieving 609 entries, with 36 articles included in the analysis according to the selection criteria. The selected studies provided data on the material's physicochemical properties, the methods of zinc incorporation, and the biological effects of ZnHA on bone cells. The production of ZnHA typically involves the wet chemical synthesis of HA and ZnHA precursors, followed by deposition on substrates using processes such as liquid precursor plasma spraying (LPPS). Characterization techniques confirmed the successful incorporation of zinc into the HA lattice. The findings indicated that zinc incorporation into HA at low concentrations is non-cytotoxic and beneficial for bone cells. ZnHA was found to stimulate cell proliferation, adhesion, and the production of osteogenic factors, thereby promoting in vitro mineralization. However, the optimal zinc concentration for the desired effects varied across studies, making it challenging to establish a standardized concentration. ZnHA materials are biocompatible and enhance osteoblast proliferation and differentiation. However, the mechanisms of zinc release and the ideal concentrations for optimal tissue regeneration require further investigation. Standardizing these parameters is essential for the effective clinical application of ZnHA.

The decellularised extracellular matrix (dECM) of in vitro cell culture is a naturally derived biomaterial formed by the removal of cellular components. The compositions of molecules in the extracellular matrix (ECM) differ depending on various factors, including the culture conditions. Cell-derived ECM provides a 3-dimensional structure that has a complex influence on cell signalling, which in turn affects cell survival and differentiation. This review describes the effects of dECM derived from mesenchymal stem cells (MSCs) on cell responses, including cell migration, cell proliferation, and cell differentiation in vitro. Published articles were searched in the PubMed databases in 2005 to 2022, with assigned keywords (MSCs and decellularisation and cell culture). The 41 articles were reviewed, with the following criteria. (1) ECM was produced exclusively from MSCs; (2) decellularisation processes were performed; and (3) the dECM production was discussed in terms of culture systems and specific supplementations that are suitable for creating the dECM biomaterials. The dECM derived from MSCs supports cell adhesion, enhances cell proliferation, and promotes cell differentiation. Importantly, dECM derived from dental MSCs shows promise in regenerative dentistry applications. Therefore, the literature strongly supports cell-based dECMs as a promising option for innovative tissue engineering approaches for regenerative medicine., Competing Interests: Conflict of interest None disclosed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Regenerative dentistry aims to enhance the structure and function of oral tissues and organs. Modern tissue engineering harnesses cell and gene-based therapies to advance traditional treatment approaches. Studies have demonstrated the potential of mesenchymal stem cells (MSCs) in regenerative dentistry, with some progressing to clinical trials. This review comprehensively examines animal studies that have utilized MSCs for various therapeutic applications. Additionally, it seeks to bridge the gap between related findings and the practical implementation of MSC therapies, offering insights into the challenges and translational aspects involved in transitioning from preclinical research to clinical applications., Highlights: To achieve this objective, we have focused on the protocols and achievements related to pulp-dentin, alveolar bone, and periodontal regeneration using dental-derived MSCs in both animal and clinical studies. Various types of MSCs, including dental-derived cells, bone-marrow stem cells, and umbilical cord stem cells, have been employed in root canals, periodontal defects, socket preservation, and sinus lift procedures. Results of such include significant hard tissue reconstruction, functional pulp regeneration, root elongation, periodontal ligament formation, and cementum deposition. However, cell-based treatments for tooth and periodontium regeneration are still in early stages. The increasing demand for stem cell therapies in personalized medicine underscores the need for scientists and responsible organizations to develop standardized treatment protocols that adhere to good manufacturing practices, ensuring high reproducibility, safety, and cost-efficiency., Conclusion: Cell therapy in regenerative dentistry represents a growing industry with substantial benefits and unique challenges as it strives to establish sustainable, long-term, and effective oral tissue regeneration solutions., Competing Interests: Declaration of competing interest The authors declared no potential competing of interests with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

Pregnancy induces significant changes in oral health because of hormonal fluctuations, making it a crucial period for preventive measures. Dental stem cells (DSCs), particularly those derived from the dental pulp and periodontal ligaments, offer promising avenues for regenerative therapies and, possibly, preventive interventions. While the use of DSCs already includes various applications in regenerative dentistry in the general population, their use during pregnancy requires careful consideration. This review explores recent advancements, challenges, and prospects in using DSCs to address oral health issues, possibly during pregnancy. Critical aspects of the responsible use of DSCs in pregnant women are discussed, including safety, ethical issues, regulatory frameworks, and the need for interdisciplinary collaborations. We aimed to provide a comprehensive understanding of leveraging DSCs to improve maternal oral health.

Introduction: Tooth 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., Methods: The current study examined tooth bud regeneration with dental pulp stem cells induced by a dentin derivative signal in a rabbit's jaw., Result: A tooth bud was regenerated; the morphology and structure of it were typical, and it was post-Bell stage., Conclusions: In 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., (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Tooth loss or damage poses great threaten to oral and general health. While contemporary clinical treatments have enabled tooth restoration to a certain extent, achieving functional tooth regeneration remains a challenging task due to the intricate and hierarchically organized architecture of teeth. The past few decades have seen a rapid development of three-dimensional (3D) printing technology, which has provided new breakthroughs in the field of tissue engineering and regenerative dentistry. This review outlined the bioactive materials and stem/progenitor cells used in dental regeneration, summarized recent advancements in the application of 3D printing technology for tooth and tooth-supporting tissue regeneration, including dental pulp, dentin, periodontal ligament, alveolar bone and so on. It also discussed current obstacles and potential future directions, aiming to inspire innovative ideas and encourage further development in regenerative medicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Zhang and Guo.)

The dental pulp is the inner part of the tooth responsible for properly functioning during its lifespan. Apart from the very big biological heterogeneity of dental cells, tooth microenvironments differ a lot in the context of mechanical properties-ranging from 5.5 kPa for dental pulp to around 100 GPa for dentin and enamel. This physical heterogeneity and complexity plays a key role in tooth physiology and in turn, is a great target for a variety of therapeutic approaches. First of all, physical mechanisms are crucial for the pain propagation process from the tooth surface to the nerves inside the dental pulp. On the other hand, the modulation of the physical environment affects the functioning of dental pulp cells and thus is important for regenerative medicine. In the present review, we describe the physiological significance of biomechanical processes in the physiology and pathology of dental pulp. Moreover, we couple those phenomena with recent advances in the fields of bioengineering and pharmacology aiming to control the functioning of dental pulp cells, reduce pain, and enhance the differentiation of dental cells into desired lineages. The reviewed literature shows great progress in the topic of bioengineering of dental pulp-although mainly in vitro. Apart from a few positions, it leaves a gap for necessary filling with studies providing the mechanisms of the mechanical control of dental pulp functioning in vivo.

Regenerative dentistry is a rapidly evolving field in dentistry, which has been driven by advancements in biomedical engineering research and the rising treatment expectations and demands that exceed the scope of conventional approaches. Tissue engineering, the foundation of regenerative dentistry, mainly focuses on 3 key components: stem cells, bioactive molecules, and scaffolds. Dental tissue-derived stem cells are especially significant in this regard due to their remarkable properties. Regenerative techniques have provided novel approaches to many conventional treatment strategies in various disciplines of dentistry. For instance, regenerative endodontic procedures such as pulp revascularisation have provided an alternative approach to conventional root canal treatment. In addition, conventional surgical and nonsurgical periodontal treatment is being taken over by modified approaches of guided tissue regeneration with the aid of 3-dimensional bioprinting and computer-aided design, which has revolutionised oral and maxillofacial tissue engineering. This review presents a concise overview of the latest treatment strategies that have emerged into clinical practice, potential future technologies, and the role of dental tissue-derived stem cells in regenerative dentistry., Competing Interests: Conflict of interest None disclosed., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

Autophagy is an evolutionarily conserved intracellular catabolic process that recycles and degrades proteins, organelles and pathogens. It is an endogenous defence mechanism regulating multiple cellular pathways like apoptosis, inflammation, immune response and pathogen clearance and acts as a modulator of pathogenesis. This article highlights the emerging role of autophagy in inflammation and regeneration of human dental pulp. It emphasizes exploring autophagy and autophagy agonists as potential targets for the development of novel therapeutic interventions., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Oral and Maxillofacial Pathology.)

Objective: The application of stem cells in regenerative medicine depends on their biological properties. This scoping review aimed to compare the features of periodontal ligament stem cells (PDLSSCs) with stem cells derived from other sources., Design: An electronic search in PubMed/Medline, Embase, Scopus, Google Scholar and Science Direct was conducted to identify in vitro and in vivo studies limited to English language., Results: Overall, 65 articles were included. Most comparisons were made between bone marrow stem cells (BMSCs) and PDLSCs. BMSCs were found to have lower proliferation and higher osteogenesis potential in vitro and in vivo than PDLSCs; on the contrary, dental follicle stem cells and umbilical cord mesenchymal stem cells (UCMSCs) had a higher proliferative ability and lower osteogenesis than PDLSCs. Moreover, UCMSCs exhibited a higher apoptotic rate, hTERT expression, and relative telomerase length. The immunomodulatory function of adipose-derived stem cells and BMSCs was comparable to PDLSCs. Gingival mesenchymal stem cells showed less sensitivity to long-term culture. Both pure and mixed gingival cells had lower osteogenic ability compared to PDLSCs. Comparison of dental pulp stem cells (DPSCs) with PDLSCs regarding proliferation rate, osteo/adipogenesis, and immunomodulatory properties was contradictory; however, in vivo bone formation of DPSCs seemed to be lower than PDLSCs., Conclusion: In light of the performed comparative studies, PDLSCs showed comparable results to stem cells derived from other sources; however, further in vivo studies are needed to determine the actual pros and cons of stem cells in comparison to each other., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Regenerative 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., Methods: Different 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)., Results: Scanning 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)., Significance: BNC 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The purpose of this case series was to demonstrate the use of a magnesium membrane for repairing the perforated membrane in both direct and indirect approaches, as well as its application in instances where there has been a tear of the Schneiderian membrane., Case Presentation: The case series included four individual cases, each demonstrating the application of a magnesium membrane followed by bone augmentation using a mixture of xenograft and allograft material in the sinus cavity. In the first three cases, rupture of Schneiderian membrane occurred as a result of tooth extraction, positioning of the dental implant, or as a complication during the procedure. In the fourth case, Schneiderian membrane was perforated as a result of the need to aspirate a polyp in the maxillary sinus. In case one, 10 mm of newly formed bone is visible four months after graft placement. Other cases showed between 15 and 20 mm of newly formed alveolar bone. No residual magnesium membrane was seen on clinical inspection. The vertical and horizontal augmentations proved stable and the dental implants were placed in the previously grafted sites., Conclusion: Within the limitations of this case series, postoperative clinical examination, and panoramic and CBCT images demonstrated that resorbable magnesium membrane is a viable material for sinus lift and Schneiderian membrane repair. The case series showed successful healing and formation of new alveolar bone with separation of the oral cavity and maxillary sinus in four patients., (© 2023. The Author(s).)

Background: Stem cells are present in most of the tissues in the craniofacial complex and play a major role in tissue homeostasis and repair. These cells are characterized by their capacity to differentiate into multiple cell types and to self-renew to maintain a stem cell pool throughout the life of the tissue., Types of Studies Reviewed: The authors discuss original data from experiments and comparative analyses and review articles describing the identification and characterization of stem cells of the oral cavity., Results: Every oral tissue except enamel, dentin, and cementum contains stem cells for the entire life span. These stem cells self-renew to maintain a pool of cells that can be activated to replace terminally differentiated cells (for example, odontoblasts) or to enable wound healing (for example, dentin bridge in pulp exposures and healing of periodontal tissues after surgery). In addition, dental stem cells can differentiate into functional blood vessels and nerves. Initial clinical trials have shown that transplanting dental pulp stem cells into disinfected necrotic teeth has allowed for the recovery of tooth vitality and vertical and horizontal root growth in immature teeth with incomplete root formation., Practical Implications: As a consequence of these groundbreaking discoveries, stem cell banks are now offering services for the cryopreservation of dental stem cells. The future use of stem cell-based therapies in the clinic will depend on the collaboration of clinicians and researchers in projects designed to understand whether these treatments are safe, efficacious, and clinically feasible., (Copyright © 2023 American Dental Association. Published by Elsevier Inc. All rights reserved.)

The Robin sequence is a congenital anomaly characterized by a triad of features: micrognathia, glossoptosis, and airway obstruction. This comprehensive historical review maps the evolution of approaches and appliances for its treatment from the past to the current modern possibilities of an interdisciplinary combination of modern engineering, medicine, materials, and computer science combined approach with emphasis on designing appliances inspired by nature and individual human anatomy. Current biomimetic designs are clinically applied, resulting in appliances that are more efficient, comfortable, sustainable, and safer than legacy traditional designs. This review maps the treatment modalities that have been used for patients with a Robin sequence over the years. Early management of the Robin sequence focused primarily on airway maintenance and feeding support, while current management strategies involve both nonsurgical and surgical interventions and biomimetic biocompatible personalized appliances. The goal of this paper was to provide a review of the evolution of management strategies for patients with the Robin sequence that led to the current interdisciplinary biomimetic approaches impacting the future of Robin Sequence treatment with biomimetics at the forefront.

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 in vitro 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 in vivo. These studies pave the way for future regenerative dentistry., Competing Interests: Declaration of interests A.A., S.H.-D., Y.T.Z., D.D.E., Y.W., A.P.P., H.Z., J.M., D.B., and H.R.-B. are co-inventors on a patent application entitled “Human IPSC Derived Ameloblasts and Uses Thereof” (PCT/US2022/053517 filed 12/20/2022 and published 7/6/2023)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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.

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.

3D printing offers attractive opportunities for large-volume bone regeneration in the oro-dental and craniofacial regions. This is enabled by the development of CAD-CAM technologies that support the design and manufacturing of anatomically accurate meshes and scaffolds. This review describes the main 3D-printing technologies utilized for the fabrication of these patient-matched devices, and reports on their pre-clinical and clinical performance including the occurrence of complications for vertical bone augmentation and craniofacial applications. Furthermore, the regulatory pathway for approval of these devices is discussed, highlighting the main hurdles and obstacles. Finally, the review elaborates on a variety of strategies for increasing bone regeneration capacity and explores the future of 4D bioprinting and biodegradable metal 3D printing., (© 2023 The Authors. Periodontology 2000 published by John Wiley & Sons Ltd.)

Synthetic bone grafting materials play a significant role in various medical applications involving bone regeneration and repair. Their ability to mimic the properties of natural bone and promote the healing process has contributed to their growing relevance. While calcium-phosphates and their composites with various polymers and biopolymers are widely used in clinical and experimental research, the diverse range of available polymer-based materials poses challenges in selecting the most suitable grafts for successful bone repair. This review aims to address the fundamental issues of bone biology and regeneration while providing a clear perspective on the principles guiding the development of synthetic materials. In this study, we delve into the basic principles underlying the creation of synthetic bone composites and explore the mechanisms of formation for biologically important complexes and structures associated with the various constituent parts of these materials. Additionally, we offer comprehensive information on the application of biologically active substances to enhance the properties and bioactivity of synthetic bone grafting materials. By presenting these insights, our review enables a deeper understanding of the regeneration processes facilitated by the application of synthetic bone composites.

Mesenchymal stem cells currently play an important role in the tissue engineering field in developing new regenerative approaches. The oral cavity is a rich source of mesenchymal stem cells, and introducing the use of dental stem cells, characterized by a multilineage differentiation potential, immunomodulatory activity and repair capacity, offers a good perspective for clinical dentistry. Human periapical cyst mesenchymal stem cells (hPCy-MSCs) represent a new category of dental stem cells, being collected from pathological tissue and exhibiting MSCs-like properties. As studies have described, these new identified cells possess the same characteristics as those described in MSCs, exhibiting plasticity, a high proliferation rate and the potential to differentiate into osteogenic, adipogenic and neural lineages. Reusing the biological tissue that is considered pathologic offers a new perspective for the development of further clinical applications. The identification and characterization of MSCs in the human periapical cysts allows for a better understanding of the molecular interactions, the potential healing capacity and the mechanisms of inducing the local osteogenic process, integrated in the microenvironment. Although their involvement in regenerative medicine research is recent, they exhibit important properties that refer them for the development of clinical applications in dentistry.

Statins are the first line of treatment for hyperlipidaemia. Along with lowering lipids, it also lowers mortality and cardiovascular risk. Statins play a major role in maintaining the homeostasis of the oral cavity via a number of different mechanisms. It includes regeneration of dentin and pulp by differentiation and increased development of mineralized tissue via the bone morphogenetic proteins (BMP)-2 Pathway. It shows effective bone health by leading to osteogenic differentiation mesenchymal stem cells, by facilitating epithelization process in wound healing, anti-inflammatory, antioxidant, antimicrobial, antiviral, and fungicidal properties. To the finest of the information we have, there have been very few comprehensive studies that have investigated the effects of statin drugs on various aspects of dental and oral health. As a result, the main objective of this review was to examine the effect of statins on oral health applications. According to the findings of our extensive review, statins have noteworthy and promising effects on several aspects of oral health, including dental pulp cells, chronic periodontitis, alveolar bone loss, orthodontic tooth movement, and so on. Nevertheless, it is concluded that local or even systemic administration of simvastatin should be regarded as an innovative, easily accessible, and safe therapeutic agent that has a significant impact on enhancing the oral health., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kabra et al.)

Three-dimensional (3D) bioprinting is a unique combination of technological advances in 3D printing and tissue engineering. It has emerged as a promising approach to address the dilemma in current dental treatments faced by clinicians in order to repair or replace injured and diseased tissues. The exploration of 3D bioprinting technology provides high reproducibility and precise control of the bioink containing the desired cells and biomaterial over the architectural and dimensional features of the scaffolds in fabricating functional tissue constructs that are specific to the patient treatment need. In recent years, the dental applications of different 3D bioprinting techniques, types of novel bioinks, and the types of cells used have been extensively explored. Most of the findings noted significant challenges compared to the non-biological 3D printing approach in constructing the bioscaffolds that mimic native tissues. Hence, this review focuses solely on the implementation of 3D bioprinting techniques and strategies based on cell-laden bioinks. It discusses the in vitro applications of 3D-bioprinted scaffolds on cell viabilities, cell functionalities, differentiation ability, and expression of the markers as well as the in vivo evaluations of the implanted bioscaffolds on the animal models for bone, periodontal, dentin, and pulp tissue regeneration. Finally, it outlines some perspectives for future developments in dental applications.

Three-dimensional bioprinting technology appears to be a promising solution for the treatment and reconstruction of a wide range of maxillofacial bone defects. In this review, the authors discuss different bioprinting solutions and options in the context of the 4 factors of bone healing: structures or scaffolds, osteogenic cells, growth factors, and stabilization (diamond concept of healing), as well as the influence of a 5th factor - vascularization. Bone is a complex tissue; hence, bone bioprinting may require different technical approaches and mixed methods. Ultraviolet (UV) crosslinkable hydrogels, such as gelatin methacryloyl (GelMA), are among the most promising bioinks; they are enhanced by hydroxyapatite or 1-2.5 mm beta-tricalcium phosphate (β-TCP) granules and porous scaffolds with recommended pore sizes greater than 300 μm. The advantages of mesenchymal stem cells (MSCs) are their significant availability, low tumorigenicity, and great potential for differentiation into osteoblasts or endothelial cells (ECs). Although growth factors require advanced delivery systems, they provide excellent improvement in the functionality of printed tissues. A proper vasculature system supplies cells with oxygen and nutrients, removes waste products, promotes osteogenesis, prevents ischemic necrosis, and improves the mechanical properties of bone. With all of these aspects perfectly balanced and working in synergy, the clinical use of bioprinting is only a matter of time.

Objectives: Evaluate molecularly the role of P 11 -4 self-assembly peptide in dentin remineralization and its interaction with collagen I., Methods: The calcium-responsive P 11 -4 peptide was analyzed by intrinsic fluorescence emission spectrum, circular dichroism spectrum (CD), and atomic force microscope (AFM). Differential light scattering was used to monitor the nucleation growth rate of calcium phosphate nanocrystals in the absence or in the presence of P 11 -4. AFM was used to analyze the radial size (nm) of calcium phosphate nanocrystals formed in the absence or in the presence of P 11 -4, as well as to verify the spatial structure of P 11 -4 in the absence or in the presence of Ca 2+ ., Results: The interaction of Ca 2+ with the P 11 -4 (K D = 0.58 ± 0.06 mM) promotes the formation of β-sheet antiparallel structure, leads to its precipitation in saturated solutions of Ca/P = 1.67 and induces the formation of parallel large fibrils (0.6 - 1.5 µm). P 11 -4 organized the HAP nucleation by reducing both the growth rate and size variability of nanocrystals, analyzed by the F test (p < 0.0001, N = 30). P 11 -4 interacts (K D = 0.75 ± 0.06 μM) with the KGHRGFSGL motif present at the C-terminal collagen telopeptide domain. P 11 -4 also increased the amount of HAP and collagen in the MDPC-23 cells., Significance: The presented data propose a mechanism that will help future clinical and/or basic research to better understand a molecule able to inhibit structural collagen loss and help the impaired tissue to remineralize., (Copyright © 2023 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Introduction: Although there have been many studies on stem cells, few have investigated how neurotransmitters and stem cell proliferation interact to regenerate dental pulp. Dental pulp regeneration is an innovative procedure for reviving dental pulp, if feasible for the entire tooth. Upon tooth injury, activated platelets release serotonin and dopamine in bulk to mobilize dental pulp stem cells to mediate natural dental repair. This has induced research on the role of neurotransmitters in increasing the proliferation rate of stem cells. This review also covers prospective future treatments for dental pulp regeneration., Methods: A literature search was performed via PubMed and ScienceDirect from 2001 to 2022, using the keywords "neurotransmitter," "stem cell," "tooth regeneration," "tooth repair," "regenerative dentistry," and "dental pulp." Different inclusion/exclusion criteria were used, and the search was restricted to English articles., Results: Nine publications reporting neurotransmitter interactions with stem cells for tooth and pulp regeneration were selected., Conclusion: Neurotransmitters were found to interact with dental stem cells. Evidence pointing to neurotransmitters as a factor in the increased proliferation of stem cells was found. This review thus gives hope for tooth pulp regeneration and repair., (© 2023 The Authors.)

The ongoing coronavirus disease 2019 (COVID-19) pandemic highlights the importance of developing point-of-care (POC) antibody tests for monitoring the COVID-19 immune response upon viral infection or following vaccination, which requires three key aspects to achieve optimal monitoring, including three-dimensional (3D)-printed POC devices, mobile health (mHealth), and noninvasive sampling. As a critical tissue engineering concept, additive manufacturing (AM, also known as 3D printing) enables accurate control over the dimensional and architectural features of the devices. mHealth refers to the use of portable digital devices, such as smartphones, tablet computers, and fitness and medical wearables, to support health, which facilitates contact tracing, and telehealth consultations during the pandemic. Compared with invasive biosample (blood), saliva is of great importance in the spread and surveillance of COVID-19 as a noninvasive diagnostic method for virus detection and immune status monitoring. However, investigations into 3D-printed POC antibody test and mHealth using noninvasive saliva are relatively limited. Further exploration of 3D-printed antibody POC tests and mHealth applications to monitor antibody production for either disease onset or immune response following vaccination is warranted. This review briefly describes the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and immune response after infection and vaccination, then discusses current widely used binding antibody tests using blood samples and enzyme-linked immunosorbent assays on two-dimensional microplates before focusing upon emerging POC technological platforms, such as field-effect transistor biosensors, lateral flow assay, microfluidics, and AM for fabricating immunoassays, and the possibility of their combination with mHealth. This review proposes that noninvasive biofluid sampling combined with 3D POC antibody tests and mHealth technologies is a promising and novel approach for POC detection and surveillance of SARS-CoV-2 immune response. Furthermore, as key concepts in dentistry, the application of 3D printing and mHealth was also included to facilitate the appreciation of cutting edge techniques in regenerative dentistry. This review highlights the potential of 3D printing and mHealth in both COVID-19 immunity monitoring and regenerative dentistry.

Different biomaterials, from synthetic products to autologous or heterologous grafts, have been suggested for the preservation and regeneration of bone. The aim of this study is to evaluate the effectiveness of autologous tooth as a grafting material and examine the properties of this material and its interactions with bone metabolism. PubMed, Scopus, Cochrane Library, and Web of Science were searched to find articles addressing our topic published from 1 January 2012 up to 22 November 2022, and a total of 1516 studies were identified. Eighteen papers in all were considered in this review for qualitative analysis. Demineralized dentin can be used as a graft material, since it shows high cell compatibility and promotes rapid bone regeneration by striking an ideal balance between bone resorption and production; it also has several benefits, such as quick recovery times, high-quality newly formed bone, low costs, no risk of disease transmission, the ability to be performed as an outpatient procedure, and no donor-related postoperative complications. Demineralization is a crucial step in the tooth treatment process, which includes cleaning, grinding, and demineralization. Since the presence of hydroxyapatite crystals prevents the release of growth factors, demineralization is essential for effective regenerative surgery. Even though the relationship between the bone system and dysbiosis has not yet been fully explored, this study highlights an association between bone and gut microbes. The creation of additional scientific studies to build upon and enhance the findings of this study should be a future objective of scientific research.

Stem cell-based therapies remain at the forefront of tissue engineering and regenerative medicine because stem cells are a unique cell source with enormous potential to treat incurable diseases and even extend lifespans. The search for the best stem cell candidates continues to evolve and in recent years, dental stem cells have received significant attention due to their easy accessibility, high plasticity, and multipotential properties. Dental stem cells have been the subject of extensive research in both animal models and human clinical trials over the past two decades, and have demonstrated significant potential in ocular therapy, bone tissue engineering, and, of course, therapeutic applications in dentistry such as regenerative endodontics and periodontal tissue regeneration. These new sources of cells may be advantageous for cellular therapy and the advancement of regenerative medicine strategies, such as allogeneic transplantation or therapy with extracellular vesicles (EVs), which are functional nanoscale membrane vesicles produced by cells. This chapter discusses the accumulating research findings on cell-based regenerative therapy utilizing dental stem cells and their derived EVs, which could be a viable tool for the treatment of a variety of diseases and hence extremely valuable to mankind in the long run., (Copyright © 2023. Published by Elsevier Inc.)

Dental mesenchymal stem cells (MSCs) are characterized by unlimited self-renewal ability and high multidirectional differentiation potential. Since dental MSCs can be easily isolated and exhibit a high capability to differentiate into odontogenic cells, they are considered as attractive therapeutic agents in regenerative dentistry. Recently, MSC-derived extracellular vesicles (MSC-EVs) have attracted widespread attention as carriers for cell-free therapy due to their potential functions. Many studies have shown that MSC-EVs can mediate microenvironment at tissue damage site, and coordinate the regeneration process. Additionally, MSC-EVs can mediate intercellular communication, thus affecting the phenotypes and functions of recipient cells. In this review, we mainly summarized the types of MSCs that could be potentially applied in regenerative dentistry, the possible molecular cargos of MSC-EVs, and the major effects of MSC-EVs on the therapeutic induction of osteogenic differentiation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Tissue engineering offers a great potential in regenerative dentistry and to this end, three dimensional (3D) bioprinting has been emerging nowadays to enable the incorporation of living cells into the biomaterials (such a mixture is referred as a bioink in the literature) to create scaffolds. However, the bioinks available for scaffold bioprinting are limited, particularly for dental tissue engineering, due to the complicated, yet compromised, printability, mechanical and biological properties simultaneously imposed on the bioinks. This paper presents our study on the development of a novel bioink from carboxymethyl chitosan (CMC) and alginate (Alg) for bioprinting scaffolds for enamel tissue regeneration. CMC was used due to its antibacterial ability and superior cell interaction properties, while Alg was added to enhance the printability and mechanical properties as well as to regulate the degradation rate. The bioinks with three mixture ratios of Alg and CMC (2-4, 3-3 and 4-2) were prepared, and then printed into the calcium chloride crosslinker solution (100 mM) to form a 3D structure of scaffolds. The printed scaffolds were characterized in terms of structural, swelling, degradation, and mechanical properties, followed by their in vitro characterization for enamel tissue regeneration. The results showed that the bioinks with higher concentrations of Alg were more viscous and needed higher pressure for printing; while the printed scaffolds were highly porous and showed a high degree of printability and structural integrity. The hydrogels with higher CMC ratios had higher swelling ratios, faster degradation rates, and lower compressive modulus. Dental epithelial cell line, HAT-7, could maintain high viability in the printed constructs after 1, 7 and 14 d of culture. HAT-7 cells were also able to maintain their morphology and secrete alkaline phosphatase after 14 d of culture in the 3D printed scaffolds, suggesting the capacity of these cells for mineral deposition and enamel-like tissue formation. Among all combinations Alg4%-CMC2% and in a less degree 2%Alg-4%CMC showed the higher potential to promote ameloblast differentiation, Ca and P deposition and matrix mineralization in vitro . Taken together, Alg-CMC has been illustrated to be suitable to print scaffolds with dental epithelial cells for enamel tissue regeneration., (Creative Commons Attribution license.)

This paper presents a proof-of-concept study on the biocolonization of 3D-printed hydroxyapatite scaffolds with mesenchymal stem cells (MSCs). Three-dimensional (3D) printed biomimetic bone structure made of calcium deficient hydroxyapatite (CDHA) intended as a future bone graft was made from newly developed composite material for FDM printing. The biopolymer polyvinyl alcohol serves in this material as a thermoplastic binder for 3D molding of the printed object with a passive function and is completely removed during sintering. The study presents the material, the process of fused deposition modeling (FDM) of CDHA scaffolds, and its post-processing at three temperatures (1200, 1300, and 1400 °C), as well it evaluates the cytotoxicity and biocompatibility of scaffolds with MTT and LDH release assays after 14 days. The study also includes a morphological evaluation of cellular colonization with scanning electron microscopy (SEM) in two different filament orientations (rectilinear and gyroid). The results of the MTT assay showed that the tested material was not toxic, and cells were preserved in both orientations, with most cells present on the material fired at 1300 °C. Results of the LDH release assay showed a slight increase in LDH leakage from all samples. Visual evaluation of SEM confirmed the ideal post-processing temperature of the 3D-printed FDM framework for samples fired at 1300 °C and 1400 °C, with a porosity of 0.3 mm between filaments. In conclusion, the presented fabrication and colonization of CDHA scaffolds have great potential to be used in the tissue engineering of bones.

With the proven relationship between oral and general health and the growing aging population, it is pivotal to provide accessible therapeutic approaches to regenerate oral tissues and restore clinical function. However, despite sharing many core concepts with medicine, dentistry has fallen behind the progress in precision medicine and regenerative treatments. Stem cell therapies are a promising avenue for tissue regeneration, however, ethical, safety and cost issues may limit their clinical use. With the significance of paracrine signalling in stem cell and tissue regeneration, extracellular space comprising of the cell secretome, and the extracellular matrix can serve as a potent source for tissue regeneration. Extravesicles are secreted and naturally occurring vesicles with biologically active cargo that can be harvested from the extracellular space. These vesicles have shown great potential as disease biomarkers and can be used in regenerative medicine. As a cell free therapy, secretome and extracellular vesicles can be stored and transferred easily and pose less ethical and safety risks in clinical application. Since there are currently many reviews on the secretome and the biogenesis, characterization and function of extracellular vesicles, here we look at the therapeutic potential of extracellular space to drive oral tissue regeneration and the current state of the field in comparison to regenerative medicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Birjandi and Sharpe.)

Background: Ongoing research in the dental field has begun to focus on the use of injectable platelet-rich fibrin (I-PRF) as a regenerative tool with the potential to prompt tissue regeneration. In this regard, this systematic scoping review aimed to collect, map, and appraise the in vitro and in vivo studies regarding the role of I-PRF in or soft and hard tissue regeneration in relation to oral and maxillofacial structures., Methods: A systematic electronic search of Medline, Scopus, Web of Science, and Embase databases was performed from 2000 to December 2021 using a combination of keywords. All in vitro and in vivo studies, written in English and concerning the potential role of I-PRF in regenerative dentistry were considered., Results: In total, 18 in vitro studies, 5 animal studies, 6 case reports, and 31 clinical studies have evaluated the effect of I-PRF on oral and maxillofacial soft and hard tissue regeneration. The investigated studies verified the anti-inflammatory, anti-microbial efficacy and the positive effects of I-PRF application for wound, periodontal, bone, cartilage, and pulp regeneration, as well as acceleration in tooth movement during orthodontic treatment., Conclusions: Current literature approves the feasibility of I-PRF application as a promising regenerative adjunct to dental procedures., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022Published by Elsevier Ltd on behalf of The Japanese Association for Dental Science. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/.)

Alginate is a natural marine biopolymer that has been widely used in biomedical applications, but research on its use as an endodontic material is still sparse in the literature. This pioneer review aims to summarize the emerging roles of alginate and to outline its prospective applications as a core biomaterial in endodontics. Ten electronic databases and five textbooks were used to perform a search of English-language literature on the use of alginate in endodontics published between January 1980 and June 2022. The risk of bias (RoB) of each included study was assessed using the Office of Health Assessment and Translation (OHAT) tool. Subsequently, studies were categorized into three tiers to represent the overall risk. Qualitative analysis was performed, and the articles were sorted into different thematic categories. An initial search yielded a total of 1491 articles, but only 13 articles were chosen. For most domains, all the studies were rated with 'probably low' or 'definitely low' RoB, except for domains 2 and 6. All included studies fall in the Tier 1 category and were either in vitro, in vivo, or ex vivo. Four thematic categories were identified: endodontic regeneration, intracanal medicament, filing material, and chelating agent. Based on the available evidence, alginate has emerged as a cell carrier and scaffold in regenerative endodontics, a microcapsule delivery system for intracanal medicaments, a chelating agent reinforcing material, and a root canal sealer. More well-designed experiments and clinical trials are needed to warrant the promising advent of this hydrogel-based biomaterial.

Introduction: During cell-free regenerative endodontic therapy, both stem cells from apical papilla (SCAPs) and periodontal ligament cells (PDLCs) are possible cell sources because of their proximity. Nonetheless, the regenerative ability of PDLCs and SCAPs under the induction of concentrated growth factors (CGFs) remains unclear., Methods: PDLCs and SCAPs were treated with various concentrations of CGF-conditioned medium (CCM). The effects of CCM with or without Porphyromonas gingivalis lipopolysaccharide (LPS) on cell migration, odonto/osteogenic differentiation, and the expression of inflammatory cytokines were assessed. Dentin matrix transplants composed of PDLCs or SCAPs cell sheets coupled with CGF were put subcutaneously in immunocompromised mice for 8 weeks to explore their regenerative characteristics in vivo., Results: CCM dose dependently enhanced the migration, proliferation, and odonto/osteogenic differentiation of PDLCs and SCAPs. CCM alleviated LPS-inhibited odonto/osteogenic differentiation of PDLCs and SCAPs as well as the LPS-induced up-regulation of inflammatory cytokines. In vivo, the newly regenerated tissue and microvessels formed by PDLCs and SCAPs were significantly increased under the induction of CGF. SCAPs mainly regenerated pulp/dentinlike tissues and a large number of microvessels, whereas PDLCs mainly formed bone/cementumlike structures., Conclusions: Overall, PDLCs excelled in cell proliferation, migration, and osteogenic differentiation, whereas SCAPs outperformed PDLCs in terms of angiogenic and odontogenic differentiation. The biological differences between PDLCs and SCAPs provided a possible theoretical basis for the formation of bone/cementum/periodontal ligament-like tissues after cell-free regenerative endodontic therapy., (Copyright © 2022. Published by Elsevier Inc.)

Non-coding RNAs (ncRNAs) represent a research hotspot by playing a key role in epigenetic and transcriptional regulation of diverse biological functions and due to their involvement in different diseases, including oral inflammatory diseases. Based on ncRNAs' suitability for salivary biomarkers and their involvement in neuropathic pain and tissue regeneration signaling pathways, the present narrative review aims to highlight the potential clinical applications of ncRNAs in oral inflammatory diseases, with an emphasis on salivary diagnostics, regenerative dentistry, and precision medicine for neuropathic orofacial pain.

Injectable hydrogels, as carriers, offer great potential to incorporate cells or growth factors for dental tissue regeneration. Notably, the development of injectable hydrogels with appropriate structures and properties has been a challenging task, leaving much to be desired in terms of cytocompatibility, antibacterial and self-healing properties, as well as the ability to support dental stem cell functions. This paper presents our study on the development of a novel self-cross-linkable hydrogel composed of oxidized alginate and carboxymethyl chitosan and its characterization as a cell carrier for dental enamel regeneration in vitro. Oxidized alginate was synthesized with 60% theoretical oxidation degree using periodate oxidation and characterized by Fourier Transform Infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and Ultraviolet-visible absorption spectroscopy. Then, hydrogels were prepared at three varying weight ratios of oxidized alginate to carboxymethyl chitosan (4:1, 3:1, and 2:1) through Schiff base reactions, which was confirmed by Fourier Transform Infrared spectroscopy. The hydrogels were characterized in terms of gelation time, swelling ratio, structure, injectability, self-healing, antibacterial properties, and in vitro characterization for enamel regeneration. The results demonstrated that, among the three hydrogels examined, the one with the highest ratio of oxidized alginate (i.e., 4:1) had the fastest gelation time and the lowest swelling ability, and that all hydrogels were formed with highly porous structures and were able to be injected through a 20-gauge needle without clogging. The injected hydrogels could be rapidly reformed with the self-healing property. The hydrogels also showed antibacterial properties against two cariogenic bacteria: Streptococcus mutans and Streptococcus sobrinus . For in vitro enamel regeneration, a dental epithelial cell line, HAT-7, was examined, demonstrating a high cell viability in the hydrogels during injection. Furthermore, HAT-7 cells encapsulated in the hydrogels showed alkaline phosphatase production and mineral deposition, as well as maintaining their round morphology, after 14 days of in vitro culture. Taken together, this study has provided evidence that the oxidized alginate-carboxymethyl chitosan hydrogels could be used as an injectable cell carrier for dental enamel tissue engineering applications.

Application of mesenchymal stem cells (MSC) in regenerative therapeutic procedures is becoming an increasingly important topic in medicine. Since the first isolation of dental tissue-derived MSC, there has been an intense investigation on the characteristics and potentials of these cells in regenerative dentistry. Their multidifferentiation potential, self-renewal capacity, and easy accessibility give them a key role in stem cell-based therapy. So far, several different dental stem cell types have been discovered and their potential usage is found in most of the major dental medicine branches. These cells are also researched in multiple fields of medicine for the treatment of degenerative and inflammatory diseases. In this review, we summarized dental MSC sources and analyzed their treatment modalities with particular emphasis on temporomandibular joint osteoarthritis (TMJ OA).

In modern dentistry, a minimally invasive management of early caries lesions or early-stage erosive tooth wear (ETW) with synthetic remineralization systems has become indispensable. In addition to fluoride, which is still the non-plus-ultra in these early caries/ETW treatments, a number of new developments are in the test phase or have already been commercialized. Some of these systems claim that they are comparable or even superior to fluoride in terms of their ability to remineralize enamel. Besides, their use can help avoid some of the risks associated with fluoride and support treatments of patients with a high risk of caries. Two individual non-fluoride systems can be distinguished; intrinsic and extrinsic remineralization approaches. Intrinsic (protein/peptide) systems adsorb to hydroxyapatite crystals/organics located within enamel prisms and accumulate endogenous calcium and phosphate ions from saliva, which ultimately leads to the re-growth of enamel crystals. Extrinsic remineralization systems function on the basis of the external (non-saliva) supply of calcium and phosphate to the crystals to be re-grown. This article, following an introduction into enamel (re)mineralization and fluoride-assisted remineralization, discusses the requirements for non-fluoride remineralization systems, particularly their mechanisms and challenges, and summarizes the findings that underpin the most promising advances in enamel remineralization therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

In dentistry, problems of craniofacial, osteochondral, periodontal tissue, nerve, pulp or endodontics injuries, and osteoarthritis need regenerative therapy. The use of stem cells in dental tissue engineering pays a lot of increased attention, but there are challenges for its clinical applications. Therefore, cell-free-based tissue engineering using exosomes isolated from stem cells is regarded an alternative approach in regenerative dentistry. However, practical use of exosome is restricted by limited secretion capability of cells. For future regenerative treatment with exosomes, efficient strategies for large-scale clinical applications are being studied, including the use of ceramics-based scaffold to enhance exosome production and secretion which can resolve limited exosome secretory from the cells when compared with the existing methods available. Indeed, more research needs to be done on these strategies going forward., Competing Interests: Financial & competing interests disclosure This study is supported by Indonesia Collaborative Research (RKI) Funding Scheme under World Class University Acceleration Program from the Ministry of Education, Culture, Research, and Technology of the Republic of Indonesia, with a contract number 810/UN1/Ditlit/Dit-Lit/PT/2020. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2021 Ika Dewi Ana.)

Conventional bone grafting procedures used to treat bone defects have several limitations. An important aspect of bone tissue engineering is developing novel bone substitute biomaterials for bone grafts to repair orthopedic defects. Considerable attention has been given to chitosan, a natural biopolymer primarily extracted from crustacean shells, which offers desirable characteristics, such as being biocompatible, biodegradable, and osteoconductive. This review presents an overview of the chitosan-based biomaterials for bone tissue engineering (BTE). It covers the basic knowledge of chitosan in terms of biomaterials, the traditional and novel strategies of the chitosan scaffold fabrication process, and their advantages and disadvantages. Furthermore, this paper integrates the relevant contributions in giving a brief insight into the recent research development of chitosan-based scaffolds and their limitations in BTE. The last part of the review discusses the next-generation smart chitosan-based scaffold and current applications in regenerative dentistry and future directions in the field of mineralized tissue regeneration.