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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Tissue engineering is an emerging field in dentistry, and stem cell research has shown promise in regenerating new tissue. The three essential components for tissue engineering are stem cells, scaffolds, and growth/differentiation factors. Numerous studies have been conducted in regenerative medicine, and more recently in regenerative dentistry, utilizing different signals. In a pioneering study, dentin derivative signal (DDS), which was self-administered, was used as a differentiation factor for dental pulp stem cells to promote dentinogenesis in vitro. The study demonstrated that DDS can stimulate dental pulp stem cells to differentiate into other dental tissues, such as dentin. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

Dental implant utilization has emerged as a contemporary strategy for rectifying dental arch anomalies. However, the effective management of potential complications is paramount. Peri-implantitis, characterized by inflammation and bone resorption around dental implants, resembles periodontitis but specifically affects implant sites. Restoring lost peri-implant tissues poses a multifaceted challenge, with bioprinting methods showing promise as a viable solution. Three-dimensional bioprinting represents a forefront advancement in tissue engineering, traditionally focusing on scaffolds, cells, and signaling pathways. This systematic review aims to aggregate and synthesize data concerning bioprinting’s application in peri-implantitis treatment. Adhering to PRISMA guidelines, the review conducted an extensive literature search across PubMed, Scopus, Google Scholar, and ScienceDirect. Importantly, the search timeframe was not limited, reflecting the scarcity of available information on the subject. Bioprinting advancements offer auspicious avenues for refining treatment modalities, prompting clinicians to explore optimal solutions for establishing ideal anatomical conditions. In essence, this systematic review underscores 3D bioprinting’s potential in peri-implantitis management, highlighting its pivotal role in contemporary dental medicine and its capacity to reshape clinical approaches toward achieving optimal outcomes.

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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Dental implant utilization has emerged as a contemporary strategy for rectifying dental arch anomalies. However, the effective management of potential complications is paramount. Peri-implantitis, characterized by inflammation and bone resorption around dental implants, resembles periodontitis but specifically affects implant sites. Restoring lost peri-implant tissues poses a multifaceted challenge, with bioprinting methods showing promise as a viable solution. Three-dimensional bioprinting represents a forefront advancement in tissue engineering, traditionally focusing on scaffolds, cells, and signaling pathways. This systematic review aims to aggregate and synthesize data concerning bioprinting's application in peri-implantitis treatment. Adhering to PRISMA guidelines, the review conducted an extensive literature search across PubMed, Scopus, Google Scholar, and ScienceDirect. Importantly, the search timeframe was not limited, reflecting the scarcity of available information on the subject. Bioprinting advancements offer auspicious avenues for refining treatment modalities, prompting clinicians to explore optimal solutions for establishing ideal anatomical conditions. In essence, this systematic review underscores 3D bioprinting's potential in peri-implantitis management, highlighting its pivotal role in contemporary dental medicine and its capacity to reshape clinical approaches toward achieving optimal outcomes. [ABSTRACT FROM AUTHOR]

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.

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.

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. [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

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. The current study examined tooth bud regeneration with dental pulp stem cells induced by a dentin derivative signal in a rabbit's jaw. A tooth bud was regenerated; the morphology and structure of it were typical, and it was post–Bell stage. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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). 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). 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. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract 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.

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.

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.

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Dental Pulp Stem Cells (DPSCs) offer great potential in regenerative medicine. Odontoblasts are naturally occurring cells that are responsible for constructing dentin for restorative dental purposes. Yet, their potential for use in the restoration of non-dental tissues is also being explored. Because of their similarities to BMSCs, DPSCs may be useful in musculoskeletal regenerative medicine, and they may be easily separated from teeth that have been pulled. Information on stem cells in dental pulp, transplantation, and immunomodulation was culled from the databases Scopus, PubMed, Web of Science, Science Direct, and Google Scholar. Differentiated Pluripotent Stem Cells (DPSCs) are not derived from bone marrow like BMSCs are. These phenotypic and genetic distinctions from BMSCs are being used in neurological and other settings. Pulp tissue regeneration and the therapeutic potential of DPSCs were discussed in this article. Prior to discussing their extensive uses in regenerative medicine, this article provides a brief background on the discovery and function of DPSCs. [ABSTRACT FROM AUTHOR]

Host modulation therapy (HMT) is one periodontitis treatment option for patient with risk factors that have a negative impact on the host response and oral health are difficult to maintain. Despite the potential for bacterial resistance, one of the HMTs is sub-antimicrobial-dose doxycycline. Eichhornia crassipes has anti-inflammatory, antibacterial, anti-bone resorption, and proosteogenesis properties. Using bioinformatics, study the active compounds stigmasterol, quercetin, and anthocyanin in E. crassipes as an HMT candidate. Stigmasterol, quercetin, and anthocyanin were used to prepare the sample. A chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) study was performed on the compounds to assess their physicochemical characteristics, water solubility, and drug-likeness using the SWISS-ADME program. Docking simulation and molecular interaction prediction were carried out and exhibited in the form of 2D and 3D visualizations for negative binding energy. Stigmasterol, quercetin, and anthocyanin behave as drug-like chemicals with variable degrees of toxicity ranging from medium to low. Stigmasterol has the highest amount of negative binding affinity. Stigmasterol is predicted to have an inhibitory effect on nuclear factor kappa beta, tumor necrosis factor-alpha, toll-like receptor-2, matrix metalloproteinase (MMP)-1, MMP-9, tartateresistant acid phosphatase, nuclear factor-associated T-cell-1, interleukin-1β, peptidoglycan, flagellin, and dectin, while also having the potential to modulate Interleukin-10, tissue inhibitor matrix. Stigmasterol exhibits greater negative binding activity to antibacterial, bone remodeling, growth factor, and inflammatory cytokine indicators than quercetin, and E. crassipes anthocyanin may be a promising HMT candidate, in silico. [ABSTRACT FROM AUTHOR]

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. 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. Nine publications reporting neurotransmitter interactions with stem cells for tooth and pulp regeneration were selected. 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. [ABSTRACT FROM AUTHOR]

Introduction: In the field of dentistry, natural polymers are being investigated for their potential in tissue engineering. Alginate and chitosan are commonly used scaffolds due to their biodegradable nature, compatibility, and structure similarv to that of the extracellular matrix. Quercetin, a flavonoid with various biological properties, is combined with these scaffolds to enhance tissue repair and regeneration, ultimately improving wound healing in dental applications.Aim: To incorporate quercetin into alginate-chitosan scaffolds and evaluate their regenerative potential in dentistry through characterization and assessment of biocompatibility. Materials and methods: Quercetin was impregnated onto the alginate-chitosan scaffold, then characterized using Fourier TransformInfraRed (FT-IR) and Scanning Electron Microscopy (SEM). Annexin V PI apoptotic assay and Hemolytic assay were done for checking its biocompatibility. Results and discussion: FT-IR has strong absorption bands at 3305, 1595, 1408, 1290, 941, and 819 cm−1, with wavelengths ranging from 4,000-500 cm-1. SEM analysis confirmed quercetin impregnation onto the alginate-chitosan scaffold. Based on our findings, the combination of quercetin and alginate-chitosan scaffolds exhibits improved biocompatibility towards Peripheral blood mononuclear cells (PBMC), as determined by Annexin V - PI assay and hemolytic assay, indicating potential for dental regenerative applications.Conclusions: Quercetin impregnated onto an alginate-chitosan scaffold is reported to be biocompatible using flow cytometry and hemolytic assay. Further extensive investigation is necessary before considering their use in regenerative dentistry. [ABSTRACT FROM AUTHOR]

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.

Modular tissue engineering has emerged as a promising manufacturing strategy for the regeneration of multifaceted cohesive tissues. Scaffold-free approaches combine different cells to form the complex architecture of tissues by assembling heterogeneous molecular building blocks. The objective of this research is to delve into the advances in neoteric modular tissue engineering strategies in regenerative dentistry. For this, a bibliographic review was carried out in the period between 2018 and 2022, in the databases: Scopus, Pubmed and Web of Science. Of the 557 articles initially obtained, 20 met the inclusion criteria. The cell sheet paradigm is beneficial in endodontic and periodontal applications. Human cell-based implantable devices have proven their effectiveness in terms of safety and affordability for a diverse range of clinical outcomes. Given the volatility of the efficacy and long-term safety of regenerative dentistry, financial models are needed to help facilitate patient access to these therapies. Impediments also arise during the manufacturing of cellular products and with approved regulatory establishments. [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Tooth defect and loss are common clinical diseases in stomatology. With the extension of life expectancy, there is an increasing demand for tooth tissue and whole tooth regeneration. Compared with traditional oral prosthetic treatment, tooth regeneration has unique advantages and has become one of the hotspots towards oral biomedical treatment. In this review, we discussed the development and challenges of tooth regeneration based on cells and materials, including tooth enamel, dentin, dental pulp, cementum, dentin-pulp complex, and the whole tooth regeneration, in order to provide a comprehensive, up-to-date, illustrative overview of tooth regeneration issues. The mechanisms of the regeneration were also summarized and discussed. Moreover, this review hints the future perspective and research direction of tooth regeneration in the challenging field of regenerative dentistry.

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.