Hydrogel scaffold for dental pulp regeneration: a systematic review.

In recent years, great progress has been made in research on the treatment of pulpitis, mainly due to the rapid development of basic and clinical researches in this field, and some achievement from basic research has been applied in clinical practice. Advances in the diagnostic methods for pulpitis can help the clinicians to recognize the true state of pulpitis more accurately and to adopt the corresponding treatment methods including indirect/direct pulp capping, pulpotomy, pulp regeneration and root canal therapy. The new theory of pulpitis diagnosis and the studies on immune defense, repair function of dental pulp and new pulp capping materials have significantly improved the success rate of vital pulp therapy. For diffuse coronary pulpitis or radicular pulpitis, which is difficult to achieve vital pulp therapy successfully, methods of pulp revascularization, cell homing and pulp stem cells-mediated pulp regeneration can also be used as treatment options in addition to root canal therapy. The present article focuses on the research progress on pulpitis treatments and related clinical transformation practices, in order to provide reference on vital pulp therapy and pulp regeneration for clinicians.

In recent years, substantial progress has been made in pulp regeneration therapy. Unlike conventional root canal therapy (RCT) and vital pulp therapy (VPT), pulp regeneration therapy not only restores the physiological structure and function of damaged teeth but also facilitates root development in immature teeth. Biomaterials play a pivotal role in this process, as they must exhibit biocompatibility, suitable pore architecture, and controlled degradability to support both vascular and neural regeneration. With advancements in biomaterial technology, the clinical application of pulp regeneration therapy has achieved remarkable success by closely mimicking the natural pulp microenvironment, offering a more biological approach for treating pulp-related diseases. This review provides a comprehensive overview of the key biological components essential for pulp regeneration and highlights recent innovations in biomaterials for this therapy. Furthermore, we examine the mechanisms through which biomaterials enhance pulp regeneration and suggest potential strategies for further improvement. Finally, we discuss emerging trends and future opportunities in this rapidly evolving field.

Tissue engineering in dentistry is revolutionizing the regeneration of dental pulp. The dental pulp is a specialized connective tissue that plays an important role in maintaining tooth health and supporting healing processes. However, exposure of the pulp to harmful factors, such as infections or trauma, can negatively impact its function, leading to inflammation, tissue necrosis, and ultimately pulp loss. As a solution to these challenges, tissue-engineered vital pulp therapies (VPTs) are emerging as an alternative to conventional root canal treatments. These therapies aim to preserve the vitality of the pulp, stimulate natural healing processes, and restore the dentin-pulp structure. Regenerative dentistry is also exploring tissue repair through innovations such as three-dimensional (3D) bioprinting, exosome-based therapies, and novel scaffold structures.This chapter explores the potential of tissue engineering in dental pulp regeneration, focusing on the role of stem cells, growth factors, scaffolds, and bioactive materials. In particular, stem cells derived from dental pulp are critical to this process due to their ability to differentiate into odontoblast-like cells and promote dentin production. The combination of these stem cells with bioactive scaffolds that release growth factors can significantly enhance the healing of pulp tissue. Furthermore, innovative materials, such as calcium silicate-based materials and bioactive glasses, have shown promising results in pulp regeneration and restorative dentin formation. While the future of these therapies is promising, challenges such as clinical application, long-term efficacy, and cost-effectiveness remain. As research advances, the importance of interdisciplinary collaboration and clinical trials will grow in overcoming these barriers.

Vital pulp therapy is a way to preserve the vitality and function of pulp damaged by trauma, caries or restorative procedures. Vital pulp therapy procedures include direct pulp capping, indirect pulp capping, partial and coronal pulpotomy treatments where diseased pulp tissue is removed. Over the years, the focus of vital pulp therapy has been on the preservation of the radicular pulp in immature permanent teeth to ensure the completion of root formation (apexogenesis). Today, it has been reported that vital pulp therapy can be considered as an alternative to root canal treatment, including in teeth with certain conditions that are considered to have irreversibly inflamed pulp. Coronal amputation therapy, a vital pulp treatment, involves complete removal of the coronal pulp, placement of a biologically acceptable material into the pulp chamber and restoration. The covering material must be able to relieve inflammation and initiate healing of the pulp tissue and allow new dentin tissue to form. The oldest material used in pulpotomy is calcium hydroxide. Mineral trioxide aggregate, which is a more recent material, is frequently preferred today due to its biocompatible and bioactive properties. In this case report, the results of 4 cases of coronal pulpotomy with mineral trioxide aggregate in young permanent teeth with a follow-up of 18 months are presented.

Recent advancements in hydrogels as novel tissue engineering scaffolds for dental pulp regeneration

Cell encapsulation technology holds promise for the sustained and controlled delivery of different therapeutic proteins. Alginate-poly-L-lysine-alginate (APA) microcapsules represent one of the most widely studied alginate-polycation microcapsules. On the basis of this technology, two types of hydrogel-based scaffolds have been developed and analyzed with the aim of improving the retention and the retrieval of erythropoietin (Epo) secreting cell-loaded microcapsules in the tissue where they are implanted. Furthermore, these hydrogels may help to reduce the post-transplant inflammation and pericapsular fibrotic overgrowth typically observed around capsules. The hydrogel-based scaffolds could be administered as implantable forms (preformed scaffolds) or injectable forms (in situ formed scaffolds). The in vitro studies confirmed the correct adaptation of the enclosed cells to the scaffolds in terms of viability and protein expression. The posterior implantation of the cell-loaded capsules containing hydrogel-based scaffolds in mice revealed that the hematocrit levels were maintained up to 80% for at least 2 months. The histological analysis of the explanted microcapsules performed at that point showed that pericapsular overgrowth was reduced when cell-loaded microcapsules were enclosed in the hydrogels scaffolds. Incorporating microencapsulated cells within hydrogel-based scaffolds may help to improve their administration protocol and retention while reducing post-transplantation inflammation.

Combined Regenerative and Vital Pulp Therapies in an Immature Mandibular Molar: A Case Report

Introduction:Vital pulp therapy (VPT) aims to preserve the health and maintain life of the tooth pulp which has been compromised by caries, trauma or restorative procedures. Recently, enamel matrix derivative (EMD) has been introduced as a material for vital pulp therapy. The aim of this review is to critically analyze and summarize the available literature on EMD for VPT. Methods and Materials:Online databases (PubMED/MEDLINE, Google Scholar, ISI Web of Science, and Wiley-Online) were searched by using the following keywords in various combinations: Enamel Matrix Derivative, Emdogain, ‘Vital Pulp Therapy, ‘Apexogenisis’, Apexification, Pulp Capping, Endodontics, Dentine and Pulpotomy for studies indexed from January 1949 to April 2016. We used an English-limited search in Google.co.uk for the missing grey literature. All studies fulfilling the selection criteria were carefully reviewed for the focused question: “Does using EMD in VPT, compared with other materials, result in better clinical, radiographic and histological outcomes?”. Results:The primary search resulted in 18 articles of which, 14 articles (including 6 animal studies and 6 clinical trials and 2 case reports) met the inclusion criteria for this review and hence were included. The number of teeth tested in the animal studies ranged from 8 to 144 including pigs, rats and dogs teeth. A number of studies used EMD in the experimental group in comparison with calcium hydroxide, propylene glycol alginate (PGA) and MTA as a control. The observation period ranged from 1 to 2 months and 4 out of 6 animal trials reported more favorable outcomes with EMD while two studies reported comparable outcomes. Conclusion:Although EMD has potential for various applications in endodontics, studies conducted to date have failed to demonstrate any significant advantage of EMD over conventional VPT materials. Additionally, the 5-year and 10-year survival rate of EMD-treated teeth is not yet known. Hence, studies with a longer follow-up periods are required to deduce the long-term viability of teeth treated with EMD.

The zone of calcified cartilage (ZCC) is the mineralized region between the hyaline cartilage and subchondral bone and is critical in cartilage repair. A new non-stoichiometric calcium silicate (10% Ca substituted by Mg; CSi-Mg10) has been demonstrated to be highly bioactive in an osteogenic environment in vivo. This study is aimed to systematically evaluate the potential to regenerate osteochondral interface with different amount of Ca-Mg silicate in hydrogel-based scaffolds, and to compare with the scaffolds containing conventional Ca-phosphate biomaterials. Hydrogel-based porous scaffolds combined with 0–6% CSi-Mg10, 6% β-tricalcium phosphate (β-TCP) or 6% nanohydroxyapatite (nHAp) were made with three-dimensional (3D) printing. An increase in CSi-Mg10 content is desirable for promoting the hypertrophy and mineralization of chondrocytes, as well as cell proliferation and matrix deposition. Osteogenic and chondrogenic induction were both up-regulated in a dose-dependent manner. In comparison with the scaffolds containing 6% β-TCP or nHAp, human deep zone chondrocytes (hDZCs) seeded on CSi-Mg10 scaffold of equivalent concentration exhibited higher mineralization. It is noteworthy that the hDZCs in the 6% CSi-Mg10 scaffolds maintained a higher expression of the calcified cartilage zone specific extracellular matrix marker and hypertrophic marker, collagen type X. Immunohistochemical and Alizarin Red staining reconfirmed these findings. The study demonstrated that hydrogel-based hybrid scaffolds containing 6% CSi-Mg10 are particularly desirable for inducing the formation of calcified cartilage.

Purpose:Nonsurgical root canal therapy (NSRCT) is indicated for management of permanent teeth diagnosed with symptomatic irreversible pulpitis. However, recent research has suggested that vital pulp therapy (VPT) may be a less invasive option in these cases. The purpose of this systematic review was to evaluate the outcomes of VPT, using hydraulic calcium silicate cements (HCSCs) including complete and partial pulpotomies in permanent posterior teeth with symptomatic irreversible pulpitis.Materials and Methods:The PRISMA recommendations were adhered to. The search approach used electronic databases from PubMed, EMBASE, the Cochrane Library, and grey literature. The Newcastle-Ottawa Scale, ROBINS-I, and Cochrane Collaboration Risk of Bias tools were used to evaluate the quality of the selected studies.Results:The initial database search turned up 142 papers, of which 3 prospective cohort studies and 9 randomised controlled trials were selected for analysis. For three, seven, and two articles, the risk of bias was rated as “high” or “serious,” “fair,” and “low,” respectively. The success rates for VPT using HCSCs typically ranged from 78% to 90% one to five years following VPT. The results of the VPT and NSRCT were equivalent at one and five years, according to two articles. Although the intra-operative pulp assessment is essential for VPT treatments, most studies did not provide a thorough account of this process or the time required to achieve haemostasis. Three studies reported sample sizes that were < 23 teeth. The 12 studies that were analysed revealed successful VPT procedures using HCSCs in permanent posterior teeth that had symptomatic irreversible pulpitis, with radiographic success rates ranging from 81% to 90%. Two articles claimed that the results of VPT and root canal therapy were equivalent.Conclusion:When considering VPT as an alternative to NSRCT, appropriate case selection and outcome criteria must be created. This data highlights the need for additional studies contrasting the longer-term effects of different treatment regimens.

Vital pulp therapy (VPT) aims to preserve dental pulp after injury and has gained significant popularity due to advancements in materials and understanding of pulp biology. While bibliometric analyses are common in various fields, none have been conducted specifically for the 100 most-cited articles on VPT. This bibliometric study analyzed the 100 most-cited VPT papers using data from Web of Science (WoS-CC), Scopus, and Google Scholar. Articles were manually reviewed to extract key bibliometric data, including titles, citation counts, citation density, authorship, country of origin, publication year, journal, study design, and VPT type. The articles collectively received 19,782 citations, with the oldest from 1966 and the most recent from 2019, having 803 and 104 citations, respectively. Key journals included the Journal of Endodontics, International Endodontic Journal, and Dental Materials. Review articles were the predominant study design, followed by clinical, laboratory, and basic research studies. Eight of the top 20 articles focused on the properties of mineral trioxide aggregate (MTA). Torabinejad and Parirokh were notable contributors before 2010, while Duncan, Bjørndal, and Simon were prominent after 2010. VPT research has increased significantly post-2010, with a notable shift in focus from early studies on calcium hydroxide to more recent studies on MTA's biocompatibility and its use as a pulp capping agent. This analysis provides a comprehensive list of the top 100 cited VPT articles, offering valuable insights for researchers, students, and clinicians. The study highlights key trends and influential contributions in the field of VPT research.

Tissue engineering: Hydrogel scaffolds and mechanical properties as key design parameters.

Dentin pulp has a complex function as a major unit in maintaining the vitality of teeth. In this sense, the Wnt/β-Catenin pathway has a vital part in tooth development, maintenance, repair, and regeneration by controlling physiological activities such as growth, differentiation, and migration. This pathway consists of a network of proteins, such as Wnt signaling molecules, which interact with receptors of targeted cells and play a role in development and adult tissue homeostasis. The Wnt signals are specific spatiotemporally, suggesting its intricate mechanism in development, regulation, repair, and regeneration by the formation of tertiary dentin. This review provides an overview of the recent advances in the Wnt/β-Catenin signaling pathway in dentin and pulp regeneration, how different proteins, molecules, and ligands influence this pathway, either upregulating or silencing it, and how it may be used in the future for clinical dentistry, in vital pulp therapy as an effective treatment for dental caries, as an alternative approach for root canal therapy, and to provide a path for therapeutic and regenerative dentistry.

Dental pulp regeneration strategies: A review of status quo and recent advances

Dental pulp-dentin complex defects remain a major unresolved problem in oral medicines. Clinical therapeutic methods including root canal therapy and vital pulp therapy are both considered as conservative strategies, which are incapable of repairing the pulp-dentin complex defects. Although biomaterial-based strategies show remarkable progress in antibacterial, anti-inflammatory, and pulp regeneration, the important modulatory effects of nerves within pulp cavity have been greatly overlooked, making it challenging to achieve functional pulp-dentin complex regeneration. In this study, we propose an injectable bioceramics-containing composite hydrogel in combination of Li-Ca-Si (LCS) bioceramics and gelatin methacrylate matrix with photo-crosslinking properties. Due to the sustained release of bioactive Li, Ca and Si ions from LCS, the composite hydrogels possess multiple functions of promoting the neurogenic differentiation of Schwann cells, odontogenic differentiation of dental pulp stem cells, and neurogenesis-odontogenesis couples in vitro. In addition, the in vivo results showed that LCS-containing composite hydrogel can significantly promote the pulp-dentin complex repair. More importantly, LCS bioceramics-containing composite hydrogel can induce the growth of nerve fibers, leading to the re-innervation of pulp tissues. Taken together, the study suggests that LCS bioceramics can induce the innervation of pulp-dentin complex repair, offering a referable strategy of designing multifunctional filling materials for functional periodontal tissue regeneration.