Innovative approaches to regenerate teeth by tissue engineering

In recent years, scientists in almost every medical sector moved the focus to tissue transplantation and stem cell-based therapies for organ and tissue regeneration. In dentistry, it is of great interest in this regard to restore natural teeth with the help of stem cell-based regeneration of soft tissues and hard tooth structures. Many studies have been published in which structures resembling teeth were constructed using stem cells. In most of these studies, carrier materials (scaffolds) were used, which were colonized with cells and then implanted into an animal. Apart from this, scaffold-free approaches based on cell aggregation have also been published. Although animal studies on tooth regeneration have been very promising, much more research is needed until this can be applied in human.     

富血小板血浆支架诱导牙髓再生的体内研究

目的：探讨不同浓度的富血小板血浆（PRP）支架在体内诱导牙髓组织再生的能力。方法将小型猪乳牙牙根段进行化学预备,采用二次离心法制备PRP,根据注入根管中的成分不同将研究分为4组：（1）阴性对照组,即全血组;（2）100％ PRP组;（3）50％ PRP组;（4）空白组,即空的牙根段;每组5个样本,分别植入裸鼠背部皮下,于术后5周处死动物,取出样本进行组织学观察。结果植入5周后,100％ PRP组根管内充满了炎性细胞,50％ PRP组根管内有少量牙髓样的组织生成。结论合适浓度的PRP作为生物支架在体内再生牙髓样的组织是可行的。     

Polymeric scaffolds for dental pulp tissue engineering: A review

ObjectivesThe purpose of this review is to describe recent developments in pulp tissue engineering using scaffolds and/or stem cells. It is crucial to understand how this approach can revitalize damaged dentin-pulp tissue. Widespread scaffold materials, both natural and synthetic, and their fabrication methods, and stem-progenitor cells with the potential of pulp regeneration will be discussed.Data and SourcesA review of literature was conducted through online databases, including MEDLINE by using the PubMed search engine, Scopus, and the Cochrane Library.Study SelectionStudies were selected based on relevance, with a preference given to recent research, particularly from the past decade.ConclusionsThe use of biomaterial scaffolds and stem cells can be safe and potent for the regeneration of pulp tissue and re-establishment of tooth vitality. Natural and synthetic polymers have distinct advantages and limitations and in vitro and in vivo testing have produced positive results for cell attachment, proliferation, and angiogenesis. The type of biomaterial used for scaffold fabrication also facilitates stem cell differentiation into odontoblasts and the resulting biochemistry of tissue repair for each polymer and cell type was discussed. Multiple methods of scaffold design exist for pulp tissue engineering, which demonstrates the variability in tissue engineering applications in endodontics. This review explains the potential of evidence-based tissue engineering strategies and outcomes in pulp regeneration.     

The efficacy of mesenchymal stem cells to regenerate and repair dental structures

OBJECTIVES: Identification, characterization, and potential application of mesenchymal stem cells (MSC) derived from human dental tissues. METHODS: Dental pulp and periodontal ligament were obtained from normal human impacted third molars. The tissues were digested in collagenase/dispase to generate single cell suspensions. Cells were cultured in alpha-MEM supplemented with 20% fetal bovine serum, 2 mM l-glutamine, 100 microM l-ascorbate-2-phosphate. Magnetic and fluorescence activated cell sorting were employed to characterize the phenotype of freshly isolated and ex vivo expanded cell populations. The developmental potential of cultured cells was assessed following co-transplantation with hydroxyapetite/tricalcium phosphate (HA/TCP) particles into immunocompromised mice for 8 weeks. RESULTS: MSC were identified in adult human dental pulp (dental pulp stem cells, DPSC), human primary teeth (stem cells from human exfoliated deciduous teeth, SHED), and periodontal ligament (periodontal ligament stem cells, PDLSC) by their capacity to generate clongenic cell clusters in culture. Ex vivo expanded DPSC, SHED, and PDLSC populations expressed a heterogeneous assortment of makers associated with MSC, dentin, bone, smooth muscle, neural tissue, and endothelium. PDLSC were also found to express the tendon specific marker, Scleraxis. Xenogeneic transplants containing HA/TCP with either DPSC or SHED generated donor-derived dentin-pulp-like tissues with distinct odontoblast layers lining the mineralized dentin-matrix. In parallel studies, PDLSC generated cementum-like structures associated with PDL-like connective tissue when transplanted with HA/TCP into immunocompromised mice. CONCLUSION: Collectively, these data revealed the presence of distinct MSC populations associated with dental structures with the potential of stem cells to regenerate living human dental tissues in vivo.     

Proliferation of mature ex vivo human dental pulp using tissue engineering scaffolds

Introduction

The purpose of this study was to measure and compare the proliferation of mature human dental pulp tissue using three types of tissue engineering scaffolds.

Methods

Mature human teeth were collected immediately after extraction for routine dental treatment reasons. Three types of tissue engineering scaffolds were investigated (1) open-polylactic acid (polymer) scaffolds, (2) bovine collagen (collagen) scaffolds, and (3) calcium phosphate bioceramic (calcium phosphate) scaffolds. The scaffolds were placed in direct contact with the dental pulp of the tooth slices from 7 to 30 days. Neutral-red dye was added to the culture media to stain metabolically active cells. The specimens were processed for histology. The numbers of proliferating cells were counted per unit area of scaffold according to ISO criteria.

Results

The proliferating dental pulp cells had a fibroblast phenotype, no cells of other phenotypes were observed, and none of the cells appeared to be mineralizing. The average rate of mature vital dental cell proliferation was 1.305 cells per day in the calcium phosphate scaffolds compared with 7.195 (a rate increase of 551%) in the collagen scaffolds and 13.885 (a rate increase of 1,064%) in the polymer scaffolds.

Conclusions

Tissue engineering scaffolds can enhance the proliferation of mature dental pulp tissue. The rate of dental pulp proliferation is dependent on the chemical composition of the scaffold. Within the limitations of this study, the polymer scaffolds were more optimal than collagen or calcium phosphate scaffolds for mature dental pulp proliferation.     

Nanofibrous scaffolds for dental and craniofacial applications

Tissue-engineering solutions often harness biomimetic materials to support cells for functional tissue regeneration. Three-dimensional scaffolds can create a multi-scale environment capable of facilitating cell adhesion, proliferation, and differentiation. One such multi-scale scaffold incorporates nanofibrous features to mimic the extracellular matrix along with a porous network for the regeneration of a variety of tissues. This review will discuss nanofibrous scaffold synthesis/fabrication, biological effects of nanofibers, their tissue- engineering applications in bone, cartilage, enamel, dentin, and periodontium, patient-specific scaffolds, and incorporated growth factor delivery systems. Nanofibrous scaffolds cannot only further the field of craniofacial regeneration but also advance technology for tissue-engineered replacements in many physiological systems.     

Bone regeneration with self-assembling peptide nanofiber scaffolds in tissue engineering for osseointegration of dental implants

The aim of this study was to evaluate the correlation between the osseointegration of dental implants and tissue-engineered bone using a nanofiber scaffold, PuraMatrix (PM). The first molar and all premolars in the mandibular regions of dogs were extracted, and three bone defects were prepared with a trephine bur on both sides of the mandible after 4 weeks. The experimental groups were as follows: (1) PM, (2) PM and dog mesenchymal stem cells (dMSCs), (3) PM, dMSCs, and platelet-rich plasma, and (4) control (defect only). Implants were placed in the prepared areas 8 weeks later and were assessed by histologic and histomorphometric analyses (bone-to-implant contact [BIC]). The BICs for groups 1, 2, 3, and 4 were 40.77%, 50.35%, 55.64%, and 30.57%, respectively. The findings indicate that PM may be useful as a scaffold for bone regeneration around dental implants.     

干细胞和支架与牙髓再生及其血运重建

在牙髓再生中,获取干细胞的方法包括干细胞移植、细胞归巢和诱导出血。干细胞移植可产生异位的牙髓样组织,可控制移植细胞的数量并选择对牙髓再生潜在效能最佳的细胞亚种。细胞归巢是指利用信号分子招募宿主内源性干细胞至需治疗的牙体根管中增殖和分化,形成牙髓-牙本质样组织。诱导根尖出血进入根管为年轻恒牙牙髓再生的一个重要步骤。支架是细胞在合成组织时的支撑结构,可促进细胞黏附,为牙髓再生提供有利的环境。牙髓再生离不开血运重建或者血管再生,感染控制、根管预处理、冠方封闭等操作,可为牙髓再生包括其血运重建提供适宜的环境。总之,组织工程技术在牙髓领域的应用发展为牙髓再生带来了新的希望。     

牙髓再生支架材料的研究进展

牙髓再生是一种治疗年轻恒牙牙髓感染或坏死的新技术。该方法能促进未发育完全的牙齿根尖孔闭合,使根管壁增厚且牙根增长。为提高牙髓再生的成功率,需有合适的支架提供三维空间位置定位并调节干细胞的分化、增殖或代谢。支架是牙髓再生的关键因素,目前已发现多种支架有应用于牙髓再生的潜力,它们来自生物提取或人工合成,各有优势。生物提取支架主要包括血凝块、富血小板血浆、富血小板纤维蛋白、多糖、胶原、丝、脱细胞细胞外基质等,人工合成支架主要包括聚合物、生物陶瓷及复合支架。本文对上述多种牙髓再生支架材料的性能和应用前景方面的进展作一综述。     

Histamine-releasing activity of dental materials employed as root canal filling

Four samples of dental materials (DM) estd for root canal filling, Septodent (S), Zinkoxide (Z), Foredent (F) and Cialite Regular (CR), were studied for their ability in vitro to release histamine (HR) employing the computerized fiber glass based histamine release assay using whole blood from allergic patients and healthy donors. It was found that F induced high and S low levels of HR from blood basophils from both allergic and non-allergic subjects. Z and CR did not induce HR from blood basophils similar to the negative control. The HR assay may be a useful method for preliminary investigation of DM employed for root canal fillings for safety as well as for selection of specific DM for individual patients.     

Experimental oral foreign body reactions. Commonly employed dental materials

Foreign bodies and tissue reactions to foreign materials are commonly encountered in the oral cavity. The more common lesions include apical deposition of endodontic materials, mucosal amalgam and graphite tattoos, myospherulosis, oil granulomas, and traumatically introduced dental materials and instruments. Since many foreign materials are unidentifiable histologically, commonly used dental materials were experimentally implanted subcutaneously in rats to assess local host responses and characterize the nature of these materials microscopically. The histologic characteristics of these foreign body reactions are detailed herein. The implanted materials corresponded to reactions seen in human subjects.     

Radiographic criteria employed to diagnose and treat approximal caries by final-year dental students in Mexico City

Abstract A total of 407 final-year dental students in Mexico City were asked about the radiographic criteria they employed when assessing treatment needs for caries in a standardized patient case. 45.2% of participants would restore lesions confined to enamel; 60.7% believed that a lesion which had not passed the dentino-enamel junction would cavitate; and 65.4% said it would take on average 6 months or less for a lesion to progress from outer enamel to the dentino-enamel junction. Radiographic criteria appeared to reflect fears of rapid, inevitable progression of lesions. While local caries experiences had been reported to be high, there seems to be room for re-evaluating some clinical criteria employed to manage caries.     

Complement activation links inflammation to dental tissue regeneration

Clinical Oral Investigations - Complement is an efficient plasma immune surveillance system. It initiates inflammation by inducing vascular modifications and attracting immune cells expressing...     

Fibre guiding scaffolds for periodontal tissue engineering

The periodontium is a highly hierarchically organized organ composed of gingiva, alveolar bone, periodontal ligament and cementum. Periodontitis leads to the destruction of hard and soft tissues ultimately leading to a loss of the teeth supporting apparatus. Current treatments are capable of limiting the disease progression; however, true regeneration, characterized by perpendicularly oriented periodontal ligament fibre attachment to cementum on the root surface remains challenging. Tissue engineering approaches have been developed to enhance regeneration via micro-engineered topographical features, purposely designed to guide the insertion of the regenerated ligament to the root surface. This review reports on the recent advancements in scaffold manufacturing methodologies for generating fibre guiding properties and provides a critical insight in the current limitations of these techniques for the formation of functional periodontal attachment.     

水凝胶支架材料在牙髓再生中的研究进展

近年来用于牙髓再生的支架材料逐渐被重视,并成为研究热点。其中水凝胶凭借其一定的韧性、流变性、良好的生物相容性和可降解性等优势越来越广泛地应用于牙髓再生的研究中。水凝胶在调控干细胞命运、调节生长因子释放、装载抗菌抗炎药物等方面都发挥着重要作用。本文就水凝胶支架材料在牙髓再生中的研究进展作一综述。     

Surgical lasers and hard dental tissue

The cutting of dental hard tissue during restorative procedures presents considerable demands on the ability to selectively remove diseased carious tissue, obtain outline and retention form and maintain the integrity of supporting tooth tissue without structural weakening. In addition, the requirement to preserve healthy tissue and prevent further breakdown of the restoration places the choice of instrumentation and clinical technique as prime factors for the dental surgeon. The quest for an alternative treatment modality to the conventional dental turbine has been, essentially, patient-driven and has led to the development of various mechanical and chemical devices. The review of the literature has endorsed the beneficial effects of current laser machines. However utopian, there is additional evidence to support the development of ultra-short (nano- and femto-second) pulsed lasers that are stable in use and commercially viable, to deliver more efficient hard tissue ablation with less risk of collateral thermal damage. This paper explores the interaction of laser energy with dental hard tissues and bone and the integration of current laser wavelengths into restorative and surgical dentistry.