Dental Tissue Engineering and Regeneration; Perspectives on Stem Cells, Bioregulators, and Porous Scaffolds
Perihan Selcan Gungor-Ozkerim1, Abdulmonem Alshihri2, 3, * 1 Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
2 Department of Restorative and Biomaterials, Harvard School of Dental Medicine, Boston, MA, 02115USA
3 Department of Prosthetic and Biomaterial Sciences, College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia
Abstract
Dental/orofacial tissue engineering is an emerging field that offers alternative solutions for dental problems resulting from pathologies such as caries, trauma, periodontal disease and others. Various stem cell types such as bone marrow stem cells (BMSCs) and adipose tissue-derived stem cells (ADSCs) can be employed as cell sources for dental tissue repair. In particular, dental tissue-derived stem cells such as dental pulp stem cells (DPSCS) and dental follicle stem cells (DFSCs) can be utilized due to their favorable origin and properties. On the other hand, natural and synthetic polymers are used to fabricate 3D dental tissue scaffolds to support cellular activities. Several bioregulators such as cytokines and growth factors can also be incorporated to induce cells interaction and cell-scaffold integration. The literature on the regeneration of dental tissues via tissue engineering principles presents numerous results that are superior to the traditional methods, which are vital for advancing dental therapy. Herein, the types, properties, and applications of dental stem cells (DSCs) were reviewed, as well as the tissue engineering and regeneration strategies for different types of dental tissues.
Keywords: 3D scaffolds, Alveolar bone, Dental pulp, Dental tissue engineering, Dental follicle, Growth factors, Intrabony defect, Periodontium, Periodontal ligament, Stem cells, Tissue regeneration.
* Corresponding author Abdulmonem A. Alshihri: Restorative and Biomaterial Sciences, Harvard School of Dental Medicine, Boston, MA, 02115, USA, Department of Prosthetic and Biomaterial Sciences, College of Dentistry, King Saud University, Riyadh, 11545, Saudi Arabia; Tel: +966114677333; Fax: +966114679015; E-mail: [email protected] INTRODUCTION
Tissue engineering is an emerging field that utilizes cells, scaffolds, and bioactive signaling factors - individually or combined- for tissues replacement, repair and regenerative purposes. Dental tissue engineering and regenerative dental medicine represent translational research and interventional therapeutic concepts to overcome several clinical limitations. These engineering and regenerative concepts cover a wide range of applicability in different dentoalveolar and oro-facial branches of dentistry [1-3]. The numerous applications of dental and mesenchymal stem cells are attributed to their common properties of self-renewal, high proliferation rate, and multilineage differentiation ability. Therefore, there is a considerable interest in their potentials as an alternative stem cell source to tackle issues involving mesenchymal or non-mesenchymal cell derivatives [4, 5]. Dental stem cells can be isolated from different dental tissues, such as dental pulp, periodontal ligament or tooth follicle.
Different clinical situations could result in teeth removal in which these teeth could serve as a source of stem cells. For example extracted third molars (wisdom teeth), teeth that are extracted for orthodontic reasons, and exfoliated deciduous teeth. Isolation and cryopreservation of these cells are of researchersâ interest because of their relative ease of collection, attractive applications and reparative potential. In this chapter, various dental tissue-derived stem cells, their applications and regenerative capacity in tissue engineering are presented.
DENTAL STEM CELLS
Stem cells, in general, possess main features of self-renewal and multilineage-differentiation capability. Stem cells have been isolated and differentiated from different parts of the body. Hence, they are categorized based on their source and location. They however differ according to lineages of differentiation [6]. Various populations of stem cells have been isolated and grown from different parts of dental tissues and are classified accordingly as; dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), dental follicle stem cells (DFSCs), stem cells from human exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP) and (BMSCs) bone marrow. Moreover, dental stem cells have attracted a considerable interest in their use for other, non-dental, medical applications as well [4].
Dental Pulp Stem Cells
The dental pulp is the unmineralized connective tissue occupying the central core of a tooth. It is highly vascularized and innervated tissue of ectomesenchymal origin. The dental pulp provides sensory and protective functions, and is responsible for the formation and nutrition of the surrounding dentin [7, 8]. Histologically, dental pulp tissue is composed of various types of cells. Fibroblasts and undifferentiated mesenchymal cells are the predominant cells of the pulp, which correspond to its reparatory and defensive functions [9]. These mesenchymal progenitor cells are referred to as dental pulp stem cells (DPSCs). In 2000, DPSCs were discovered and studied by Gronthos et al [10]. Their findings revealed that DPSCs are clonogenic with high proliferation capacity, and are able to regenerate new tissue. Numerous studies [11-14] demonstrated the potential of DPSCs as qualified stem cells because of their multi-lineage differentiation ability and self-renewal capacity. Moreover, DPSCs exhibited a significantly higher proliferation rate and better multilineage differentiation compared to bone marrow stem cells (BMSCs) [11, 14, 15]. These qualities were related to the neural crest origin and embryonic cell-like behavior of DPSCs, as opposed to the BMSCsâ mesodermal origin [12, 16, 17]. Another important aspect of DPSCs is their Abundancy ,which is a critical factor for cellular pool availability. The availability of DPSCs is of importance for conducting and translating research into clinical therapeutic applications [18]. However, the clinical use of DPSCs could be associated with potential immunosuppressive [19] and immunomodulating [20] responses, which are crucial limitations.
Similar to DPSCs isolated from human permanent teeth [21], stem cells can also be derived from human deciduous (primary) teeth pulp. These cells are called stem cells from human exfoliated deciduous teeth (SHED) [7, 18, 22]. In 2003, Dr. Shi discovered SHED. These cells, compared to DPSCs, possess higher proliferation and less maturation rates during cell passage, as well as higher potentials for differentiation to a variety of cells [23].
Another form of tooth-related stem cells were found in apical papilla (SCAP) by Sonoyama et al. These cells are able to differentiate into mineralized tissue-producing cells where they reside in teethâs roots to aid in root formation [8, 24, 25]. Furthermore, a group of researchers reported a discovery of embryonic-like stem cells in human dental pulp, which were characterized by embryonic lineage markers [26].
Although DPSCs are relatively new compared to their counterparts, such a...