Abstract

Oral and craniofacial bone defects caused by congenital disease or trauma are widespread. In the case of severe alveolar bone defect, autologous bone grafting has been considered a “gold standard”; however, the procedure has several disadvantages, including limited supply, resorption, donor site morbidity, deformity, infection, and bone graft rejection. In the last few decades, bone tissue engineering combined with stem cell-based therapy may represent a possible alternative to current bone augmentation techniques. The number of studies investigating different cell-based bone tissue engineering methods to reconstruct alveolar bone damage is rapidly rising. As an interdisciplinary field, bone tissue engineering combines the use of osteogenic cells (stem cells/progenitor cells), bioactive molecules, and biocompatible scaffolds, whereas stem cells play a pivotal role. Therefore, our work highlights the osteogenic potential of various dental tissue-derived stem cells and induced pluripotent stem cells (iPSCs), the progress in differentiation techniques of iPSCs into osteoprogenitor cells, and the efforts that have been made to fabricate the most suitable and biocompatible scaffold material with osteoinductive properties for successful bone graft generation. Moreover, we discuss the application of stem cell-derived exosomes as a compelling new form of “stem-cell free” therapy.

Highlights

  • The restoration of severe periodontal defects, such as damage to the alveolar bone or soft periodontal tissue, is still a complex and challenging field for clinicians

  • This study demonstrated that the combination of SB431542 with calcium phosphate cement scaffold greatly enhanced proliferation, osteogenic differentiation, and bone mineral synthesis of induced pluripotent stem cells (iPSCs)-mesenchymal stem cells/stromal cells (MSCs)

  • The osteoinductive effect of this protocol was refined by its combination with a 3D scaffold to establish a xeno-free 3D osteogenic system [82]. Another recent study published by Li et al (2021) evaluated the effect of distal-less homeobox 3 (DLX3) on the proliferation and osteogenic differentiation of iPSC-MSCs

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Summary

Introduction

The restoration of severe periodontal defects, such as damage to the alveolar bone or soft periodontal tissue, is still a complex and challenging field for clinicians. In comparison with the control group, bone regeneration was significantly enhanced in groups who received pre-differentiated GMSCs treated with BMP2 and seeded on PuraMatrixTM [41] Another promising stem cell derived from dental tissue is PDLSCs. A periodontal ligament is specialized connective tissue responsible for the regeneration of adjacent periodontal structures. According to comprehensive metaanalyses of preclinical studies focused on the therapeutic potential of five cell lineages (PDLSCs, BMSCs, DPSCs, GMSCs, and ADSCs) in periodontal tissue regeneration, PDLSCs and BMSCs were the most effective in new alveolar bone, cementum, and periodontal ligament formation [49]. In the most recent study, Qu et al (2021) compared the osteogenic potential of four dental-derived MSCs, including DPSCs, PDLSCs, DFSCs, and alveolar bone-derived MSCs (ABMMSCs). Despite the abovementioned auspicious studies, there is undoubtedly a demand for future investigations focused on a better understanding of the biology of dental tissue-derived MSCs

Osteogenic Differentiation of iPSCs
Scaffolds Suitable for Alveolar Bone Regeneration
Extracellular Vesicles—New Therapeutic Agents in Bone Regeneration
Isolation Method
Findings
Conclusions and Future Perspectives

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