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Sedek EM, Holiel AA. Next-Generation Strategies for Enamel Repair and Regeneration: Advances in Biomaterials and Translational Challenges. Tissue Eng Regen Med 2025:10.1007/s13770-025-00725-w. [PMID: 40347432 DOI: 10.1007/s13770-025-00725-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2025] [Revised: 03/26/2025] [Accepted: 04/15/2025] [Indexed: 05/12/2025] Open
Abstract
BACKGROUND Enamel regeneration and remineralization are critical for restoring enamel integrity, as natural enamel lacks the ability to regenerate due to the absence of ameloblasts. The increasing prevalence of dental caries and the irreversible nature of enamel damage highlight the need for advanced repair strategies. METHODS This review examines the latest advancements in enamel regeneration and remineralization, focusing on biomaterials, nanotechnology-based approaches, and bioengineering strategies. Google Scholar, Scopus (Elsevier), and PubMed databases were used for the selection of literature. The search included key terms such as "enamel regeneration," "biomimetic enamel repair," "stem cell-based enamel regeneration," "nanotechnology in enamel repair," "hydroxyapatite enamel remineralization," and "biomaterials for enamel remineralization." RESULTS Various strategies have been explored for enamel remineralization, including self-assembling peptides, dendrimers, hydrogels, and electrospun mats, each demonstrating varying success in laboratory and preclinical studies. While casein-phosphopeptide-stabilized amorphous calcium phosphate (CPP-ACP) combined with fluoride remains a widely used clinical remineralization agent, integrating CPP-ACP with nanotechnology is an emerging area requiring further research. Enamel bioengineering approaches utilizing stem/progenitor cells offer potential, though challenges remain in achieving clinical translation. CONCLUSION Despite advancements, replicating the hierarchical structure and mechanical properties of natural enamel remains challenging. Nanotechnology-driven approaches, bioengineered scaffolds, and interdisciplinary collaboration hold promise for optimizing enamel regeneration techniques. Further research is necessary to enhance clinical applicability and develop scalable, effective treatments for enamel restoration.
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Affiliation(s)
- Eman M Sedek
- Dental Biomaterials Department, Faculty of Dentistry, Alexandria University, Alexandria, Egypt
| | - Ahmed A Holiel
- Conservative Dentistry Department, Faculty of Dentistry, Alexandria University, Alexandria, Egypt.
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Alnasser M, Alshammari AH, Siddiqui AY, Alothmani OS, Issrani R, Iqbal A, Khattak O, Prabhu N. Tissue Regeneration on Rise: Dental Hard Tissue Regeneration and Challenges-A Narrative Review. SCIENTIFICA 2024; 2024:9990562. [PMID: 38690100 PMCID: PMC11057954 DOI: 10.1155/2024/9990562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 03/01/2024] [Accepted: 03/27/2024] [Indexed: 05/02/2024]
Abstract
Background As people live longer, there is an increasing need for hard tissue regeneration and whole-tooth regeneration. Despite the advancements in the field of medicine, the field of regenerative dentistry is still challenging due to the complexity of dental hard tissues. Cross-disciplinary collaboration among material scientists, cellular biologists, and odontologists aimed at developing strategies and uncovering solutions related to dental tissue regeneration. Methodology. A search of the literature was done for pertinent research. Consistent with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 Statement, the electronic databases looked at were PubMed, Science Direct, Scopus, and Google Scholar, with the keyword search "hard dental tissue regeneration." Results Database analysis yielded a total of 476 articles. 222 duplicate articles have been removed in total. Articles that have no connection to the directed regeneration of hard dental tissue were disregarded. The review concluded with the inclusion of four studies that were relevant to our research objective. Conclusion Current molecular signaling network investigations and novel viewpoints on cellular heterogeneity have made advancements in understanding of the kinetics of dental hard tissue regeneration possible. Here, we outline the fundamentals of stem hard dental tissue maintenance, regeneration, and repair, as well as recent advancements in the field of hard tissue regeneration. These intriguing findings help establish a framework that will eventually enable basic research findings to be utilized towards oral health-improving medicines.
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Affiliation(s)
- Muhsen Alnasser
- Department of Restorative Dental Sciences, College of Dentistry, Jouf University, Sakaka, Saudi Arabia
| | | | - Amna Yusuf Siddiqui
- Department of Endodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Osama Shujaa Alothmani
- Department of Endodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Rakhi Issrani
- Department of Preventive Dentistry, College of Dentistry, Jouf University, Sakaka, Saudi Arabia
- Department of Research Analytics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
| | - Azhar Iqbal
- Department of Restorative Dental Sciences, College of Dentistry, Jouf University, Sakaka, Saudi Arabia
| | - Osama Khattak
- Department of Restorative Dental Sciences, College of Dentistry, Jouf University, Sakaka, Saudi Arabia
| | - Namdeo Prabhu
- Department of Oral and Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Jouf University, Sakaka, Saudi Arabia
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Montazerian M, Baino F, Fiume E, Migneco C, Alaghmandfard A, Sedighi O, DeCeanne AV, Wilkinson CJ, Mauro JC. Glass-ceramics in dentistry: Fundamentals, technologies, experimental techniques, applications, and open issues. PROGRESS IN MATERIALS SCIENCE 2023; 132:101023. [DOI: 10.1016/j.pmatsci.2022.101023] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Dalir Abdolahinia E, Safari Z, Sadat Kachouei SS, Zabeti Jahromi R, Atashkar N, Karbalaeihasanesfahani A, Alipour M, Hashemzadeh N, Sharifi S, Maleki Dizaj S. Cell homing strategy as a promising approach to the vitality of pulp-dentin complexes in endodontic therapy: focus on potential biomaterials. Expert Opin Biol Ther 2022; 22:1405-1416. [PMID: 36345819 DOI: 10.1080/14712598.2022.2142466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Elaheh Dalir Abdolahinia
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zahra Safari
- Faculty of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
| | | | | | - Nastaran Atashkar
- Department of Orthodontics, Faculty of Dentistry, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Mahdieh Alipour
- Center for Craniofacial Regeneration, Department of Oral and Craniofacial Sciences, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA, United States
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nastaran Hashemzadeh
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
- Pharmaceutical Analysis Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Simin Sharifi
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Solmaz Maleki Dizaj
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Dental Biomaterials, Tabriz University of Medical Sciences, Tabriz, Iran
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Dalir Abdolahinia E, Ilbeygi Taher S, Abdali Dehdezi P, Ataei A, Azizi M, Afra N, Afshar Fard S, Sharifi S. Strategies and Challenges in the Treatment of Dental Enamel. Cells Tissues Organs 2022; 212:485-498. [PMID: 35780769 DOI: 10.1159/000525790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 06/14/2022] [Indexed: 11/19/2022] Open
Abstract
Enamel tissue, the hardest body tissue, which covers the outside of the tooth shields the living tissue, but it erodes and disintegrates in the acidic environment of the oral cavity. On the one hand, mature enamel is cell-free and, if damaged, does not regenerate. Tooth sensitivity and decay are caused by enamel loss. On the other hand, the tissue engineering approach is challenging because of the unique structure of tooth enamel. To develop an exemplary method for dental enamel rebuilding, accurate knowledge of the structure of tooth enamel, knowing how it is created and how proteins interact in its structure, is critical. Furthermore, novel techniques in tissue engineering for using stem cells to develop enamel must be established. This article aims to discuss current attempts to regenerate enamel using synthetic materials methods, recent advances in enamel tissue engineering, and the prospects of enamel biomimetics to find unique insights into future possibilities for repairing enamel tissue, perhaps the most fascinating of all tooth tissues.
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Affiliation(s)
- Elaheh Dalir Abdolahinia
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
- Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | | | - Atefe Ataei
- Department of Periodontics, School of Dentistry, Birjand University of Medical Sciences, Birjand, Iran
| | - Majid Azizi
- Department of Periodontics, School of Dentistry, Birjand University of Medical Sciences, Birjand, Iran
| | - Narges Afra
- Faculty of Dentistry, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | | | - Simin Sharifi
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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6
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Mohabatpour F, Chen X, Papagerakis S, Papagerakis P. Novel trends, challenges and new perspectives for enamel repair and regeneration to treat dental defects. Biomater Sci 2022; 10:3062-3087. [PMID: 35543379 DOI: 10.1039/d2bm00072e] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Dental enamel is the hardest tissue in the human body, providing external protection for the tooth against masticatory forces, temperature changes and chemical stimuli. Once enamel is damaged/altered by genetic defects, dental caries, trauma, and/or dental wear, it cannot repair itself due to the loss of enamel producing cells following the tooth eruption. The current restorative dental materials are unable to replicate physico-mechanical, esthetic features and crystal structures of the native enamel. Thus, development of alternative approaches to repair and regenerate enamel defects is much needed but remains challenging due to the structural and functional complexities involved. This review paper summarizes the clinical aspects to be taken into consideration for the development of optimal therapeutic approaches to tackle dental enamel defects. It also provides a comprehensive overview of the emerging acellular and cellular approaches proposed for enamel remineralization and regeneration. Acellular approaches aim to artificially synthesize or re-mineralize enamel, whereas cell-based strategies aim to mimic the natural process of enamel development given that epithelial cells can be stimulated to produce enamel postnatally during the adult life. The key issues and current challenges are also discussed here, along with new perspectives for future research to advance the field of regenerative dentistry.
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Affiliation(s)
- Fatemeh Mohabatpour
- Division of Biomedical Engineering, University of Saskatchewan, 57 Campus Dr., S7N 5A9, SK, Canada. .,College of Dentistry, University of Saskatchewan, 105 Wiggins Rd, Saskatoon, S7N 5E4, SK, Canada
| | - Xiongbiao Chen
- Division of Biomedical Engineering, University of Saskatchewan, 57 Campus Dr., S7N 5A9, SK, Canada. .,Department of Mechanical Engineering, University of Saskatchewan, 57 Campus Dr., Saskatoon, S7N 5A9, SK, Canada
| | - Silvana Papagerakis
- Division of Biomedical Engineering, University of Saskatchewan, 57 Campus Dr., S7N 5A9, SK, Canada. .,Department of Surgery, College of Medicine, University of Saskatchewan, 107 Wiggins Rd B419, S7N 0 W8, SK, Canada
| | - Petros Papagerakis
- Division of Biomedical Engineering, University of Saskatchewan, 57 Campus Dr., S7N 5A9, SK, Canada. .,College of Dentistry, University of Saskatchewan, 105 Wiggins Rd, Saskatoon, S7N 5E4, SK, Canada
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Gan L, Liu Y, Cui DX, Pan Y, Wan M. New insight into dental epithelial stem cells: Identification, regulation, and function in tooth homeostasis and repair. World J Stem Cells 2020; 12:1327-1340. [PMID: 33312401 PMCID: PMC7705464 DOI: 10.4252/wjsc.v12.i11.1327] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 08/21/2020] [Accepted: 09/15/2020] [Indexed: 02/06/2023] Open
Abstract
Tooth enamel, a highly mineralized tissue covering the outermost area of teeth, is always damaged by dental caries or trauma. Tooth enamel rarely repairs or renews itself, due to the loss of ameloblasts and dental epithelial stem cells (DESCs) once the tooth erupts. Unlike human teeth, mouse incisors grow continuously due to the presence of DESCs that generate enamel-producing ameloblasts and other supporting dental epithelial lineages. The ready accessibility of mouse DESCs and wide availability of related transgenic mouse lines make mouse incisors an excellent model to examine the identity and heterogeneity of dental epithelial stem/progenitor cells; explore the regulatory mechanisms underlying enamel formation; and help answer the open question regarding the therapeutic development of enamel engineering. In the present review, we update the current understanding about the identification of DESCs in mouse incisors and summarize the regulatory mechanisms of enamel formation driven by DESCs. The roles of DESCs during homeostasis and repair are also discussed, which should improve our knowledge regarding enamel tissue engineering.
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Affiliation(s)
- Lu Gan
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ying Liu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Di-Xin Cui
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yue Pan
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Mian Wan
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
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Tissue Engineering Approaches for Enamel, Dentin, and Pulp Regeneration: An Update. Stem Cells Int 2020; 2020:5734539. [PMID: 32184832 PMCID: PMC7060883 DOI: 10.1155/2020/5734539] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Accepted: 01/07/2020] [Indexed: 12/12/2022] Open
Abstract
Stem/progenitor cells are undifferentiated cells characterized by their exclusive ability for self-renewal and multilineage differentiation potential. In recent years, researchers and investigations explored the prospect of employing stem/progenitor cell therapy in regenerative medicine, especially stem/progenitor cells originating from the oral tissues. In this context, the regeneration of the lost dental tissues including enamel, dentin, and the dental pulp are pivotal targets for stem/progenitor cell therapy. The present review elaborates on the different sources of stem/progenitor cells and their potential clinical applications to regenerate enamel, dentin, and the dental pulpal tissues.
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Smith AJ, Sharpe PT. Biological tooth replacement and repair. PRINCIPLES OF TISSUE ENGINEERING 2020:1187-1199. [DOI: 10.1016/b978-0-12-818422-6.00066-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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10
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Pushpalatha C, Nagaraja S, Sowmya SV, Kamala C. Biomaterials in Tooth Tissue Engineering. MATERIALS HORIZONS: FROM NATURE TO NANOMATERIALS 2019:91-115. [DOI: 10.1007/978-981-13-9977-0_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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11
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Toriumi T, Kawano E, Yamanaka K, Kaneko T, Oka A, Yuguchi M, Isokawa K, Honda M. Odontogenic Tissue Generation Derived from Human Induced Pluripotent Stem Cells Using Tissue Engineering Application. J HARD TISSUE BIOL 2018. [DOI: 10.2485/jhtb.27.257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Affiliation(s)
- Taku Toriumi
- Department of Oral Anatomy, School of Dentistry, Aichi Gakuin University
- Department of Anatomy, Nihon University School of Dentistry
| | - Eisuke Kawano
- Department of Periodontology, Nihon University School of Dentistry
| | | | | | | | - Maki Yuguchi
- Department of Anatomy, Nihon University School of Dentistry
| | | | - Masaki Honda
- Department of Oral Anatomy, School of Dentistry, Aichi Gakuin University
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12
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Honda MJ, Shinohara Y, Hata KI, Ueda M. Subcultured Odontogenic Epithelial Cells in Combination with Dental Mesenchymal Cells Produce Enamel–Dentin-Like Complex Structures. Cell Transplant 2017; 16:833-47. [PMID: 18088003 DOI: 10.3727/000000007783465208] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
We showed in a previous study that odontogenic epithelial cells can be selectively cultured from the enamel organ in serum-free medium and expanded using feeder layers of 3T3-J2 cells. The subcultured odontogenic epithelial cells retain the capacity for ameloblast-related gene expression, as shown by semiquantitative RT-PCR. The purpose of the present study was to evaluate the potential of subcultured odontogenic epithelial cells to form tooth structures in cell–polymer constructs maintained in vivo. Enamel organs from 6-month-old porcine third molars were dissociated into single odontogenic epithelial cells and subcultured on feeder layers of 3T3-J2 cells. Amelogenin expression was detected in the subcultured odontogenic epithelial cells by immunostaining and Western blotting. The subcultured odontogenic epithelial cells were seeded onto collagen sponge scaffolds in combination with fresh dental mesenchymal cells, and transplanted into athymic rats. After 4 weeks, enamel–dentin-like complex structures were present in the implanted constructs. These results show that our culture system produced differentiating ameloblast-like cells that were able to secrete amelogenin proteins and form enamel-like tissues in vivo. This application of the subculturing technique provides a foundation for further tooth-tissue engineering and for improving our understanding of ameloblast biology.
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Affiliation(s)
- M. J. Honda
- Tooth Regeneration, Division of Stem Cell Engineering, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
| | - Y. Shinohara
- Tooth Regeneration, Division of Stem Cell Engineering, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
| | - K. I. Hata
- Japan Tissue Engineering Co. Ltd, Aichi 443-0022, Japan
| | - M. Ueda
- Department of Oral and Maxillofacial Surgery, Nagoya University Postgraduate School of Medicine, Aichi 466-8550, Japan
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Mapping the milestones in tooth regeneration: Current trends and future research. Med J Armed Forces India 2017; 72:S24-S30. [PMID: 28050065 DOI: 10.1016/j.mjafi.2016.05.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Accepted: 05/10/2016] [Indexed: 11/22/2022] Open
Abstract
Research into finding the perfect replacement for lost dentition is an ever-evolving and rapidly advancing subject involving many scientific disciplines. The present consensus appears to be that regeneration of tooth in morphological and functional form is the ideal answer to lost tooth replacement. This article traces the milestones in this elusive search for the ultimate tooth replacement. The various research developments are highlighted that are aimed at the final goal of being able to "re-grow a natural tooth". Whole tooth regeneration is technically challenging and further research into this field of complex molecular biology, embryology, biomaterials and stem cells is required to answer the unsolved questions. However, the milestones that have been crossed in the attempts at whole tooth regeneration have been remarkable and the future is quite promising. This article highlights the noteworthy research work that is being done in the field of whole tooth regeneration with a view to not only inform the clinicians of the significant developments but also inspire them to actively participate in this rapidly evolving field.
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Hosseini S, Jahangir S, Eslaminejad MB. Tooth tissue engineering. BIOMATERIALS FOR ORAL AND DENTAL TISSUE ENGINEERING 2017:467-501. [DOI: 10.1016/b978-0-08-100961-1.00027-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Bakopoulou A, Leyhausen G, Geurtsen W, Koidis P. Dental Tissue Engineering Research and Translational Approaches towards Clinical Application. ORAL HEALTHCARE AND TECHNOLOGIES 2017:186-220. [DOI: 10.4018/978-1-5225-1903-4.ch004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Stem cell-based dental tissue regeneration is a new and exciting field that has the potential to transform the way that we practice dentistry. It is, however, imperative its clinical application is supported by solid basic and translational research. In this way, the full extent of the potential risks involved in the use of these technologies will be understood, and the means to prevent them will be discovered. Therefore, the aim of this chapter is to analyze the state-of-the-science with regard to dental pulp stem cell research in dental tissue engineering, the new developments in biomimetic scaffold materials customized for dental tissue applications, and to give a prospectus with respect to translational approaches of these research findings towards clinical application.
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Schmalz G, Smith AJ. Pulp development, repair, and regeneration: challenges of the transition from traditional dentistry to biologically based therapies. J Endod 2016; 40:S2-5. [PMID: 24698689 DOI: 10.1016/j.joen.2014.01.018] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
The traditional concept of replacing diseased tooth/pulp tissues by inert materials (restoration) is being challenged by recent advances in pulp biology leading to regenerative strategies aiming at the generation of new vital tissue. New tissue formation in the pulp chamber can be observed after adequate infection control and the formation of a blood clot. However, differentiation of true odontoblasts is still more speculative, and the approach is largely limited to immature teeth with open apices. A more systematic approach may be provided by the adoption of the tissue engineering concepts of using matrices, suitable (stem) cells, and signaling molecules to direct tissue events. With these tools, pulplike constructs have already been generated in experimental animals. However, a number of challenges still remain for clinical translation of pulp regeneration (eg, the cell source [resident vs nonresident stem cells, the latter associated with cell-free approaches], mechanisms of odontoblast differentiation, the pulp environment, the role of infection and inflammation, dentin pretreatment to release fossilized signaling molecules from dentin, and the provision of suitable matrices). Transition as a process, defined by moving from one form of "normal" to another, is based not only on the progress of science but also on achieving change to established treatment concepts in daily practice. However, it is clear that the significant recent achievements in pulp biology are providing an exciting platform from which clinical translation of dental pulp regeneration can advance.
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Affiliation(s)
- Gottfried Schmalz
- Department of Operative Dentistry and Periodontology, University Medical Centre Regensburg, Regensburg, Germany.
| | - Anthony J Smith
- Oral Biology, School of Dentistry, University of Birmingham, St Chads Queensway, Birmingham, United Kingdom
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Tan L, Wang J, Yin S, Zhu W, Zhou G, Cao Y, Cen L. Regeneration of dentin–pulp-like tissue using an injectable tissue engineering technique. RSC Adv 2015; 5:59723-59737. [DOI: 10.1039/c5ra06481c] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025] Open
Abstract
An injectable tissue engineering technique to regenerate dentin–pulp complex.
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Affiliation(s)
- Linhua Tan
- Department of Plastic and Reconstructive Surgery
- Shanghai 9th People’s Hospital
- Shanghai Jiao Tong University School of Medicine
- Shanghai
- China
| | - Jun Wang
- Department of Pediatric Dentistry
- School of Stomatology
- Ninth People’s Hospital
- Medical College
- Shanghai Jiaotong University
| | - Shuo Yin
- National Tissue Engineering Center of China
- Shanghai
- China
| | - Wenting Zhu
- Department of Pediatric Dentistry
- School of Stomatology
- Ninth People’s Hospital
- Medical College
- Shanghai Jiaotong University
| | - Guangdong Zhou
- Department of Plastic and Reconstructive Surgery
- Shanghai 9th People’s Hospital
- Shanghai Jiao Tong University School of Medicine
- Shanghai
- China
| | - Yilin Cao
- Department of Plastic and Reconstructive Surgery
- Shanghai 9th People’s Hospital
- Shanghai Jiao Tong University School of Medicine
- Shanghai
- China
| | - Lian Cen
- Department of Plastic and Reconstructive Surgery
- Shanghai 9th People’s Hospital
- Shanghai Jiao Tong University School of Medicine
- Shanghai
- China
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18
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(Tony) Smith AJ, Sharpe PT. Biological Tooth Replacement and Repair. PRINCIPLES OF TISSUE ENGINEERING 2014:1471-1485. [DOI: 10.1016/b978-0-12-398358-9.00070-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Goudouri O, Theodosoglou E, Kontonasaki E, Will J, Chrissafis K, Koidis P, Paraskevopoulos K, Boccaccini A. Development of highly porous scaffolds based on bioactive silicates for dental tissue engineering. MATERIALS RESEARCH BULLETIN 2014; 49:399-404. [DOI: 10.1016/j.materresbull.2013.09.027] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Nasu M, Nakahara T, Tominaga N, Tamaki Y, Ide Y, Tachibana T, Ishikawa H. Isolation and characterization of vascular endothelial cells derived from fetal tooth buds of miniature swine. In Vitro Cell Dev Biol Anim 2013; 49:189-95. [PMID: 23435856 DOI: 10.1007/s11626-013-9584-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2012] [Accepted: 01/25/2013] [Indexed: 12/23/2022]
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Abstract
BACKGROUND As a result of numerous rapid and exciting developments in tissue engineering technology, scientists are able to regenerate a fully functional tooth in animal models, from a bioengineered tooth germ. Advances in technology, together with our understanding of the mechanisms of tooth development and studies dealing with dentally derived stem cells, have led to significant progress in the field of tooth regeneration. AIM AND DESIGN This review focuses on some of the recent advances in tooth bioengineering technology, the signalling pathways in tooth development, and in dental stem cell biology. These factors are highlighted in respect of our current knowledge of tooth regeneration. RESULTS AND CONCLUSION An understanding of these new approaches in tooth regeneration should help to prepare clinicians to use this new and somewhat revolutionary therapy while also enabling them to partake in future clinical trials. Tooth bioengineering promises to be at the forefront of the next generation of dental treatments.
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Affiliation(s)
- Ying Wang
- Department of Orthodontics, School of Dental Medicine, State University of New York at Buffalo, Buffalo, NY 14214, USA
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22
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Sunil P, Manikandhan R, Muthu M, Abraham S. Stem cell therapy in oral and maxillofacial region: An overview. J Oral Maxillofac Pathol 2012; 16:58-63. [PMID: 22434942 PMCID: PMC3303525 DOI: 10.4103/0973-029x.92975] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Cells with unique capacity for self-renewal and potency are called stem cells. With appropriate biochemical signals stem cells can be transformed into desirable cells. The idea behind this article is to shortly review the obtained literature on stem cell with respect to their properties, types and advantages of dental stem cells. Emphasis has been given to the possibilities of stem cell therapy in the oral and maxillofacial region including regeneration of tooth and craniofacial defects.
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Affiliation(s)
- Pm Sunil
- Department of Oral and Maxillofacial Pathology, Rajah Mutiah Dental College, Annamalai University, Annamalai Nagar, Chidambaram, India
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23
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Štembírek J, Kyllar M, Putnová I, Stehlík L, Buchtová M. The pig as an experimental model for clinical craniofacial research. Lab Anim 2012; 46:269-79. [PMID: 22969144 DOI: 10.1258/la.2012.012062] [Citation(s) in RCA: 81] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
The pig represents a useful, large experimental model for biomedical research. Recently, it has been used in different areas of biomedical research. The aim of this study was to review the basic anatomical structures of the head region in the pig in relation to their use in current research. Attention was focused on the areas that are frequently affected by pathological processes in humans: the oral cavity with teeth, salivary gland, orbit, nasal cavity and paranasal sinuses, maxilla, mandible and temporomandibular joint. Not all of the structures have an equal morphology in the pig and human, and these morphological dissimilarities must be taken into account before choosing the pig as an experimental model for regenerative medicine.
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Affiliation(s)
- J Štembírek
- Institute of Animal Physiology and Genetics, vvi, Academy of Sciences of Czech Republic, Brno, Czech Republic
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24
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Effect of vitronectin bound to insulin-like growth factor-I and insulin-like growth factor binding protein-3 on porcine enamel organ-derived epithelial cells. Int J Dent 2012; 2012:386282. [PMID: 22567008 PMCID: PMC3332072 DOI: 10.1155/2012/386282] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2011] [Accepted: 01/17/2012] [Indexed: 11/17/2022] Open
Abstract
The aim of this paper was to determine whether the interaction between IGF, IGFBP, and VN modulates the functions of porcine EOE cells. Enamel organs from 6-month-old porcine third molars were dissociated into single epithelial cells and subcultured on culture dishes pretreated with VN, IGF-I, and IGFBP-3 (IGF-IGFBP-VN complex). The subcultured EOE cells retained their capacity for ameloblast-related gene expression, as shown by semiquantitative reverse transcription-polymerase chain reaction. Amelogenin expression was detected in the subcultured EOE cells by immunostaining. The subcultured EOE cells were then seeded onto collagen sponge scaffolds in combination with fresh dental mesenchymal cells and transplanted into athymic rats. After 4 weeks, enamel-dentin-like complex structures were present in the implanted constructs. These results show that EOE cells cultured on IGF-IGFBP-VN complex differentiated into ameloblasts-like cells that were able to secrete amelogenin proteins and form enamel-like tissues in vivo. Functional assays demonstrated that the IGF/IGFBP/VN complex significantly enhanced porcine EOE cell proliferation and tissue forming capacity for enamel. This is the first study to demonstrate a functional role of the IGF-IGFBP-VN complex in EOE cells. This application of the subculturing technique provides a foundation for further tooth-tissue engineering and for improving our understanding of ameloblast biology.
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25
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Abstract
All over the world a large number of people suffer from tooth diseases like dental caries, tooth abscess, and plaques. Tooth loss or damage, which occurs frequently in our society are generally repaired by applying several conventional methods, such as root-canal treatment, direct pulp capping and dental implants. These methods are quite painful, create damage to the surrounding tooth tissues and also may at times have adverse side-effects. The limitations of the conventional methods can be overcome by applying the concept of tooth tissue engineering. Tooth tissue engineering is the application of biosciences and engineering to regenerate a biofunctional tooth, which can be used to replace the missing tooth or repair the damaged tooth. Tissue engineering involves three key elements - cell, scaffold and growth factors, which interact with each other to regenerate a specific tissue. The success of tissue engineering depends on the proper selection of these three key elements and understanding the interactions among them. To bring us close to the realization of a tissue-engineered tooth, immense progress is going on in understanding how tooth is first developed, and there is a good advancement in tooth regeneration. In this review, “tooth tissue engineering” will be discussed, along with the recent advancements and challenges in bring a biofunctional tooth from laboratory out into clinical use.
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26
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Tsuchiya S, Honda MJ. In vivo transplantation and tooth repair. Methods Mol Biol 2012; 887:123-134. [PMID: 22566052 DOI: 10.1007/978-1-61779-860-3_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
Cell scaffold-based tooth engineering research was started by 2000 at Forsyth Institute corroborated with Dr. Vacanti's team at Massachusetts General Hospital. The first work was published in 2002 in Journal of Dental Research, in which we particularly focused on cells from postnatal tooth because of its clinical application. However, making a functional tooth from postnatal cells is still ways away. Alternatively, we formulated a partial replacement of the tooth by engineering the root of the tooth. Here, we describe a new technique in which the root of the third molar is used to replace missing teeth.
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Affiliation(s)
- Shuhei Tsuchiya
- Department of Anatomy, Nihon University School of Dentistry, Tokyo, Japan
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27
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Local regeneration of dentin-pulp complex using controlled release of fgf-2 and naturally derived sponge-like scaffolds. Int J Dent 2011; 2012:190561. [PMID: 22174717 PMCID: PMC3227515 DOI: 10.1155/2012/190561] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2011] [Accepted: 09/08/2011] [Indexed: 01/09/2023] Open
Abstract
Restorative and endodontic procedures have been recently developed in an attempt to preserve the vitality of dental pulp after exposure to external stimuli, such as caries infection or traumatic injury. When damage to dental pulp is reversible, pulp wound healing can proceed, whereas irreversible damage induces pathological changes in dental pulp, eventually requiring its removal. Nonvital teeth lose their defensive abilities and become severely damaged, resulting in extraction. Development of regeneration therapy for the dentin-pulp complex is important to overcome limitations with presently available therapies. Three strategies to regenerate the dentin-pulp complex have been proposed; regeneration of the entire tooth, local regeneration of the dentin-pulp complex from amputated dental pulp, and regeneration of dental pulp from apical dental pulp or periapical tissues. In this paper, we focus on the local regeneration of the dentin-pulp complex by application of exogenous growth factors and scaffolds to amputated dental pulp.
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28
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Yang KC, Wang CH, Chang HH, Chan WP, Chi CH, Kuo TF. Fibrin glue mixed with platelet-rich fibrin as a scaffold seeded with dental bud cells for tooth regeneration. J Tissue Eng Regen Med 2011; 6:777-85. [PMID: 22034398 DOI: 10.1002/term.483] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2010] [Revised: 01/25/2011] [Accepted: 07/12/2011] [Indexed: 01/06/2023]
Abstract
Odontogenesis is a complex process with a series of epithelial-mesenchymal interactions and odontogenic molecular cascades. In tissue engineering of teeth from stem cells, platelet-rich fibrin (PRF), which is rich in growth factors and cytokines, may improve regeneration. Accordingly, PRF was added into fibrin glue to enrich the microenvironment with growth factors. Unerupted second molar tooth buds were harvested from miniature swine and cultured in vitro for 3 weeks to obtain dental bud cells (DBCs). Whole blood was collected for the preparation of PRF and fibrin glue before surgery. DBCs were suspended in fibrin glue and then enclosed with PRF, and the DBC-fibrin glue-PRF composite was autografted back into the original alveolar sockets. Radiographic and histological examinations were used to identify the regenerated tooth structure 36 weeks after implantation. Immunohistochemical staining was used to detect proteins specific to tooth regeneration. One pig developed a complete tooth with crown, root, pulp, enamel, dentin, odontoblast, cementum, blood vessels, and periodontal ligaments in indiscriminate shape. Another animal had an unerupted tooth that expressed cytokeratin 14, dentin matrix protein-1, vascular endothelial growth factor, and osteopontin. This study demonstrated, using autogenic cell transplantation in a porcine model, that DBCs seeded into fibrin glue-PRF could regenerate a complete tooth.
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Affiliation(s)
- Kai-Chiang Yang
- Department of Organ Reconstruction, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
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29
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Regeneration Approaches for Dental Pulp and Periapical Tissues with Growth Factors, Biomaterials, and Laser Irradiation. Polymers (Basel) 2011. [DOI: 10.3390/polym3041776] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
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30
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Tsujigiwa H, Katase N, Sathi GA, Buery RR, Hirata Y, Kubota M, Nakano K, Kawakami T, Nagatsuka H. Transplanted Bone Marrow derived Cells Differentiated toTooth, Bone and Connective Tissues in Mice. J HARD TISSUE BIOL 2011. [DOI: 10.2485/jhtb.20.147] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
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31
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Ohara T, Itaya T, Usami K, Ando Y, Sakurai H, Honda MJ, Ueda M, Kagami H. Evaluation of scaffold materials for tooth tissue engineering. J Biomed Mater Res A 2010; 94:800-5. [PMID: 20336748 DOI: 10.1002/jbm.a.32749] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Recently, the possibility of tooth tissue engineering has been reported. Although there are a number of available materials, information about scaffolds for tooth tissue engineering is still limited. To improve the manageability of tooth tissue engineering, the effect of scaffolds on in vivo tooth regeneration was evaluated. Collagen and fibrin were selected for this study based on the biocompatibility to dental papilla-derived cells and the results were compared with those of polyglycolic acid (PGA) fiber and beta-tricalcium phosphate (beta-TCP) porous block, which are commonly used for tooth, dentin and bone tissue engineering. Isolated porcine tooth germ-derived cells were seeded onto one of those scaffolds and transplanted to the back of nude mice. Tooth bud-like structures were observed more frequently in collagen and fibrin gels than on PGA or beta-TCP, while the amount of hard tissue formation was less. The results showed that collagen and fibrin gel support the initial regeneration process of tooth buds possibly due to their ability to support the growth of epithelial and mesenchymal cells. On the other hand, maturation of tooth buds was difficult in fibrin and collagen gels, which may require other factors.
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Affiliation(s)
- Takayuki Ohara
- Research and Development Center, Hitachi Medical Corporation, Kashiwa, Japan
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32
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Honda MJ, Imaizumi M, Tsuchiya S, Morsczeck C. Dental follicle stem cells and tissue engineering. J Oral Sci 2010; 52:541-552. [PMID: 21206155 DOI: 10.2334/josnusd.52.541] [Citation(s) in RCA: 119] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Adult stem cells are multipotent and can be induced experimentally to differentiate into various cell lineages. Such cells are therefore a key part of achieving the promise of tissue regeneration. The most studied stem cells are those of the hematopoietic and mesenchymal lineages. Recently, mesenchymal stem cells were demonstrated in dental tissues, including dental pulp, periodontal ligament, and dental follicle. The dental follicle is a loose connective tissue that surrounds the developing tooth. Dental follicle stem cells could therefore be a cell source for mesenchymal stem cells. Indeed, dental follicle is present in impacted teeth, which are commonly extracted and disposed of as medical waste in dental practice. Dental follicle stem cells can be isolated and grown under defined tissue culture conditions, and recent characterization of these stem cells has increased their potential for use in tissue engineering applications, including periodontal and bone regeneration. This review describes current knowledge and recent developments in dental follicle stem cells and their application.
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Affiliation(s)
- Masaki J Honda
- Department of Anatomy, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
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33
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Kuo TF, Lin HC, Hung AT, Yang KC, Lin HF, Tanng TK, Chen ST, Wang AHJ. GELATIN–CHONDROITIN–HYALURONAN TRI-COPOLYMER SCAFFOLD SEEDED WITH DENTAL BUD CELLS FOR ODONTOGENESIS: AN EX VIVOSTUDY ON NUDE MICE. BIOMEDICAL ENGINEERING: APPLICATIONS, BASIS AND COMMUNICATIONS 2010; 22:535-547. [DOI: 10.4015/s1016237210002274] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
A biologically regenerated tooth may provide a new treatment for tooth loss. In this study, a tissue engineering approach was applied to demonstrate the tooth regeneration. The dental buds of the second molar tooth from 1.5-month-old miniature pigs were harvested by surgical operation before eruption. The dental bud tissues were cultured and expanded in vitro for three weeks to obtain dental bud cells (DBCs). The phenotypes of DBCs were identified with a flowcytometry, and the DBCs were seeded into a gelatin–chondroitin–hyaluronan tri-copolymer (GCHT) scaffold. The DBCs/GCHT scaffold constructs were implanted under dermis of nude mice's thoracic dorsum. Mice were sacrificed at predetermined intervals, and the developing tooth-like tissues were harvested for histological examinations. The present results of flowcytometry showed that the DBCs expressed specific surface markers of mesenchymal stem cells. Animal study revealed that the tooth-like structures expressed cytokeratin 14 at 4, 8, and 12 weeks postoperatively. The vascular endothelial growth factor was expressed on 12 weeks. Dentin-like mineralized tissue and dentin genetic-like cells were generated that expressed dentin martrix protein-1 on 16 and 20 weeks. Osteocytes were formed on 24 weeks and expressed osteopontin. This study reveals that the DBCs combined with an appropriate scaffold regenerated tooth-like structure with specific proteins for odontogenesis in nude mice.
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Affiliation(s)
- Tzong-Fu Kuo
- Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taiwan
| | - Hsin-Chi Lin
- Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taiwan
| | - An-Ting Hung
- Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taiwan
- Institute of Biological Chemistry, Academia Sinica, Taiwan
| | - Kai-Chiang Yang
- Institute of Biomedical Engineering, National Taiwan University, Taiwan
| | - Huei-Feng Lin
- Institute of Biomedical Engineering, National Taiwan University, Taiwan
- Division of Medical Engineering, National Health Research Institute, Taiwan
| | | | | | - Andrew HJ Wang
- Institute of Biological Chemistry, Academia Sinica, Taiwan
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34
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Kuo TF, Lin HC, Yang KC, Lin FH, Chen MH, Wu CC, Chang HH. Bone marrow combined with dental bud cells promotes tooth regeneration in miniature pig model. Artif Organs 2010; 35:113-21. [PMID: 21083830 DOI: 10.1111/j.1525-1594.2010.01064.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Growth factors and morphogens secreted by bone marrow mesenchymal stem cells (BMSCs) of bone marrow fluid may promote tooth regeneration. Accordingly, a tissue engineering approach was utilized to develop an economical strategy for obtaining the growth factors and morphogens from BMSCs. Unerupted second molar tooth buds harvested from miniature pigs were cultured in vitro to obtain dental bud cells (DBCs). Bone marrow fluid, which contains BMSCs, was collected from the porcine mandible before operation. DBCs suspended in bone marrow fluid were seeded into a gelatin/chondoitin-6-sulfate/hyaluronan tri-copolymer scaffold (GCHT scaffold). The DBCs/bone marrow fluid/GCHT scaffold was autografted into the original alveolar sockets of the pigs. Radiographic and histological examinations were applied to identify the structure of regenerated tooth at 40 weeks postimplantation. The present results showed that one pig developed a complete tooth with crown, root, pulp, enamel, dentin, odontoblast, cementum, blood vessel, and periodontal ligament in indiscriminate shape. Three animals had an unerupted tooth that expressed dentin matrix protein-1, vascular endothelial growth factor, and osteopontin; and two other pigs also had dental-like structure with dentin tubules. This study reveals that DBCs adding bone marrow fluid and a suitable scaffold can promote the tooth regeneration in autogenic cell transplantation.
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Affiliation(s)
- Tzong-Fu Kuo
- Institute of Veterinary Medicine, College of Veterinary Medicine, National Taiwan University, Taipei, Taiwan
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35
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Tsuchiya S, Ohshima S, Yamakoshi Y, Simmer JP, Honda MJ. Osteogenic differentiation capacity of porcine dental follicle progenitor cells. Connect Tissue Res 2010; 51:197-207. [PMID: 20053131 DOI: 10.3109/03008200903267542] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
This study examined the effect of extracellular matrix (ECM) on the osteogenic differentiation capacity and osteogenesis of dental follicle cells. Single cell-derived porcine dental follicle cells (DFC-I) obtained at the early stage of crown formation in tooth were subcultured and characterized using periodontal ligament cells (PDLC) and bone marrow-derived mesenchymal stem cells (BMSC) as comparison cell populations. The effect of ECM constituents including collagen type I, fibronectin, laminin, and collagen type IV on the differentiation of DFC-1 into osteogenic-lineage cells was evaluated in vitro. In addition, the DFC-1, PDLC, and BMSC populations were compared for osteogenic capacity in vitro by Alizarin red staining and in vivo by transplantation. DFC-I showed different features from PDLC and BMSC. Different components of ECM had different effects on the differentiation of DFC-1 into osteogenic-lineage cells in vitro. Alkaline phosphatase activity and matrix mineralization as early- and late-stage markers of osteogenesis, respectively, supported the differentiation of DFC-1 into osteogenic-related cells in vitro. All three cell types showed equivalent osteogenic capacity in vivo at 4 weeks postoperatively. There were no statistically significant differences among the cell populations with respect to capacity for bone formation. These results suggest a potential application for dental follicle cells in bone-tissue engineering.
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Affiliation(s)
- Shuhei Tsuchiya
- Department of Anatomy, Nihon University School of Dentistry, Division of Stem Cell Engineering, Institute of Medical Science, University of Tokyo, Tokyo, Japan
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36
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Honda MJ, Tsuchiya S, Shinohara Y, Shinmura Y, Sumita Y. Recent advances in engineering of tooth and tooth structures using postnatal dental cells. JAPANESE DENTAL SCIENCE REVIEW 2010. [DOI: 10.1016/j.jdsr.2009.10.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
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37
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Abstract
Mesenchymal stem cells (MSCs) resident in bone marrow are one of the most studied and clinically important populations of adult stem cells. Cells with, similar properties to these MSCs have been described in several different tooth tissues and the potential ease with which these dental MSCs could be obtained from patients has prompted great interest in these cells as a source of MSCs for cell-based therapeutics. In this review we address the current state of knowledge regarding these cells, their properties, origins, locations, functions and potential uses in tooth tissue engineering and repair. We discuss some of the key controversies and outstanding issues, not least of which whether dental stem cells actually exist.
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Affiliation(s)
- Andrea Mantesso
- Guy's Hospital, Dental Institute, Kings College London, Department of Craniofacial Development, London SE1 9RT, UK
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38
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Sumita Y, Tsuchiya S, Asahina I, Kagami H, Honda MJ. The location and characteristics of two populations of dental pulp cells affect tooth development. Eur J Oral Sci 2009; 117:113-21. [PMID: 19320719 DOI: 10.1111/j.1600-0722.2008.00603.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
This study investigated the characteristics of two dental pulp cell populations during the early stages of crown formation in porcine teeth. A transplantation method was developed to reproduce epithelial cell-mesenchymal cell interactions during odontogenesis (tooth development). The technique allowed two types of cells/tissue to be combined in vivo. Populations of cells localized in the cervical loop epithelium region, dental pulp horn, and dental pulp core chambers were isolated and dissociated into single cells. Each population was examined for its gene-expression pattern using both semiquantitative and quantitative reverse transcription-polymerase chain reaction (RT-PCR) analyses, and for its tissue-formation capability by combining the cervical loop epithelial cells with either pulp horn cells or pulp core cells on biodegradable collagen scaffolds that were subsequently examined using histology and immunohistology. Gene-expression patterns showed that pulp horn cells were more mature than pulp core cells. Cervical loop epithelial cells combined with pulp horn cells mainly reconstituted dentin-cementum structures. By contrast, cervical loop epithelial cells combined with pulp core cells reconstituted enamel-dentin structures. These results suggest that mesenchymal cells residing in a specific location of the pulp possess a specific tissue-formation potential when combined with epithelial cells.
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Affiliation(s)
- Yoshinori Sumita
- Division of Stem Cell Engineering, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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39
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Hacking SA, Khademhosseini A. Applications of microscale technologies for regenerative dentistry. J Dent Res 2009; 88:409-21. [PMID: 19493883 DOI: 10.1177/0022034509334774] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
While widespread advances in tissue engineering have occurred over the past decade, many challenges remain in the context of tissue engineering and regeneration of the tooth. For example, although tooth development is the result of repeated temporal and spatial interactions between cells of ectoderm and mesoderm origin, most current tooth engineering systems cannot recreate such developmental processes. In this regard, microscale approaches that spatially pattern and support the development of different cell types in close proximity can be used to regulate the cellular microenvironment and, as such, are promising approaches for tooth development. Microscale technologies also present alternatives to conventional tissue engineering approaches in terms of scaffolds and the ability to direct stem cells. Furthermore, microscale techniques can be used to miniaturize many in vitro techniques and to facilitate high-throughput experimentation. In this review, we discuss the emerging microscale technologies for the in vitro evaluation of dental cells, dental tissue engineering, and tooth regeneration.
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Affiliation(s)
- S A Hacking
- Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, PRB, Rm 252, 65 Landsdowne Street, Cambridge, MA 02139, USA
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40
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Ommerborn MA, Schneider K, Raab WHM. Tissue Engineering and Its Applications in Dentistry. FUNDAMENTALS OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE 2009:921-938. [DOI: 10.1007/978-3-540-77755-7_64] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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41
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Tooth-forming potential in embryonic and postnatal tooth bud cells. Med Mol Morphol 2008; 41:183-92. [PMID: 19107607 DOI: 10.1007/s00795-008-0416-9] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2008] [Accepted: 09/02/2008] [Indexed: 12/20/2022]
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42
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Affiliation(s)
- Adele L Boskey
- Musculoskeletal Integrity Program, Hospital for Special Surgery, 535 East 70th Street, New York, New York 10021, USA.
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43
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Kuo TF, Huang AT, Chang HH, Lin FH, Chen ST, Chen RS, Chou CH, Lin HC, Chiang H, Chen MH. Regeneration of dentin-pulp complex with cementum and periodontal ligament formation using dental bud cells in gelatin-chondroitin-hyaluronan tri-copolymer scaffold in swine. J Biomed Mater Res A 2008; 86:1062-8. [PMID: 18067171 DOI: 10.1002/jbm.a.31746] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
The purpose of this study is to use a tissue engineering approach for tooth regeneration. The swine dental bud cells (DBCs) were isolated from the developing mandibular teeth, expanded in vitro, and cultured onto cylinder scaffold gelatin-chrondroitin-hyaluronan-tri-copolymer (GCHT). After culturing in vitro, the DBCs/GCHT scaffold was autografted back into the original alveolar socket. Hematoxylin and eosin (H&E) staining combined with immunohistochemical staining were applied for identification of regenerated tooth structure. After 36-week post-transplantation, tooth-like structures, including well-organized dentin-pulp complex, cementum, and periodontal ligament, were evident in situ in two of six experimental animals. The size of the tooth structure (1 x 0.5 x 0.5 cm(3) and 0.5 x 0.5 x 0.5 cm(3) size) appeared to be dictated by the size of the GCHT scaffold (1 x 1 x 1.5 cm(3)). The third swine was demonstrated with irregular dentin-bony like calcified tissue about 1 cm in diameter without organized tooth or periodontal ligament formation. The other three swine in the experimental group showed normal bone formation and no tooth regeneration in the transplantation sites. The successful rate of tooth regeneration from DBCs/GCHT scaffolds' was about 33.3%. In the control group, three swine's molar teeth buds were removed without DBCs/GCHT implantation, the other three swine received GCHT scaffold implants without DBCs. After evaluation, no regenerated tooth was found in the transplantation site of the control group. The current results using DBSs/GCHT scaffold autotransplantation suggest a technical breakthrough for tooth regeneration.
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Affiliation(s)
- Tzong-Fu Kuo
- Graduate Institute of Veterinary Medicine, National Taiwan University, Taipei, Taiwan
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44
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Ikeda E, Tsuji T. Growing bioengineered teeth from single cells: potential for dental regenerative medicine. Expert Opin Biol Ther 2008; 8:735-44. [PMID: 18476785 DOI: 10.1517/14712598.8.6.735] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The ultimate goal of regenerative therapy is to develop fully functioning bioengineered organs that can replace organs lost or damaged due to disease, injury or aging. Dental regenerative medicine has made the most progress and is the most useful model for the consideration of strategies in future organ replacement therapies. OBJECTIVE This review describes strategies that have been pursued to date and experiments currently being conducted to bioengineer teeth in anticipation of the production of fully functional organs. METHODS To realize the practical application of 'bioengineered tooth' transplantation therapy, four major hurdles must be overcome. The present status of the hurdles to this therapy are described and discussed in this review. RESULTS/CONCLUSION The bioengineering techniques developed for tooth regeneration will in the future make substantial contributions to the ability to grow primordial organs in vitro and also to grow fully functioning organs, such as the liver, kidney and heart.
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Affiliation(s)
- Etsuko Ikeda
- Faculty of Industrial Science and Technology Tokyo University of Science, Department of Biological Science and Technology, Noda, Chiba 278-8510, Japan
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Yu J, Shi J, Jin Y. Current Approaches and Challenges in Making a Bio-Tooth. TISSUE ENGINEERING PART B-REVIEWS 2008; 14:307-19. [PMID: 18665759 DOI: 10.1089/ten.teb.2008.0165] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Affiliation(s)
- Jinhua Yu
- Institute of Stomatology, Nanjing Medical University, Nanjing, Jiangsu, P.R. China
- Department of Endodontics, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China
- Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China
| | - Junnan Shi
- Department of Endodontics, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China
| | - Yan Jin
- Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China
- Department of Oral Histology & Pathology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China
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Fujita S, Seki S, Fujiwara M, Ikeda T. Midkine expression correlating with growth activity and tooth morphogenesis in odontogenic tumors. Hum Pathol 2008; 39:694-700. [DOI: 10.1016/j.humpath.2007.09.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2007] [Revised: 09/14/2007] [Accepted: 09/18/2007] [Indexed: 02/04/2023]
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Abstract
Salivary gland destruction occurs as a result of various pathological conditions such as radiation therapy for head and neck cancer and Sjögren's syndrome. As saliva possesses self-cleaning and antibacterial capability, hyposalivation is known to deteriorate dental caries and periodontal disease. Furthermore, hyposalivation causes mastication and swallowing problems, burning sensation of the mouth and dysgeusia. Currently available treatments for dry mouth are prescription for artificial saliva, moisturizers and medications which induce salivation from the residual tissue. Unfortunately, these treatments cannot restore the acini functions. This review focuses on various efforts to restore the function of damaged salivary gland. First, the possibility of salivary gland regeneration and tissue engineering is discussed with reference to stem cells, growth factors and scaffold materials. Second, the current status of gene transfer to salivary glands is discussed.
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Affiliation(s)
- H Kagami
- Department of Tissue Engineering, Nagoya University School of Medicine, Nagoya, Japan.
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Overview : Developmental Biology of Hertwig's Epithelial Root Sheath (HERS) and Tooth Root Formation. J Oral Biosci 2008. [DOI: 10.1016/s1349-0079(08)80001-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Ohshima H. Overview: Developmental Biology of Hertwig's Epithelial Root Sheath (HERS) and Tooth Root Formation. J Oral Biosci 2008. [DOI: 10.2330/joralbiosci.50.147] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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Chen RS, Chen YJ, Chen MH, Young TH. Cell-surface interactions of rat tooth germ cells on various biomaterials. J Biomed Mater Res A 2007; 83:241-8. [PMID: 17618501 DOI: 10.1002/jbm.a.31475] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
This is the first study to explore the effect of biomaterial on tooth germ cell adhesion and proliferation in vitro. The purpose of this study is to evaluate the effects of cell-surface interactions of tooth germ cells on biomaterials with various surface hydrophilicities. The biomaterials used in this study included polyvinyl alcohol (PVA), poly(lactic-co-glycolic acid) (PLGA), poly(ethylene-co-vinyl alcohol; EVAL), and polyvinylidene fluoride (PVDF). Cell morphology was observed by photomicroscopy. Cell growth was assayed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction activity and the characteristic expression of amelogenin and collagen type I in tooth germ cells was investigated using immunocytochemistry. The results indicated that adhesion and proliferation of tooth germ cells to biomaterials with moderate hydrophilicity/hydrophobicity was superior compared to most hydrophobic material PVDF or mosthydrophilic material PVA in this study. Cellular adhesion and proliferation was evident on all tested biomaterials except PVA. The cell spheroids on PVA appeared not to be proliferated and remained as well as reattachable to tissue culture plates. In conclusion, biomaterials with moderate hydrophilicity are suitable for adhesion and proliferation of tooth germ cells. The material PVA may be a good biomaterial for maintaining tooth germ cells in three-dimensional biological restoration.
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Affiliation(s)
- Rung-Shu Chen
- Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei 100, Taiwan
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