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Kim D, Kim SG. Cell Homing Strategies in Regenerative Endodontic Therapy. Cells 2025; 14:201. [PMID: 39936992 PMCID: PMC11817319 DOI: 10.3390/cells14030201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 01/24/2025] [Accepted: 01/28/2025] [Indexed: 02/13/2025] Open
Abstract
Cell homing, a process that leverages the body's natural ability to recruit cells and repair damaged tissues, presents a promising alternative to cell transplantation methods. Central to this approach is the recruitment of endogenous stem/progenitor cells-such as those from the apical papilla, bone marrow, and periapical tissues-facilitated by chemotactic biological cues. Moreover, biomaterial scaffolds embedded with signaling molecules create supportive environments, promoting cell migration, adhesion, and differentiation for the regeneration of the pulp-dentin complex. By analyzing in vivo animal studies using cell homing strategies, this review explores how biomolecules and scaffold materials enhance the recruitment of endogenous stem cells to the site of damaged dental pulp tissue, thereby promoting repair and regeneration. It also examines the key principles, recent advancements, and current limitations linked to cell homing-based regenerative endodontic therapy, highlighting the interplay of biomaterials, signaling molecules, and their broader clinical implications.
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Affiliation(s)
- David Kim
- Center for Dental and Craniofacial Research, Columbia University College of Dental Medicine, New York, NY 10032, USA;
| | - Sahng G. Kim
- Division of Endodontics, Columbia University College of Dental Medicine, New York, NY 10032, USA
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Kim SG. Dehydrated Human Amnion-Chorion Membrane as a Bioactive Scaffold for Dental Pulp Tissue Regeneration. Biomimetics (Basel) 2024; 9:771. [PMID: 39727775 PMCID: PMC11727341 DOI: 10.3390/biomimetics9120771] [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: 10/30/2024] [Revised: 12/11/2024] [Accepted: 12/17/2024] [Indexed: 12/28/2024] Open
Abstract
The dehydrated human amnion-chorion membranes (dHACMs) derived from the human placenta have emerged as a promising biomaterial for dental pulp regeneration owing to their unique biological and structural properties. The purpose of this review is to explore the potentials of dHACMs in dental pulp tissue engineering, focusing on their ability to promote cellular proliferation, differentiation, angiogenesis, and neurogenesis. dHACMs are rich in extracellular matrix proteins and growth factors such as TGF-β1, FGF2, and VEGF. They also exhibit significant anti-inflammatory and antimicrobial properties, creating an optimal environment for dental pulp regeneration. The applications of dHACMs in regenerative endodontic procedures are discussed, highlighting their ability to support the formation of dentin and well-vascularized pulp-like tissue. This review demonstrates that dHACMs hold significant potential for enhancing the success of pulp regeneration and offer a biologically based approach to preserve tooth vitality and improve tooth survival. Future research is expected to focus on conducting long-term clinical studies to establish their efficacy and safety.
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Affiliation(s)
- Sahng G Kim
- Division of Endodontics, Columbia University College of Dental Medicine, New York, NY 10032, USA
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Mittal N, Baranwal HC, Aggarwal H, Kharat S, Samad S, Ayubi A. Comparison of double antibiotic chitosan hydrogel scaffold with platelet-rich fibrin in regeneration in immature necrotic permanent teeth - Randomized controlled trial. JOURNAL OF CONSERVATIVE DENTISTRY AND ENDODONTICS 2024; 27:1251-1260. [PMID: 39959016 PMCID: PMC11823575 DOI: 10.4103/jcde.jcde_609_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 11/23/2024] [Accepted: 12/07/2024] [Indexed: 02/18/2025]
Abstract
Background Fibrin, a natural hydrogel, can act as scaffold for tissue regeneration. Antibiotic-loading of hydrogels can create an infection-free environment for stem cell proliferation and maturation. Aim To compare regenerative endodontic potential of three groups (antibiotic-loaded hydrogel, chitosan-loaded hydrogel, and double antibiotic-loaded chitosan hydrogel) in immature necrotic permanent teeth with platelet rich fibrin (PRF). Materials and Methods Fifty-six immature necrotic teeth with periapical lesions were included in simple randomized parallel-controlled superiority trial. Patients aged 10-35 years were assigned into four groups based on scaffolds used: Group 1 (PRF), Group 2 (double antibiotic-loaded [metronidazole and ciprofloxacin] chitosan hydrogel), Group 3 (double antibiotic-loaded hydrogel), and Group 4 (chitosan-loaded hydrogel). One patient per group was lost to follow-up. Regenerative outcomes (change in apex size, root length, radicular dentin thickness, and periapical healing) were assessed at 12 months, through double-blinding and compared postprocedure using cone-beam computed tomography. Statistical Analysis Based on normality distribution, change in apex size (ANOVA test) while root length, radicular dentin thickness (Kruskal-Wallis test), and periapical healing (paired t-test) were used. Results Group 2 showed superior regenerative outcomes (P = 0.001) compared to groups 1, 4 after 12 months, and no significant difference with Group 3. Conclusion Double antibiotic-loaded chitosan produced significantly superior outcomes compared to PRF in promoting apexogenesis in immature permanent teeth with necrosed pulp.
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Affiliation(s)
- Neelam Mittal
- Department of Conservative Dentistry and Endodontics, Faculty of Dental Sciences, Institute of Medical Sciences, BHU, Varanasi, Uttar Pradesh, India
| | - Harakh Chand Baranwal
- Department of Conservative Dentistry and Endodontics, Faculty of Dental Sciences, Institute of Medical Sciences, BHU, Varanasi, Uttar Pradesh, India
| | - Harshitaa Aggarwal
- Department of Conservative Dentistry and Endodontics, Faculty of Dental Sciences, Institute of Medical Sciences, BHU, Varanasi, Uttar Pradesh, India
| | - Shubham Kharat
- Department of Conservative Dentistry and Endodontics, Faculty of Dental Sciences, Institute of Medical Sciences, BHU, Varanasi, Uttar Pradesh, India
| | - Silviya Samad
- Department of Conservative Dentistry and Endodontics, Faculty of Dental Sciences, Institute of Medical Sciences, BHU, Varanasi, Uttar Pradesh, India
| | - Aiyman Ayubi
- Department of Conservative Dentistry and Endodontics, Faculty of Dental Sciences, Institute of Medical Sciences, BHU, Varanasi, Uttar Pradesh, India
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Quigley RM, Kearney M, Kennedy OD, Duncan HF. Tissue engineering approaches for dental pulp regeneration: The development of novel bioactive materials using pharmacological epigenetic inhibitors. Bioact Mater 2024; 40:182-211. [PMID: 38966600 PMCID: PMC11223092 DOI: 10.1016/j.bioactmat.2024.06.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 06/05/2024] [Accepted: 06/06/2024] [Indexed: 07/06/2024] Open
Abstract
The drive for minimally invasive endodontic treatment strategies has shifted focus from technically complex and destructive root canal treatments towards more conservative vital pulp treatment. However, novel approaches to maintaining dental pulp vitality after disease or trauma will require the development of innovative, biologically-driven regenerative medicine strategies. For example, cell-homing and cell-based therapies have recently been developed in vitro and trialled in preclinical models to study dental pulp regeneration. These approaches utilise natural and synthetic scaffolds that can deliver a range of bioactive pharmacological epigenetic modulators (HDACis, DNMTis, and ncRNAs), which are cost-effective and easily applied to stimulate pulp tissue regrowth. Unfortunately, many biological factors hinder the clinical development of regenerative therapies, including a lack of blood supply and poor infection control in the necrotic root canal system. Additional challenges include a need for clinically relevant models and manufacturing challenges such as scalability, cost concerns, and regulatory issues. This review will describe the current state of bioactive-biomaterial/scaffold-based engineering strategies to stimulate dentine-pulp regeneration, explicitly focusing on epigenetic modulators and therapeutic pharmacological inhibition. It will highlight the components of dental pulp regenerative approaches, describe their current limitations, and offer suggestions for the effective translation of novel epigenetic-laden bioactive materials for innovative therapeutics.
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Affiliation(s)
- Ross M. Quigley
- Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin (TCD), University of Dublin, Lincoln Place, Dublin, Ireland
- Department of Anatomy and Regenerative Medicine, and Tissue Engineering Research Group, Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences, Dublin, Ireland
| | - Michaela Kearney
- Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin (TCD), University of Dublin, Lincoln Place, Dublin, Ireland
| | - Oran D. Kennedy
- Department of Anatomy and Regenerative Medicine, and Tissue Engineering Research Group, Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences, Dublin, Ireland
- The Trinity Centre for Biomedical Engineering (TCBE) and the Advanced Materials and Bioengineering Research Centre (AMBER), Royal College of Surgeons in Ireland (RCSI) and Trinity College Dublin (TCD), Dublin, Ireland
| | - Henry F. Duncan
- Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin (TCD), University of Dublin, Lincoln Place, Dublin, Ireland
- The Trinity Centre for Biomedical Engineering (TCBE) and the Advanced Materials and Bioengineering Research Centre (AMBER), Royal College of Surgeons in Ireland (RCSI) and Trinity College Dublin (TCD), Dublin, Ireland
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Huang L, Chen X, Yang X, Zhang Y, Qiu X. GelMA-based hydrogel biomaterial scaffold: A versatile platform for regenerative endodontics. J Biomed Mater Res B Appl Biomater 2024; 112:e35412. [PMID: 38701383 DOI: 10.1002/jbm.b.35412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 02/26/2024] [Accepted: 04/13/2024] [Indexed: 05/05/2024]
Abstract
Endodontic therapy, while generally successful, is primarily limited to mature teeth, hence the pressing need to explore regenerative approaches. Gelatin methacryloyl (GelMA) hydrogels have emerged as pivotal biomaterials, promising a bright future for dental pulp regeneration. Despite advancements in tissue engineering and biomaterials, achieving true pulp tissue regeneration remains a formidable task. GelMA stands out for its injectability, rapid gelation, and excellent biocompatibility, serving as the cornerstone of scaffold materials. In the pursuit of dental pulp regeneration, GelMA holds significant potential, facilitating the delivery of stem cells, growth factors, and other vital substances crucial for tissue repair. Presently, in the field of dental pulp regeneration, researchers have been diligently utilizing GelMA hydrogels as engineering scaffolds to transport various effective substances to promote pulp regeneration. However, existing research is relatively scattered and lacks comprehensive reviews and summaries. Therefore, the primary objective of this article is to elucidate the application of GelMA hydrogels as regenerative scaffolds in this field, thereby providing clear direction for future researchers. Additionally, this article provides a comprehensive discussion on the synthesis, characterization, and application of GelMA hydrogels in root canal therapy regeneration. Furthermore, it offers new application strategies and profound insights into future challenges, such as optimizing GelMA formulations to mimic the complex microenvironment of pulp tissue and enhancing its integration with host tissues.
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Affiliation(s)
| | - Xuan Chen
- Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, China
| | - XiaoXia Yang
- Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, China
| | - Yinchun Zhang
- Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, China
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Zhao B, Zhang Q, Yang H, Yu S, Fu R, Shi S, Wang Y, Zhou W, Cui Y, Guo Q, Zhang X. Peptide KN-17-Loaded Supramolecular Hydrogel Induces the Regeneration of the Pulp-Dentin Complex. ACS Biomater Sci Eng 2024; 10:2523-2533. [PMID: 38445444 DOI: 10.1021/acsbiomaterials.3c01376] [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] [Indexed: 03/07/2024]
Abstract
Regenerating the pulp-dentin complex remains a decisive factor during apexification for immature permanent teeth. Peptide KN-17, which was modified based on the structure of cecropin B, could effectively interfere with bacterial growth and induce the migration of human bone marrow stromal cells (hBMSCs). This study aimed to investigate the effect of KN-17 on the tissue regeneration. To our surprise, KN-17 can significantly stimulate angiogenesis in vitro and in vivo, which may provide a guarantee for apical closure. Herein, a novel peptide/KN-17 coassembled hydrogel is developed via a heating-cooling process. Npx-FFEY/KN-17 supramolecular hydrogel can induce vessel development, stimulate odontogenic differentiation of human dental pulp stem cells (hDPSCs), and exert an antibacterial effect on Enterococcus faecalis (E. faecalis). Furthermore, coronal pulp excised rat molars are supplied with KN-17 or KN-17-loaded hydrogel and transplanted subcutaneously in BALB/c-nu mice. After 4 weeks, the hydrogel Npx-FFEY/KN-17 stimulates the formation of multiple odontoblast-like cells and dentin-like structures. Our findings demonstrate that the KN-17-loaded hydrogel can promote the regeneration of the pulp-dentin complex for continued root development.
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Affiliation(s)
- Borui Zhao
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, China
| | - Qian Zhang
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, China
| | - Houzhi Yang
- Tianjin Medical University, Tianjin 300070, China
| | - Shuipeng Yu
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, China
| | - Rui Fu
- Tianjin Medical University, Tianjin 300070, China
| | - Shurui Shi
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, China
| | - Yuanyuan Wang
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, China
| | - Wei Zhou
- Immunology, Microenvironment & Metastasis Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, United States
| | - Yange Cui
- Program in Gene Expression and Regulation, The Wistar Institute, Philadelphia, Pennsylvania 19104, United States
| | - Qingxiang Guo
- College of Chemical Engineering, Inner Mongolia University of Technology, Hohhot 010051, China
| | - Xi Zhang
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, China
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Omerkić Dautović D, Hodžić B, Omerkić S. Application of Stem Cells in Dentistry: A Review Article. IFMBE PROCEEDINGS 2024:726-745. [DOI: 10.1007/978-3-031-49068-2_75] [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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Zawadzka-Knefel A, Rusak A, Mrozowska M, Machałowski T, Żak A, Haczkiewicz-Leśniak K, Kulus M, Kuropka P, Podhorska-Okołów M, Skośkiewicz-Malinowska K. Chitin scaffolds derived from the marine demosponge Aplysina fistularis stimulate the differentiation of dental pulp stem cells. Front Bioeng Biotechnol 2023; 11:1254506. [PMID: 38033818 PMCID: PMC10682193 DOI: 10.3389/fbioe.2023.1254506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 10/24/2023] [Indexed: 12/02/2023] Open
Abstract
The use of stem cells for tissue regeneration is a prominent trend in regenerative medicine and tissue engineering. In particular, dental pulp stem cells (DPSCs) have garnered considerable attention. When exposed to specific conditions, DPSCs have the ability to differentiate into osteoblasts and odontoblasts. Scaffolds are critical for cell differentiation because they replicate the 3D microenvironment of the niche and enhance cell adhesion, migration, and differentiation. The purpose of this study is to present the biological responses of human DPSCs to a purified 3D chitin scaffold derived from the marine demosponge Aplysina fistularis and modified with hydroxyapatite (HAp). Responses examined included proliferation, adhesion, and differentiation. The control culture consisted of the human osteoblast cell line, hFOB 1.19. Electron microscopy was used to examine the ultrastructure of the cells (transmission electron microscopy) and the surface of the scaffold (scanning electron microscopy). Cell adhesion to the scaffolds was determined by neutral red and crystal violet staining methods. An alkaline phosphatase (ALP) assay was used for assessing osteoblast/odontoblast differentiation. We evaluated the expression of osteogenic marker genes by performing ddPCR for ALP, RUNX2, and SPP1 mRNA expression levels. The results show that the chitin biomaterial provides a favorable environment for DPSC and hFOB 1.19 cell adhesion and supports both cell proliferation and differentiation. The chitin scaffold, especially with HAp modification, isolated from A. fistularis can make a significant contribution to tissue engineering and regenerative medicine.
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Affiliation(s)
- Anna Zawadzka-Knefel
- Department of Conservative Dentistry with Endodontics, Wroclaw Medical University, Wroclaw, Poland
| | - Agnieszka Rusak
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Monika Mrozowska
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Tomasz Machałowski
- Institute of Chemical Technology and Engineering, Faculty of Chemical Technology, Poznan University of Technology, Poznan, Poland
| | - Andrzej Żak
- Electron Microscopy Laboratory, Faculty of Chemistry, Wroclaw University of Science and Technology, Wroclaw, Poland
| | | | - Michał Kulus
- Division of Ultrastructural Research, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Piotr Kuropka
- Division of Histology and Embryology, Department of Biostructure and Animal Physiology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland
| | - Marzenna Podhorska-Okołów
- Division of Ultrastructural Research, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
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9
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Chen S, Wang Z, Lu H, Yang R, Wu J. Crucial Factors Influencing the Involvement of Odontogenic Exosomes in Dental Pulp Regeneration. Stem Cell Rev Rep 2023; 19:2632-2649. [PMID: 37578647 DOI: 10.1007/s12015-023-10597-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/16/2023] [Indexed: 08/15/2023]
Abstract
Recent progress in exosome based studies has revealed that they possess several advantages over cells, including "cell-free" properties, low immunogenicity and ethical controversy, high biological safety and effective action. These characteristics confer exosomes significant advantages that allow them to overcome the limitations associated with traditional "cell therapy" by circumventing the issues of immune rejection, scarcity of donor cells, heterogeneity, and ethical concerns. Identification of a complete and effective radical treatment for irreversible pulpal disease, a common clinical problem, continues to pose challenges. Although traditional root canal therapy remains the primary clinical treatment, it does not fully restore the physiological functions of pulp. Although stem cell transplantation appears to be a relatively viable treatment strategy for pulp disease, issues such as cell heterogeneity and poor regeneration effects remain problematic. Dental pulp regeneration strategies based on "cell-free" exosome therapies explored by numerous studies appear to have shown significant advantages. In particular, exosomes derived from odontogenic stem cells have demonstrated considerable potential in tooth tissue regeneration engineering, and continue to exhibit superior therapeutic effects compared to non-odontogenic stem cell-derived exosomes. However, only a few studies have comprehensively summarised their research results, particularly regarding the critical factors involved in the process. Therefore, in this study, our purpose was to review the effects exerted by odontogenic exosomes on pulp regeneration and to analyse and discus crucial factors related to this process, thereby providing scholars with a feasible and manageable new concept with respect to regeneration schemes.
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Affiliation(s)
- San Chen
- Department of Endodontics, School of Stomatology/Affiliated Stomatological Hospital, Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Zijie Wang
- Department of Endodontics, School of Stomatology/Affiliated Stomatological Hospital, Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Hongqiao Lu
- Department of Endodontics, School of Stomatology/Affiliated Stomatological Hospital, Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Runze Yang
- Department of Endodontics, School of Stomatology/Affiliated Stomatological Hospital, Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Jiayuan Wu
- Department of Endodontics, School of Stomatology/Affiliated Stomatological Hospital, Zunyi Medical University, Zunyi, 563000, Guizhou, China.
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Atia GAN, Shalaby HK, Ali NG, Morsy SM, Ghobashy MM, Attia HAN, Barai P, Nady N, Kodous AS, Barai HR. New Challenges and Prospective Applications of Three-Dimensional Bioactive Polymeric Hydrogels in Oral and Craniofacial Tissue Engineering: A Narrative Review. Pharmaceuticals (Basel) 2023; 16:702. [PMID: 37242485 PMCID: PMC10224377 DOI: 10.3390/ph16050702] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 04/26/2023] [Accepted: 04/26/2023] [Indexed: 05/28/2023] Open
Abstract
Regenerative medicine, and dentistry offers enormous potential for enhancing treatment results and has been fueled by bioengineering breakthroughs over the previous few decades. Bioengineered tissues and constructing functional structures capable of healing, maintaining, and regenerating damaged tissues and organs have had a broad influence on medicine and dentistry. Approaches for combining bioinspired materials, cells, and therapeutic chemicals are critical in stimulating tissue regeneration or as medicinal systems. Because of its capacity to maintain an unique 3D form, offer physical stability for the cells in produced tissues, and replicate the native tissues, hydrogels have been utilized as one of the most frequent tissue engineering scaffolds during the last twenty years. Hydrogels' high water content can provide an excellent conditions for cell viability as well as an architecture that mimics real tissues, bone, and cartilage. Hydrogels have been used to enable cell immobilization and growth factor application. This paper summarizes the features, structure, synthesis and production methods, uses, new challenges, and future prospects of bioactive polymeric hydrogels in dental and osseous tissue engineering of clinical, exploring, systematical and scientific applications.
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Affiliation(s)
- Gamal Abdel Nasser Atia
- Department of Oral Medicine, Periodontology, and Diagnosis, Faculty of Dentistry, Suez Canal University, Ismailia P.O. Box 41522, Egypt
| | - Hany K. Shalaby
- Department of Oral Medicine, Periodontology and Oral Diagnosis, Faculty of Dentistry, Suez University, Suez P.O. Box 43512, Egypt
| | - Naema Goda Ali
- Department of Oral Medicine, Periodontology, and Diagnosis, Faculty of Dentistry, Suez Canal University, Ismailia P.O. Box 41522, Egypt
| | - Shaimaa Mohammed Morsy
- Department of Oral Medicine, Periodontology, and Diagnosis, Faculty of Dentistry, Suez Canal University, Ismailia P.O. Box 41522, Egypt
| | - Mohamed Mohamady Ghobashy
- Radiation Research of Polymer Chemistry Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo P.O. Box 13759, Egypt
| | - Hager Abdel Nasser Attia
- Department of Molecular Biology and Chemistry, Faculty of Science, Alexandria University, Alexandria P.O. Box 21526, Egypt
| | - Paritosh Barai
- Department of Biochemistry and Molecular Biology, Primeasia University, Dhaka 1213, Bangladesh
| | - Norhan Nady
- Polymeric Materials Research Department, Advanced Technology and New Materials Research Institute (ATNMRI), City of Scientific Research and Technological Applications (SRTA-City), New Borg Elarab, Alexandria P.O. Box 21934, Egypt
| | - Ahmad S. Kodous
- Department of Radiation Biology, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority (EAEA), Cairo P.O. Box 13759, Egypt
| | - Hasi Rani Barai
- Department of Mechanical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea
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Jajoo SS, Chaudhary SM, Patil K, Kunte S, Lakade L, Jagtap C. A Systematic Review on Polyester Scaffolds in Dental Three-dimensional Cell Printing: Transferring Art from the Laboratories to the Clinics. Int J Clin Pediatr Dent 2023; 16:494-498. [PMID: 37496946 PMCID: PMC10367294 DOI: 10.5005/jp-journals-10005-2609] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/28/2023] Open
Abstract
Objective The purpose of this systematic review is to describe developments in three-dimensional (3D) cell printing in the formation of dental pulp tissue using polyester as a scaffold to revitalize the damaged dental pulp tissue. Materials and methods A literature search for all the data published in PubMed and Google Scholar from January 2000 to April 2022 was conducted. Articles with the keywords 3D cell printing, scaffolds, polyester, dental pulp, and dentistry were used. Inclusion criteria consisted of any publication in electronic or print media directly studying or commenting on the use of polyester scaffolds in 3D cell printing technology in the regeneration of dental pulp. A total of 528 articles were selected, of which 27 duplicates and 286 irrelevant articles were discarded. A total of 215 articles were finally included in the systematic review. Result and conclusion For dental pulp regeneration, several scaffolds have been discovered to be appealing. Polylactic acid (PLA), polyglycolic acid (PGA), and their copolymers are nontoxic and biocompatible synthetic polyesters that degrade by hydrolysis and have received Food and Drug Administration (FDA) approval for a variety of applications. This review paper is intended to spark new ideas for using a certain scaffold in a specific regenerative approach to produce the desired pulp-dentin complex.
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Affiliation(s)
- Sakshi S Jajoo
- Department of Pedodontics, Dental College and Hospital, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India
| | - Shweta M Chaudhary
- Department of Pedodontics, Dental College and Hospital, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India
| | - Krishna Patil
- Department of Pedodontics, Dental College and Hospital, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India
| | - Sanket Kunte
- Department of Pedodontics, Dental College and Hospital, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India
| | - Laxmi Lakade
- Department of Pedodontics, Dental College and Hospital, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India
| | - Chetana Jagtap
- Department of Pedodontics, Dental College and Hospital, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India
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Arias Z, Nizami MZI, Chen X, Chai X, Xu B, Kuang C, Omori K, Takashiba S. Recent Advances in Apical Periodontitis Treatment: A Narrative Review. Bioengineering (Basel) 2023; 10:bioengineering10040488. [PMID: 37106675 PMCID: PMC10136087 DOI: 10.3390/bioengineering10040488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 04/07/2023] [Accepted: 04/15/2023] [Indexed: 04/29/2023] Open
Abstract
Apical periodontitis is an inflammatory response caused by pulp infection. It induces bone resorption in the apical and periapical regions of the tooth. The most conservative approach to treat this condition is nonsurgical endodontic treatment. However, clinical failure has been reported with this approach; thus, alternative procedures are required. This review highlights recent literature regarding advanced approaches for the treatment of apical periodontitis. Various therapies, including biological medications, antioxidants, specialized pro-resolving lipid mediators, and stem cell therapy, have been tested to increase the success rate of treatment for apical periodontitis. Some of these approaches remain in the in vivo phase of research, while others have just entered the translational research phase to validate clinical application. However, a detailed understanding of the molecular mechanisms that occur during development of the immunoinflammatory reaction in apical periodontitis remains unclear. The aim of this review was to summarize advanced approaches for the treatment of apical periodontitis. Further research can confirm the potential of these alternative nonsurgical endodontic treatment approaches.
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Affiliation(s)
- Zulema Arias
- Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Mohammed Zahedul Islam Nizami
- Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong, Prince Philip Dental Hospital, 34 Hospital Road, Sai Ying Pun, Hong Kong SAR 999077, China
| | - Xiaoting Chen
- Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Xinyi Chai
- Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Bin Xu
- Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Canyan Kuang
- Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Kazuhiro Omori
- Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Shogo Takashiba
- Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
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13
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Ganesh V, Seol D, Gomez-Contreras PC, Keen HL, Shin K, Martin JA. Exosome-Based Cell Homing and Angiogenic Differentiation for Dental Pulp Regeneration. Int J Mol Sci 2022; 24:466. [PMID: 36613910 PMCID: PMC9820194 DOI: 10.3390/ijms24010466] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 12/21/2022] [Accepted: 12/24/2022] [Indexed: 12/29/2022] Open
Abstract
Exosomes have attracted attention due to their ability to promote intercellular communication leading to enhanced cell recruitment, lineage-specific differentiation, and tissue regeneration. The object of this study was to determine the effect of exosomes on cell homing and angiogenic differentiation for pulp regeneration. Exosomes (DPSC-Exos) were isolated from rabbit dental pulp stem cells cultured under a growth (Exo-G) or angiogenic differentiation (Exo-A) condition. The characterization of exosomes was confirmed by nanoparticle tracking analysis and an antibody array. DPSC-Exos significantly promoted cell proliferation and migration when treated with 5 × 108/mL exosomes. In gene expression analysis, DPSC-Exos enhanced the expression of angiogenic markers including vascular endothelial growth factor A (VEGFA), Fms-related tyrosine kinase 1 (FLT1), and platelet and endothelial cell adhesion molecule 1 (PECAM1). Moreover, we identified key exosomal microRNAs in Exo-A for cell homing and angiogenesis. In conclusion, the exosome-based cell homing and angiogenic differentiation strategy has significant therapeutic potential for pulp regeneration.
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Affiliation(s)
- Venkateswaran Ganesh
- Department of Orthopedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USA
- Department of Roy J. Carver Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA
| | - Dongrim Seol
- Department of Orthopedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USA
- Department of Orthodontics, University of Iowa, Iowa City, IA 52242, USA
| | | | - Henry L. Keen
- Iowa Institute of Human Genetics, University of Iowa, Iowa City, IA 52242, USA
| | - Kyungsup Shin
- Department of Orthodontics, University of Iowa, Iowa City, IA 52242, USA
| | - James A. Martin
- Department of Orthopedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USA
- Department of Roy J. Carver Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA
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14
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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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15
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Louvrier A, Kroemer M, Terranova L, Meyer F, Tissot M, Euvrard E, Gindraux F, Meyer C, Rolin G. Development of a biomimetic bioreactor for regenerative endodontics research. J Tissue Eng Regen Med 2022; 16:998-1007. [PMID: 36005295 DOI: 10.1002/term.3346] [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: 02/17/2022] [Revised: 06/02/2022] [Accepted: 07/26/2022] [Indexed: 12/15/2022]
Abstract
In the context of regenerative endodontics research with the development of biomaterials, this work aimed to develop and test a prototype biomimetic bioreactor of a human tooth. The bioreactor was designed to reproduce a shaped dental canal connected with a cavity reproducing the periapical region and irrigated through two fluidic channels intended to reproduce the apical residual vascular supply. A test biomaterial composed of polylactic acid/polycaprolactone-tannic acid (PLA/PCL-TA) was produced by electrospinning/electrospraying and calibrated to be inserted in a dental canal. This biomaterial was first used to evaluate its imbibition capacity and the oximetry inside the bioreactor. Then, Dental Pulp Stem Cells (DPSCs) were cultured on PLA/PCL-TA cones for 1-3 weeks in the bioreactor; afterward cell adhesion, proliferation, and migration were histologically assessed. Complete imbibition biomaterial was obtained in 10 min and oximetry was stable over time. In the bioreactor, DPSCs were able to adhere, proliferate and migrate onto the surface and inside the biomaterial. In conclusion, this bioreactor was used successfully to test a biomaterial intended to support pulp regeneration and constitutes a new in vitro experimental model closer to clinical reality.
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Affiliation(s)
- Aurélien Louvrier
- Chirurgie Maxillo-Faciale, Stomatologie et Odontologie Hospitalière, CHU Besançon, Besançon, France.,University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France
| | - Marie Kroemer
- University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France.,Pharmacie Centrale, CHU Besançon, Besançon, France
| | - Lisa Terranova
- Université de Strasbourg, INSERM, UMR_S 1121 Biomatériaux et Bioingénierie, FMTS, Strasbourg, France
| | - Florent Meyer
- Université de Strasbourg, INSERM, UMR_S 1121 Biomatériaux et Bioingénierie, FMTS, Strasbourg, France
| | - Marion Tissot
- University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France
| | - Edouard Euvrard
- Chirurgie Maxillo-Faciale, Stomatologie et Odontologie Hospitalière, CHU Besançon, Besançon, France.,University Bourgogne Franche-Comté, Laboratoire Nano Médecine, Imagerie, Thérapeutique, Besançon, France
| | - Florelle Gindraux
- University Bourgogne Franche-Comté, Laboratoire Nano Médecine, Imagerie, Thérapeutique, Besançon, France
| | - Christophe Meyer
- Chirurgie Maxillo-Faciale, Stomatologie et Odontologie Hospitalière, CHU Besançon, Besançon, France.,University Bourgogne Franche-Comté, Laboratoire Nano Médecine, Imagerie, Thérapeutique, Besançon, France
| | - Gwenaël Rolin
- University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France.,INSERM CIC-1431, CHU Besançon, Besançon, France
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16
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Bang JY, Youn KE, Kim RH, Song M. Effect of the amnion-chorion or collagen membrane as a matrix on the microenvironment during a regenerative endodontic procedure. J Endod 2022; 48:1285-1293.e2. [PMID: 35850299 DOI: 10.1016/j.joen.2022.07.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 06/13/2022] [Accepted: 07/06/2022] [Indexed: 12/29/2022]
Abstract
INTRODUCTION During regenerative endodontic procedures, the microenvironment of the canal is formed by the degree of disinfection and release of ions from the applied materials onto the top surface. This study aimed to characterize the effects of amnion-chorion membrane (ACM) and collagen membrane (CM) on pulp-dentin regeneration compared to calcium silicate cements (CSCs), focusing on cell migration, mineralization potential, anti-inflammation, and angiogenesis. METHODS Two CSCs and two membranes were used: ProRoot® MTA (PM; Dentsply, Tulsa, OK, USA), RetroMTA® (RM; BioMTA, Seoul, Korea), Collagen Membrane® (CM; Genoss, Suwon, Korea), and BioXclude® (ACM; Snoasis Medical, Colorado, USA). Transwell and scratch assays were used to evaluate cell migration and wound healing. Mineralization potential was evaluated using alkaline phosphatase (ALP) activity, alizarin red S staining, and quantitative real-time-polymerase chain reaction (qRT-PCR) for the expression of marker genes. qRT-PCR was used to measure the levels of angiogenic genes and inflammatory mediators. An endothelial tube formation assay was used to assess angiogenesis. RESULTS The membranes showed superior migration and wound healing compared with CSCs. Except for RM, PM and the two membranes showed high ALP activity and mineralization nodule formation and upregulated mRNA expression of markers for mineralization. Membranes upregulated the mRNA of angiogenesis genes and increased the capillary tube formation of endothelial cells compared to CSCs. Furthermore, the membrane matrix decreased the expression of inflammatory genes. CONCLUSIONS CM and ACM showed prominent cell migration, angiogenesis, and healing effects against inflammation, as well as comparable mineralization potential compared to CSCs, recommending the use of membrane as a matrix.
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Affiliation(s)
- Ji Young Bang
- Department of Conservative Dentistry, College of Dentistry, Dankook University, Cheonan, Korea
| | - Kyeong Eun Youn
- Department of Conservative Dentistry, College of Dentistry, Dankook University, Cheonan, Korea
| | - Reuben H Kim
- The Shapiro Family Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, CA, USA; Section of Restorative Dentistry, UCLA School of Dentistry, Los Angeles, CA, USA
| | - Minju Song
- Department of Conservative Dentistry, College of Dentistry, Dankook University, Cheonan, Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Korea.
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17
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Kwack KH, Lee HW. Clinical Potential of Dental Pulp Stem Cells in Pulp Regeneration: Current Endodontic Progress and Future Perspectives. Front Cell Dev Biol 2022; 10:857066. [PMID: 35478967 PMCID: PMC9035692 DOI: 10.3389/fcell.2022.857066] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 03/18/2022] [Indexed: 12/12/2022] Open
Abstract
Dental caries is a common disease that not only destroys the rigid structure of the teeth but also causes pulp necrosis in severe cases. Once pulp necrosis has occurred, the most common treatment is to remove the damaged pulp tissue, leading to a loss of tooth vitality and increased tooth fragility. Dental pulp stem cells (DPSCs) isolated from pulp tissue exhibit mesenchymal stem cell-like characteristics and are considered ideal candidates for regenerating damaged dental pulp tissue owing to their multipotency, high proliferation rate, and viability after cryopreservation. Importantly, DPSCs do not elicit an allogeneic immune response because they are non-immunogenic and exhibit potent immunosuppressive properties. Here, we provide an up-to-date review of the clinical applicability and potential of DPSCs, as well as emerging trends in the regeneration of damaged pulp tissue. In addition, we suggest the possibility of using DPSCs as a resource for allogeneic transplantation and provide a perspective for their clinical application in pulp regeneration.
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Affiliation(s)
- Kyu Hwan Kwack
- Department of Dentistry, Graduate School, Kyung Hee University, Seoul, South Korea
| | - Hyeon-Woo Lee
- Department of Pharmacology, School of Dentistry, Graduate School, Institute of Oral Biology, Kyung Hee University, Seoul, South Korea
- *Correspondence: Hyeon-Woo Lee,
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18
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Cell-Based Transplantation versus Cell Homing Approaches for Pulp-Dentin Complex Regeneration. Stem Cells Int 2021; 2021:8483668. [PMID: 34646323 PMCID: PMC8505125 DOI: 10.1155/2021/8483668] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 08/01/2021] [Accepted: 08/19/2021] [Indexed: 12/19/2022] Open
Abstract
Regenerative dentistry has paved the way for a new era for the replacement of damaged dental tissues. Whether the causative factor is dental caries, trauma, or chemical insult, the loss of the pulp vitality constitutes one of the major health problems worldwide. Two regenerative therapies were introduced for a fully functional pulp-dentin complex regeneration, namely, cell-based (cell transplantation) and cell homing (through revascularization or homing by injection of stem cells in situ or intravenously) therapies, with each demonstrating advantages as well as drawbacks, especially in clinical application. The present review is aimed at elaborating on these two techniques in the treatment of irreversibly inflamed or necrotic pulp, which is aimed at regenerating a fully functional pulp-dentin complex.
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19
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Liang Y, Ma R, Chen L, Dai X, Zuo S, Jiang W, Hu N, Deng Z, Zhao W. Efficacy of i-PRF in regenerative endodontics therapy for mature permanent teeth with pulp necrosis: study protocol for a multicentre randomised controlled trial. Trials 2021; 22:436. [PMID: 34229752 PMCID: PMC8261915 DOI: 10.1186/s13063-021-05401-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 06/25/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Dental pulp necrosis, a common health problem, is traditionally treated with root canal therapy; however, it fails in restoring the vitality of damaged pulp. Most studies regarding regenerative endodontic therapy (RET) are limited to the treatment of immature necrotic teeth. Given that injectable platelet-rich fibrin (i-PRF) has shown great potential in regenerative medicine as a novel platelet concentration, this study is designed to explore whether i-PRF can serve as a biological scaffold, extending the indications for RET and improving the clinical feasibility of RET in mature permanent teeth with pulp necrosis. METHODS This is a randomised, double-blind, controlled, multicentre clinical trial designed to evaluate the clinical feasibility of RET for mature permanent teeth with pulp necrosis and to compare the efficacy of i-PRF and blood clots as scaffolds in RET. A total of 346 patients will be recruited from three centres and randomised at an allocation ratio of 1:1 to receive RET with either a blood clot or i-PRF. The changes in subjective symptoms, clinical examinations, and imaging examinations will be tracked longitudinally for a period of 24 months. The primary outcome is the success rate of RET after 24 months. The secondary outcome is the change in pulp vitality measured via thermal and electric pulp tests. In addition, the incidence of adverse events such as discolouration, reinfection, and root resorption will be recorded for a safety evaluation. DISCUSSION This study will evaluate the clinical feasibility of RET in mature permanent teeth with pulp necrosis, providing information regarding the efficacy, benefits, and safety of RET with i-PRF. These results may contribute to changes in the treatment of pulp necrosis in mature permanent teeth and reveal the potential of i-PRF as a novel biological scaffold for RET. TRIAL REGISTRATION ClinicalTrials.gov NCT04313010 . Registered on 19 March 2020.
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Affiliation(s)
- Yuee Liang
- Department of Stomatology, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Avenue North, Guangzhou, 510515, China
| | - Rongyang Ma
- Department of Stomatology, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Avenue North, Guangzhou, 510515, China
| | - Lijuan Chen
- Department of Stomatology, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Avenue North, Guangzhou, 510515, China
| | - Xingzhu Dai
- Department of Stomatology, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Avenue North, Guangzhou, 510515, China
| | - Shiya Zuo
- Department of Stomatology, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Avenue North, Guangzhou, 510515, China
| | - Weiyi Jiang
- Department of Stomatology, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Avenue North, Guangzhou, 510515, China
| | - Naiming Hu
- Department of Stomatology, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Avenue North, Guangzhou, 510515, China
| | - Zilong Deng
- Department of Stomatology, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Avenue North, Guangzhou, 510515, China.
| | - Wanghong Zhao
- Department of Stomatology, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Avenue North, Guangzhou, 510515, China.
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20
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Sevari SP, Ansari S, Moshaverinia A. A narrative overview of utilizing biomaterials to recapitulate the salient regenerative features of dental-derived mesenchymal stem cells. Int J Oral Sci 2021; 13:22. [PMID: 34193832 PMCID: PMC8245503 DOI: 10.1038/s41368-021-00126-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 05/26/2021] [Accepted: 06/03/2021] [Indexed: 02/06/2023] Open
Abstract
Tissue engineering approaches have emerged recently to circumvent many limitations associated with current clinical practices. This elegant approach utilizes a natural/synthetic biomaterial with optimized physiomechanical properties to serve as a vehicle for delivery of exogenous stem cells and bioactive factors or induce local recruitment of endogenous cells for in situ tissue regeneration. Inspired by the natural microenvironment, biomaterials could act as a biomimetic three-dimensional (3D) structure to help the cells establish their natural interactions. Such a strategy should not only employ a biocompatible biomaterial to induce new tissue formation but also benefit from an easily accessible and abundant source of stem cells with potent tissue regenerative potential. The human teeth and oral cavity harbor various populations of mesenchymal stem cells (MSCs) with self-renewing and multilineage differentiation capabilities. In the current review article, we seek to highlight recent progress and future opportunities in dental MSC-mediated therapeutic strategies for tissue regeneration using two possible approaches, cell transplantation and cell homing. Altogether, this paper develops a general picture of current innovative strategies to employ dental-derived MSCs combined with biomaterials and bioactive factors for regenerating the lost or defective tissues and offers information regarding the available scientific data and possible applications.
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Affiliation(s)
- Sevda Pouraghaei Sevari
- Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA
| | - Sahar Ansari
- Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA
| | - Alireza Moshaverinia
- Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
- California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.
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21
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Kim SG. A Cell-Based Approach to Dental Pulp Regeneration Using Mesenchymal Stem Cells: A Scoping Review. Int J Mol Sci 2021; 22:4357. [PMID: 33921924 PMCID: PMC8122243 DOI: 10.3390/ijms22094357] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/18/2021] [Accepted: 04/20/2021] [Indexed: 02/07/2023] Open
Abstract
Despite the recent explosion of investigations on dental pulp regeneration using various tissue engineering strategies, the translation of the findings from such studies into therapeutic applications has not been properly achieved. The purpose of this scoping review was to systematically review the efficacy of mesenchymal stem cell transplantation for dental pulp regeneration. A literature search was conducted using five electronic databases from their inception to January 2021 and supplemented by hand searches. A total of 17 studies, including two clinical trials and 15 animal studies using orthotopic pulp regeneration models, were included for the review. The risk of bias for the individual studies was assessed. This scoping review demonstrated that the regeneration of vascularized pulp-like tissue was achieved using the stem cell transplantation strategy in animal models. Autologous cell transplantation in two clinical studies also successfully regenerated vascularized vital tissue. Dental pulp stem cell subpopulations, such as mobilized dental pulp stem cells, injectable scaffolds such as atelocollagen, and a granulocyte-colony forming factor, were the most commonly used for pulp regeneration. The overall risk of bias was unclear for animal studies and was moderate or judged to raise some concerns for clinical studies. More high-quality clinical studies are needed to further determine the safety and efficacy of the stem cell transplantation strategy for dental pulp regeneration.
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Affiliation(s)
- Sahng G Kim
- Division of Endodontics, Columbia University College of Dental Medicine, New York, NY 10032, USA
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22
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Kim SG, Solomon CS. Regenerative Endodontic Therapy in Mature Teeth Using Human-Derived Composite Amnion-Chorion Membrane as a Bioactive Scaffold: A Pilot Animal Investigation. J Endod 2021; 47:1101-1109. [PMID: 33887306 DOI: 10.1016/j.joen.2021.04.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/03/2021] [Accepted: 04/09/2021] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Human-derived composite amnion-chorion membrane (ACM) has been used for various regenerative treatments. The aim of this pilot study was to investigate the effectiveness of the ACM as a scaffold for pulp regeneration in mature canine teeth. METHODS A total of 24 roots from mature premolars in dogs were included for regenerative procedures using blood clots (BC) (group 1, n = 8), collagen membrane (CM) (group 2, n = 8), and ACM (group 3, n = 8). Each tooth was left open through a buccal access to induce root canal infection and inflammation. The root canals were disinfected with 1.5% NaOCl and calcium hydroxide intracanal medicament. After 2 weeks, bleeding was evoked to induce blood clot formation (group 1) or before the placement of the membranes (groups 2 and 3). After 12 weeks, the animals were euthanized for histologic assessment. The histologic data including intracanal fibrous connective tissue, odontoblast-like cell lining, intracanal mineralized tissue, periapical inflammation, and apical closure were qualitatively and quantitively analyzed. RESULTS Histologic analysis revealed that intracanal fibrous connective tissue was identified in all groups, but a higher volume of the fibrous tissues was formed in the ACM group. Odontoblast-like cells were only observed in the ACM group. The intracanal mineralized tissue was observed only in the BC and CM groups. The BC group showed more periapical inflammation than the ACM group (P < .05). Apical closure was more often found in the CM group than the BC group (P < .05). CONCLUSIONS More intracanal fibrous tissue and odontoblast-like cell lining, and less periapical inflammation were observed after regenerative endodontic treatment in mature teeth using the ACM than blood clot alone or blood clot with collagen membrane. The use of the ACM may be useful for a cell-homing-based pulp regeneration in mature teeth.
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Affiliation(s)
- Sahng G Kim
- Division of Endodontics, Columbia University, College of Dental Medicine, New York, New York.
| | - Charles S Solomon
- Division of Endodontics, Columbia University, College of Dental Medicine, New York, New York
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23
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Bekhouche M, Bolon M, Charriaud F, Lamrayah M, Da Costa D, Primard C, Costantini A, Pasdeloup M, Gobert S, Mallein-Gerin F, Verrier B, Ducret M, Farges JC. Development of an antibacterial nanocomposite hydrogel for human dental pulp engineering. J Mater Chem B 2021; 8:8422-8432. [PMID: 32804177 DOI: 10.1039/d0tb00989j] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Hydrogel-based regenerative endodontic procedures (REPs) are considered to be very promising therapeutic strategies to reconstruct the dental pulp (DP) tissue in devitalized human teeth. However, the success of the regeneration process is limited by residual bacteria that may persist in the endodontic space after the disinfection step and contaminate the biomaterial. The aim of this work was to develop an innovative fibrin hydrogel incorporating clindamycin (CLIN)-loaded Poly (d,l) Lactic Acid (PLA) nanoparticles (NPs) to provide the hydrogel with antibacterial properties. CLIN-PLA-NPs were synthesized by a surfactant-free nanoprecipitation method and their microphysical properties were assessed by dynamic light scattering, electrophoretic mobility and scanning electron microscopy. Their antimicrobial efficacy was evaluated on Enteroccocus fæcalis by the determination of the minimal inhibitory concentration (MIC) and the minimal biofilm inhibition and eradication concentrations (MBIC and MBEC). Antibacterial properties of the nanocomposite hydrogel were verified by agar diffusion assays. NP distribution into the hydrogel and release from it were evaluated using fluorescent PLA-NPs. NP cytotoxicity was assessed on DP mesenchymal stem cells (DP-MSCs) incorporated into the hydrogel. Type I collagen synthesis was investigated after 7 days of culture by immunohistochemistry. We found that CLIN-PLA-NPs displayed a drug loading of 10 ± 2 μg per mg of PLA polymer and an entrapment efficiency of 43 ± 7%. Antibiotic loading did not affect NP size, polydispersity index and zeta potential. The MIC for Enterococcus fæcalis was 32 μg mL-1. MBIC50 and MBEC50 were 4 and 16 μg mL-1, respectively. CLIN-PLA-NPs appeared homogenously distributed throughout the hydrogel. CLIN-PLA-NP-loaded hydrogels clearly inhibited E. faecalis growth. DP-MSC viability and type I collagen synthesis within the fibrin hydrogel were not affected by CLIN-PLA-NPs. In conclusion, CLIN-PLA-NP incorporation into the fibrin hydrogel gave the latter antibacterial and antibiofilm properties without affecting cell viability and function. This formulation could help establish an aseptic environment supporting DP reconstruction and, accordingly, might be a valuable tool for REPs.
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Affiliation(s)
- M Bekhouche
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France and Faculté d'Odontologie, Université de Lyon, Université Lyon 1, Lyon, France
| | - M Bolon
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France
| | - F Charriaud
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France
| | - M Lamrayah
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France
| | - D Da Costa
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France and Adjuvatis®, Lyon, France
| | | | - A Costantini
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France
| | - M Pasdeloup
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France
| | - S Gobert
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France
| | - F Mallein-Gerin
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France
| | - B Verrier
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France
| | - M Ducret
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France and Faculté d'Odontologie, Université de Lyon, Université Lyon 1, Lyon, France and Hospices Civils de Lyon, Service de Consultations et Traitements Dentaires, Lyon, France
| | - J-C Farges
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France and Faculté d'Odontologie, Université de Lyon, Université Lyon 1, Lyon, France and Hospices Civils de Lyon, Service de Consultations et Traitements Dentaires, Lyon, France
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Singh H, Rathee K, Kaur A, Miglani N. Pulp Regeneration in an Immature Maxillary Central Incisor Using Hyaluronic Acid Hydrogel. Contemp Clin Dent 2021; 12:94-98. [PMID: 33967547 PMCID: PMC8092086 DOI: 10.4103/ccd.ccd_149_20] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 06/18/2020] [Accepted: 07/18/2020] [Indexed: 11/21/2022] Open
Abstract
Pulp regenerative procedure is one of the treatment options for endodontically involved immature permanent teeth. The regenerative endodontic procedure was performed in a child of 9 years. After thorough canal disinfection using triple antibiotic paste for 21 days, bleeding was induced from the apex to provide for the stem cells. After that hyaluronic acid (HA) hydrogel was introduced into the canal space to act as injectable scaffold for pulp regeneration. This was followed by mineral trioxide aggregate placement to provide tight seal from the coronal aspect. Later, the tooth was restored with composite restoration. This approach offers the clinicians great opportunity to physiologically strengthen the immature root walls. The present report presents a regenerative endodontic procedure with HA hydrogel for a traumatized central incisor with arrested root development. The continued root development in the present case suggests that this treatment option may be able to resume the root maturation process in immature teeth with open apices.
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Affiliation(s)
- Harveen Singh
- Department of Periodontics, Genesis Institute of Dental Sciences and Research, Ferozepur, Punjab, India
| | - Kirti Rathee
- Department of Conservative and Endodontics, Inderprastha Dental College and Hospital, Ghaziabad, Uttar Pradesh, India
| | - Amandeep Kaur
- Department of Periodontics, Maharaja Ganga Singh Dental College and Research Centre, Sri Ganganagar, Rajasthan, India
| | - Neha Miglani
- Demonstrator, J.N. Kapoor DAV Centenary Dental College, Yamunanagar, Haryana, India
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25
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Sismanoglu S, Ercal P. Dentin-Pulp Tissue Regeneration Approaches in Dentistry: An Overview and Current Trends. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1298:79-103. [PMID: 32902726 DOI: 10.1007/5584_2020_578] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Conventional treatment approaches in irreversible pulpitis and apical periodontitis include the disinfection of the pulp space followed by filling with various materials, which is commonly known as the root canal treatment. Disadvantages including the loss of tooth vitality and defense mechanism against carious lesions, susceptibility to fractures, discoloration and microleakage led to the development of regenerative therapies for the dentin pulp-complex. The goal of dentin-pulp tissue regeneration is to reestablish the physiological pulp function such as pulp sensibility, pulp repair capability by mineralization and pulp immunity. Recent dentin-pulp tissue regeneration approaches can be divided into cell homing and cell transplantation. Cell based approaches include a suitable scaffold for the delivery of potent stem cells with or without bioactive molecules into the root canal system while cell homing is based on the recruitment of host endogenous stem cells from the resident tissue including periapical region or dental pulp. This review discusses the recent treatment modalities in dentin-pulp tissue regeneration through tissue engineering and current challenges and trends in this field of research.
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Affiliation(s)
- Soner Sismanoglu
- Department of Restorative Dentistry, Faculty of Dentistry, Altinbas University, Istanbul, Turkey
| | - Pınar Ercal
- Department of Oral Surgery, Faculty of Dentistry, Altinbas University, Istanbul, Turkey.
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Abdel Hafiz Abdel Rahim AS, Abdelgawad F, Abd Alsamed AM, Moheb DM, Wahab El-Dokky NA. Case Report: Single visit photo-activated disinfection in regenerative endodontics. F1000Res 2020; 8:1519. [PMID: 32934793 PMCID: PMC7475962 DOI: 10.12688/f1000research.20118.2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/07/2020] [Indexed: 01/05/2023] Open
Abstract
Background: Root canal disinfection is considered critical for achieving successful regenerative endodontic procedures. Photo-activated disinfection is a novel disinfection method that can help to achieve the goal of regenerative endodontics. This article reports the clinical and radiographic results after single visit regenerative endodontics using photo-activated disinfection. Methods: An 8.5-year-old girl complained of fractured upper right central incisor. Pulp necrosis was diagnosed on the basis of clinical findings. The root canal was irrigated with sodium hypochlorite solution (1.5%) followed by saline. Then, the canal was dried with paper points. A combination of a photosensitizer solution and low power laser light were applied. EDTA solution was used as a final irrigant. Bleeding was induced, followed by placement of collagen resorbable matrix and white mineral trioxide aggregate. Two days later, the tooth was sealed and restored with permanent filling. Results: Clinical findings revealed no pain on percussion or palpation tests. Radiographic examination revealed an increase in root length, an increase of apical root thickness and apical closure at the 12-month follow-up period. Conclusion: Regenerative endodontics using photo-activated disinfection achieved successful outcomes in the necrotic immature permanent tooth.
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Affiliation(s)
| | - Fatma Abdelgawad
- Pediatric Dentistry and Dental Public Health Department, Faculty of Dentistry, Cairo University, Cairo, 11553, Egypt
| | - Ahmed M Abd Alsamed
- Oral and Maxillofacial Radiology Department, Faculty of Dentistry, Cairo University, Cairo, 11553, Egypt
| | - Dalia Mohamed Moheb
- Pediatric Dentistry and Dental Public Health Department, Faculty of Dentistry, Cairo University, Cairo, 11553, Egypt
| | - Norhan Abdel Wahab El-Dokky
- Pediatric Dentistry and Dental Public Health Department, Faculty of Dentistry, Cairo University, Cairo, 11553, Egypt
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27
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Ayoub S, Cheayto A, Bassam S, Najar M, Berbéri A, Fayyad-Kazan M. The Effects of Intracanal Irrigants and Medicaments on Dental-Derived Stem Cells Fate in Regenerative Endodontics: An update. Stem Cell Rev Rep 2020; 16:650-660. [PMID: 32394343 DOI: 10.1007/s12015-020-09982-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Regenerative endodontics is a biologically based treatment designed for immature permanent teeth with necrotic pulp to replace dentin and root structures, as well as dental pulp cells. This procedure has become a part of novel modality in endodontics therapeutic manner, and it is considered as an alternative to apexification. In the last decade, numerous case reports, which describe this procedure, have been published. This therapeutic approach succeeded due to its lower financial cost and ease of performance. Although the clinical protocol of this procedure is not standardized and the effects of irrigants and medicaments on dental stem cells fate remain somewhat ambiguous, however when successful, it is an improvement of endodontics treatment protocols which leads to continued root development, increased dentinal wall thickness, and apical closure of immature teeth. To ensure a successful regenerative procedure, it is essential to investigate the appropriate disinfection protocols and the use of biocompatible molecules in order to control the release of growth factors and the differentiation of stem cells. This is the first review in the literature to summarize the present knowledge regarding the effect of intracanal irrigants and medicaments on the dental derived stem cells fate in regenerative endodontic procedures.
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Affiliation(s)
- Sara Ayoub
- Department of Prosthodontics, Faculty of Dental Medicine, Lebanese University, Hadath, Beirut, Lebanon
| | - Ali Cheayto
- Department of Restorative Dentistry and Endodontics, Faculty of Dental Medicine, Lebanese University, Hadath, Beirut, Lebanon
| | - Sanaa Bassam
- Department of Restorative Dentistry and Endodontics, Faculty of Dental Medicine, Lebanese University, Hadath, Beirut, Lebanon
| | - Mehdi Najar
- Genetics and Immune Cell Therapy Unit, Faculty of Sciences, University Mohammed Premier, Oujda, Morocco
- Osteoarthritis Research Unit, Department of Medicine, Research Center (CRCHUM), University of Montreal Hospital, University of Montreal, Montreal, QC, Canada
| | - Antoine Berbéri
- Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, Lebanese University, Hadath, Beirut, Lebanon
| | - Mohammad Fayyad-Kazan
- Laboratory of Cancer biology and Molecular Immunology, Faculty of Sciences-I, Lebanese University, Hadath, Beirut, Lebanon.
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon.
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Jang JH, Moon JH, Kim SG, Kim SY. Pulp regeneration with hemostatic matrices as a scaffold in an immature tooth minipig model. Sci Rep 2020; 10:12536. [PMID: 32719323 PMCID: PMC7385085 DOI: 10.1038/s41598-020-69437-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 07/07/2020] [Indexed: 12/19/2022] Open
Abstract
Control of blood clotting in root canal systems is one of the most critical and difficult concerns for regenerative endodontics therapy (RET). The purpose of this study was to investigate the effects of using gelatin- and fibrin-based hemostatic hydrogels as a scaffold on pulp regeneration in a minipig model. Cell viability of human dental pulp stem cells cultured three-dimensionally in gelatin-based and fibrin-based scaffolds was evaluated by MTT and live/dead assay. RET was performed on 24 immature premolars with an autologous blood clot (PC), gelatin-based and fibrin-based hemostatic matrices (GM and FM), or without the insertion of a scaffold (NC). The follow-up period was 12 weeks. Radiographic and histologic assessments for pulp regeneration were performed. Gelatin-based scaffolds exhibited significantly higher cell viability than fibrin-based scaffolds after 15 days (P < 0.05). The PC and GM groups showed favorable root development without inflammation and newly mineralized tissue deposited in the root canal system, while FM group presented inflammatory changes with the continuation of root development. The NC group exhibited internal root resorption with periapical lesions. The application of GM in RET led to favorable clinical outcomes of root development without inflammatory changes compared to conventional RET. Our results suggest that GM may serve as a viable regenerative scaffold for pulp regeneration.
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Affiliation(s)
- Ji-Hyun Jang
- Department of Conservative Dentistry, School of Dentistry, Kyung Hee University, Seoul, Korea
| | - Joung-Ho Moon
- Department of Conservative Dentistry and Dental Research Institute, School of Dentistry, Seoul National University, 101 Daehakno, Jongno-gu, Seoul, 03080, Korea
| | - Sahng Gyoon Kim
- Division of Endodontics, College of Dental Medicine, Columbia University, New York, NY, USA.
| | - Sun-Young Kim
- Department of Conservative Dentistry and Dental Research Institute, School of Dentistry, Seoul National University, 101 Daehakno, Jongno-gu, Seoul, 03080, Korea.
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Wen R, Wang X, Lu Y, Du Y, Yu X. The combined application of rat bone marrow mesenchymal stem cells and bioceramic materials in the regeneration of dental pulp-like tissues. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2020; 13:1492-1499. [PMID: 32782667 PMCID: PMC7414504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 06/03/2020] [Indexed: 06/11/2023]
Abstract
This study aims to observe the effects of the combined application of rat bone marrow mesenchymal stem cells (rBMSCs) and a bioceramic material on pulp-like tissue formation. Rat incisor root fragments without pulp tissues were prepared and filled with a collagen scaffold seeded with rBMSCs, while one side of the root segment was covered by a bioceramic material (iRoot BP). After they were cultured for 12 hours, the root fragments were implanted subcutaneously for 3 months. Hematoxylin and eosin (HE) staining was applied to observe the biocompatibility and the formation of pulp-like tissues. The incisor root fragments were divided into three parts (BP1/3, M1/3, and D1/3) to analyze the areas and the number of new vessels. Immunohistochemical staining of the neuroendocrine marker PGP9.5, the dentin sialophosphoprotein (DSPP), and the vascular endothelial growth factor (VEGF) was applied to observe the formation of the pulp-like tissues. Root fragments filled with only the collagen scaffold were used as a control. Three months after the implantation, the root fragments were collected, and they were surrounded by a transparent tissue membrane with a good blood supply. The root fragment cavity was filled with pink vascularized pulp-like tissue. According to the HE results, iRoot BP had good biocompatibility with the new pulp-like tissues and a few infiltrating inflammatory cells. Increases in the number and area of the new blood vessels were observed in BP1/3 compared with the other two parts. The PGP9.5 and DSPP expressions showed that the newly formed tissues were similar to normal pulp tissues. iRoot BP has good biocompatibility and increases the number and area of new blood vessels. The combined application of stem cells and bioceramic materials may be a better method for pulp revascularization.
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Affiliation(s)
- Ruixue Wen
- School of Stomatology, Binzhou Medical CollegeYantai 264000, Shandong, China
- Department of Endodontics, Jinan Stomatological HospitalJinan 250001, Shandong, China
| | - Xin Wang
- Department of Endodontics, Yantai Stomatological HospitalYantai 264200, Shandong, China
| | - Yongchao Lu
- School of Stomatology, Binzhou Medical CollegeYantai 264000, Shandong, China
- Department of Endodontics, Jinan Stomatological HospitalJinan 250001, Shandong, China
| | - Yi Du
- Department of Endodontics, Jinan Stomatological HospitalJinan 250001, Shandong, China
| | - Xijiao Yu
- Department of Endodontics, Jinan Stomatological HospitalJinan 250001, Shandong, China
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Rizk HM, Salah AL-Deen MS, Emam AA. Pulp Revascularization/Revitalization of Bilateral Upper Necrotic Immature Permanent Central Incisors with Blood Clot vs Platelet-rich Fibrin Scaffolds-A Split-mouth Double-blind Randomized Controlled Trial. Int J Clin Pediatr Dent 2020; 13:337-343. [PMID: 33149405 PMCID: PMC7586471 DOI: 10.5005/jp-journals-10005-1788] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
OBJECTIVES Clinical and radiographic evaluation of the regeneration of bilateral necrotic upper permanent central incisors with open apex using blood clot (BC) and platelet-rich fibrin (PRF) scaffolds. TRIAL DESIGN Split-mouth double-blind parallel arm randomized controlled clinical trial. MATERIALS AND METHODS Randomization and blinding: The study started with 15 patients with bilateral necrotic upper permanent central incisors with open apex. Computer-generated tables were used to allocate treatments. The two maxillary central incisors were randomly assigned to either the control (BC scaffold) or the examined (PRF scaffold) groups. Participants: Thirteen patients aged 8-14 years fulfilled the study requirements. Follow-up was performed for 3, 6, 9, and 12 months. Standardized radiographs were collected each 3 months, and difference in measurements was calculated using Image J software. Primary outcomes measured were sinus/fistula formation, pain complaint, mobility grade, and swelling presence/absence. Radiographic: Root length elongation and increase in root thickness. Secondary outcomes were sensibility test and crown color change. Radiographic: Change in bone density and apical diameter. Radiographs that were standardized used during the follow-up time, and occurred changes were calculated using Image J software. RESULTS One patient was lost during follow-up; therefore, 24 treated teeth were analyzed, they showed 100% success rate. Platelet-rich fibrin teeth displayed a statistically significant growth in radiographic root length and width, increased periapical bone density, and a reduction in apical diameter when compared with BC. At the end of the follow-up period, all treated teeth were negative to sensibility test. Blood clot displayed greater crown discoloration in comparison to PRF group. CONCLUSION For teeth with open apex and necrotic pulp, revascularization using PRF is an appropriate substitute to BC. HOW TO CITE THIS ARTICLE Rizk HM, Salah AL-Deen MS, Emam AA. Pulp Revascularization/Revitalization of Bilateral Upper Necrotic Immature Permanent Central Incisors with Blood Clot vs Platelet-rich Fibrin Scaffolds-A Split-mouth Double-blind Randomized Controlled Trial. Int J Clin Pediatr Dent 2020;13(4):337-343.
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Affiliation(s)
- Hazim Mohamed Rizk
- Department of Pediatric Dentistry, Faculty of Dentistry, Suez Canal University, Ismailia, Egypt
| | | | - Asmaa Aly Emam
- Department of Pediatric Dentistry, Faculty of Dentistry, Suez Canal University, Ismailia, Egypt
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Abstract
INTRODUCTION Bioactive molecule carrier systems (BACS) are biomaterial-based substrates that facilitate the delivery of active signaling molecules for different biologically based therapeutic applications, which include regenerative endodontic procedures. Tissue regeneration or organized repair in regenerative endodontic procedures is governed by the dynamic orchestration of interactions between stem/progenitor cells, bioactive molecules, and extracellular matrix. BACS aid in mimicking some of the complex physiological processes, overcoming some of the challenges faced in the clinical translation of regenerative endodontic procedures. AREAS COVERED This narrative review addresses the role of BACS in stem/progenitor cell proliferation, migration, and differentiation with the application for dentin-pulp tissue engineering both in vitro and in vivo. BACS shield the bioactivity of the immobilized molecules against environmental factors, while its design allows the pre-programmed release of bioactive molecules in a spatial and temporal-controlled manner. The polymeric and non-polymeric materials used to synthesize micro and nanoscale-based BACS are reviewed. EXPERT OPINION Comprehensive characterization of well-designed and customized BACS is necessary to be able to deliver multiple bioactive molecules in spatiotemporally controlled manner and to address the release kinetics required for potential in vivo application. This warrants further laboratory-based experiments and rigorous clinical investigations to enable their clinical translation for regenerative endodontic procedures.
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Affiliation(s)
- Anil Kishen
- The Kishen Lab, Dental Research Institute, University of Toronto , Toronto, ON, Canada.,Faculty of Dentistry, University of Toronto , Toronto, ON, Canada.,School of Graduate Studies, University of Toronto , Toronto, ON, Canada.,Department of Dentistry, Mount Sinai Health System, Mount Sinai Hospital , Toronto, ON, Canada
| | - Hebatullah Hussein
- The Kishen Lab, Dental Research Institute, University of Toronto , Toronto, ON, Canada.,Faculty of Dentistry, University of Toronto , Toronto, ON, Canada
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Haugen HJ, Basu P, Sukul M, Mano JF, Reseland JE. Injectable Biomaterials for Dental Tissue Regeneration. Int J Mol Sci 2020; 21:E3442. [PMID: 32414077 PMCID: PMC7279163 DOI: 10.3390/ijms21103442] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Accepted: 05/08/2020] [Indexed: 12/17/2022] Open
Abstract
Injectable biomaterials scaffolds play a pivotal role for dental tissue regeneration, as such materials are highly applicable in the dental field, particularly when compared to pre-formed scaffolds. The defects in the maxilla-oral area are normally small, confined and sometimes hard to access. This narrative review describes different types of biomaterials for dental tissue regeneration, and also discusses the potential use of nanofibers for dental tissues. Various studies suggest that tissue engineering approaches involving the use of injectable biomaterials have the potential of restoring not only dental tissue function but also their biological purposes.
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Affiliation(s)
- Håvard Jostein Haugen
- Department of Biomaterials, Institute of Clinical Dentistry, Faculty of Odontology, University of Oslo, 0317 Oslo, Norway; (P.B.); (M.S.); (J.E.R.)
| | - Poulami Basu
- Department of Biomaterials, Institute of Clinical Dentistry, Faculty of Odontology, University of Oslo, 0317 Oslo, Norway; (P.B.); (M.S.); (J.E.R.)
| | - Mousumi Sukul
- Department of Biomaterials, Institute of Clinical Dentistry, Faculty of Odontology, University of Oslo, 0317 Oslo, Norway; (P.B.); (M.S.); (J.E.R.)
| | - João F Mano
- CICECO – Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal;
| | - Janne Elin Reseland
- Department of Biomaterials, Institute of Clinical Dentistry, Faculty of Odontology, University of Oslo, 0317 Oslo, Norway; (P.B.); (M.S.); (J.E.R.)
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Ivica A, Deari S, Patcas R, Weber FE, Zehnder M. Transforming Growth Factor Beta 1 Distribution and Content in the Root Dentin of Young Mature and Immature Human Premolars. J Endod 2020; 46:641-647. [PMID: 32139264 DOI: 10.1016/j.joen.2020.01.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 01/10/2020] [Accepted: 01/21/2020] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Transforming growth factor beta 1 (TGF-β1) is a key morphogen in regenerative endodontics; yet, its location within the hard tissue phase of dentin and its availability in mature roots have not been fully elucidated. METHODS Young mature (n = 8) and immature (n = 11) roots from sound premolars were obtained from 13 orthodontic patients aged 17 ± 1 and 12 ± 1 years, respectively. Roots were cleaned of organic remnants in 5% sodium hypochlorite. The width of the minor foramen was measured using a digital microscope. TGF-β1 distribution was assessed in 3 roots per group by immunostaining combined with confocal laser scanning microscopy. The root dentin of the remaining 13 roots was powdered and decalcified in 17% EDTA to determine the overall levels of hard tissue-embedded TGF-β1 by enzyme-linked immunosorbent assay. Data were compared between groups using the Student t test (α = .05). RESULTS The minor foramen was 168 ± 49 μm versus 557 ± 295 μm in mature compared with immature roots (P < .05). TGF-β1 was highly stainable toward the pulp space in both groups. It was clearly associated with peritubular dentin and apparently absent in nontubular outer dentin. TGF-β1 content was 115 ± 31 pg and 74 ± 35 pg/100 mg mature versus immature root dentin, respectively (P > .05). CONCLUSIONS TGF-β1 is deposited into the peritubular dentin. It should be possible to release this molecule in regenerative endodontic procedures from young mature roots as well as immature roots.
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Affiliation(s)
- Anja Ivica
- Department of Cranio-Maxillofacial and Oral Surgery, Center of Dental Medicine, University of Zurich, Zurich, Switzerland; Department of Oral Biotechnology and Bioengineering, Center of Dental Medicine, University of Zurich, Zurich, Switzerland
| | - Shengjile Deari
- Clinic of Preventive Dentistry, Periodontology and Cariology, Center of Dental Medicine, University of Zurich, Zurich, Switzerland
| | - Raphael Patcas
- Clinic of Orthodontics and Pediatric Dentistry, Center of Dental Medicine, University of Zurich, Zurich, Switzerland
| | - Franz E Weber
- Department of Cranio-Maxillofacial and Oral Surgery, Center of Dental Medicine, University of Zurich, Zurich, Switzerland; Department of Oral Biotechnology and Bioengineering, Center of Dental Medicine, University of Zurich, Zurich, Switzerland
| | - Matthias Zehnder
- Clinic of Preventive Dentistry, Periodontology and Cariology, Center of Dental Medicine, University of Zurich, Zurich, Switzerland.
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Pulp-Derived Exosomes in a Fibrin-Based Regenerative Root Filling Material. J Clin Med 2020; 9:jcm9020491. [PMID: 32054086 PMCID: PMC7074310 DOI: 10.3390/jcm9020491] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 02/05/2020] [Accepted: 02/07/2020] [Indexed: 12/13/2022] Open
Abstract
Regenerative endodontics has been described as a paradigm shift in dentistry, despite its current limitation to immature teeth and reparative rather than regenerative outcomes. Cell-free treatments are favored because of regulatory issues. However, the recruitment of host-derived stem cells to the desired site remains challenging. We investigated whether dental pulp-derived exosomes, which are extracellular vesicles that contain proteins, lipids, RNA, and DNA and thus mirror their parental cells, may be used for this purpose. The use of exosomes may present appreciable advantages over the direct use of transplanted stem cells due to a higher safety profile, easier isolation, preservation, and handling. Here we harvested exosomes from a cultured third-molar pulp cell and assessed them by transmission electron microscopy and Western blotting. Human mesenchymal stem cells (MSCs) were exposed to these exosomes to assess exosome uptake, cell migration, and proliferation. In addition, a fibrin gel (i.e., a diluted fibrin sealant), was assessed as a delivery system for the exosomes. Our results show that exosomes attracted MSCs, and the fibrin gel enhanced their effect. Moreover, exosomes improved the proliferation of MSCs. Therefore, we propose that pulp-derived exosomes in combination with a fibrin gel could be a powerful combination for clinical translation towards improved cell-free regenerative endodontics and thus represent a new way to fill dental hard tissues.
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Shah D, Lynd T, Ho D, Chen J, Vines J, Jung HD, Kim JH, Zhang P, Wu H, Jun HW, Cheon K. Pulp-Dentin Tissue Healing Response: A Discussion of Current Biomedical Approaches. J Clin Med 2020; 9:jcm9020434. [PMID: 32033375 PMCID: PMC7074340 DOI: 10.3390/jcm9020434] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 01/23/2020] [Accepted: 01/31/2020] [Indexed: 12/12/2022] Open
Abstract
Dental pulp tissue exposed to mechanical trauma or cariogenic process results in root canal and/or periapical infections, and conventionally treated with root canal procedures. The more recent regenerative endodontic procedure intends to achieve effective root canal disinfection and adequate pulp–dentin tissue regeneration; however, numerous limitations are reported. Because tooth is composed of vital soft pulp enclosed by the mineralized hard tissue in a highly organized structure, complete pulp–dentin tissue regeneration has been challenging to achieve. In consideration of the limitations and unique dental anatomy, it is important to understand the healing and repair processes through inflammatory-proliferative-remodeling phase transformations of pulp–dentin tissue. Upon cause by infectious and mechanical stimuli, the innate defense mechanism is initiated by resident pulp cells including immune cells through chemical signaling. After the expansion of infection and damage to resident pulp–dentin cells, consequent chemical signaling induces pluripotent mesenchymal stem cells (MSCs) to migrate to the injury site to perform the tissue regeneration process. Additionally, innovative biomaterials are necessary to facilitate the immune response and pulp–dentin tissue regeneration roles of MSCs. This review highlights current approaches of pulp–dentin tissue healing process and suggests potential biomedical perspective of the pulp–dentin tissue regeneration.
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Affiliation(s)
- Dishant Shah
- Department of Biomedical Engineering, University of Alabama at Birmingham, 1825 University Blvd, Birmingham, AL 35294, USA; (D.S.); (T.L.); (D.H.); (J.C.); (J.V.); (H.-W.J.)
| | - Tyler Lynd
- Department of Biomedical Engineering, University of Alabama at Birmingham, 1825 University Blvd, Birmingham, AL 35294, USA; (D.S.); (T.L.); (D.H.); (J.C.); (J.V.); (H.-W.J.)
| | - Donald Ho
- Department of Biomedical Engineering, University of Alabama at Birmingham, 1825 University Blvd, Birmingham, AL 35294, USA; (D.S.); (T.L.); (D.H.); (J.C.); (J.V.); (H.-W.J.)
| | - Jun Chen
- Department of Biomedical Engineering, University of Alabama at Birmingham, 1825 University Blvd, Birmingham, AL 35294, USA; (D.S.); (T.L.); (D.H.); (J.C.); (J.V.); (H.-W.J.)
| | - Jeremy Vines
- Department of Biomedical Engineering, University of Alabama at Birmingham, 1825 University Blvd, Birmingham, AL 35294, USA; (D.S.); (T.L.); (D.H.); (J.C.); (J.V.); (H.-W.J.)
| | - Hwi-Dong Jung
- Department of Oral & Maxillofacial Surgery College of Dentistry, Yonsei University, 50-1 Yonsei-Ro, Seodeamun-Gu, Seoul 03722, Korea;
| | - Ji-Hun Kim
- Department of Dentistry, Wonju College of Medicine, Yonsei University, 20 Il-San-ro, Wonju, Gangwon-Do 26426, Korea;
| | - Ping Zhang
- Department of Pediatric Dentistry, University of Alabama at Birmingham, 1919 7th Avenue S, Birmingham, AL 35294, USA; (P.Z.); (H.W.)
| | - Hui Wu
- Department of Pediatric Dentistry, University of Alabama at Birmingham, 1919 7th Avenue S, Birmingham, AL 35294, USA; (P.Z.); (H.W.)
| | - Ho-Wook Jun
- Department of Biomedical Engineering, University of Alabama at Birmingham, 1825 University Blvd, Birmingham, AL 35294, USA; (D.S.); (T.L.); (D.H.); (J.C.); (J.V.); (H.-W.J.)
| | - Kyounga Cheon
- Department of Pediatric Dentistry, University of Alabama at Birmingham, 1919 7th Avenue S, Birmingham, AL 35294, USA; (P.Z.); (H.W.)
- Correspondence: ; Tel.: +1-205-975-4303
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Abdel Hafiz Abdel Rahim AS, Abdelgawad F, Abd Alsamed AM, Moheb DM, Wahab El-Dokky NA. Case Report: Single visit photo-activated disinfection in regenerative endodontics. F1000Res 2019; 8:1519. [PMID: 32934793 DOI: 10.12688/f1000research.20118.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/20/2019] [Indexed: 01/15/2023] Open
Abstract
Background: Root canal disinfection is considered critical for achieving successful regenerative endodontic procedures. Photo-activated disinfection is a novel disinfection method that can help to achieve the goal of regenerative endodontics. This article reports the clinical and radiographic results after single visit regenerative endodontics using photo-activated disinfection. Methods: An 8.5-year-old girl complained of fractured upper right central incisor. Pulp necrosis was diagnosed on the basis of clinical findings. The root canal was irrigated with sodium hypochlorite solution (1.5%) followed by saline. Then, the canal was dried with paper points. A combination of a photosensitizer solution and low power laser light were applied. EDTA solution was used as a final irrigant. Bleeding was induced, followed by placement of collagen resorbable matrix and white mineral trioxide aggregate. Two days later, the tooth was sealed and restored with permanent filling. Results: Clinical findings revealed no pain on percussion or palpation tests. Radiographic examination revealed an increase in root length, an increase of apical root thickness and apical closure at the 12-month follow-up period. Conclusion: Regenerative endodontics using photo-activated disinfection achieved successful outcomes in the necrotic immature permanent tooth.
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Affiliation(s)
| | - Fatma Abdelgawad
- Pediatric Dentistry and Dental Public Health Department, Faculty of Dentistry, Cairo University, Cairo, 11553, Egypt
| | - Ahmed M Abd Alsamed
- Oral and Maxillofacial Radiology Department, Faculty of Dentistry, Cairo University, Cairo, 11553, Egypt
| | - Dalia Mohamed Moheb
- Pediatric Dentistry and Dental Public Health Department, Faculty of Dentistry, Cairo University, Cairo, 11553, Egypt
| | - Norhan Abdel Wahab El-Dokky
- Pediatric Dentistry and Dental Public Health Department, Faculty of Dentistry, Cairo University, Cairo, 11553, Egypt
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Disturbed bone remodelling activity varies in different stages of experimental, gradually progressive apical periodontitis in rats. Int J Oral Sci 2019; 11:27. [PMID: 31451690 PMCID: PMC6802676 DOI: 10.1038/s41368-019-0058-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2018] [Revised: 05/23/2019] [Accepted: 06/27/2019] [Indexed: 02/05/2023] Open
Abstract
Bone remodelling keeps going through the lifespan of human by bone formation and bone resorption. In the craniofacial region, mandibles act as the main force for biting and chewing, and also become susceptible to a common bone-loss disease, namely, apical periodontitis, once infected dental pulp is not treated timely, during which bone resorption occurs from the apical foramen to the apical bone area. Although conventional root canal treatment (RCT) can remove the most of the infection, chronical apical periodontitis due to incomplete removal of dental pulp and subsequent microleakage will become refractory and more challenging, and this process has scarcely been specifically studied as a bone remodelling issue in rat models. Therefore, to study chronical and refractory apical periodontitis owing to incomplete cleaning of infected dental pulp and microleackage in vivo, we establish a modified rat model of gradually progressive apical periodontitis by sealing residual necrotic dental pulp and introducing limited saliva, which simulates gradually progressive apical periodontitis, as observed in the clinical treatment of chronical and refractory apical periodontitis. We show that bone-loss is inevitable and progressive in this case of apical periodontitis, which confirms again that complete and sound root canal treatment is crucial to halt the progression of chronical and refractory apical periodontitis and promote bone formation. Interestingly, bone remodelling was enhanced at the initial stage of apical periodontitis in this model while reduced with a high osteoblast number afterwards, as shown by the time course study of the modified model. Suggesting that the pathological apical microenvironment reserve its hard tissue formation ability to some degree but in a disturbed manner. Hopefully, our findings can provide insights for future bone regenerative treatment for apical periodontitis-associated bone loss.
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Ahmadian E, Eftekhari A, Dizaj SM, Sharifi S, Mokhtarpour M, Nasibova AN, Khalilov R, Samiei M. The effect of hyaluronic acid hydrogels on dental pulp stem cells behavior. Int J Biol Macromol 2019; 140:245-254. [PMID: 31419560 DOI: 10.1016/j.ijbiomac.2019.08.119] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2019] [Revised: 08/09/2019] [Accepted: 08/13/2019] [Indexed: 01/12/2023]
Abstract
Dental caries and trauma, particularly in childhood, are among the most prevalent teeth problems, which result in the creation of cavities and probably tooth loss. Thus, novel regenerative approaches with high efficiency and less toxicity are required. Stem cell therapy along with the implementation of scaffolds has provided excellent opportunities in the regeneration of teeth structure. Hyaluronic acid (HA) hydrogels have enticed great attention in the field of regenerative medicine. The unique chemical and structural properties of HA and its derivatives have enabled their application in tissue engineering. Several factors such as the location and type of the lesion, teeth age, the type of capping materials determine the success rate of pulp therapy. HA hydrogels have been considered as biocompatible and safe scaffold supports in human dental cell therapies.
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Affiliation(s)
- Elham Ahmadian
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Students' Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Aziz Eftekhari
- Pharmacology and Toxicology Department, Maragheh University of Medical Sciences, Maragheh, Iran
| | - Solmaz Maleki Dizaj
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Simin Sharifi
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Aygun N Nasibova
- Department of Biophysics and Molecular Biology, Baku State University, Baku, Azerbaijan; Institute of Radiation Problems, National Academy of Sciences of Azerbaijan, Baku, Azerbaijan
| | - Rovshan Khalilov
- Department of Biophysics and Molecular Biology, Baku State University, Baku, Azerbaijan; Institute of Radiation Problems, National Academy of Sciences of Azerbaijan, Baku, Azerbaijan; Joint Ukraine-Azerbaijan International Research and Education Center of Nanobiotechnology and Functional Nanosystems, Drohobych Ukraine & Baku, Azerbaijan
| | - Mohammad Samiei
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran.
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Youssef AR, Emara R, Taher MM, Al-Allaf FA, Almalki M, Almasri MA, Siddiqui SS. Effects of mineral trioxide aggregate, calcium hydroxide, biodentine and Emdogain on osteogenesis, Odontogenesis, angiogenesis and cell viability of dental pulp stem cells. BMC Oral Health 2019; 19:133. [PMID: 31266498 PMCID: PMC6604301 DOI: 10.1186/s12903-019-0827-0] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Accepted: 06/19/2019] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Vital pulp therapy preserves and maintains the integrity and the health of dental pulp tissue that has been injured by trauma, caries or restorative procedures. The enhancement of cells viability and formation of reparative dentine and new blood vessels are vital determinants of the success of direct pulp capping. Therefore, the aims of this study was to evaluate and compare the in vitro osteogenic, odontogenic and angiogenic effects of mineral trioxide aggregate (MTA), calcium hydroxide [Ca(OH)2], Biodentine and Emdogain on dental pulp stem cells (DPSCs) and examine the effects of the tested materials on cell viability. METHODS DPSCs were treated with MTA, Ca(OH)2, Biodentine or Emdogain. Untreated cells were used as control. The cell viability was measured by MTT assay on day 3. Real-Time PCR with SYBR green was used to quantify the gene expression levels of osteogenic markers (alkaline phosphatase and osteopontin), odontogenic marker (dentin sialophosphoprotein) and angiogenic factor (vascular endothelial growth factor) on day 7 and day 14. RESULTS All capping materials showed variable cytotoxicity against DPSCs (77% for Emdogain, 53% for MTA, 26% for Biodentine and 16% for Ca(OH)2 compared to control (P value < 0.0001). Osteopontin (OPN) and dentin sialophosphoprotein (DSPP) gene expression was increased by all four materials. However, alkaline phosphatase (ALP) was upregulated by all materials except Emdogain. Vascular endothelial growth factor (VEGF) expression was upregulated by all four tested materials except Ca(OH)2. CONCLUSIONS Our results suggest MTA, Biodentine and Emdogain exhibit similar attributes and may score better than Ca(OH)2. Emdogain could be a promising alternative to MTA and Biodentine in enhancing pulp repair capacity following dental pulp injury. However, further future research is required to assess the clinical outcomes and compare it with the in vitro findings.
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Affiliation(s)
- Abdel-Rahman Youssef
- Department of Basic and Clinical Oral Sciences, Faculty of Dentistry, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia. .,Department of Microbiology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
| | - Ramy Emara
- Department of Restorative dentistry, Faculty of Dentistry, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia
| | - Mohiuddin M Taher
- Department of Medical Genetics, Umm-Al-Qura University, Makkah, Kingdom of Saudi Arabia.,Science and Technology Unit Umm-Al-Qura University, Makkah, Kingdom of Saudi Arabia
| | - Faisal A Al-Allaf
- Department of Medical Genetics, Umm-Al-Qura University, Makkah, Kingdom of Saudi Arabia.,Science and Technology Unit Umm-Al-Qura University, Makkah, Kingdom of Saudi Arabia
| | - Majed Almalki
- Department of Restorative dentistry, Faculty of Dentistry, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia
| | - Mazen A Almasri
- Oral Maxillofacial Surgery Department, Faculty of Dentistry, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
| | - Shahid S Siddiqui
- Department of Basic and Clinical Oral Sciences, Faculty of Dentistry, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia
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Design and characterization of a chitosan-enriched fibrin hydrogel for human dental pulp regeneration. Dent Mater 2019; 35:523-533. [DOI: 10.1016/j.dental.2019.01.018] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 12/19/2018] [Accepted: 01/03/2019] [Indexed: 12/12/2022]
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Hong S, Li L, Cai W, Jiang B. The potential application of concentrated growth factor in regenerative endodontics. Int Endod J 2018; 52:646-655. [PMID: 30471228 DOI: 10.1111/iej.13045] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Accepted: 11/20/2018] [Indexed: 12/12/2022]
Affiliation(s)
- S. Hong
- Department of Endodontics, School & Hospital of Stomatology Tongji University Shanghai Engineering Research Center of Tooth Restoration and Regeneration Shanghai China
| | - L. Li
- Department of Endodontics, School & Hospital of Stomatology Tongji University Shanghai Engineering Research Center of Tooth Restoration and Regeneration Shanghai China
| | - W. Cai
- Center for Translational Neurodegeneration and Regenerative Therapy Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai China
| | - B. Jiang
- Department of Endodontics, School & Hospital of Stomatology Tongji University Shanghai Engineering Research Center of Tooth Restoration and Regeneration Shanghai China
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Patel J, Sheth T, Thakore D, Dhamat D. Biomimetics in Endodontics: A Review of the Changing Trends in Endodontics. JOURNAL OF ADVANCED ORAL RESEARCH 2018. [DOI: 10.1177/2320206818816186] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Newer scientific technological advancement in dentistry provides an array of projects such as molecular biology, cell culturing, tissue grafting, and tissue engineering. Conventional root canal treatment, apexification with biomaterials, and extractions are the procedures of choice to treat a nonvital tooth. These treatment options do not give predictable outcomes in the regeneration of the pulp tissue. This can be easily achieved by regenerative endodontics wherein the diseased or a nonvital tooth is replaced by a healthy and functional pulp-dentin complex. The rationale for regenerative endodontics follows tissue engineering techniques. This article reviews the shift in regenerative endodontic techniques.
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Affiliation(s)
- Jalak Patel
- Atria Complex-1, Opposite Bank of India, Manjapur Main Road, Vadodara, Gujarat, India
| | - Tejal Sheth
- Department of Periodontics and Oral Implantology, Ahmedabad Dental College and Hospital, Gandhinagar, Gujarat, India
| | - Dhwanit Thakore
- Department of Periodontics and Oral Implantology, Ahmedabad Dental College and Hospital, Gandhinagar, Gujarat, India
| | - Dharmesh Dhamat
- Atria Complex-1, Opposite Bank of India, Manjapur Main Road, Vadodara, Gujarat, India
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Metlerska J, Fagogeni I, Nowicka A. Efficacy of Autologous Platelet Concentrates in Regenerative Endodontic Treatment: A Systematic Review of Human Studies. J Endod 2018; 45:20-30.e1. [PMID: 30446403 DOI: 10.1016/j.joen.2018.09.003] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 06/26/2018] [Accepted: 09/09/2018] [Indexed: 12/12/2022]
Abstract
INTRODUCTION The latest research concerns the use of platelet concentrates, which are introduced into the root canal. The aim of this study was to examine the effectiveness of platelet-rich fibrin and platelet-rich plasma in regenerative endodontics. METHODS This literature review was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The literature search included all publications without a year limit. The last search was performed on January 31, 2018. An electronic search was performed using MEDLINE (PubMed), Cochrane, and Scopus. Articles were selected that addressed the following research question: Is the use of platelet concentrates effective in regenerative endodontics? The necessary information was extracted by 2 authors independently using a standardized form. RESULTS The search resulted in 426 titles from all databases, and 26 studies met the inclusion criteria. Five were randomized trials, and the others were case reports. All described cases were asymptomatic. Only 3 cases from randomized trials were unsuccessful. Ten of the case reports found positive results for pulp vitality. In randomized trials, the teeth treated with platelet concentrates showed better results for pulp vitality. In almost all cases, they also described thickening and lengthening of the root wall and closure of the apical foramen, which are important for successful treatment of permanent teeth. CONCLUSIONS This review showed that procedures using autologous platelet concentrates were successful in treating permanent teeth with root development. However, more long-term clinical studies are needed.
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Affiliation(s)
- Joanna Metlerska
- Doctoral Studies of the Faculty of Dentistry, Pomeranian Medical University in Szczecin, Szczecin, Poland.
| | - Irini Fagogeni
- Doctoral Studies of the Faculty of Dentistry, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Alicja Nowicka
- Department of Conservative Dentistry and Endodontics, Pomeranian Medical University in Szczecin, Szczecin, Poland
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Suresh N, Arul B, Kowsky D, Natanasabapathy V. Successful Regenerative Endodontic Procedure of a Nonvital Immature Permanent Central Incisor Using Amniotic Membrane as a Novel Scaffold. Dent J (Basel) 2018; 6:dj6030036. [PMID: 30072584 PMCID: PMC6162468 DOI: 10.3390/dj6030036] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Revised: 07/14/2018] [Accepted: 07/17/2018] [Indexed: 11/16/2022] Open
Abstract
Successful regenerative endodontic procedure was performed in nonvital immature permanent central incisor (Stage-4 root development) using human amniotic membrane (HAM) as a novel scaffold. The treatment was performed according to the American Association of Endodontics guidelines with minimal canal instrumentation, 1% Sodium hypochlorite as irrigant and calcium hydroxide as intracanal medicament. During the second appointment, HAM was placed as a scaffold and Biodentine™ was layered over the HAM with glass ionomer cement and resin composite as coronal seal. Preoperative and post-operative cone beam computed tomography (at three years) was taken to assess the treatment outcome. The resolution of disease process and increase in canal width, as well as positive response to pulp sensitivity tests, were observed by the end of three years. There was approximately 78–86% reduction in the volume of periapical lesion size. This case report confirms that HAM can be used as a scaffold material for successful regenerative endodontic procedure (REP).
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Affiliation(s)
- Nandini Suresh
- Department of Conservative Dentistry and Endodontics, Faculty of Dental Sciences, Meenakshi Academy of Higher Education and Research (MAHER), Alapakkam Main Road, Maduravoyal 600095, India.
| | - Buvaneshwari Arul
- Department of Conservative Dentistry and Endodontics, Faculty of Dental Sciences, Meenakshi Academy of Higher Education and Research (MAHER), Alapakkam Main Road, Maduravoyal 600095, India.
| | - Dinesh Kowsky
- Department of Conservative Dentistry and Endodontics, Faculty of Dental Sciences, Meenakshi Academy of Higher Education and Research (MAHER), Alapakkam Main Road, Maduravoyal 600095, India.
| | - Velmurugan Natanasabapathy
- Department of Conservative Dentistry and Endodontics, Faculty of Dental Sciences, Meenakshi Academy of Higher Education and Research (MAHER), Alapakkam Main Road, Maduravoyal 600095, India.
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He L, Kim SG, Gong Q, Zhong J, Wang S, Zhou X, Ye L, Ling J, Mao JJ. Regenerative Endodontics for Adult Patients. J Endod 2018; 43:S57-S64. [PMID: 28844305 DOI: 10.1016/j.joen.2017.06.012] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The goal of endodontics is to save teeth. Since inception, endodontic treatments are performed to obturate disinfected root canals with inert materials such as gutta-percha. Although teeth can be saved after successful endodontic treatments, they are devitalized and therefore susceptible to reinfections and fractures. The American Association of Endodontists (AAE) has made a tremendous effort to revitalize disinfected immature permanent teeth in children and adolescents with diagnoses including pulp necrosis or apical periodontitis. The American Dental Association (ADA) in 2011 issued several clinical codes for regenerative endodontic procedures or apical revascularization in necrotic immature permanent teeth in children and adolescents. These AAE and ADA initiatives have stimulated robust interest in devising a multitude of tissue engineering approaches for dental pulp and dentin regeneration. Can the concept of regenerative endodontics be extended to revitalize mature permanent teeth with diagnoses including irreversible pulpitis and/or pulp necrosis in adults? The present article was written not only to summarize emerging findings to revitalize mature permanent teeth in adult patients but also to identify challenges and strategies that focus on realizing the goal of regenerative endodontics in adults. We further present clinical cases and describe the biological basis of potential regenerative endodontic procedures in adults. This article explores the frequently asked question if regenerative endodontic therapies should be developed for dental pulp and/or dentin regeneration in adults, who consist of the great majority of endodontic patients.
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Affiliation(s)
- Ling He
- Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China; Columbia University Medical Center, Center for Craniofacial Regeneration, New York, NY
| | - Sahng G Kim
- Division of Endodontics, College of Dental Medicine, Columbia University, New York, New York
| | - Qimei Gong
- Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China; Columbia University Medical Center, Center for Craniofacial Regeneration, New York, NY
| | - Juan Zhong
- Columbia University Medical Center, Center for Craniofacial Regeneration, New York, NY; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Sainan Wang
- Columbia University Medical Center, Center for Craniofacial Regeneration, New York, NY; Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology, Beijing, China
| | - Xuedong Zhou
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Ling Ye
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Junqi Ling
- Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
| | - Jeremy J Mao
- Columbia University Medical Center, Center for Craniofacial Regeneration, New York, NY.
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Almeida LDF, Babo PS, Silva CR, Rodrigues MT, Hebling J, Reis RL, Gomes ME. Hyaluronic acid hydrogels incorporating platelet lysate enhance human pulp cell proliferation and differentiation. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2018; 29:88. [PMID: 29904797 DOI: 10.1007/s10856-018-6088-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2017] [Accepted: 05/14/2018] [Indexed: 06/08/2023]
Abstract
The restoration of dentine-pulp complex remains a challenge for dentists; nonetheless, it has been poorly addressed. An ideal system should modulate the host response, as well as enable the recruitment, proliferation and differentiation of relevant progenitor cells. Herein was proposed a photocrosslinkable hydrogel system based on hyaluronic acid (HA) and platelet lysate (PL). PL is a cocktail of growth factors (GFs) and cytokines involved in wound healing orchestration, obtained by the cryogenic processing of platelet concentrates, and was expected to provide the HA hydrogels specific biochemical cues to enhance pulp cells' recruitment, proliferation and differentiation. Stable HA hydrogels incorporating PL (HAPL) were prepared after photocrosslinking of methacrylated HA (Met-HA) previously dissolved in PL, triggered by the Ultra Violet activated photoinitiator Irgacure 2959. Both the HAPL and plain HA hydrogels were shown to be able to recruit cells from a cell monolayer of human dental pulp stem cells (hDPSCs) isolated from permanent teeth. The hDPCs were also seeded directly over the hydrogels (5 × 104 cells/hydrogel) and cultured in osteogenic conditions. Cell metabolism and DNA quantification were higher, in all time-points, for PL supplemented hydrogels (p < 0,05). Alkaline phosphatase (ALPL) activity and calcium quantification peaks were observed for the HAPL group at 21 days (p < 0,05). The gene expression for ALPL and COLIA1 was up-regulated at 21 days to HAPL, compared with HA group (p < 0,05). Within the same time point, the gene expression for RUNX2 did not differ between the groups. Overall, data demonstrated that the HA hydrogels incorporating PL increased the cellular metabolism and stimulate the mineralized matrix deposition by hDPSCs, providing clear evidence of the potential of the proposed system for the repair of damaged pulp/dentin tissue and endodontics regeneration.
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Affiliation(s)
- Leopoldina D F Almeida
- Department of Clinical and Social Dentistry, Federal University of Paraíba, João Pessoa, PB, Brazil
- Department of Orthodontics and Pediatric Dentistry, Araraquara Dental School, State of São Paulo University, Araraquara, SP, Brazil
- 3B's Research Group, I3Bs-Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, 4805-017, Portugal
| | - Pedro S Babo
- 3B's Research Group, I3Bs-Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, 4805-017, Portugal
| | - Cristiana R Silva
- 3B's Research Group, I3Bs-Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, 4805-017, Portugal
| | - Márcia T Rodrigues
- 3B's Research Group, I3Bs-Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, 4805-017, Portugal
| | - Josimeri Hebling
- Department of Orthodontics and Pediatric Dentistry, Araraquara Dental School, State of São Paulo University, Araraquara, SP, Brazil
| | - Rui L Reis
- 3B's Research Group, I3Bs-Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, 4805-017, Portugal
- The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, 4805-017, Barco, Guimarães, Portugal
| | - Manuela E Gomes
- 3B's Research Group, I3Bs-Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal.
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, 4805-017, Portugal.
- The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, 4805-017, Barco, Guimarães, Portugal.
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Itoh Y, Sasaki JI, Hashimoto M, Katata C, Hayashi M, Imazato S. Pulp Regeneration by 3-dimensional Dental Pulp Stem Cell Constructs. J Dent Res 2018; 97:1137-1143. [PMID: 29702010 DOI: 10.1177/0022034518772260] [Citation(s) in RCA: 102] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Dental pulp regeneration therapy for the pulpless tooth has attracted recent attention, and clinical trial studies are underway with the tissue engineering approach. However, there remain many concerns, including the extended period for regenerating the dental pulp. In addition, the use of scaffolds increases the risk of inflammation and infection. To establish a basic technology for novel dental pulp regenerative therapy that allows transplant of pulp-like tissue, we attempted to fabricate scaffold-free 3-dimensional (3D) cell constructs composed of dental pulp stem cells (DPSCs). Furthermore, we assessed viability of these 3D DPSC constructs for dental pulp regeneration through in vitro and in vivo studies. For the in vitro study, we obtained 3D DPSC constructs by shaping sheet-like aggregates of DPSCs with a thermoresponsive hydrogel. DPSCs within constructs remained viable even after prolonged culture; furthermore, 3D DPSC constructs possessed a self-organization ability necessary to serve as a transplant tissue. For the in vivo study, we filled the human tooth root canal with DPSC constructs and implanted it subcutaneously into immunodeficient mice. We found that pulp-like tissues with rich blood vessels were formed within the human root canal 6 wk after implantation. Histologic analyses revealed that transplanted DPSCs differentiated into odontoblast-like mineralizing cells at sites in contact with dentin; furthermore, human CD31-positive endothelial cells were found at the center of regenerated tissue. Thus, the self-organizing ability of 3D DPSC constructs was active within the pulpless root canal in vivo. In addition, blood vessel-rich pulp-like tissues can be formed with DPSCs without requiring scaffolds or growth factors. The technology established in this study allows us to prepare DPSC constructs with variable sizes and shapes; therefore, transplantation of DPSC constructs shows promise for regeneration of pulpal tissue in the pulpless tooth.
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Affiliation(s)
- Y Itoh
- 1 Department of Biomaterials Science, Osaka University Graduate School of Dentistry, Osaka, Japan.,2 Department of Restorative Dentistry and Endodontology, Osaka University Graduate School of Dentistry, Osaka, Japan
| | - J I Sasaki
- 1 Department of Biomaterials Science, Osaka University Graduate School of Dentistry, Osaka, Japan
| | - M Hashimoto
- 3 Institute of Dental Research, Osaka Dental University, Osaka, Japan
| | - C Katata
- 1 Department of Biomaterials Science, Osaka University Graduate School of Dentistry, Osaka, Japan.,2 Department of Restorative Dentistry and Endodontology, Osaka University Graduate School of Dentistry, Osaka, Japan
| | - M Hayashi
- 2 Department of Restorative Dentistry and Endodontology, Osaka University Graduate School of Dentistry, Osaka, Japan
| | - S Imazato
- 1 Department of Biomaterials Science, Osaka University Graduate School of Dentistry, Osaka, Japan
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Abstract
The main purpose of the present systematic review was to evaluate the efficacy of platelet concentrates in pulpotomy of human teeth. Our systematic search included Medline, Embase, CINAHL, PsycINFO, Scopus, key journals, and review articles; the date of the last search was July 30, 2017. We graded the methodological quality of the studies by Cochrane Risk of Bias tool. Four randomized controlled trails were included in the present systematic review. The number of study participants ranged from 28 to 50, with a mean of 45.5. The age of study participants ranged between 4 and 25 years. In three of the included studies, platelet-rich fibrin (autologous) was used and in one study lyophilized freeze-dried platelet (allogenic) was used as pulpotomy material. Calcium hydroxide and mineral trioxide aggregate were used in control groups. The quality assessment rated three studies as being of fair quality and one study as poor quality. Two of the included studies showed a 100% success of pulpotomy with platelet concentrates and two studies showed more than 80% of success, but the difference between control group and platelet concentrates group was not statistically significant. To conclude, the number of publications that met all inclusion criteria was found to be very limited and no significant difference was reported in the studies comparing platelet concentrates with other materials in pulpotomy. The present results point to the need for high-quality randomized controlled trials in further research.
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Affiliation(s)
- Roshan Noor Mohamed
- a Department of Pedodontics, Faculty of Dentistry , Taif University , Taif , KSA
| | - Sakeenabi Basha
- b Department of Preventive and Community Dentistry, Faculty of Dentistry , Taif University , Taif , KSA
| | - Yousef Al-Thomali
- c Department of Orthodontics, Faculty of Dentistry , Taif University , Taif , KSA
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Janjić K, Cvikl B, Kurzmann C, Moritz A, Agis H. Do hypoxia and L-mimosine modulate sclerostin and dickkopf-1 production in human dental pulp-derived cells? Insights from monolayer, spheroid and tooth slice cultures. BMC Oral Health 2018. [PMID: 29523112 PMCID: PMC5845180 DOI: 10.1186/s12903-018-0492-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background To understand the responses of the dental pulp to hypoxia is of high relevance for regenerative endodontics and dental traumatology. Here, we aimed to reveal the effects of hypoxia and the hypoxia mimetic agent L-mimosine (L-MIM) on the production of sclerostin (SOST) and dickkopf-1 (DKK-1) in human dental pulp-derived cells (DPC). Methods DPC in monolayer, spheroid and tooth slice cultures were treated with L-MIM or hypoxia. Resazurin-based toxicity and MTT assays were performed to determine cell viability. mRNA and protein levels of SOST and DKK-1 were measured with quantitative reverse transcription PCR and ELISA, respectively. To validate the hypoxia-like response, SDF-1, VEGF and IL-8 were assessed. In addition Western blots for HIF-1α, HIF-2α and HIF-3α were done. Results Cells were vital upon treatment procedures and showed increased levels of HIF-1α, and HIF-2α. In monolayer cultures, mRNA levels of SOST and DKK-1 were downregulated by L-MIM and hypoxia, respectively. A significant downregulation of SOST by hypoxia was found at the protein level compared to untreated cells while the effect on DKK-1 and the impact of L-MIM on SOST and DKK-1 did not reach the level of significance at the protein level. In spheroid cultures, mRNA levels of SOST and DKK-1 were downregulated by L-MIM. A significant downregulation of DKK-1 upon hypoxia treatment was found at the protein level while the impact of hypoxia on SOST and the effect of L-MIM on SOST and DKK-1 did not reach the level of significance. SOST and DKK-1 were also produced in tooth slices, but no pronounced modulation by L-MIM or hypoxia was found. Evaluation of SDF-1, VEGF and IL-8 showed a hypoxia-like response in the culture models. Conclusions There is no pronounced influence of hypoxia and L-MIM on DPC viability, SOST and DKK-1 protein production. However, the specific response depends on the culture model and the level of evaluation (mRNA or protein). These results deepen our understanding about the role of hypoxia and the potential impacts of hypoxia-based strategies on dental pulp.
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Affiliation(s)
- Klara Janjić
- Department of Conservative Dentistry and Periodontology, School of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090, Vienna, Austria.,Austrian Cluster for Tissue Regeneration, Donaueschingenstr. 13, Vienna, 1200, Austria
| | - Barbara Cvikl
- Department of Conservative Dentistry and Periodontology, School of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090, Vienna, Austria.,Austrian Cluster for Tissue Regeneration, Donaueschingenstr. 13, Vienna, 1200, Austria.,Department of Preventive, Restorative and Pediatric Dentistry, University of Bern, Freiburgstrasse 7, Bern, 3010, Switzerland
| | - Christoph Kurzmann
- Department of Conservative Dentistry and Periodontology, School of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090, Vienna, Austria.,Austrian Cluster for Tissue Regeneration, Donaueschingenstr. 13, Vienna, 1200, Austria
| | - Andreas Moritz
- Department of Conservative Dentistry and Periodontology, School of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090, Vienna, Austria.,Austrian Cluster for Tissue Regeneration, Donaueschingenstr. 13, Vienna, 1200, Austria
| | - Hermann Agis
- Department of Conservative Dentistry and Periodontology, School of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090, Vienna, Austria. .,Austrian Cluster for Tissue Regeneration, Donaueschingenstr. 13, Vienna, 1200, Austria.
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Athirasala A, Tahayeri A, Thrivikraman G, França CM, Monteiro N, Tran V, Ferracane J, Bertassoni LE. A dentin-derived hydrogel bioink for 3D bioprinting of cell laden scaffolds for regenerative dentistry. Biofabrication 2018; 10:024101. [PMID: 29320372 DOI: 10.1088/1758-5090/aa9b4e] [Citation(s) in RCA: 106] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Recent studies in tissue engineering have adopted extracellular matrix (ECM) derived scaffolds as natural and cytocompatible microenvironments for tissue regeneration. The dentin matrix, specifically, has been shown to be associated with a host of soluble and insoluble signaling molecules that can promote odontogenesis. Here, we have developed a novel bioink, blending printable alginate (3% w/v) hydrogels with the soluble and insoluble fractions of the dentin matrix. We have optimized the printing parameters and the concentrations of the individual components of the bioink for print accuracy, cell viability and odontogenic potential. We find that, while viscosity, and hence printability of the bioinks, was greater in the formulations containing higher concentrations of alginate, a higher proportion of insoluble dentin matrix proteins significantly improved cell viability; where a 1:1 ratio of alginate and dentin (1:1 Alg-Dent) was most suitable. We further demonstrate high retention of the soluble dentin molecules within the 1:1 Alg-Dent hydrogel blends, evidencing renewed interactions between these molecules and the dentin matrix post crosslinking. Moreover, at concentrations of 100 μg ml-1, these soluble dentin molecules significantly enhanced odontogenic differentiation of stem cells from the apical papilla encapsulated in bioprinted hydrogels. In summary, the proposed novel bioinks have demonstrable cytocompatibility and natural odontogenic capacity, which can be a used to reproducibly fabricate scaffolds with complex three-dimensional microarchitectures for regenerative dentistry in the future.
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Affiliation(s)
- Avathamsa Athirasala
- Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, OHSU School of Dentistry, Portland, OR, United States of America
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