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Rajasekar V, Abdalla MM, Neelakantan P, Yiu CKY. Cellular dynamics and signalling mechanisms in dentine repair: A narrative review. Int Endod J 2025. [PMID: 40491185 DOI: 10.1111/iej.14261] [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: 01/26/2025] [Revised: 05/12/2025] [Accepted: 05/13/2025] [Indexed: 06/11/2025]
Abstract
BACKGROUND Bioactive molecules have gained significant attention in regenerative medicine due to their ability to boost the reparative properties of stem cells, including those in the dental pulp. This narrative review aims to deepen our understanding of the dynamics of bioactive molecules in the dental pulp and their role in enhancing hard tissue reparative processes. OBJECTIVES (i) To discuss the role of different cells and the critical pathways involved in dentine formation through direct (reparative) or indirect (infection control and immunomodulatory) mechanisms. (ii) To highlight how innovative therapeutic strategies could be employed to target key molecules for successful dentine repair and regeneration. METHODS The review encompassed all years up to the search period. Databases such as PubMed, Scopus and Medline were utilized to gather relevant studies. The search strategy involved specific signalling molecules such as Transforming growth factor-β1 (TGF-β), Bone Morphogenetic Proteins (BMP), Small Integrin Binding Ligand N-linked Glycoproteins (SIBLING) and growth factors. Cell types including odontoblasts, fibroblasts, immune cells and dental pulp stem cells (DPSCs) were of interest. Additionally, signalling pathways like Wnt, Notch, Shh, amongst others, were investigated for their roles in repair mechanisms. Key terms were combined using Boolean operators [Cell type] AND [signalling molecules] AND/OR [dentine], [Cell type] AND/OR [signalling pathways] AND/OR [dentine] to include studies addressing the interaction of these components in enhancing repair processes. DISCUSSION Key molecules such as TGF-β1, BMP and SIBLING proteins effectively enhance the dentine reparative response, whilst other molecules such as complement proteins and antimicrobial peptides primarily activate immune cells and facilitate pathogen clearance to promote the regenerative capabilities of DPSCs. This well-orchestrated interaction emphasizes the need to investigate the effects of these molecules on all cells within the dental pulp. Morphogenic signalling molecules such as BMP-2, -4 and -7, and Wnt show temporal, yet significant regenerative properties, whilst Shh and Notch present inconsistent effects on dentine regeneration, and a consensus on their roles and properties in dentine repair has yet to be reached. CONCLUSIONS This review highlights the critical role of bioactive molecules in dentine repair to guide the development of next-generation bioinspired therapeutics for vital pulp therapy.
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Affiliation(s)
- Vidhyashree Rajasekar
- Division of Paediatric Dentistry and Orthodontics, Faculty of Dentistry, The University of Hong Kong, Hong Kong, SAR, Hong Kong
| | - Mohamed Mahmoud Abdalla
- Dental Biomaterials, Faculty of Dental Medicine Al-Azhar University, Cairo, Egypt
- Division of Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong, Hong Kong, SAR, Hong Kong
| | - Prasanna Neelakantan
- Faculty of Medicine and Dentistry, Mike Petryk School of Dentistry, University of Alberta, Edmonton, Alberta, Canada
- Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada
- Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada
| | - Cynthia K Y Yiu
- Division of Paediatric Dentistry and Orthodontics, Faculty of Dentistry, The University of Hong Kong, Hong Kong, SAR, Hong Kong
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Tian M, Keshavarz M, Demircali AA, Han B, Yang G. Localized Microrobotic Delivery of Enzyme-Responsive Hydrogel-Immobilized Therapeutics to Suppress Triple-Negative Breast Cancer. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2025; 21:e2408813. [PMID: 39692188 PMCID: PMC12051738 DOI: 10.1002/smll.202408813] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 12/09/2024] [Indexed: 12/19/2024]
Abstract
Triple-negative breast cancer (TNBC), characterized by its aggressive metastatic propensity and lack of effective targeted therapeutic options, poses a major challenge in oncological management. A proof-of-concept neoadjuvant strategy aimed at inhibiting TNBC tumor growth and mitigating metastasis through a localized delivery of chemotherapeutics is reported in this paper. This approach addresses the limitations in payload capacity and stimuli responsiveness commonly associated with microrobotics in oncology. A hydrogel-based system is developed for the immobilization of chemotherapeutic agents, subsequently encapsulated within magnetically responsive microrobots. This design leverages external magnetic fields to facilitate the precise navigation and localization of the therapeutic agents directly to the tumor site. The efficacy of this approach is demonstrated in an animal model, in which a significant 14-fold reduction in tumor size and suppression of metastasis to critical organs such as the liver and lungs are observed. Crucially, the drug release mechanism is engineered to be responsive to the tumor microenvironment and is regulated by the overexpression of the enzymatic activity of matrix metalloproteinases (MMP2 and MMP9) in TNBC tumors, triggering the degradation of the hydrogel matrix, leading to controlled release of the immobilized therapeutic drug. This ensures that the therapeutic action is localized, reducing systemic toxicity and enhancing treatment efficacy. These findings suggest that this neoadjuvant approach holds promise for broader applications in other cancer types.
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Affiliation(s)
- Mingzhen Tian
- Institute of Medical Robotics, School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai200240China
| | - Meysam Keshavarz
- The Hamlyn Centre, Institute of Global Health InnovationImperial College LondonLondonSouth KensingtonSW7 2AZUK
| | - Ali Anil Demircali
- Department of Metabolism, Digestion, and Reproduction, Faculty of MedicineImperial College LondonLondonSW7 2AZUK
| | - Bing Han
- Institute of Medical Robotics, School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai200240China
| | - Guang‐Zhong Yang
- Institute of Medical Robotics, School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai200240China
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Nakazato H, Onodera S, Aida N, Furusawa M, Azuma T. Comprehensive analysis of transcription factors involved in odontoblast differentiation mechanism. Med Mol Morphol 2024; 57:253-267. [PMID: 38987402 DOI: 10.1007/s00795-024-00389-w] [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: 12/28/2023] [Accepted: 04/18/2024] [Indexed: 07/12/2024]
Abstract
Primary cultured odontoblasts rapidly lose their tissue-specific phenotype. To identify transcription factors (TF) that are important for the maintenance of the odontoblast phenotype, primary cultures of C57BL/6 J mouse dental mesenchymal cells (DMC) were isolated, and expression of TF and odontoblast marker genes in cells immediately after isolation and 2 days after culture were comprehensively evaluated and compared using RNA-sequencing (RNA-seq). The expression of odontoblast markers in mouse dental mesenchymal cells decreased rapidly after isolation. In addition, the expression of Hedgehog-related, Notch-related, and immediate- early gene (IEG)-related transcription factors significantly decreased. Forced expression of these genes in lentiviral vectors, together with fibroblast growth factor 4 (FGF4), fibroblast growth factor 9 (FGF9), and the Wnt pathway activator CHIR99021, significantly induced the expression of odontogenic marker genes. These results indicate, for the first time, that Notch signaling and early genes may be important for maintaining odontoblast cultures. Furthermore, simultaneous stimulation of FGF, Wnt, Hedgehog, Notch pathways, and IEG transcription factors cooperatively promoted the maintenance of the odontoblast phenotype. These results suggest that the Hedgehog and Notch signaling pathways may play an important role in maintaining odontoblast phenotypes, in addition to FGF and Wnt signaling.
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Affiliation(s)
- Haruka Nakazato
- Department of Endodontics, Tokyo Dental College, 2-9-18 Kanda-Misaki-Chou, Chiyoda, Tokyo, 101-0061, Japan
| | - Shoko Onodera
- Department of Biochemistry, Tokyo Dental College, 2-9-18 Kanda-Misaki-Chou, Chiyoda, Tokyo, 101-0061, Japan
| | - Natsuko Aida
- Department of Biochemistry, Tokyo Dental College, 2-9-18 Kanda-Misaki-Chou, Chiyoda, Tokyo, 101-0061, Japan
| | - Masahiro Furusawa
- Department of Endodontics, Tokyo Dental College, 2-9-18 Kanda-Misaki-Chou, Chiyoda, Tokyo, 101-0061, Japan
| | - Toshifumi Azuma
- Department of Biochemistry, Tokyo Dental College, 2-9-18 Kanda-Misaki-Chou, Chiyoda, Tokyo, 101-0061, Japan.
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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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5
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Shamszadeh S, Shirvani A, Asgary S. The Role of Growth Factor Delivery Systems on Cellular Activities of Dental Stem Cells: A Systematic Review (Part II). Curr Stem Cell Res Ther 2024; 19:587-610. [PMID: 35692144 DOI: 10.2174/1574888x17666220609093939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 03/09/2022] [Accepted: 03/29/2022] [Indexed: 11/22/2022]
Abstract
OBJECTIVE The current systematic review aims to provide the available ex vivo evidence evaluating the biological interactions of dental stem cells (DSCs) and growth factor delivery systems. METHODS Following the Preferred Reporting Items for a Systematic Reviews and Meta-Analyses (PRISMA) guidelines, systematic search was conducted in the electronic databases (PubMed/Medline, Scopus, Web of Science, and Google Scholar) up to January 2022. Studies evaluating the biological interactions of DSCs and growth factor delivery systems were included. The outcome measures were cell cytocompatibility, mineralization, and differentiation. RESULTS Sixteen studies were selected for the qualitative synthesis. The following growth factor delivery systems exhibit adequate cytocompatibility, enhanced mineralization, and osteo/odontoblast differentiation potential of DSCs: 1) Fibroblast growth factor (FGF-2)-loaded-microsphere and silk fibroin, 2) Bone morphogenic protein-2 (BMP-2)-loaded-microsphere and mesoporous calcium silicate scaffold, 3) Transforming growth factor Beta 1 (TGF-ß1)-loaded-microsphere, glass ionomer cement (GIC), Bio-GIC and liposome, 4) TGF-ß1-loaded-nanoparticles/scaffold, 5) Vascular endothelial growth factor (VEGF)-loaded-fiber and hydrogel, 6) TGF-ß1/VEGF-loaded-nanocrystalline calcium sulfate/hydroxyapatite/calcium sulfate, 7) Epidermal growth factor-loaded- nanosphere, 8) Stem cell factor/DSCs-loaded-hydrogel and Silk fibroin, 9) VEGF/BMP-2/DSCs-loaded-Three-dimensional matrix, 10) VEGF/DSCs-loaded-microsphere/hydrogel, and 11) BMP-2/DSCs and VEGF/DSCs-loaded-Collagen matrices. The included delivery systems showed viability, except for Bio-GIC on day 3. The choice of specific growth factors and delivery systems (i.e., BMP-2-loaded-microsphere and VEGF-loaded-hydrogel) resulted in a greater gene expression. CONCLUSIONS This study, with low-level evidence obtained from ex vivo studies, suggests that growth factor delivery systems induce cell proliferation, mineralization, and differentiation toward a therapeutic potential in regenerative endodontics.
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Affiliation(s)
- Sayna Shamszadeh
- Iranian Center for Endodontic Research, Research Institute of Dental Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Armin Shirvani
- Iranian Center for Endodontic Research, Research Institute of Dental Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeed Asgary
- Iranian Center for Endodontic Research, Research Institute of Dental Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Sequeira DB, Diogo P, Gomes BPFA, Peça J, Santos JMM. Scaffolds for Dentin-Pulp Complex Regeneration. MEDICINA (KAUNAS, LITHUANIA) 2023; 60:7. [PMID: 38276040 PMCID: PMC10821321 DOI: 10.3390/medicina60010007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 11/24/2023] [Accepted: 12/18/2023] [Indexed: 01/27/2024]
Abstract
Background and Objectives: Regenerative dentistry aims to regenerate the pulp-dentin complex and restore those of its functions that have become compromised by pulp injury and/or inflammation. Scaffold-based techniques are a regeneration strategy that replicate a biological environment by utilizing a suitable scaffold, which is considered crucial for the successful regeneration of dental pulp. The aim of the present review is to address the main characteristics of the different scaffolds, as well as their application in dentin-pulp complex regeneration. Materials and Methods: A narrative review was conducted by two independent reviewers to answer the research question: What type of scaffolds can be used in dentin-pulp complex regeneration? An electronic search of PubMed, EMBASE and Cochrane library databases was undertaken. Keywords including "pulp-dentin regeneration scaffold" and "pulp-dentin complex regeneration" were used. To locate additional reports, reference mining of the identified papers was undertaken. Results: A wide variety of biomaterials is already available for tissue engineering and can be broadly categorized into two groups: (i) natural, and (ii) synthetic, scaffolds. Natural scaffolds often contain bioactive molecules, growth factors, and signaling cues that can positively influence cell behavior. These signaling molecules can promote specific cellular responses, such as cell proliferation and differentiation, crucial for effective tissue regeneration. Synthetic scaffolds offer flexibility in design and can be tailored to meet specific requirements, such as size, shape, and mechanical properties. Moreover, they can be functionalized with bioactive molecules, growth factors, or signaling cues to enhance their biological properties and the manufacturing process can be standardized, ensuring consistent quality for widespread clinical use. Conclusions: There is still a lack of evidence to determine the optimal scaffold composition that meets the specific requirements and complexities needed for effectively promoting dental pulp tissue engineering and achieving successful clinical outcomes.
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Affiliation(s)
- Diana B. Sequeira
- Institute of Endodontics, Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal (P.D.)
- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal;
- Center for Innovation and Research in Oral Sciences (CIROS), Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal
| | - Patrícia Diogo
- Institute of Endodontics, Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal (P.D.)
- Center for Innovation and Research in Oral Sciences (CIROS), Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal
| | - Brenda P. F. A. Gomes
- Department of Restorative Dentistry, Division of Endodontics, Piracicaba Dental School, State University of Campinas—UNICAMP, Piracicaba 13083-970, Brazil;
| | - João Peça
- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal;
- Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, 3000-456 Coimbra, Portugal
| | - João Miguel Marques Santos
- Institute of Endodontics, Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal (P.D.)
- Center for Innovation and Research in Oral Sciences (CIROS), Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal
- Coimbra Institute for Clinical and Biomedical Research (iCBR) and Center of Investigation on Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
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Washio A, Kérourédan O, Tabata Y, Kokabu S, Kitamura C. Effect of Bioactive Glasses and Basic Fibroblast Growth Factor on Dental Pulp Cells. J Funct Biomater 2023; 14:568. [PMID: 38132822 PMCID: PMC10744375 DOI: 10.3390/jfb14120568] [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: 10/17/2023] [Revised: 12/15/2023] [Accepted: 12/15/2023] [Indexed: 12/23/2023] Open
Abstract
Ideal regeneration of hard tissue and dental pulp has been reported with the use of a combination of bioactive glass and basic fibroblast growth factor (bFGF). However, no previous study has investigated the molecular mechanisms underlying the processes induced by this combination in dental pulp cells. This study aimed to examine the cellular phenotype and transcriptional changes induced by the combination of bioactive glass solution (BG) and bFGF in dental pulp cells using phase-contrast microscopy, a cell counting kit-8 assay, alkaline phosphatase staining, and RNA sequence analysis. bFGF induced elongation of the cell process and increased the number of cells. Whereas BG did not increase ALP activity, it induced extracellular matrix-related genes in the dental pulp. In addition, the combination of BG and bFGF induces gliogenesis-related genes in the nervous system. This is to say, bFGF increased the viability of dental pulp cells, bioactive glass induced odontogenesis, and a dual stimulation with bioactive glass and bFGF induced the wound healing of the nerve system in the dental pulp. Taken together, bioactive glass and bFGF may be useful for the regeneration of the dentin-pulp complex.
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Affiliation(s)
- Ayako Washio
- Division of Endodontics and Restorative Dentistry, Department of Oral Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Japan;
| | - Olivia Kérourédan
- National Institute of Health and Medical Research (INSERM), U1026 BIOTIS, University of Bordeaux, 146 Rue Léo Saignat, 33076 Bordeaux, France;
| | - Yasuhiko Tabata
- Laboratory of Biomaterials, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan;
| | - Shoichiro Kokabu
- Division of Molecular Signaling and Biochemistry, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Japan;
| | - Chiaki Kitamura
- Division of Endodontics and Restorative Dentistry, Department of Oral Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Japan;
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Atia GA, Shalaby HK, Roomi AB, Ghobashy MM, Attia HA, Mohamed SZ, Abdeen A, Abdo M, Fericean L, Bănățean Dunea I, Atwa AM, Hasan T, Mady W, Abdelkader A, Ali SA, Habotta OA, Azouz RA, Malhat F, Shukry M, Foda T, Dinu S. Macro, Micro, and Nano-Inspired Bioactive Polymeric Biomaterials in Therapeutic, and Regenerative Orofacial Applications. Drug Des Devel Ther 2023; 17:2985-3021. [PMID: 37789970 PMCID: PMC10543943 DOI: 10.2147/dddt.s419361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 08/12/2023] [Indexed: 10/05/2023] Open
Abstract
Introducing dental polymers has accelerated biotechnological research, advancing tissue engineering, biomaterials development, and drug delivery. Polymers have been utilized effectively in dentistry to build dentures and orthodontic equipment and are key components in the composition of numerous restorative materials. Furthermore, dental polymers have the potential to be employed for medication administration and tissue regeneration. To analyze the influence of polymer-based investigations on practical medical trials, it is required to evaluate the research undertaken in this sector. The present review aims to gather evidence on polymer applications in dental, oral, and maxillofacial reconstruction.
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Affiliation(s)
- Gamal A Atia
- Department of Oral Medicine, Periodontology, and Diagnosis, Faculty of Dentistry, Suez Canal University, Ismailia, Egypt
| | - Hany K Shalaby
- Department of Oral Medicine, Periodontology and Oral Diagnosis, Faculty of Dentistry, Suez University, Suez, Egypt
| | - Ali B Roomi
- Department of Quality Assurance, University of Thi-Qar, Thi-Qar, Iraq
- Department of Medical Laboratory, College of Health and Medical Technology, National University of Science and Technology, Thi-Qar, Iraq
| | - Mohamed M Ghobashy
- Radiation Research of Polymer Chemistry Department, National Center for Radiation Research and Technology (NCRRT), Atomic Energy Authority, Cairo, Egypt
| | - Hager A Attia
- Department of Molecular Biology and Chemistry, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Sara Z Mohamed
- Department of Removable Prosthodontics, Faculty of Dentistry, Suez Canal University, Ismailia, Egypt
| | - Ahmed Abdeen
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Toukh, Egypt
| | - Mohamed Abdo
- Department of Animal Histology and Anatomy, School of Veterinary Medicine, Badr University in Cairo (BUC), Badr City, Egypt
- Department of Anatomy and Embryology, Faculty of Veterinary Medicine, University of Sadat City, Sadat, Egypt
| | - Liana Fericean
- Department of Biology and Plant Protection, Faculty of Agriculture. University of Life Sciences “King Michael I” from Timișoara, Timișoara, Romania
| | - Ioan Bănățean Dunea
- Department of Biology and Plant Protection, Faculty of Agriculture. University of Life Sciences “King Michael I” from Timișoara, Timișoara, Romania
| | - Ahmed M Atwa
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt
| | - Tabinda Hasan
- Department of Basic Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Wessam Mady
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Afaf Abdelkader
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha, Egypt
| | - Susan A Ali
- Department of Radiodiagnosis, Faculty of Medicine, Ain Shams University, Abbassia, 1181, Egypt
| | - Ola A Habotta
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
| | - Rehab A Azouz
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Farag Malhat
- Department of Pesticide Residues and Environmental Pollution, Central Agricultural Pesticide Laboratory, Agricultural Research Center, Giza, Egypt
| | - Mustafa Shukry
- Department of Physiology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt
| | - Tarek Foda
- Oral Health Sciences Department, Temple University’s Kornberg School of Dentistry, Philadelphia, PA, USA
| | - Stefania Dinu
- Department of Pedodontics, Faculty of Dental Medicine, Victor Babes University of Medicine and Pharmacy Timisoara, Timisoara, 300041, Romania
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9
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Duncan HF, Kobayashi Y, Kearney M, Shimizu E. Epigenetic therapeutics in dental pulp treatment: Hopes, challenges and concerns for the development of next-generation biomaterials. Bioact Mater 2023; 27:574-593. [PMID: 37213443 PMCID: PMC10199232 DOI: 10.1016/j.bioactmat.2023.04.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 04/11/2023] [Accepted: 04/11/2023] [Indexed: 05/23/2023] Open
Abstract
This opinion-led review paper highlights the need for novel translational research in vital-pulp-treatment (VPT), but also discusses the challenges in translating evidence to clinics. Traditional dentistry is expensive, invasive and relies on an outmoded mechanical understanding of dental disease, rather than employing a biological perspective that harnesses cell activity and the regenerative-capacity. Recent research has focussed on developing minimally-invasive biologically-based 'fillings' that preserve the dental pulp; research that is shifting the paradigm from expensive high-technology dentistry, with high failure rates, to smart restorations targeted at biological processes. Current VPTs promote repair by recruiting odontoblast-like cells in a material-dependent process. Therefore, exciting opportunities exist for development of next-generation biomaterials targeted at regenerative processes in the dentin-pulp complex. This article analyses recent research using pharmacological-inhibitors to therapeutically-target histone-deacetylase (HDAC) enzymes in dental-pulp-cells (DPCs) that stimulate pro-regenerative effects with limited loss of viability. Consequently, HDAC-inhibitors have the potential to enhance biomaterial-driven tissue responses at low concentration by influencing the cellular processes with minimal side-effects, providing an opportunity to develop a topically-placed, inexpensive bio-inductive pulp-capping material. Despite positive results, clinical translation of these innovations requires enterprise to counteract regulatory obstacles, dental-industry priorities and to develop strong academic/industry partnerships. The aim of this opinion-led review paper is to discuss the potential role of therapeutically-targeting epigenetic modifications as part of a topical VPT strategy in the treatment of the damaged dental pulp, while considering the next steps, material considerations, challenges and future for the clinical development of epigenetic therapeutics or other 'smart' restorations in VPT.
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Affiliation(s)
- Henry F. Duncan
- Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin, University of Dublin, Lincoln Place, Dublin, Ireland
| | - Yoshifumi Kobayashi
- Department of Oral Biology, Rutgers School of Dental Medicine, Newark, NJ, USA
| | - Michaela Kearney
- Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin, University of Dublin, Lincoln Place, Dublin, Ireland
| | - Emi Shimizu
- Department of Oral Biology, Rutgers School of Dental Medicine, Newark, NJ, USA
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Zhang Z, Bi F, Guo W. Research Advances on Hydrogel-Based Materials for Tissue Regeneration and Remineralization in Tooth. Gels 2023; 9:gels9030245. [PMID: 36975694 PMCID: PMC10048036 DOI: 10.3390/gels9030245] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 03/14/2023] [Accepted: 03/17/2023] [Indexed: 03/29/2023] Open
Abstract
Tissue regeneration and remineralization in teeth is a long-term and complex biological process, including the regeneration of pulp and periodontal tissue, and re-mineralization of dentin, cementum and enamel. Suitable materials are needed to provide cell scaffolds, drug carriers or mineralization in this environment. These materials need to regulate the unique odontogenesis process. Hydrogel-based materials are considered good scaffolds for pulp and periodontal tissue repair in the field of tissue engineering due to their inherent biocompatibility and biodegradability, slow release of drugs, simulation of extracellular matrix, and the ability to provide a mineralized template. The excellent properties of hydrogels make them particularly attractive in the research of tissue regeneration and remineralization in teeth. This paper introduces the latest progress of hydrogel-based materials in pulp and periodontal tissue regeneration and hard tissue mineralization and puts forward prospects for their future application. Overall, this review reveals the application of hydrogel-based materials in tissue regeneration and remineralization in teeth.
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Affiliation(s)
- Zhijun Zhang
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Pediatric Dentistry, West China School of Stomatology, Sichuan University, Chengdu 610041, China
| | - Fei Bi
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Weihua Guo
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Pediatric Dentistry, West China School of Stomatology, Sichuan University, Chengdu 610041, China
- Yunnan Key Laboratory of Stomatology, The Affiliated Hospital of Stomatology, School of Stomatology, Kunming Medical University, Kunming 650500, China
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Li K, O'Dwyer R, Yang F, Cymerman J, Li J, Feldman JD, Simon M, Rafailovich M. Enhancement of acellular biomineralization, dental pulp stem cell migration, and differentiation by hybrid fibrin gelatin scaffolds. Dent Mater 2023; 39:305-319. [PMID: 36746694 DOI: 10.1016/j.dental.2023.01.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 01/16/2023] [Accepted: 01/31/2023] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The current in vitro study aims to evaluate cross-linked hydrogels with and without the addition of fibrin that could potentially be used in endodontic regeneration as a scaffold material. METHODS Synthesis of gelatin/fibrin scaffold, and performing nanoscale characterization using cryo-electron microscopy, dynamic rheology, and XRF for structure property relations; plating dental pulp stem cells and determining mineralization, migration, and differentiation using rt-PCR, XRF, and Raman spectroscopy. RESULTS Cryo electron imaging shows gelatin and fibrin, when gelled separately to form classical rectangular cross-linked networks, where the modulus scales inversely with the cube root of the mesh size. When gelled together, a network with a fundamentally different structure is formed, which has higher ductility and when placed as a scaffold in osteogenic media, produces twice the mineral content. Immunofluorescence, RT-PCR and Rahman Spectroscopy indicate that the hybrid gel enhances cell migration, induces odontogenic differentiation of dental pulp stem cells, and promotes formation of dentin. SIGNIFICANCE The mechanical properties of the hybrid gel scaffold enhance in-migration of stem cells and subsequent differentiation, which are critical for regenerative procedures. Under acellular conditions, placement of the hybrid gel enhances biomineralization, which would strengthen the root if used as a scaffold for endodontic regeneration. Our in vitro findings are consistent with previous in vivo studies which show improved mineralization when bleeding is induced into the canal, given that fibrin is a primary component in blood clotting. Therefore, insertion of the hybrid gelatin-fibrin scaffold could enable more reproducible and consistent outcomes if used for regenerative endodontic treatment (RET).
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Affiliation(s)
- Kao Li
- Department of Materials Science and Chemical Engineering, Stony Brook University, Stony Brook, NY 11794, USA; Shandong Institute of Petroleum and Chemical Technology, Doying, Shandong 257061, China
| | - Rita O'Dwyer
- Department of Periodontology, Division of Endodontics, School of Dental Medicine, Stony Brook University, NY 11794, USA; Department of Oral Biology and Pathology, Stony Brook University Medical Center, Stony Brook, NY 11794, USA
| | - Fan Yang
- Department of Materials Science and Chemical Engineering, Stony Brook University, Stony Brook, NY 11794, USA
| | - Jerome Cymerman
- Department of Periodontology, Division of Endodontics, School of Dental Medicine, Stony Brook University, NY 11794, USA; Department of Oral Biology and Pathology, Stony Brook University Medical Center, Stony Brook, NY 11794, USA
| | - Juyi Li
- Department of Materials Science and Chemical Engineering, Stony Brook University, Stony Brook, NY 11794, USA
| | - Jake D Feldman
- Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Marcia Simon
- Department of Oral Biology and Pathology, Stony Brook University Medical Center, Stony Brook, NY 11794, USA
| | - Miriam Rafailovich
- Department of Materials Science and Chemical Engineering, Stony Brook University, Stony Brook, NY 11794, USA.
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12
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Tayanloo-Beik A, Nikkhah A, Roudsari PP, Aghayan H, Rezaei-Tavirani M, Nasli-Esfahani E, Mafi AR, Nikandish M, Shouroki FF, Arjmand B, Larijani B. Application of Biocompatible Scaffolds in Stem-Cell-Based Dental Tissue Engineering. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1409:83-110. [PMID: 35999347 DOI: 10.1007/5584_2022_734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
Abstract
Tissue engineering as an important field in regenerative medicine is a promising therapeutic approach to replace or regenerate injured tissues. It consists of three vital steps including the selection of suitable cells, formation of 3d scaffolds, and adding growth factors. Mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs) are mentioned as two main sources for this approach that have been used for the treatment of various types of disorders. However, the main focus of literature in the field of dental tissue engineering is on utilizing MSCs. On the other hand, biocompatible scaffolds play a notable role in this regenerative process which is mentioned to be harmless with acceptable osteoinductivity. Their ability in inhibiting inflammatory responses also makes them powerful tools. Indeed, stem cell functions should be supported by biomaterials acting as scaffolds incorporated with biological signals. Naturally derived polymeric scaffolds and synthetically engineered polymeric/ceramic scaffolds are two main types of scaffolds regarding their materials that are defined further in this review. Various strategies of tissue bioengineering can affect the regeneration of dentin-pulp complex, periodontium regeneration, and whole teeth bioengineering. In this regard, in vivo/ex vivo experimental models have been developed recently in order to perform preclinical studies of dental tissue engineering which make it more transferable to be used for clinic uses. This review summarizes dental tissue engineering through its different components. Also, strategies of tissue bioengineering and experimental models are introduced in order to provide a perspective of the potential roles of dental tissue engineering to be used for clinical aims.
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Affiliation(s)
- Akram Tayanloo-Beik
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Amirabbas Nikkhah
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Peyvand Parhizkar Roudsari
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamidreza Aghayan
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Ensieh Nasli-Esfahani
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmad Rezazadeh Mafi
- Department of Radiation Oncology, Imam Hossein Hospital, Shaheed Beheshti Medical University, Tehran, Iran
| | - Mohsen Nikandish
- AJA Cancer Epidemiology Research and Treatment Center (AJA- CERTC), AJA University of Medical Sciences, Tehran, Iran
| | - Fatemeh Fazeli Shouroki
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Babak Arjmand
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
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13
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Development of Growth Factor Releasing Hyaluronic Acid-Based Hydrogel for Pulp Regeneration: A Preliminary Study. Gels 2022; 8:gels8120825. [PMID: 36547349 PMCID: PMC9778203 DOI: 10.3390/gels8120825] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/09/2022] [Accepted: 12/09/2022] [Indexed: 12/15/2022] Open
Abstract
Growth factors play essential roles as signaling molecules in pulp regeneration. We investigated the effect of a hyaluronic acid (HA)-collagen hybrid hydrogel with controlled release of fibroblast growth factor (FGF)-2 and platelet-derived growth factor (PDGF)-BB on human pulp regeneration. The cell interaction and cytotoxicity of the HA-collagen hybrid hydrogel, the release kinetics of each growth factor, and the effects of the released growth factors on pulp cell proliferation were examined. The vitality of pulp cells was maintained. The amounts of FGF-2 and PDGF-BB released over 7 days were 68% and 50%, respectively. Groups with a different concentration of growth factor (FGF-2: 100, 200, 500, and 1000 ng/mL; PDGF-BB: 10, 50, 100, 200, and 500 ng/mL) were experimented on days 1, 3, 5, and 7. Considering FGF-2 concentration, significantly increased pulp cell proliferation was observed on days 1, 3, 5, and 7 in the 100 ng/mL group and on days 3, 5, and 7 in the 200 ng/mL group. In the case of PDGF-BB concentration, significantly increased pulp cell proliferation was observed at all four time points in the 100 ng/mL group and on days 3, 5, and 7 in the 50, 200, and 500 ng/mL groups. This indicates that the optimal concentration of FGF-2 and PDGF-BB for pulp cell proliferation was 100 ng/mL and that the HA-collagen hybrid hydrogel has potential as a controlled release delivery system for FGF-2 and PDGF-BB.
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14
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Liu L, Li X, Bu W, Jin N, Meng Y, Wang Y, Wang D, Xu X, Zhou D, Sun H. Carbon dots enhance extracellular matrix secretion for dentin-pulp complex regeneration through PI3K/Akt/mTOR pathway-mediated activation of autophagy. Mater Today Bio 2022; 16:100344. [PMID: 35833197 PMCID: PMC9272035 DOI: 10.1016/j.mtbio.2022.100344] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/24/2022] [Accepted: 06/25/2022] [Indexed: 12/11/2022] Open
Abstract
Pulp injury is one of the most common clinical diseases, and severe cases are usually associated with the functional loss of the tooth, while the current clinical treatment modality is only a cavity filling procedure without the regeneration of the dentin-pulp complex, thus leading to a devitalized and brittle tooth. In this study, carbon dots (CDots) with excellent biocompatibility are prepared from ascorbic acid and polyethyleneimine via a hydrothermal method. The as-prepared CDots can enhance extracellular matrix (ECM) secretion of human dental pulp stem cells (DPSCs), giving rise to increased cell adhesion on ECM and a stronger osteogenic/odontogenic differentiation capacity of DPSCs. Further, the mechanism underlying CDots-enhanced ECM secretion is revealed by the transcriptome analysis, Western blot assay and molecular dynamics simulation, identifying that the pharmacological activities of CDots are originated from a reasonable activation of the autophagy, which is mediated by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway. Based on the abundant CDots-induced ECM and thereby the reinforcement of the cell-ECM adhesion, an intact dental pulp stem cell sheet can be achieved, which in return promote in vivo the efficient regeneration of dentin-pulp complex as well as blood vessels.
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Affiliation(s)
- Lili Liu
- Hospital of Stomatology, Jilin University, Changchun, 130021, PR China
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Jilin University, Changchun, 130021, PR China
| | - Xianjing Li
- Hospital of Stomatology, Jilin University, Changchun, 130021, PR China
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Jilin University, Changchun, 130021, PR China
| | - Wenhuan Bu
- School and Hospital of Stomatology, China Medical University, Shenyang, 110122, PR China
| | - Nianqiang Jin
- School and Hospital of Stomatology, China Medical University, Shenyang, 110122, PR China
| | - Yuan Meng
- School and Hospital of Stomatology, China Medical University, Shenyang, 110122, PR China
| | - Yi Wang
- Graduate Program in Applied Physics, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208, USA
| | - Duan Wang
- Hospital of Stomatology, Jilin University, Changchun, 130021, PR China
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Jilin University, Changchun, 130021, PR China
| | - Xiaowei Xu
- Hospital of Stomatology, Jilin University, Changchun, 130021, PR China
| | - Ding Zhou
- Hospital of Stomatology, Jilin University, Changchun, 130021, PR China
| | - Hongchen Sun
- Hospital of Stomatology, Jilin University, Changchun, 130021, PR China
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15
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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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16
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Jindal S, Awasthi R, Goyal K, Kulkarni GT. Hydrogels for localized drug delivery: A special emphasis on dermatologic applications. Dermatol Ther 2022; 35:e15830. [DOI: 10.1111/dth.15830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 08/06/2022] [Accepted: 09/12/2022] [Indexed: 11/28/2022]
Affiliation(s)
- Shammy Jindal
- Laureate Institute of Pharmacy, Kathog Jawalamukhi Himachal Pradesh India
| | - Rajendra Awasthi
- Department of Pharmaceutical Sciences School of Health Sciences & Technology, University of Petroleum and Energy Studies (UPES), Energy Acres, P.O. Bidholi, Via‐Prem Nagar Dehradun Uttarakhand India
| | - Kamya Goyal
- Laureate Institute of Pharmacy, Kathog Jawalamukhi Himachal Pradesh India
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17
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Agrawal P, Nikhade P, Chandak M, Ikhar A, Bhonde R. Dentin Matrix Metalloproteinases: A Futuristic Approach Toward Dentin Repair and Regeneration. Cureus 2022; 14:e27946. [PMID: 36120221 PMCID: PMC9464706 DOI: 10.7759/cureus.27946] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 08/12/2022] [Indexed: 11/05/2022] Open
Abstract
Matrix metalloproteinases (MMPs) have been linked to modulating healing during the production of tertiary dentin, as well as the liberation of physiologically active molecules and the control of developmental processes. Although efforts to protect dentin have mostly centered on preventing these proteases from doing their jobs, their role is actually much more intricate and crucial for dentin healing than anticipated. The role of MMPs as bioactive dentin matrix components involved in dentin production, repair, and regeneration is examined in the current review. The mechanical characteristics of dentin, especially those of reparative and reactionary dentin, and the established functions of MMPs in dentin production are given particular attention. Because they are essential parts of the dentin matrix, MMPs should be regarded as leading applicants for dentin regeneration.
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18
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Moghanian A, Cecen B, Nafisi N, Miri Z, Rosenzweig DH, Miri AK. Review of Current Literature for Vascularized Biomaterials in Dental Repair. Biochem Eng J 2022. [DOI: 10.1016/j.bej.2022.108545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
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19
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Terranova L, Louvrier A, Hébraud A, Meyer C, Rolin G, Schlatter G, Meyer F. Highly Structured 3D Electrospun Conical Scaffold: A Tool for Dental Pulp Regeneration. ACS Biomater Sci Eng 2021; 7:5775-5787. [PMID: 34846849 DOI: 10.1021/acsbiomaterials.1c00900] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
New procedures envisioned for dental pulp regeneration after pulpectomy include cell homing strategy. It involves host endogenous stem cell recruitment and activation. To meet this cell-free approach, we need to design a relevant scaffold to support cell migration from tissues surrounding the dental root canal. A composite membrane made of electrospun poly(lactic acid) nanofibers and electrosprayed polycaprolactone with tannic acid (TA) microparticles which mimics the architecture of the extracellular matrix was first fabricated. After rolling the membrane in the form of a 3D conical scaffold and subsequently coating it with gelatin, it can be directly inserted into the root canal. The porous morphology of the construct was characterized by SEM at different length scales. It was shown that TA was released from the 3D conical scaffold after 2 days in PBS at 37 °C. Biocompatibility studies were first assessed by seeding human dental pulp stem cells (DPSCs) on planar membranes coated or not coated with gelatin to compare the surfaces. After 24 h, the results highlighted that the gelatin-coating increased the membrane biocompatibility and cell viability. Similar DPSC morphology and proliferation on both membrane surfaces were observed. The culture of DPSCs on conical scaffolds showed cell colonization in the whole cone volume, proving that the architecture of the conical scaffold was suitable for cell migration.
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Affiliation(s)
- Lisa Terranova
- Biomaterials and Bioengineering, Université de Strasbourg, Institut National de la Santé et de la Recherche Médicale, Unité mixte de recherche 1121, Strasbourg 67000, France.,Université de Strasbourg, Institut de Chimie et Procédés pour l'Energie, l'Environnement et la Santé ICPEES UMR 7515, CNRS, Strasbourg 67000, France
| | - Aurélien Louvrier
- Service de chirurgie maxillo-faciale, stomatologie et odontologie hospitalière, CHU Besançon, Besançon F-25000, France.,Université Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, Besançon F-25000, France
| | - Anne Hébraud
- Université de Strasbourg, Institut de Chimie et Procédés pour l'Energie, l'Environnement et la Santé ICPEES UMR 7515, CNRS, Strasbourg 67000, France
| | - Christophe Meyer
- Service de chirurgie maxillo-faciale, stomatologie et odontologie hospitalière, CHU Besançon, Besançon F-25000, France
| | - Gwenaël Rolin
- Université Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, Besançon F-25000, France.,Inserm CIC-1431, CHU Besançon, Besançon F-25000, France
| | - Guy Schlatter
- Université de Strasbourg, Institut de Chimie et Procédés pour l'Energie, l'Environnement et la Santé ICPEES UMR 7515, CNRS, Strasbourg 67000, France
| | - Florent Meyer
- Biomaterials and Bioengineering, Université de Strasbourg, Institut National de la Santé et de la Recherche Médicale, Unité mixte de recherche 1121, Strasbourg 67000, France.,Pôle de médecine et chirurgie bucco-dentaires, Hôpitaux Universitaires de Strasbourg, Strasbourg 67000, France
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Zhang SY, Ren JY, Yang B. Priming strategies for controlling stem cell fate: Applications and challenges in dental tissue regeneration. World J Stem Cells 2021; 13:1625-1646. [PMID: 34909115 PMCID: PMC8641023 DOI: 10.4252/wjsc.v13.i11.1625] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 05/14/2021] [Accepted: 08/27/2021] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stromal cells (MSCs) have attracted intense interest in the field of dental tissue regeneration. Dental tissue is a popular source of MSCs because MSCs can be obtained with minimally invasive procedures. MSCs possess distinct inherent properties of self-renewal, immunomodulation, proangiogenic potential, and multilineage potency, as well as being readily available and easy to culture. However, major issues, including poor engraftment and low survival rates in vivo, remain to be resolved before large-scale application is feasible in clinical treatments. Thus, some recent investigations have sought ways to optimize MSC functions in vitro and in vivo. Currently, priming culture conditions, pretreatment with mechanical and physical stimuli, preconditioning with cytokines and growth factors, and genetic modification of MSCs are considered to be the main strategies; all of which could contribute to improving MSC efficacy in dental regenerative medicine. Research in this field has made tremendous progress and continues to gather interest and stimulate innovation. In this review, we summarize the priming approaches for enhancing the intrinsic biological properties of MSCs such as migration, antiapoptotic effect, proangiogenic potential, and regenerative properties. Challenges in current approaches associated with MSC modification and possible future solutions are also indicated. We aim to outline the present understanding of priming approaches to improve the therapeutic effects of MSCs on dental tissue regeneration.
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Affiliation(s)
- Si-Yuan Zhang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jia-Yin Ren
- Department of Oral Radiology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Bo Yang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
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21
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Samiei M, Fathi M, Barar J, Fathi N, Amiryaghoubi N, Omidi Y. Bioactive hydrogel-based scaffolds for the regeneration of dental pulp tissue. J Drug Deliv Sci Technol 2021. [DOI: 10.1016/j.jddst.2021.102600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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22
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Liu K, Yu S, Ye L, Gao B. The Regenerative Potential of bFGF in Dental Pulp Repair and Regeneration. Front Pharmacol 2021; 12:680209. [PMID: 34354584 PMCID: PMC8329335 DOI: 10.3389/fphar.2021.680209] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Accepted: 06/22/2021] [Indexed: 02/05/2023] Open
Abstract
Regenerative endodontic therapy intends to induce the host’s natural wound-healing process, which can restore the vitality, immunity, and sensitivity of the inflammatory or necrotic pulp tissue destroyed by infection or trauma. Myriads of growth factors are critical in the processes of pulp repair and regeneration. Among the key regulatory factors are the fibroblast growth factors, which have turned out to be the master regulators of both organogenesis and tissue homeostasis. Fibroblast growth factors, a family composed of 22 polypeptides, have been used in tissue repair and regeneration settings, in conditions as diverse as burns, ulcers, bone-related diseases, and spinal cord injuries. Meanwhile, in dentistry, the basic fibroblast growth factor is the most frequently investigated. Thereby, the aim of this review is 2-fold: 1) foremost, to explore the underlying mechanisms of the bFGF in dental pulp repair and regeneration and 2) in addition, to shed light on the potential therapeutic strategies of the bFGF in dental pulp–related clinical applications.
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Affiliation(s)
- Keyue Liu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Sijing Yu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Ling Ye
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Bo Gao
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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23
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Huang X, Li Z, Liu A, Liu X, Guo H, Wu M, Yang X, Han B, Xuan K. Microenvironment Influences Odontogenic Mesenchymal Stem Cells Mediated Dental Pulp Regeneration. Front Physiol 2021; 12:656588. [PMID: 33967826 PMCID: PMC8100342 DOI: 10.3389/fphys.2021.656588] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 03/23/2021] [Indexed: 12/21/2022] Open
Abstract
Dental pulp as a source of nutrition for the whole tooth is vulnerable to trauma and bacterial invasion, which causes irreversible pulpitis and pulp necrosis. Dental pulp regeneration is a valuable method of restoring the viability of the dental pulp and even the whole tooth. Odontogenic mesenchymal stem cells (MSCs) residing in the dental pulp environment have been widely used in dental pulp regeneration because of their immense potential to regenerate pulp-like tissue. Furthermore, the regenerative abilities of odontogenic MSCs are easily affected by the microenvironment in which they reside. The natural environment of the dental pulp has been proven to be capable of regulating odontogenic MSC homeostasis, proliferation, and differentiation. Therefore, various approaches have been applied to mimic the natural dental pulp environment to optimize the efficacy of pulp regeneration. In addition, odontogenic MSC aggregates/spheroids similar to the natural dental pulp environment have been shown to regenerate well-organized dental pulp both in preclinical and clinical trials. In this review, we summarize recent progress in odontogenic MSC-mediated pulp regeneration and focus on the effect of the microenvironment surrounding odontogenic MSCs in the achievement of dental pulp regeneration.
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Affiliation(s)
- Xiaoyao Huang
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Zihan Li
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Anqi Liu
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Xuemei Liu
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Hao Guo
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Meiling Wu
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Xiaoxue Yang
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Bing Han
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Kun Xuan
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
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Alipour M, Ashrafihelan J, Salehi R, Aghazadeh Z, Rezabakhsh A, Hassanzadeh A, Firouzamandi M, Heidarzadeh M, Rahbarghazi R, Aghazadeh M, Saghati S. In vivo evaluation of biocompatibility and immune modulation potential of poly(caprolactone)-poly(ethylene glycol)-poly(caprolactone)-gelatin hydrogels enriched with nano-hydroxyapatite in the model of mouse. J Biomater Appl 2021; 35:1253-1263. [PMID: 33632003 DOI: 10.1177/0885328221998525] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Biocompatible, biodegradable, and injectable hydrogels are a novel and promising approach for bone regeneration. In this study, poly(caprolactone)-poly(ethylene glycol)-poly(caprolactone) (PCL-PEG-PCL), PCL-PEG-PCL-gelatin (Gel), PCL-PEG-PCL-Gel/nano-hydroxyapatite (nHA) injectable hydrogels were synthesized and evaluated in a mouse model of subcutaneous transplantation after 14 days. PCL-PEG-PCL-Gel and PCL-PEG-PCL-Gel/nHA hydrogels were fabricated with in situ precipitation method. Structure, intermolecular interaction, and the reaction between the PCL-PEG-PCL, Gel, and nHA were evaluated using a scanning electron microscope (SEM), Fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (H-NMR), and carbon nuclear magnetic resonance (C-NMR). Fourteen days after subcutaneous injection, the existence of an immune system reaction was investigated using Hematoxylin and Eosin (H&E) staining. Using immunofluorescence imaging, the number of CD68+ cells was determined in the periphery of the hydrogel. The CD8/CD4 lymphocyte ratio was also calculated in blood samples. We monitored the expression of CCL-2, BCL-2, IL-10, and CD31 using real-time PCR assay. The chemical evaluation revealed the successful integration of Gel and nHA to the PCL-PEG-PCL backbone. Histological examination showed the lack of inflammation at the site of injection. No toxicological effects were determined in hepatic and renal tissues. The addition of nHA to the PCL-PEG-PCL-Gel decreased biodegradation time. None of the hydrogels caused statistically significant differences in the number of CD68 cells (p > 0.05). The CD8/CD4 lymphocyte ratio remained unchanged in all groups (p > 0.05). Compared to the PCL-PEG-PCL group, the addition of nHA and Gel increased the expression of CCL-2, BCL-2, IL-10, and CD31 (p < 0.05). In conclusion, the current study showed that PCL-PEG-PCL-Gel/nHA hydrogels could be used in in vivo conditions without prominent toxic effects and inflammatory responses.
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Affiliation(s)
- Mahdieh Alipour
- Dental and Periodontal Research Center, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Javad Ashrafihelan
- Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
| | - Roya Salehi
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zahra Aghazadeh
- Stem Cell Research Center and Department of Oral Medicine, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Aysa Rezabakhsh
- Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Armin Hassanzadeh
- Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
| | | | - Morteza Heidarzadeh
- Stem Cell Research Center and Department of Oral Medicine, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Rahbarghazi
- Stem Cell Research Center and Department of Oral Medicine, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Marziyeh Aghazadeh
- Stem Cell Research Center and Department of Oral Medicine, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sepideh Saghati
- Department of Tissue Engineering, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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Huang G, Xu L, Wu J, Wang S, Dong Y. Gelatin/bioactive glass composite scaffold for promoting the migration and odontogenic differentiation of bone marrow mesenchymal stem cells. POLYMER TESTING 2021; 93:106915. [DOI: 10.1016/j.polymertesting.2020.106915] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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26
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Jose M, Rajagopal V, Thankam FG. Oral tissue regeneration: Current status and future perspectives. REGENERATED ORGANS 2021:169-187. [DOI: 10.1016/b978-0-12-821085-7.00009-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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27
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Abbass MMS, El-Rashidy AA, Sadek KM, Moshy SE, Radwan IA, Rady D, Dörfer CE, Fawzy El-Sayed KM. Hydrogels and Dentin-Pulp Complex Regeneration: From the Benchtop to Clinical Translation. Polymers (Basel) 2020; 12:E2935. [PMID: 33316886 PMCID: PMC7763835 DOI: 10.3390/polym12122935] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 11/08/2020] [Accepted: 11/10/2020] [Indexed: 02/06/2023] Open
Abstract
Dentin-pulp complex is a term which refers to the dental pulp (DP) surrounded by dentin along its peripheries. Dentin and dental pulp are highly specialized tissues, which can be affected by various insults, primarily by dental caries. Regeneration of the dentin-pulp complex is of paramount importance to regain tooth vitality. The regenerative endodontic procedure (REP) is a relatively current approach, which aims to regenerate the dentin-pulp complex through stimulating the differentiation of resident or transplanted stem/progenitor cells. Hydrogel-based scaffolds are a unique category of three dimensional polymeric networks with high water content. They are hydrophilic, biocompatible, with tunable degradation patterns and mechanical properties, in addition to the ability to be loaded with various bioactive molecules. Furthermore, hydrogels have a considerable degree of flexibility and elasticity, mimicking the cell extracellular matrix (ECM), particularly that of the DP. The current review presents how for dentin-pulp complex regeneration, the application of injectable hydrogels combined with stem/progenitor cells could represent a promising approach. According to the source of the polymeric chain forming the hydrogel, they can be classified into natural, synthetic or hybrid hydrogels, combining natural and synthetic ones. Natural polymers are bioactive, highly biocompatible, and biodegradable by naturally occurring enzymes or via hydrolysis. On the other hand, synthetic polymers offer tunable mechanical properties, thermostability and durability as compared to natural hydrogels. Hybrid hydrogels combine the benefits of synthetic and natural polymers. Hydrogels can be biofunctionalized with cell-binding sequences as arginine-glycine-aspartic acid (RGD), can be used for local delivery of bioactive molecules and cellularized with stem cells for dentin-pulp regeneration. Formulating a hydrogel scaffold material fulfilling the required criteria in regenerative endodontics is still an area of active research, which shows promising potential for replacing conventional endodontic treatments in the near future.
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Affiliation(s)
- Marwa M. S. Abbass
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 11562, Egypt; (M.M.S.A.); (S.E.M.); (I.A.R.); (D.R.)
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 11562, Egypt; (A.A.E.-R.); (K.M.S.)
| | - Aiah A. El-Rashidy
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 11562, Egypt; (A.A.E.-R.); (K.M.S.)
- Biomaterials Department, Faculty of Dentistry, Cairo University, Cairo 11562, Egypt
| | - Khadiga M. Sadek
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 11562, Egypt; (A.A.E.-R.); (K.M.S.)
- Biomaterials Department, Faculty of Dentistry, Cairo University, Cairo 11562, Egypt
| | - Sara El Moshy
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 11562, Egypt; (M.M.S.A.); (S.E.M.); (I.A.R.); (D.R.)
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 11562, Egypt; (A.A.E.-R.); (K.M.S.)
| | - Israa Ahmed Radwan
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 11562, Egypt; (M.M.S.A.); (S.E.M.); (I.A.R.); (D.R.)
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 11562, Egypt; (A.A.E.-R.); (K.M.S.)
| | - Dina Rady
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 11562, Egypt; (M.M.S.A.); (S.E.M.); (I.A.R.); (D.R.)
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 11562, Egypt; (A.A.E.-R.); (K.M.S.)
| | - Christof E. Dörfer
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, 24105 Kiel, Germany;
| | - Karim M. Fawzy El-Sayed
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 11562, Egypt; (A.A.E.-R.); (K.M.S.)
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, 24105 Kiel, Germany;
- Oral Medicine and Periodontology Department, Faculty of Dentistry, Cairo University, Cairo 11562, Egypt
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Fischer NG, Münchow EA, Tamerler C, Bottino MC, Aparicio C. Harnessing biomolecules for bioinspired dental biomaterials. J Mater Chem B 2020; 8:8713-8747. [PMID: 32747882 PMCID: PMC7544669 DOI: 10.1039/d0tb01456g] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Dental clinicians have relied for centuries on traditional dental materials (polymers, ceramics, metals, and composites) to restore oral health and function to patients. Clinical outcomes for many crucial dental therapies remain poor despite many decades of intense research on these materials. Recent attention has been paid to biomolecules as a chassis for engineered preventive, restorative, and regenerative approaches in dentistry. Indeed, biomolecules represent a uniquely versatile and precise tool to enable the design and development of bioinspired multifunctional dental materials to spur advancements in dentistry. In this review, we survey the range of biomolecules that have been used across dental biomaterials. Our particular focus is on the key biological activity imparted by each biomolecule toward prevention of dental and oral diseases as well as restoration of oral health. Additional emphasis is placed on the structure-function relationships between biomolecules and their biological activity, the unique challenges of each clinical condition, limitations of conventional therapies, and the advantages of each class of biomolecule for said challenge. Biomaterials for bone regeneration are not reviewed as numerous existing reviews on the topic have been recently published. We conclude our narrative review with an outlook on the future of biomolecules in dental biomaterials and potential avenues of innovation for biomaterial-based patient oral care.
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Affiliation(s)
- Nicholas G Fischer
- Minnesota Dental Research Center for Biomaterials and Biomechanics, University of Minnesota, 16-250A Moos Tower, 515 Delaware St. SE, Minneapolis, Minnesota 55455, USA.
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Biomimetic Aspects of Oral and Dentofacial Regeneration. Biomimetics (Basel) 2020; 5:biomimetics5040051. [PMID: 33053903 PMCID: PMC7709662 DOI: 10.3390/biomimetics5040051] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 10/09/2020] [Accepted: 10/10/2020] [Indexed: 12/12/2022] Open
Abstract
Biomimetic materials for hard and soft tissues have advanced in the fields of tissue engineering and regenerative medicine in dentistry. To examine these recent advances, we searched Medline (OVID) with the key terms “biomimetics”, “biomaterials”, and “biomimicry” combined with MeSH terms for “dentistry” and limited the date of publication between 2010–2020. Over 500 articles were obtained under clinical trials, randomized clinical trials, metanalysis, and systematic reviews developed in the past 10 years in three major areas of dentistry: restorative, orofacial surgery, and periodontics. Clinical studies and systematic reviews along with hand-searched preclinical studies as potential therapies have been included. They support the proof-of-concept that novel treatments are in the pipeline towards ground-breaking clinical therapies for orofacial bone regeneration, tooth regeneration, repair of the oral mucosa, periodontal tissue engineering, and dental implants. Biomimicry enhances the clinical outcomes and calls for an interdisciplinary approach integrating medicine, bioengineering, biotechnology, and computational sciences to advance the current research to clinics. We conclude that dentistry has come a long way apropos of regenerative medicine; still, there are vast avenues to endeavour, seeking inspiration from other facets in biomedical research.
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Le HHM, Vang D, Amer N, Vue T, Yee C, Kaou H, Harrison JS, Xiao N, Lin-Cereghino J, Lin-Cereghino GP, Thor D. Enhancement of cell proliferation and motility of mammalian cells grown in co-culture with Pichia pastoris expressing recombinant human FGF-2. Protein Expr Purif 2020; 176:105724. [PMID: 32846209 DOI: 10.1016/j.pep.2020.105724] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 07/28/2020] [Accepted: 07/30/2020] [Indexed: 11/25/2022]
Abstract
Many studies examining the biological function of recombinant proteins and their effects on the physiology of mammalian cells stipulate that the proteins be purified before being used as therapeutic agents. In this study, we explored the possibility of using unpurified recombinant proteins to treat mammalian cells. The recombinant protein was used directly from the expression source and the biological function was compared to purified commercially available, equivalent protein. The model for this purpose was recombinant FGF-2, expressed by Pichia pastoris, which was used to treat the murine fibroblast cell line, NIH/3T3. We generated a P. pastoris strain (yHL11) that constitutively secreted a biologically active recombinant FGF-2 protein containing an N-terminal c-myc epitope (Myc-FGF-2). Myc-FGF-2 was then used without purification either a) in the form of conditioned mammalian cell culture medium or b) during co-cultures of yHL11 with NIH/3T3 to induce higher proliferation and motility of NIH/3T3 cells. The effects of Myc-FGF-2 on cell physiology were comparable to commercially available FGF-2. To our knowledge, this is the first time the physiology of cultured mammalian cells had been successfully altered with a recombinant protein secreted by P. pastoris while the two species shared the same medium and culture conditions. Our data demonstrated the biological activity of unpurified recombinant FGF-2 on NIH/3T3 cells and provided a foundation for directly using unpurified recombinant proteins expressed by P. pastoris with mammalian cells, potentially as wound-healing therapeutics.
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Affiliation(s)
- Henry Hieu M Le
- Department of Biological Sciences, College of the Pacific, University of the Pacific, Stockton, CA, USA
| | - David Vang
- Department of Biomedical Science, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA, USA
| | - Nadia Amer
- Department of Biological Sciences, College of the Pacific, University of the Pacific, Stockton, CA, USA
| | - Tou Vue
- Department of Biological Sciences, College of the Pacific, University of the Pacific, Stockton, CA, USA
| | - Colwin Yee
- Department of Biological Sciences, College of the Pacific, University of the Pacific, Stockton, CA, USA
| | - Hyam Kaou
- Department of Biological Sciences, College of the Pacific, University of the Pacific, Stockton, CA, USA
| | - Joseph S Harrison
- Department of Chemistry, College of the Pacific, University of the Pacific, Stockton, CA, USA
| | - Nan Xiao
- Department of Biomedical Science, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA, USA
| | - Joan Lin-Cereghino
- Department of Biological Sciences, College of the Pacific, University of the Pacific, Stockton, CA, USA
| | - Geoff P Lin-Cereghino
- Department of Biological Sciences, College of the Pacific, University of the Pacific, Stockton, CA, USA
| | - Der Thor
- Department of Biomedical Science, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA, USA.
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Grawish ME, Grawish LM, Grawish HM, Grawish MM, El-Negoly SA. Challenges of Engineering Biomimetic Dental and Paradental Tissues. Tissue Eng Regen Med 2020; 17:403-421. [PMID: 32621282 PMCID: PMC7392996 DOI: 10.1007/s13770-020-00269-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 04/07/2020] [Accepted: 04/27/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Loss of the dental and paradental tissues resulting from trauma, caries or from systemic diseases considered as one of the most significant and frequent clinical problem to the healthcare professionals. Great attempts have been implemented to recreate functionally, healthy dental and paradental tissues in order to substitute dead and diseased tissues resulting from secondary trauma of car accidents, congenital malformations of cleft lip and palate or due to acquired diseases such as cancer and periodontal involvements. METHOD An extensive literature search has been done on PubMed database from 2010 to 2019 about the challenges of engineering a biomimetic tooth (BioTooth) regarding basic biology of the tooth and its supporting structures, strategies, and different techniques of obtaining biological substitutes for dental tissue engineering. RESULTS It has been found that great challenges need to be considered before engineering biomimetic individual parts of the tooth such as enamel, dentin-pulp complex and periodontium. In addition, two approaches have been adopted to engineer a BioTooth. The first one was to engineer a BioTooth as an individual unit and the other was to engineer a BioTooth with its supporting structures. CONCLUSION Engineering of BioTooth with its supporting structures thought to be in the future will replace the traditional and conventional treatment modalities in the field of dentistry. To accomplish this goal, different cell lines and growth factors with a variety of scaffolds at the nano-scale level are now in use. Recent researches in this area of interest are dedicated for this objective, both in vivo and in vitro. Despite progress in this field, there are still many challenges ahead and need to be overcome, many of which related to the basic tooth biology and its supporting structures and some others related to the sophisticated techniques isolating cells, fabricating the needed scaffolds and obtaining the signaling molecules.
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Affiliation(s)
- Mohammed E Grawish
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Elgomhouria St., Mansoura, 35516, Egypt.
| | - Lamyaa M Grawish
- Faculty of Oral and Dental Medicine, Delta University for Science and Technology, Costal International Road in front of Industrial Area, Mansoura, Gamasa, 11152, Egypt
| | - Hala M Grawish
- Faculty of Oral and Dental Medicine, Delta University for Science and Technology, Costal International Road in front of Industrial Area, Mansoura, Gamasa, 11152, Egypt
| | - Mahmoud M Grawish
- Mansoura Manchester Dental Program, Faculty of Dentistry, Mansoura University, Elgomhouria St., Mansoura, 35516, Egypt
| | - Salwa A El-Negoly
- Department of Dental Biomaterials, Faculty of Dentistry, Mansoura University, Elgomhouria St., Mansoura, 35516, 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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Baranova J, Büchner D, Götz W, Schulze M, Tobiasch E. Tooth Formation: Are the Hardest Tissues of Human Body Hard to Regenerate? Int J Mol Sci 2020; 21:E4031. [PMID: 32512908 PMCID: PMC7312198 DOI: 10.3390/ijms21114031] [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: 04/29/2020] [Revised: 06/02/2020] [Accepted: 06/03/2020] [Indexed: 12/12/2022] Open
Abstract
With increasing life expectancy, demands for dental tissue and whole-tooth regeneration are becoming more significant. Despite great progress in medicine, including regenerative therapies, the complex structure of dental tissues introduces several challenges to the field of regenerative dentistry. Interdisciplinary efforts from cellular biologists, material scientists, and clinical odontologists are being made to establish strategies and find the solutions for dental tissue regeneration and/or whole-tooth regeneration. In recent years, many significant discoveries were done regarding signaling pathways and factors shaping calcified tissue genesis, including those of tooth. Novel biocompatible scaffolds and polymer-based drug release systems are under development and may soon result in clinically applicable biomaterials with the potential to modulate signaling cascades involved in dental tissue genesis and regeneration. Approaches for whole-tooth regeneration utilizing adult stem cells, induced pluripotent stem cells, or tooth germ cells transplantation are emerging as promising alternatives to overcome existing in vitro tissue generation hurdles. In this interdisciplinary review, most recent advances in cellular signaling guiding dental tissue genesis, novel functionalized scaffolds and drug release material, various odontogenic cell sources, and methods for tooth regeneration are discussed thus providing a multi-faceted, up-to-date, and illustrative overview on the tooth regeneration matter, alongside hints for future directions in the challenging field of regenerative dentistry.
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Affiliation(s)
- Juliana Baranova
- Department of Biochemistry, Institute of Chemistry, University of São Paulo, Avenida Professor Lineu Prestes 748, Vila Universitária, São Paulo 05508-000, Brazil;
| | - Dominik Büchner
- Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, von-Liebig-Straße 20, 53359 Rheinbach, NRW, Germany; (D.B.); (M.S.)
| | - Werner Götz
- Oral Biology Laboratory, Department of Orthodontics, Dental Hospital of the University of Bonn, Welschnonnenstraße 17, 53111 Bonn, NRW, Germany;
| | - Margit Schulze
- Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, von-Liebig-Straße 20, 53359 Rheinbach, NRW, Germany; (D.B.); (M.S.)
| | - Edda Tobiasch
- Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, von-Liebig-Straße 20, 53359 Rheinbach, NRW, Germany; (D.B.); (M.S.)
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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: 43] [Impact Index Per Article: 8.6] [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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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: 42] [Impact Index Per Article: 8.4] [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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Evaluation of Chitosan Hydrogel for Sustained Delivery of VEGF for Odontogenic Differentiation of Dental Pulp Stem Cells. Stem Cells Int 2019; 2019:1515040. [PMID: 31949434 PMCID: PMC6942904 DOI: 10.1155/2019/1515040] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Revised: 11/14/2019] [Accepted: 11/25/2019] [Indexed: 02/05/2023] Open
Abstract
The pulpotomy with pulp capping is aimed at retaining vital pulp with reparative dentin formation. Vascular endothelial growth factor (VEGF) plays a crucial role in dentin regeneration; however, its constant administrations in the human body is still problematic. Chitosan was widely studied as an effective carrier to deliver bioactive molecules in regenerative medicine. In this study, we conducted a chitosan/β-glycerophosphate (CS/β-GP) hydrogel as a VEGF-sustained release system and explored its effects on dental pulp stem cells (DPSCs). CS/β-GP hydrogel was manufactured using a sol-gel method. SEM assay showed the spongy and porous microstructure of the lyophilized hydrogels. DPSCs cultured in the CS/β-GP hydrogel kept adhesion and vitality. CCK-8 assay tested the promoted proliferation activity of DPSCs on the hydrogel. Besides, the added VEGF protein could continually release from VEGF/CS/β-GP hydrogel. The VEGF/CS/β-GP hydrogel could promote the odontogenic differentiation of DPSCs better than VEGF treatment without hydrogel. Our results suggested that CS/β-GP hydrogel could continually release VEGF and contribute to odontogenic differentiation of DPSCs, thus may become a potential carrier of bioactive molecules in pulp capping therapy.
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IMURA K, HASHIMOTO Y, OKADA M, YOSHIKAWA K, YAMAMOTO K. Application of hydroxyapatite nanoparticle-assembled powder using basic fibroblast growth factor as a pulp-capping agent. Dent Mater J 2019; 38:713-720. [DOI: 10.4012/dmj.2018-198] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Affiliation(s)
- Kazuki IMURA
- Department of Operative Dentistry, Osaka Dental University
| | | | - Masahiro OKADA
- Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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The possible role of basic fibroblast growth factor in dental pulp. Arch Oral Biol 2019; 109:104574. [PMID: 31585238 DOI: 10.1016/j.archoralbio.2019.104574] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 08/31/2019] [Accepted: 09/22/2019] [Indexed: 12/11/2022]
Abstract
Fibroblast growth factors (FGFs) are growth factors that play an important role in tooth development, repair, and regeneration. Of the FGF families, basic fibroblast growth factor (bFGF) has been the most frequently investigated in dentistry. Numerous studies have reported advantages of bFGF, while others did not find any additional benefit. This review gives a comprehensive summary of the potential role of bFGF in dental pulp wound healing and regeneration in connection with cell proliferation and differentiation, angiogenesis, and neural differentiation from both in vitro and in vivo studies. Furthermore, the possible underlying mechanisms associated with bFGF in promoting dental pulp wound healing are discussed in this review.
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Zein N, Harmouch E, Lutz JC, Fernandez De Grado G, Kuchler-Bopp S, Clauss F, Offner D, Hua G, Benkirane-Jessel N, Fioretti F. Polymer-Based Instructive Scaffolds for Endodontic Regeneration. MATERIALS 2019; 12:ma12152347. [PMID: 31344822 PMCID: PMC6695966 DOI: 10.3390/ma12152347] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Revised: 07/19/2019] [Accepted: 07/22/2019] [Indexed: 12/22/2022]
Abstract
The challenge of endodontic regeneration is modulated by clinical conditions which determine five kinds of tissue requirements: pulp connective-tissue formation, dentin formation, revascularization, reinnervation and radicular edification. Polymer scaffolds constitute keystone of the different endodontic regenerative strategies. Indeed, scaffolds are crucial for carrying active molecules and competent cells which optimize the regeneration. Hydrogels are very beneficial for controlling viscosity and porosity of endodontic scaffolds. The nanofibrous and microporous scaffolds mimicking extracellular matrix are also of great interest for promoting dentin-pulp formation. Two main types of polymer scaffolds are highlighted: collagen and fibrin. Collagen scaffolds which are similar to native pulp tissue, are adequate for pulp connective tissue formation. Functionnalization by active biomolecules as BMP, SDF-1, G-CSF enhances their properties. Fibrin or PRF scaffolds present the advantage of promoting stem cell differentiation and concomitant revascularisation. The choice of the type of polymers (polypeptide, PCL, chitosan) can depend on its ability to deliver the active biomolecule or to build as suitable hydrogel as possible. Since 2010s, proposals to associate different types of polymers in a same scaffold have emerged for adding advantages or for offsetting a disadvantage of a polymer. Further works would study the synergetic effects of different innovative polymers composition.
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Affiliation(s)
- Naimah Zein
- French National Institute of Health and Medical Research (INSERM), Regenerative Nanomedicine, UMR 1260, FMTS, 67085 Strasbourg, France
| | - Ezeddine Harmouch
- French National Institute of Health and Medical Research (INSERM), Regenerative Nanomedicine, UMR 1260, FMTS, 67085 Strasbourg, France
| | - Jean-Christophe Lutz
- Faculté de Médecine de Strasbourg, Strasbourg, Université de Strasbourg, 67000 Strasbourg, France
- Pôle de Chirurgie Maxillo-Faciale et Stomatologie, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France
| | - Gabriel Fernandez De Grado
- French National Institute of Health and Medical Research (INSERM), Regenerative Nanomedicine, UMR 1260, FMTS, 67085 Strasbourg, France
- Faculté de Chirurgie Dentaire de Strasbourg, Université de Strasbourg, 67000 Strasbourg, France
- Hôpitaux Universitaires de Strasbourg, Pôle de Médecine et Chirurgie Bucco-Dentaires, 67000 Strasbourg, France
| | - Sabine Kuchler-Bopp
- French National Institute of Health and Medical Research (INSERM), Regenerative Nanomedicine, UMR 1260, FMTS, 67085 Strasbourg, France
| | - François Clauss
- French National Institute of Health and Medical Research (INSERM), Regenerative Nanomedicine, UMR 1260, FMTS, 67085 Strasbourg, France
- Faculté de Chirurgie Dentaire de Strasbourg, Université de Strasbourg, 67000 Strasbourg, France
- Hôpitaux Universitaires de Strasbourg, Pôle de Médecine et Chirurgie Bucco-Dentaires, 67000 Strasbourg, France
| | - Damien Offner
- French National Institute of Health and Medical Research (INSERM), Regenerative Nanomedicine, UMR 1260, FMTS, 67085 Strasbourg, France
- Faculté de Chirurgie Dentaire de Strasbourg, Université de Strasbourg, 67000 Strasbourg, France
- Hôpitaux Universitaires de Strasbourg, Pôle de Médecine et Chirurgie Bucco-Dentaires, 67000 Strasbourg, France
| | - Guoqiang Hua
- French National Institute of Health and Medical Research (INSERM), Regenerative Nanomedicine, UMR 1260, FMTS, 67085 Strasbourg, France
- Faculté de Chirurgie Dentaire de Strasbourg, Université de Strasbourg, 67000 Strasbourg, France
| | - Nadia Benkirane-Jessel
- French National Institute of Health and Medical Research (INSERM), Regenerative Nanomedicine, UMR 1260, FMTS, 67085 Strasbourg, France
- Faculté de Chirurgie Dentaire de Strasbourg, Université de Strasbourg, 67000 Strasbourg, France
| | - Florence Fioretti
- French National Institute of Health and Medical Research (INSERM), Regenerative Nanomedicine, UMR 1260, FMTS, 67085 Strasbourg, France.
- Faculté de Chirurgie Dentaire de Strasbourg, Université de Strasbourg, 67000 Strasbourg, France.
- Hôpitaux Universitaires de Strasbourg, Pôle de Médecine et Chirurgie Bucco-Dentaires, 67000 Strasbourg, France.
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Washio A, Teshima H, Yokota K, Kitamura C, Tabata Y. Preparation of gelatin hydrogel sponges incorporating bioactive glasses capable for the controlled release of fibroblast growth factor-2. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2019; 30:49-63. [PMID: 30470163 DOI: 10.1080/09205063.2018.1544474] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Gelatin hydrogel sponges incorporating bioactive glasses (Gel-BG) were fabricated. We evaluated the characteristics of Gel-BG as scaffolds from the perspective of their mechanical properties and the formation of hydroxyapatite by the incorporation of bioactive glasses (BG). In addition, the Gel-BG degradation and the profile of fibroblast growth factor-2 (FGF-2) release from the Gel-BG were examined. Every Gel-BG showed an interconnected pore structure with the pore size range of 180-200 µm. The compression modulus of sponges incorporating BG increased. The time profiles of degradation for the 72-h crosslinked gelatin hydrogel sponges incorporating 10 wt% BG (Gel-BG(10)) and 50 wt% BG (Gel-BG(50)) were analogous to that of the 24-h crosslinked gelatin hydrogel sponge without BG (Gel-BG(0)). In measuring the release of FGF-2 from Gel-BG, the Gel-BG(10) and Gel-BG(50) showed almost analogous 100% cumulative release within 28 days in vivo. Additionally, a bioactivity evaluation showed that the presence of gelatin does not affect the in vitro bioactivity of Gel-BG. These sponges showed mechanical and chemical functionality as scaffolds, featuring both the controlled release of FGF-2 and the induction of hydroxyapatite crystallization.
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Affiliation(s)
- Ayako Washio
- a Division of Endodontics and Restorative Dentistry, Department of Oral Functions , Kyushu Dental University , Kitakyushu , Japan
| | - Hiroki Teshima
- b Research and Development Department , Nippon Shika Yakuhin Co., Ltd , Shimonoseki , Japan
| | - Kazuyoshi Yokota
- b Research and Development Department , Nippon Shika Yakuhin Co., Ltd , Shimonoseki , Japan
| | - Chiaki Kitamura
- a Division of Endodontics and Restorative Dentistry, Department of Oral Functions , Kyushu Dental University , Kitakyushu , Japan
| | - Yasuhiko Tabata
- c Laboratory of Biomaterials, Department of Regeneration Science and Engineering , Institute for Frontier Life and Medical Sciences, Kyoto University , Kyoto , Japan
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Tissue Engineering of Necrotic Dental Pulp of Immature Teeth with Apical Periodontitis in Dogs: Radiographic and Histological Evaluation. J Clin Pediatr Dent 2018; 42:373-382. [PMID: 29763345 DOI: 10.17796/1053-4625-42.5.9] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
AIM To evaluate tissue engineering technology to regenerate pulp-dentin like tissues in pulp canals of immature necrotic permanent teeth with apical periodontitis in dogs. STUDY DESIGN The study was performed on 36 teeth in 12 dogs. The experiment was carried out using split mouth design. In each dog 3 teeth were selected for implementing the study procedure. Apical periodontitis was induced in Group A and B teeth. Group (A): immature upper left 2nd permanent incisors that were transplanted with a construct of autologous dental pulp stem cells with growth factors seeded in a chitosn hydrogel scaffold. Group (B): immature upper right 2nd permanent incisor that received only growth factors with scaffold. A third tooth in each dog was selected randomly for isolation of dental pulp stem cells (DPSCs). Both groups were closed with a double coronal seal of white MTA (Mineral trioxide aggregate) and glass ionomer cement. Both groups were monitored radiographically for 4 months and histologically after sacrificing the animals. RESULTS There was no statistically significant difference in radiographic findings between group (A) and group (B) for healing of radiolucencies, while there was statistically significant difference between group (A) and group (B) regarding radicular thickening, root lengthening and apical closure. Histologically, group (A) teeth showed regeneration of pulp- dentin like tissue while group (B) teeth did not show any tissue regeneration. CONCLUSION Dental pulp stem cells and growth factors incorporated in chitosan hydrogel are able to regenerate pulp- dentine like tissue and help in complete root maturation of non-vital immature permanent teeth with apical periodontitis in dogs.
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Moussa DG, Aparicio C. Present and future of tissue engineering scaffolds for dentin-pulp complex regeneration. J Tissue Eng Regen Med 2018; 13:58-75. [PMID: 30376696 DOI: 10.1002/term.2769] [Citation(s) in RCA: 86] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 07/16/2018] [Accepted: 10/18/2018] [Indexed: 02/06/2023]
Abstract
More than two thirds of the global population suffers from tooth decay, which results in cavities with various levels of lesion severity. Clinical interventions to treat tooth decay range from simple coronal fillings to invasive root canal treatment. Pulp capping is the only available clinical option to maintain the pulp vitality in deep lesions, but irreversible pulp inflammation and reinfection are frequent outcomes for this treatment. When affected pulp involvement is beyond repair, the dentist has to perform endodontic therapy leaving the tooth non-vital and brittle. On-going research strategies have failed to overcome the limitations of existing pulp capping materials so that healthy and progressive regeneration of the injured tissues is attained. Preserving pulp vitality is crucial for tooth homeostasis and durability, and thus, there is a critical need for clinical interventions that enable regeneration of the dentin-pulp complex to rescue millions of teeth annually. The identification and development of appropriate biomaterials for dentin-pulp scaffolds are necessary to optimize clinical approaches to regenerate these hybrid dental tissues. Likewise, a deep understanding of the interactions between the micro-environment, growth factors, and progenitor cells will provide design basis for the most fitting scaffolds for this purpose. In this review, we first introduce the long-lasting clinical dental problem of rescuing diseased tooth vitality, the limitations of current clinical therapies and interventions to restore the damaged tissues, and the need for new strategies to fully revitalize the tooth. Then, we comprehensively report on the characteristics of the main materials of naturally-derived and synthetically-engineered polymers, ceramics, and composite scaffolds as well as their use in dentin-pulp complex regeneration strategies. Finally, we present a series of innovative smart polymeric biomaterials with potential to overcome dentin-pulp complex regeneration challenges.
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Affiliation(s)
- Dina G Moussa
- Minnesota Dental Research Centre for Biomaterials and Biomechanics, Department of Restorative Sciences, School of Dentistry, University of Minnesota, Minneapolis, Minnesota.,Department of Conservative Dentistry, Faculty of Dentistry, Mansoura University, Mansoura, Egypt
| | - Conrado Aparicio
- Minnesota Dental Research Centre for Biomaterials and Biomechanics, Department of Restorative Sciences, School of Dentistry, University of Minnesota, Minneapolis, Minnesota
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Orti V, Collart-Dutilleul PY, Piglionico S, Pall O, Cuisinier F, Panayotov I. Pulp Regeneration Concepts for Nonvital Teeth: From Tissue Engineering to Clinical Approaches. TISSUE ENGINEERING. PART B, REVIEWS 2018; 24:419-442. [PMID: 29724156 DOI: 10.1089/ten.teb.2018.0073] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Following the basis of tissue engineering (Cells-Scaffold-Bioactive molecules), regenerative endodontic has emerged as a new concept of dental treatment. Clinical procedures have been proposed by endodontic practitioners willing to promote regenerative therapy. Preserving pulp vitality was a first approach. Later procedures aimed to regenerate a vascularized pulp in necrotic root canals. However, there is still no protocol allowing an effective regeneration of necrotic pulp tissue either in immature or mature teeth. This review explores in vitro and preclinical concepts developed during the last decade, especially the potential use of stem cells, bioactive molecules, and scaffolds, and makes a comparison with the goals achieved so far in clinical practice. Regeneration of pulp-like tissue has been shown in various experimental conditions. However, the appropriate techniques are currently in a developmental stage. The ideal combination of scaffolds and growth factors to obtain a complete regeneration of the pulp-dentin complex is still unknown. The use of stem cells, especially from pulp origin, sounds promising for pulp regeneration therapy, but it has not been applied so far for clinical endodontics, in case of necrotic teeth. The gap observed between the hope raised from in vitro experiments and the reality of endodontic treatments suggests that clinical success may be achieved without external stem cell application. Therefore, procedures using the concept of cell homing, through evoked bleeding that permit to recreate a living tissue that mimics the original pulp has been proposed. Perspectives for pulp tissue engineering in the near future include a better control of clinical parameters and pragmatic approach of the experimental results (autologous stem cells from cell homing, controlled release of growth factors). In the coming years, this therapeutic strategy will probably become a clinical reality, even for mature necrotic teeth.
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Affiliation(s)
- Valérie Orti
- LBN, Université de Montpellier , Montpellier, France
| | | | | | - Orsolya Pall
- LBN, Université de Montpellier , Montpellier, France
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Biocompatible, drug-loaded anti-adhesion barrier using visible-light curable furfuryl gelatin derivative. Int J Biol Macromol 2018; 120:915-920. [DOI: 10.1016/j.ijbiomac.2018.07.180] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 07/11/2018] [Accepted: 07/29/2018] [Indexed: 11/23/2022]
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Morotomi T, Washio A, Kitamura C. Current and future options for dental pulp therapy. JAPANESE DENTAL SCIENCE REVIEW 2018; 55:5-11. [PMID: 30733839 PMCID: PMC6354285 DOI: 10.1016/j.jdsr.2018.09.001] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Revised: 07/13/2018] [Accepted: 09/10/2018] [Indexed: 01/01/2023] Open
Abstract
Dental pulp is a connective tissue and has functions that include initiative, formative, protective, nutritive, and reparative activities. However, it has relatively low compliance, because it is enclosed in hard tissue. Its low compliance against damage, such as dental caries, results in the frequent removal of dental pulp during endodontic therapy. Loss of dental pulp frequently leads to fragility of the tooth, and eventually, a deterioration in the patient’s quality of life. With the development of biomaterials such as bioceramics and advances in pulp biology such as the identification of dental pulp stem cells, novel ideas for the preservation of dental pulp, the regenerative therapy of dental pulp, and new biomaterials for direct pulp capping have now been proposed. Therapies for dental pulp are classified into three categories; direct pulp capping, vital pulp amputation, and treatment for non-vital teeth. In this review, we discuss current and future treatment options in these therapies.
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Affiliation(s)
- Takahiko Morotomi
- Division of Endodontics and Restorative Dentistry, Department of Science of Oral Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Japan
| | - Ayako Washio
- Division of Endodontics and Restorative Dentistry, Department of Science of Oral Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Japan
| | - Chiaki Kitamura
- Division of Endodontics and Restorative Dentistry, Department of Science of Oral Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Japan
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Vidovic-Zdrilic I, Vining K, Vijaykumar A, Kalajzic I, Mooney D, Mina M. FGF2 Enhances Odontoblast Differentiation by αSMA + Progenitors In Vivo. J Dent Res 2018; 97:1170-1177. [PMID: 29649366 PMCID: PMC6169028 DOI: 10.1177/0022034518769827] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
The goal of this study was to examine the effects of early and limited exposure of perivascular cells expressing α (αSMA) to fibroblast growth factor 2 (FGF2) in vivo. We performed in vivo fate mapping by inducible Cre-loxP and experimental pulp injury in molars to induce reparative dentinogenesis. Our results demonstrate that early delivery of exogenous FGF2 to exposed pulp led to proliferative expansion of αSMA-tdTomato+ cells and their accelerated differentiation into odontoblasts. In vivo lineage-tracing experiments showed that the calcified bridge/reparative dentin in FGF2-treated pulps were lined with an increased number of Dspp+ odontoblasts and devoid of BSP+ osteoblasts. The increased number of odontoblasts derived from αSMA-tdTomato+ cells and the formation of reparative dentin devoid of osteoblasts provide in vivo evidence for the stimulatory effects of FGF signaling on odontoblast differentiation from early progenitors in dental pulp.
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Affiliation(s)
- I. Vidovic-Zdrilic
- Departments of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT, USA
| | - K.H. Vining
- John A. Paulson School of Engineering and Applied Sciences and Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA
| | - A. Vijaykumar
- Departments of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT, USA
| | - I. Kalajzic
- Departments of Reconstructive Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT, USA
| | - D.J. Mooney
- John A. Paulson School of Engineering and Applied Sciences and Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA
| | - M. Mina
- Departments of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT, USA
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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: 34] [Impact Index Per Article: 4.9] [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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da Rosa WLO, Piva E, da Silva AF. Disclosing the physiology of pulp tissue for vital pulp therapy. Int Endod J 2018; 51:829-846. [DOI: 10.1111/iej.12906] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2017] [Accepted: 01/30/2018] [Indexed: 12/23/2022]
Affiliation(s)
- W. L. O. da Rosa
- Department of Restorative Dentistry; School of Dentistry; Federal University of Pelotas; Pelotas Brazil
| | - E. Piva
- Department of Restorative Dentistry; School of Dentistry; Federal University of Pelotas; Pelotas Brazil
| | - A. F. da Silva
- Department of Restorative Dentistry; School of Dentistry; Federal University of Pelotas; Pelotas Brazil
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Ma C, Qu T, Chang B, Jing Y, Feng JQ, Liu X. 3D Maskless Micropatterning for Regeneration of Highly Organized Tubular Tissues. Adv Healthc Mater 2018; 7:10.1002/adhm.201700738. [PMID: 29121452 PMCID: PMC5803393 DOI: 10.1002/adhm.201700738] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Revised: 08/04/2017] [Indexed: 12/20/2022]
Abstract
Micropatterning is a widely used powerful tool to create highly ordered microstructures on material surfaces. However, due to technical limitations, the integration of micropatterned microstructures into bioinspired 3D scaffolds to successfully regenerate well-organized functional tissues is not achieved. In this work, a unique maskless micropatterning technology is reported to create 3D nanofibrous matrices with highly organized tubular architecture for tissue regeneration. This micropatterning method is a laser-guided, noncontact, high-precision, flexible computer programming of machining process that can create highly ordered tubules with the density ranged from 1000 to 60 000 mm-2 and the size varied from 300 nm to 30 µm in the bioinspired 3D matrix. The tubular architecture presents pivotal biophysical cues to control dental pulp stem cell alignment, migration, polarization, and differentiation. More importantly, when using this 3D tubular hierarchical matrix as a scaffold, this study successfully regenerates functional tubular dentin that has the same well-organized microstructure as its natural counterpart. This 3D maskless micropattern approach represents a powerful avenue not only for the exploration of cell-material interactions in 3D, but also for the regeneration of functional tissues with well-organized microstructures.
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Affiliation(s)
- Chi Ma
- Texas A&M University College of Dentistry, 3302 Gaston Ave, Dallas, TX, 75246, USA
| | - Tiejun Qu
- Texas A&M University College of Dentistry, 3302 Gaston Ave, Dallas, TX, 75246, USA
| | - Bei Chang
- Texas A&M University College of Dentistry, 3302 Gaston Ave, Dallas, TX, 75246, USA
| | - Yan Jing
- Texas A&M University College of Dentistry, 3302 Gaston Ave, Dallas, TX, 75246, USA
| | - Jerry Q Feng
- Texas A&M University College of Dentistry, 3302 Gaston Ave, Dallas, TX, 75246, USA
| | - Xiaohua Liu
- Texas A&M University College of Dentistry, 3302 Gaston Ave, Dallas, TX, 75246, USA
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Baldino L, Cardea S, Reverchon E. Nanostructured chitosan-gelatin hybrid aerogels produced by supercritical gel drying. POLYM ENG SCI 2017. [DOI: 10.1002/pen.24719] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Lucia Baldino
- Department of Industrial Engineering; University of Salerno; Fisciano SA 84084 Italy
| | - Stefano Cardea
- Department of Industrial Engineering; University of Salerno; Fisciano SA 84084 Italy
| | - Ernesto Reverchon
- Department of Industrial Engineering; University of Salerno; Fisciano SA 84084 Italy
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