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Qiao X, Tang J, Dou L, Yang S, Sun Y, Mao H, Yang D. Dental Pulp Stem Cell-Derived Exosomes Regulate Anti-Inflammatory and Osteogenesis in Periodontal Ligament Stem Cells and Promote the Repair of Experimental Periodontitis in Rats. Int J Nanomedicine 2023; 18:4683-4703. [PMID: 37608819 PMCID: PMC10441659 DOI: 10.2147/ijn.s420967] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 08/09/2023] [Indexed: 08/24/2023] Open
Abstract
Purpose Dental pulp stem cell-derived exosomes (DPSC-EXO), which have biological characteristics similar to those of metrocytes, have been found to be closely associated with tissue regeneration. Periodontitis is an immune inflammation and tissue destructive disease caused by plaque, resulting in alveolar bone loss and periodontal epithelial destruction. It is not clear whether DPSC-EXO can be used as an effective therapy for periodontal regeneration. The purpose of this study was not only to verify the effect of DPSC-EXO on reducing periodontitis and promoting periodontal tissue regeneration, but also to reveal the possible mechanism. Methods DPSC-EXO was isolated by ultracentrifugation. Then it characterized by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA) and Western Blot. In vitro, periodontal ligament stem cells (PDLSCs) were treated with DPSC-EXO, the abilities of cell proliferation, migration and osteogenic potential were evaluated. Furthermore, we detected the expression of IL-1β, TNF-αand key proteins in the IL-6/JAK2/STAT3 signaling pathway after simulating the inflammatory environment by LPS. In addition, the effect of DPSC-EXO on the polarization phenotype of macrophages was detected. In vivo, the experimental periodontitis in rats was established and treated with DPSC-EXO or PBS. After 4 weeks, the maxillae were collected and detected by micro-CT and histological staining. Results DPSC-EXO promoted the proliferation, migration and osteogenesis of PDLSCs in vitro. DPSC-EXO also regulated inflammation by inhibiting the IL-6/JAK2/STAT3 signaling pathway during acute inflammatory stress. In addition, the results showed that DPSC-EXO could polarize macrophages from the M1 phenotype to the M2 phenotype. In vivo, we found that DPSC-EXO could effectively reduce alveolar bone loss and promote the healing of the periodontal epithelium in rats with experimental periodontitis. Conclusion DPSC-EXO plays an important role in inhibiting periodontitis and promoting tissue regeneration. This study provides a promising acellular therapy for periodontitis.
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Affiliation(s)
- Xin Qiao
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, People’s Republic of China
- Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 401147, People’s Republic of China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, People’s Republic of China
| | - Jie Tang
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, People’s Republic of China
- Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 401147, People’s Republic of China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, People’s Republic of China
| | - Lei Dou
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, People’s Republic of China
- Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 401147, People’s Republic of China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, People’s Republic of China
| | - Shiyao Yang
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, People’s Republic of China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, People’s Republic of China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 401147, People’s Republic of China
| | - Yuting Sun
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, People’s Republic of China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, People’s Republic of China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 401147, People’s Republic of China
| | - Hongchen Mao
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, People’s Republic of China
- Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 401147, People’s Republic of China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, People’s Republic of China
| | - Deqin Yang
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, People’s Republic of China
- Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 401147, People’s Republic of China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, People’s Republic of China
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Mendoza AH, Balzarini D, Alves T, Rovai ES, Holzhausen M. Potential of Mesenchymal Stem Cell Sheets on Periodontal Regeneration: A Systematic Review of Pre-Clinical Studies. Curr Stem Cell Res Ther 2023; 18:958-978. [PMID: 35794765 DOI: 10.2174/1574888x17666220706092520] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Revised: 05/01/2022] [Accepted: 05/11/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND Cell sheet technique using mesenchymal stem cells is a high-level strategy in periodontal regenerative medicine. Although recent studies have shown the role of MSCSs in increased dental supporting tissues and bone, there is no systematic review focused specifically on assessing periodontal regeneration in orthotopic animal models. OBJECTIVE To evaluate the potential of mesenchymal stem cell sheets (MSCSs) on periodontal regeneration, compared to control, in experimental animal models Methods: Pre-clinical studies in periodontal defects of animal models were considered eligible. The electronic search included the MEDLINE, Web of Science, EMBASE and LILACS databases. The review was conducted according to the Preferred Reporting Item for Systematic Reviews and Meta-Analyses statement guidelines. RESULTS A total of 17 of the 3989 studies obtained from the electronic database search were included. MSCSs included dental follicle (DF) MSCSs, periodontal ligament (PL) MSCSs, dental pulp (DP) MSCSs, bone marrow (BM) MSCSs, alveolar periosteal (AP) MSCSs and gingival (G) MSCSs. Regarding cell sheet inducing protocol, most of the studies used ascorbic acid (52.94%). Others used culture dishes grafted with a temperature-responsive polymer (47.06%). Adverse effects were not identified in the majority of studies. Meta-analysis was not considered because of methodological heterogeneities. PDL-MSCSs were superior for periodontal regeneration enhancement compared to the control, but in an induced inflammatory microenvironment, DF-MSCSs were better. Moreover, DF-MSCSs, DP-MSCSs, and BM-MSCSs showed improved results compared to the control. CONCLUSION MSCSs can improve periodontal regeneration in animal periodontal defect models.
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Affiliation(s)
- Aldrin Huamán Mendoza
- Department of Stomatology, School of Dentistry, University of São Paulo, Av. Prof. Lineu Prestes, 2227, São Paulo, SP, Brazil
| | - Danilo Balzarini
- Department of Stomatology, School of Dentistry, University of São Paulo, Av. Prof. Lineu Prestes, 2227, São Paulo, SP, Brazil
| | - Tomaz Alves
- Department of Stomatology, School of Dentistry, University of São Paulo, Av. Prof. Lineu Prestes, 2227, São Paulo, SP, Brazil
| | - Emanuel S Rovai
- Division of Periodontology, Dental School, University of Taubaté, Rua dos Operários, 09, Centro, Taubaté, SP, Brazil
| | - Marinella Holzhausen
- Department of Stomatology, School of Dentistry, University of São Paulo, Av. Prof. Lineu Prestes, 2227, São Paulo, SP, Brazil
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Amato M, Santonocito S, Viglianisi G, Tatullo M, Isola G. Impact of Oral Mesenchymal Stem Cells Applications as a Promising Therapeutic Target in the Therapy of Periodontal Disease. Int J Mol Sci 2022; 23:13419. [PMID: 36362206 PMCID: PMC9658889 DOI: 10.3390/ijms232113419] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 10/26/2022] [Accepted: 10/31/2022] [Indexed: 11/06/2022] Open
Abstract
Periodontal disease is a chronic inflammatory condition affecting about 20-50% of people, worldwide, and manifesting clinically through the detection of gingival inflammation, clinical attachment loss, radiographically assessed resorption of alveolar bone, gingival bleeding upon probing, teeth mobility and their potential loss at advanced stages. It is characterized by a multifactorial etiology, including an imbalance of the oral microbiota, mechanical stress and systemic diseases such as diabetes mellitus. The current standard treatments for periodontitis include eliminating the microbial pathogens and applying biomaterials to treat the bone defects. However, periodontal tissue regeneration via a process consistent with the natural tissue formation process has not yet been achieved. Developmental biology studies state that periodontal tissue is composed of neural crest-derived ectomesenchyme. The aim of this review is to discuss the clinical utility of stem cells in periodontal regeneration by reviewing the relevant literature that assesses the periodontal-regenerative potential of stem cells.
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Affiliation(s)
- Mariacristina Amato
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy
| | - Simona Santonocito
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy
| | - Gaia Viglianisi
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy
| | - Marco Tatullo
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, 70122 Bari, Italy
| | - Gaetano Isola
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy
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mTOR is involved in LRP5-induced osteogenic differentiation of normal and aged periodontal ligament stem cells in vitro. J Mol Histol 2022; 53:793-804. [PMID: 36002678 DOI: 10.1007/s10735-022-10097-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 08/01/2022] [Indexed: 10/15/2022]
Abstract
Periodontal ligament stem cells (PDLSCs) plays an important role in tissue engineering. As the age increased, the cell viability and osteogenic differentiation of PDLSCs all decreased. Low density lipoprotein receptor related protein 5 (LRP5) was found to promote bone marrow mesenchymal stem cells osteogenic differentiation. Therefore, our study explored the effect of LRP5 on normal and aged PDLSCs and relative mechanism. Here, we found that the expression of LRP5 in PDLSCs of 24 week-old mice was decreased compared with PDLSCs of 5 week-old mice (n = 5). . LRP5 overexpression in PDLSCs increased the intensity of alkaline phosphatase and alizarin red staining, accompanied with upregulated the levels of RUNX family transcription factor 2, collagen type I, and β-Catenin. LRP5 knockdown displayed the opposite results in PDLSCs in vitro. LRP5 overexpression in aged PDLSCs restored part ability of osteogenic differentiation. Meantime, LRP5 increased the protein expression of phosphorylation of mammalian target of rapamycin (p-mTOR) in normal and aged PDLSCs. Immunofluorescence showed that LRP5 increased the accumulation of p-mTOR nucleus. The effect of LRP5 in promoting osteogenic differentiation of PDLSCs can be antagonized by mTOR inhibitor rapamycin. These findings suggest that LRP5 positively regulate osteogenic differentiation of normal and aged PDLSCs and may be a potential target for enlarging the application of PDLSCs in tissue regeneration.
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Fabrication of Low-Molecular-Weight Hyaluronic Acid-Carboxymethyl Cellulose Hybrid to Promote Bone Growth in Guided Bone Regeneration Surgery: An Animal Study. Polymers (Basel) 2022; 14:polym14153211. [PMID: 35956724 PMCID: PMC9370888 DOI: 10.3390/polym14153211] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 07/31/2022] [Accepted: 08/03/2022] [Indexed: 11/17/2022] Open
Abstract
Guided bone regeneration surgery is an important dental operation used to regenerate enough bone to successfully heal dental implants. When this technique is performed on maxilla sinuses, hyaluronic acid (HLA) can be used as an auxiliary material to improve the graft material handling properties. Recent studies have indicated that low-molecular hyaluronic acid (L-HLA) provides a better regeneration ability than high-molecular-weight (H-HLA) analogues. The aim of this study was to fabricate an L-HLA-carboxymethyl cellulose (CMC) hybrid to promote bone regeneration while maintaining viscosity. The proliferation effect of fabricated L-HLA was tested using dental pulp stem cells (DPSCs). The mitogen-activated protein kinase (MAPK) pathway was examined using cells cultured with L-HLA combined with extracellular-signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 inhibitors. The bone growth promotion of fabricated L-HLA/CMC hybrids was tested using an animal model. Micro-computer tomography (Micro-CT) and histological images were evaluated quantitatively to compare the differences in the osteogenesis between the H-HLA and L-HLA. Our results show that the fabricated L-HLA can bind to CD44 on the DPSC cell membranes and affect MAPK pathways, resulting in a prompt proliferation rate increase. Micro CT images show that new bone formation in rabbit calvaria defects treated with L-HLA/CMC was almost two times higher than in defects filled with H-HLA/CMC (p < 0.05) at 4 weeks, a trend that remained at 8 weeks and was confirmed by HE-stained images. According to these findings, it is reasonable to conclude that L-HLA provides better bone healing than H-HLA, and that the L-HLA/CMC fabricated in this study is a potential candidate for improving bone healing efficiency when a guided bone regeneration surgery was performed.
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Tomasello L, Fiorica C, Mauceri R, Martorana A, Palumbo FS, Pitarresi G, Pizzolanti G, Campisi G, Giordano C, Cavallaro G. Bioactive Scaffolds Based on Amine-Functionalized Gellan Gum for the Osteogenic Differentiation of Gingival Mesenchymal Stem Cells. ACS APPLIED POLYMER MATERIALS 2022; 4:1805-1815. [DOI: 10.1021/acsapm.1c01586] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Affiliation(s)
- Laura Tomasello
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties “G. D’Alessandro” (ProMISE), Laboratory of Regenerative Medicine “Aldo Galluzzo”, Piazza delle Cliniche 2, 90127, University of Palermo, Palermo 90133, Italy
| | - Calogero Fiorica
- Department of Biological Chemical and Technological Sciences and Technologies (STEBICEF), Laboratory of Biocompatible Polymers, via Archirafi 32, 90123, University of Palermo, Palermo 90133, Italy
| | - Rodolfo Mauceri
- Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), Via Liborio Giuffrè, 590127, University of Palermo, Palermo 90133, Italy
- Department of Biomedical and Dental Sciences, Morphological and Functional Images (BIOMORF), University of Messina, Messina 98122, Italy
- Department of Dental Surgery, Faculty of Dental Surgery, University of Malta, Msida 2080, Malta
| | - Annalisa Martorana
- Department of Biological Chemical and Technological Sciences and Technologies (STEBICEF), Laboratory of Biocompatible Polymers, via Archirafi 32, 90123, University of Palermo, Palermo 90133, Italy
| | - Fabio Salvatore Palumbo
- Department of Biological Chemical and Technological Sciences and Technologies (STEBICEF), Laboratory of Biocompatible Polymers, via Archirafi 32, 90123, University of Palermo, Palermo 90133, Italy
| | - Giovanna Pitarresi
- Department of Biological Chemical and Technological Sciences and Technologies (STEBICEF), Laboratory of Biocompatible Polymers, via Archirafi 32, 90123, University of Palermo, Palermo 90133, Italy
| | - Giuseppe Pizzolanti
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties “G. D’Alessandro” (ProMISE), Laboratory of Regenerative Medicine “Aldo Galluzzo”, Piazza delle Cliniche 2, 90127, University of Palermo, Palermo 90133, Italy
- Advanced Technology and Network Center (ATeN Center), Università degli Studi di Palermo, Viale delle Scienze ed. 18/A, Palermo 90133, Italy
| | - Giuseppina Campisi
- Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), Via Liborio Giuffrè, 590127, University of Palermo, Palermo 90133, Italy
| | - Carla Giordano
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties “G. D’Alessandro” (ProMISE), Laboratory of Regenerative Medicine “Aldo Galluzzo”, Piazza delle Cliniche 2, 90127, University of Palermo, Palermo 90133, Italy
| | - Gennara Cavallaro
- Department of Biological Chemical and Technological Sciences and Technologies (STEBICEF), Laboratory of Biocompatible Polymers, via Archirafi 32, 90123, University of Palermo, Palermo 90133, Italy
- Advanced Technology and Network Center (ATeN Center), Università degli Studi di Palermo, Viale delle Scienze ed. 18/A, Palermo 90133, Italy
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Bousnaki M, Beketova A, Kontonasaki E. A Review of In Vivo and Clinical Studies Applying Scaffolds and Cell Sheet Technology for Periodontal Ligament Regeneration. Biomolecules 2022; 12:435. [PMID: 35327627 PMCID: PMC8945901 DOI: 10.3390/biom12030435] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Revised: 03/06/2022] [Accepted: 03/08/2022] [Indexed: 12/14/2022] Open
Abstract
Different approaches to develop engineered scaffolds for periodontal tissues regeneration have been proposed. In this review, innovations in stem cell technology and scaffolds engineering focused primarily on Periodontal Ligament (PDL) regeneration are discussed and analyzed based on results from pre-clinical in vivo studies and clinical trials. Most of those developments include the use of polymeric materials with different patterning and surface nanotopography and printing of complex and sophisticated multiphasic composite scaffolds with different compartments to accomodate for the different periodontal tissues' architecture. Despite the increased effort in producing these scaffolds and their undoubtable efficiency to guide and support tissue regeneration, appropriate source of cells is also needed to provide new tissue formation and various biological and mechanochemical cues from the Extraccellular Matrix (ECM) to provide biophysical stimuli for cell growth and differentiation. Cell sheet engineering is a novel promising technique that allows obtaining cells in a sheet format while preserving ECM components. The right combination of those factors has not been discovered yet and efforts are still needed to ameliorate regenerative outcomes towards the functional organisation of the developed tissues.
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Affiliation(s)
| | | | - Eleana Kontonasaki
- Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; (M.B.); (A.B.)
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Characterization of Biological Properties of Dental Pulp Stem Cells Grown on an Electrospun Poly(l-lactide- co-caprolactone) Scaffold. MATERIALS 2022; 15:ma15051900. [PMID: 35269131 PMCID: PMC8911644 DOI: 10.3390/ma15051900] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 02/15/2022] [Accepted: 03/01/2022] [Indexed: 02/01/2023]
Abstract
Poly(l-lactide-co-caprolactone) (PLCL) electrospun scaffolds with seeded stem cells have drawn great interest in tissue engineering. This study investigated the biological behavior of human dental pulp stem cells (hDPSCs) grown on a hydrolytically-modified PLCL nanofiber scaffold. The hDPSCs were seeded on PLCL, and their biological features such as viability, proliferation, adhesion, population doubling time, the immunophenotype of hDPSCs and osteogenic differentiation capacity were evaluated on scaffolds. The results showed that the PLCL scaffold significantly supported hDPSC viability/proliferation. The hDPSCs adhesion rate and spreading onto PLCL increased with time of culture. hDPSCs were able to migrate inside the PLCL electrospun scaffold after 7 days of seeding. No differences in morphology and immunophenotype of hDPSCs grown on PLCL and in flasks were observed. The mRNA levels of bone-related genes and their proteins were significantly higher in hDPSCs after osteogenic differentiation on PLCL compared with undifferentiated hDPSCs on PLCL. These results showed that the mechanical properties of a modified PLCL mat provide an appropriate environment that supports hDPSCs attachment, proliferation, migration and their osteogenic differentiation on the PLCL scaffold. The good PLCL biocompatibility with dental pulp stem cells indicates that this mat may be applied in designing a bioactive hDPSCs/PLCL construct for bone tissue engineering.
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Zha K, Tian Y, Panayi AC, Mi B, Liu G. Recent Advances in Enhancement Strategies for Osteogenic Differentiation of Mesenchymal Stem Cells in Bone Tissue Engineering. Front Cell Dev Biol 2022; 10:824812. [PMID: 35281084 PMCID: PMC8904963 DOI: 10.3389/fcell.2022.824812] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 02/08/2022] [Indexed: 12/12/2022] Open
Abstract
Although bone is an organ that displays potential for self-healing after damage, bone regeneration does not occur properly in some cases, and it is still a challenge to treat large bone defects. The development of bone tissue engineering provides a new approach to the treatment of bone defects. Among various cell types, mesenchymal stem cells (MSCs) represent one of the most promising seed cells in bone tissue engineering due to their functions of osteogenic differentiation, immunomodulation, and secretion of cytokines. Regulation of osteogenic differentiation of MSCs has become an area of extensive research over the past few years. This review provides an overview of recent research progress on enhancement strategies for MSC osteogenesis, including improvement in methods of cell origin selection, culture conditions, biophysical stimulation, crosstalk with macrophages and endothelial cells, and scaffolds. This is favorable for further understanding MSC osteogenesis and the development of MSC-based bone tissue engineering.
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Affiliation(s)
- Kangkang Zha
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
| | - Yue Tian
- Department of Military Patient Management, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Institute of Orthopaedics, Chinese PLA General Hospital, Beijing, China
| | - Adriana C. Panayi
- Division of Plastic Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States
| | - Bobin Mi
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
- *Correspondence: Bobin Mi, ; Guohui Liu,
| | - Guohui Liu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
- *Correspondence: Bobin Mi, ; Guohui Liu,
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Osorio-Arciniega R, García-Hipólito M, Alvarez-Fregoso O, Alvarez-Perez MA. Composite Fiber Spun Mat Synthesis and In Vitro Biocompatibility for Guide Tissue Engineering. Molecules 2021; 26:molecules26247597. [PMID: 34946677 PMCID: PMC8704052 DOI: 10.3390/molecules26247597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 12/03/2021] [Accepted: 12/10/2021] [Indexed: 11/16/2022] Open
Abstract
Composite scaffolds are commonly used strategies and materials employed to achieve similar analogs of bone tissue. This study aims to fabricate 10% wt polylactic acid (PLA) composite fiber scaffolds by the air-jet spinning technique (AJS) doped with 0.5 or 0.1 g of zirconium oxide nanoparticles (ZrO2) for guide bone tissue engineering. ZrO2 nanoparticles were obtained by the hydrothermal method and characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). SEM and fourier-transform infrared spectroscopy (FTIR) analyzed the synthesized PLA/ZrO2 fiber scaffolds. The in vitro biocompatibility and bioactivity of the PLA/ZrO2 were studied using human fetal osteoblast cells. Our results showed that the hydrothermal technique allowed ZrO2 nanoparticles to be obtained. SEM analysis showed that PLA/ZrO2 composite has a fiber diameter of 395 nm, and the FITR spectra confirmed that the scaffolds’ chemical characteristics are not affected by the synthesized technique. In vitro studies demonstrated that PLA/ZrO2 scaffolds increased cell adhesion, cellular proliferation, and biomineralization of osteoblasts. In conclusion, the PLA/ZrO2 scaffolds are bioactive, improve osteoblasts behavior, and can be used in tissue bone engineering applications.
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Affiliation(s)
- Rodrigo Osorio-Arciniega
- Laboratorio de Bioingeniería de Tejidos, DEPeI, Facultad de Odontología, Universidad Nacional Autónoma de México, Circuito Exterior s/n. Cd. Universitaria, Coyoacán 04510, Mexico;
| | - Manuel García-Hipólito
- Instituto de Investigaciones en Materiales, Circuito Exterior s/n. Cd. Universitaria, Coyoacán 04510, Mexico; (M.G.-H.); (O.A.-F.)
| | - Octavio Alvarez-Fregoso
- Instituto de Investigaciones en Materiales, Circuito Exterior s/n. Cd. Universitaria, Coyoacán 04510, Mexico; (M.G.-H.); (O.A.-F.)
| | - Marco Antonio Alvarez-Perez
- Laboratorio de Bioingeniería de Tejidos, DEPeI, Facultad de Odontología, Universidad Nacional Autónoma de México, Circuito Exterior s/n. Cd. Universitaria, Coyoacán 04510, Mexico;
- Correspondence:
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D’Alessandro D, Ricci C, Milazzo M, Strangis G, Forli F, Buda G, Petrini M, Berrettini S, Uddin MJ, Danti S, Parchi P. Piezoelectric Signals in Vascularized Bone Regeneration. Biomolecules 2021; 11:1731. [PMID: 34827729 PMCID: PMC8615512 DOI: 10.3390/biom11111731] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 11/12/2021] [Accepted: 11/15/2021] [Indexed: 02/07/2023] Open
Abstract
The demand for bone substitutes is increasing in Western countries. Bone graft substitutes aim to provide reconstructive surgeons with off-the-shelf alternatives to the natural bone taken from humans or animal species. Under the tissue engineering paradigm, biomaterial scaffolds can be designed by incorporating bone stem cells to decrease the disadvantages of traditional tissue grafts. However, the effective clinical application of tissue-engineered bone is limited by insufficient neovascularization. As bone is a highly vascularized tissue, new strategies to promote both osteogenesis and vasculogenesis within the scaffolds need to be considered for a successful regeneration. It has been demonstrated that bone and blood vases are piezoelectric, namely, electric signals are locally produced upon mechanical stimulation of these tissues. The specific effects of electric charge generation on different cells are not fully understood, but a substantial amount of evidence has suggested their functional and physiological roles. This review summarizes the special contribution of piezoelectricity as a stimulatory signal for bone and vascular tissue regeneration, including osteogenesis, angiogenesis, vascular repair, and tissue engineering, by considering different stem cell sources entailed with osteogenic and angiogenic potential, aimed at collecting the key findings that may enable the development of successful vascularized bone replacements useful in orthopedic and otologic surgery.
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Affiliation(s)
- Delfo D’Alessandro
- Department of Surgical, Medical, Molecular Pathology and Emergency Medicine, University of Pisa, 56126 Pisa, Italy; (D.D.); (F.F.); (S.B.)
| | - Claudio Ricci
- Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (C.R.); (P.P.)
| | - Mario Milazzo
- The BioRobotics Intitute, Scuola Superiore Sant’Anna, 56024 Pontedera, Italy;
| | - Giovanna Strangis
- Department of Civil and Industrial Engineering, University of Pisa, 56122 Pisa, Italy;
| | - Francesca Forli
- Department of Surgical, Medical, Molecular Pathology and Emergency Medicine, University of Pisa, 56126 Pisa, Italy; (D.D.); (F.F.); (S.B.)
| | - Gabriele Buda
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy; (G.B.); (M.P.)
| | - Mario Petrini
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy; (G.B.); (M.P.)
| | - Stefano Berrettini
- Department of Surgical, Medical, Molecular Pathology and Emergency Medicine, University of Pisa, 56126 Pisa, Italy; (D.D.); (F.F.); (S.B.)
| | - Mohammed Jasim Uddin
- Department of Chemistry, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA;
| | - Serena Danti
- The BioRobotics Intitute, Scuola Superiore Sant’Anna, 56024 Pontedera, Italy;
- Department of Civil and Industrial Engineering, University of Pisa, 56122 Pisa, Italy;
| | - Paolo Parchi
- Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (C.R.); (P.P.)
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12
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Maxillofacial-Derived Mesenchymal Stem Cells: Characteristics and Progress in Tissue Regeneration. Stem Cells Int 2021; 2021:5516521. [PMID: 34426741 PMCID: PMC8379387 DOI: 10.1155/2021/5516521] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 07/06/2021] [Accepted: 07/15/2021] [Indexed: 12/11/2022] Open
Abstract
Maxillofacial-derived mesenchymal stem cells (MFSCs) are a particular collective type of mesenchymal stem cells (MSCs) that originate from the hard and soft tissue of the maxillofacial region. Recently, many types of MFSCs have been isolated and characterized. MFSCs have the common characteristics of being extremely accessible and amazingly multipotent and thus have become a promising stem cell resource in tissue regeneration. However, different MFSCs can give rise to different cell lineages, have different advantages in clinical use, and regulate the immune and inflammation microenvironment through paracrine mechanisms in different ways. Hence, in this review, we will concentrate on the updated new findings of all types of MFSCs in tissue regeneration and also introduce the recently discovered types of MFSCs. Important issues about proliferation and differentiation in vitro and in vivo, up-to-date clinical application, and paracrine effect of MFSCs in tissue regeneration will also be discussed. Our review may provide a better guide for the clinical use of MFSCs and further direction of research in MFSC regeneration medicine.
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Wang C, Li Y, Yu K, Jiang Z, Wang Y, Yang G. HOXA10 inhibit the osteogenic differentiation of periodontal ligament stem cells by regulating β-catenin localization and DKK1 expression. Connect Tissue Res 2021; 62:393-401. [PMID: 32299243 DOI: 10.1080/03008207.2020.1756271] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Accepted: 04/09/2020] [Indexed: 02/06/2023]
Abstract
Introduction: Human periodontal ligament stem cells (hPDLSCs) are stem cells found near the tooth periodontal ligament. These cels are involved in the regeneration of the periodontal ligament and alveolar bone during orthodontic treatment and chronic periodontitis.Objectives: The Homeobox gene HOXA10 regulates the osteogenic differentiation of stem cells. However, the role of HOXA10 in hPDLSCs remains unclear. Therefore, we studied the effects of HOXA10 on human PDLSC osteogenic differentiation in vitro.Methods: First, hPDLSCs were isolated and characterized. Second, we assessed the effects of overexpression and knockdown of HOXA10 on PDLSC osteogenic differentiation. Finally, the specific Wnt signaling pathway activator lithium chloride (LiCl) and inhibitor ICG-001 were used to investigate the involvement of the Wnt signaling pathway in HOXA10-induced regulation of osteogenic differentiation.Results: Overexpressing HOXA10 inhibited PDLSC osteogenic differentiation in vitro, shown by ALP and Alizarin Red staining, while HOXA10 knockdown demonstrated the opposite effects. HOXA10 negatively regulated nuclear β-catenin and osteogenic differentiation markers including alkaline phosphatase (ALPL) and integrin-binding sialoprotein (IBSP). Upregulating HOXA10 reduced nuclear β-catenin and increased DKK1 expression. However, HOXA10 knockdown enhanced nuclear β-catenin accumulation and reduced DKK1 expression. These negative effects on osteogenic differentiation by HOXA10 overexpression were restored by the Wnt/β-catenin pathway activator LiCl. The increased osteogenic differentiation effects of HOXA10 knockdown were antagonized by ICG-001, a Wnt pathway inhibitor.Conclusion: These data demonstrate that HOXA10 inhibits the osteogenic differentiation of periodontal ligament stem cells by regulating β-catenin localization and DKK1.
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Affiliation(s)
- Chengze Wang
- The Affiliated Stomatology Hospital, Zhejiang University, School of Medicine, Hangzhou, China
- Key Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang University School of Stomatology, Hangzhou, China
| | - Yongzheng Li
- The Affiliated Stomatology Hospital, Zhejiang University, School of Medicine, Hangzhou, China
- Key Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang University School of Stomatology, Hangzhou, China
| | - Ke Yu
- The Affiliated Stomatology Hospital, Zhejiang University, School of Medicine, Hangzhou, China
- Key Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang University School of Stomatology, Hangzhou, China
| | - Zhiwei Jiang
- The Affiliated Stomatology Hospital, Zhejiang University, School of Medicine, Hangzhou, China
- Key Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang University School of Stomatology, Hangzhou, China
| | - Ying Wang
- The Affiliated Stomatology Hospital, Zhejiang University, School of Medicine, Hangzhou, China
- Key Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang University School of Stomatology, Hangzhou, China
| | - Guoli Yang
- The Affiliated Stomatology Hospital, Zhejiang University, School of Medicine, Hangzhou, China
- Key Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang University School of Stomatology, Hangzhou, China
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14
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Magalhães FD, Sarra G, Carvalho GL, Pedroni ACF, Marques MM, Chambrone L, Gimenez T, Moreira MS. Dental tissue-derived stem cell sheet biotechnology for periodontal tissue regeneration: A systematic review. Arch Oral Biol 2021; 129:105182. [PMID: 34098416 DOI: 10.1016/j.archoralbio.2021.105182] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 05/26/2021] [Accepted: 05/27/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVE This study aimed to conduct a systematic review of the use of a cell sheet formed by mesenchymal stem cells derived from dental tissues (ddMSCs) for periodontal tissue regeneration in animal models in comparison with any other type of regenerative treatment. DESIGN PubMed and Scopus databases were searched for relevant studies up to December 2020. The review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. RESULTS Of the 1542 potentially relevant articles initially identified, 33 fulfilled the eligibility criteria and were considered for this review. Even with a wide variety of selected study methods, the periodontal tissue was always regenerated; this indicates the potential for the use of these cell sheets in the future of periodontics. However, this regeneration process is not always complete. CONCLUSION Despite the implantation, ddMSCs sheets have a great potential to be used in the regeneration of periodontal tissue. More in vivo studies should be conducted using standardized techniques for cell sheet implantation to obtain more robust evidence of the relevance of using this modality of cell therapy for periodontal tissue regeneration.
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Affiliation(s)
- Fabiana Divina Magalhães
- Graduation Dentistry Program, Ibirapuera University, Av. Interlagos 1329 - 4º, Chácara Flora, São Paulo, SP, ZIP code: 04661-100, Brazil
| | - Giovanna Sarra
- Department of Restorative Dentistry, School of Dentistry, Universidade de São Paulo, Av. Prof. Lineu Prestes 2227, São Paulo, SP, ZIP code: 05508-000, Brazil
| | - Giovanna Lopes Carvalho
- A.C. Camargo Cancer Center, Stomatology Department, Rua Tamandaré 753, Liberdade, São Paulo, SP, Zip code: 01525-001, Brazil
| | - Ana Clara Fagundes Pedroni
- Graduation Dentistry Program, Ibirapuera University, Av. Interlagos 1329 - 4º, Chácara Flora, São Paulo, SP, ZIP code: 04661-100, Brazil
| | - Márcia Martins Marques
- Graduation Dentistry Program, Ibirapuera University, Av. Interlagos 1329 - 4º, Chácara Flora, São Paulo, SP, ZIP code: 04661-100, Brazil
| | - Leandro Chambrone
- Graduation Dentistry Program, Ibirapuera University, Av. Interlagos 1329 - 4º, Chácara Flora, São Paulo, SP, ZIP code: 04661-100, Brazil
| | - Thaís Gimenez
- Graduation Dentistry Program, Ibirapuera University, Av. Interlagos 1329 - 4º, Chácara Flora, São Paulo, SP, ZIP code: 04661-100, Brazil
| | - Maria Stella Moreira
- Graduation Dentistry Program, Ibirapuera University, Av. Interlagos 1329 - 4º, Chácara Flora, São Paulo, SP, ZIP code: 04661-100, Brazil; A.C. Camargo Cancer Center, Stomatology Department, Rua Tamandaré 753, Liberdade, São Paulo, SP, Zip code: 01525-001, Brazil.
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15
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Fibrin Glue Implants Seeded with Dental Pulp and Periodontal Ligament Stem Cells for the Repair of Periodontal Bone Defects: A Preclinical Study. Bioengineering (Basel) 2021; 8:bioengineering8060075. [PMID: 34206126 PMCID: PMC8226811 DOI: 10.3390/bioengineering8060075] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 05/25/2021] [Indexed: 12/30/2022] Open
Abstract
A technology to create a cell-seeded fibrin-based implant matching the size and shape of bone defect is required to create an anatomical implant. The aim of the study was to develop a technology of cell-seeded fibrin gel implant creation that has the same shape and size as the bone defect at the site of implantation. Using computed tomography (CT) images, molds representing bone defects were created by 3D printing. The form was filled with fibrin glue and human dental pulp stem cells (DPSC). The viability, set of surface markers and osteogenic differentiation of DPSC grown in fibrin gel along with the clot retraction time were evaluated. In mice, an alveolar bone defect was created. The defect was filled with fibrin gel seeded with mouse DPSC. After 28 days, the bone repair was analyzed with cone beam CT and by histological examination. The proliferation rate, set of surface antigens and osteogenic potential of cells grown inside the scaffold and in 2D conditions did not differ. In mice, both cell-free and mouse DPSC-seeded implants increased the bone tissue volume and vascularization. In mice with cell-seeded gel implants, the bone remodeling process was more prominent than in animals with a cell-free implant. The technology of 3D-printed forms for molding implants can be used to prepare implants using components that are not suitable for 3D printing.
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16
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Zhao R, Yang R, Cooper PR, Khurshid Z, Shavandi A, Ratnayake J. Bone Grafts and Substitutes in Dentistry: A Review of Current Trends and Developments. Molecules 2021; 26:3007. [PMID: 34070157 PMCID: PMC8158510 DOI: 10.3390/molecules26103007] [Citation(s) in RCA: 262] [Impact Index Per Article: 65.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/29/2021] [Accepted: 05/13/2021] [Indexed: 02/07/2023] Open
Abstract
After tooth loss, bone resorption is irreversible, leaving the area without adequate bone volume for successful implant treatment. Bone grafting is the only solution to reverse dental bone loss and is a well-accepted procedure required in one in every four dental implants. Research and development in materials, design and fabrication technologies have expanded over the years to achieve successful and long-lasting dental implants for tooth substitution. This review will critically present the various dental bone graft and substitute materials that have been used to achieve a successful dental implant. The article also reviews the properties of dental bone grafts and various dental bone substitutes that have been studied or are currently available commercially. The various classifications of bone grafts and substitutes, including natural and synthetic materials, are critically presented, and available commercial products in each category are discussed. Different bone substitute materials, including metals, ceramics, polymers, or their combinations, and their chemical, physical, and biocompatibility properties are explored. Limitations of the available materials are presented, and areas which require further research and development are highlighted. Tissue engineering hybrid constructions with enhanced bone regeneration ability, such as cell-based or growth factor-based bone substitutes, are discussed as an emerging area of development.
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Affiliation(s)
- Rusin Zhao
- Department of Oral Science, Faculty of Dentistry, University of Otago, 310 Great King Street, Dunedin 9016, New Zealand; (R.Z.); (R.Y.); (P.R.C.)
| | - Ruijia Yang
- Department of Oral Science, Faculty of Dentistry, University of Otago, 310 Great King Street, Dunedin 9016, New Zealand; (R.Z.); (R.Y.); (P.R.C.)
| | - Paul R. Cooper
- Department of Oral Science, Faculty of Dentistry, University of Otago, 310 Great King Street, Dunedin 9016, New Zealand; (R.Z.); (R.Y.); (P.R.C.)
| | - Zohaib Khurshid
- Department of Prosthodontics and Dental Implantology, College of Dentistry, King Faisal University, Al-Ahsa 31982, Saudi Arabia;
| | - Amin Shavandi
- BioMatter Unit—École Polytechnique de Bruxelles, Université Libre de Bruxelles (ULB), Avenue F.D. Roosevelt, 50—CP 165/61, 1050 Brussels, Belgium;
| | - Jithendra Ratnayake
- Department of Oral Science, Faculty of Dentistry, University of Otago, 310 Great King Street, Dunedin 9016, New Zealand; (R.Z.); (R.Y.); (P.R.C.)
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17
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Laplace-Builhé B, Bahraoui S, Jorgensen C, Djouad F. From the Basis of Epimorphic Regeneration to Enhanced Regenerative Therapies. Front Cell Dev Biol 2021; 8:605120. [PMID: 33585444 PMCID: PMC7873919 DOI: 10.3389/fcell.2020.605120] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 12/14/2020] [Indexed: 01/01/2023] Open
Abstract
Current cell-based therapies to treat degenerative diseases such as osteoarthritis (OA) fail to offer long-term beneficial effects. The therapeutic effects provided by mesenchymal stem cell (MSC) injection, characterized by reduced pain and an improved functional activity in patients with knee OA, are reported at short-term follow-up since the improved outcomes plateau or, even worse, decline several months after MSC administration. This review tackles the limitations of MSC-based therapy for degenerative diseases and highlights the lessons learned from regenerative species to comprehend the coordination of molecular and cellular events critical for complex regeneration processes. We discuss how MSC injection generates a positive cascade of events resulting in a long-lasting systemic immune regulation with limited beneficial effects on tissue regeneration while in regenerative species fine-tuned inflammation is required for progenitor cell proliferation, differentiation, and regeneration. Finally, we stress the direct or indirect involvement of neural crest derived cells (NCC) in most if not all adult regenerative models studied so far. This review underlines the regenerative potential of NCC and the limitations of MSC-based therapy to open new avenues for the treatment of degenerative diseases such as OA.
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Affiliation(s)
| | | | - Christian Jorgensen
- IRMB, Univ Montpellier, INSERM, Montpellier, France.,CHU Montpellier, Montpellier, France
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18
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Ercal P, Pekozer GG. A Current Overview of Scaffold-Based Bone Regeneration Strategies with Dental Stem Cells. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1288:61-85. [PMID: 32185698 DOI: 10.1007/5584_2020_505] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Bone defects due to trauma or diseases still pose a clinical challenge to be resolved in the current tissue engineering approaches. As an alternative to traditional methods to restore bone defects, such as autografts, bone tissue engineering aims to achieve new bone formation via novel biomaterials used in combination with multipotent stem cells and bioactive molecules. Mesenchymal stem cells (MSCs) can be successfully isolated from various dental tissues at different stages of development including dental pulp, apical papilla, dental follicle, tooth germ, deciduous teeth, periodontal ligament and gingiva. A wide range of biomaterials including polymers, ceramics and composites have been investigated for their potential as an ideal bone scaffold material. This article reviews the properties and the manufacturing methods of biomaterials used in bone tissue engineering, and provides an overview of bone tissue regeneration approaches of scaffold and dental stem cell combinations as well as their limitations.
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Affiliation(s)
- Pınar Ercal
- Faculty of Dentistry, Department of Oral Surgery, Altinbas University, Istanbul, Turkey.
| | - Gorke Gurel Pekozer
- Faculty of Electrical and Electronics Engineering, Department of Biomedical Engineering, Yıldız Technical University, Istanbul, Turkey
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19
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Picciolo G, Peditto M, Irrera N, Pallio G, Altavilla D, Vaccaro M, Picciolo G, Scarfone A, Squadrito F, Oteri G. Preclinical and Clinical Applications of Biomaterials in the Enhancement of Wound Healing in Oral Surgery: An Overview of the Available Reviews. Pharmaceutics 2020; 12:E1018. [PMID: 33114407 PMCID: PMC7692581 DOI: 10.3390/pharmaceutics12111018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 10/19/2020] [Accepted: 10/21/2020] [Indexed: 02/07/2023] Open
Abstract
Oral surgery has undergone dramatic developments in recent years due to the use of biomaterials. The aim of the present review is to provide a general overview of the current biomaterials used in oral surgery and to comprehensively outline their impact on post-operative wound healing. A search in Medline was performed, including hand searching. Combinations of searching terms and several criteria were applied for study identification, selection, and inclusion. The literature was searched for reviews published up to July 2020. Reviews evaluating the clinical and histological effects of biomaterials on post-operative wound healing in oral surgical procedures were included. Review selection was performed by two independent reviewers. Disagreements were resolved by a third reviewer, and 41 reviews were included in the final selection. The selected papers covered a wide range of biomaterials such as stem cells, bone grafts, and growth factors. Bioengineering and biomaterials development represent one of the most promising perspectives for the future of oral surgery. In particular, stem cells and growth factors are polarizing the focus of this ever-evolving field, continuously improving standard surgical techniques, and granting access to new approaches.
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Affiliation(s)
- Giacomo Picciolo
- Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, Via C. Valeria, 98125 Messina, Italy; (G.P.); (M.P.); (D.A.); (G.O.)
| | - Matteo Peditto
- Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, Via C. Valeria, 98125 Messina, Italy; (G.P.); (M.P.); (D.A.); (G.O.)
| | - Natasha Irrera
- Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy; (N.I.); (G.P.); (M.V.); (A.S.)
- SunNutraPharma, Academic Spin-Off Company of the University of Messina, Via C. Valeria, 98125 Messina, Italy;
| | - Giovanni Pallio
- Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy; (N.I.); (G.P.); (M.V.); (A.S.)
| | - Domenica Altavilla
- Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, Via C. Valeria, 98125 Messina, Italy; (G.P.); (M.P.); (D.A.); (G.O.)
- SunNutraPharma, Academic Spin-Off Company of the University of Messina, Via C. Valeria, 98125 Messina, Italy;
| | - Mario Vaccaro
- Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy; (N.I.); (G.P.); (M.V.); (A.S.)
| | - Giuseppe Picciolo
- SunNutraPharma, Academic Spin-Off Company of the University of Messina, Via C. Valeria, 98125 Messina, Italy;
| | - Alessandro Scarfone
- Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy; (N.I.); (G.P.); (M.V.); (A.S.)
| | - Francesco Squadrito
- Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy; (N.I.); (G.P.); (M.V.); (A.S.)
- SunNutraPharma, Academic Spin-Off Company of the University of Messina, Via C. Valeria, 98125 Messina, Italy;
| | - Giacomo Oteri
- Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, Via C. Valeria, 98125 Messina, Italy; (G.P.); (M.P.); (D.A.); (G.O.)
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20
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Li Q, Yang G, Li J, Ding M, Zhou N, Dong H, Mou Y. Stem cell therapies for periodontal tissue regeneration: a network meta-analysis of preclinical studies. Stem Cell Res Ther 2020; 11:427. [PMID: 33008471 PMCID: PMC7531120 DOI: 10.1186/s13287-020-01938-7] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 09/16/2020] [Indexed: 12/18/2022] Open
Abstract
Background Periodontal tissue regeneration (PTR) is the ultimate goal of periodontal therapy. Currently, stem cell therapy is considered a promising strategy for achieving PTR. However, there is still no conclusive comparison that distinguishes clear hierarchies among different kinds of stem cells. Methods A systematic review and network meta-analysis (NMA) was performed using MEDLINE (via PubMed), EMBASE, and Web of Science up to February 2020. Preclinical studies assessing five types of stem cells for PTR were included; the five types of stem cells included periodontal ligament-derived stem cells (PDLSCs), bone marrow-derived stem cells (BMSCs), adipose tissue-derived stem cells (ADSCs), dental pulp-derived stem cells (DPSCs), and gingival-derived stem cells (GMSCs). The primary outcomes were three histological indicators with continuous variables: newly formed alveolar bone (NB), newly formed cementum (NC), and newly formed periodontal ligament (NPDL). We performed pairwise meta-analyses using a random-effects model and then performed a random-effects NMA using a multivariate meta-analysis model. Results Sixty preclinical studies assessing five different stem cell-based therapies were identified. The NMA showed that in terms of NB, PDLSCs (standardized mean difference 1.87, 95% credible interval 1.24 to 2.51), BMSCs (1.88, 1.17 to 2.59), and DPSCs (1.69, 0.64 to 2.75) were statistically more efficacious than cell carriers (CCs). In addition, PDLSCs were superior to GMSCs (1.49, 0.04 to 2.94). For NC, PDLSCs (2.18, 1.48 to 2.87), BMSCs (2.11, 1.28 to 2.94), and ADSCs (1.55, 0.18 to 2.91) were superior to CCs. For NPDL, PDLSCs (1.69, 0.92 to 2.47) and BMSCs (1.41, 0.56 to 2.26) were more efficacious than CCs, and PDLSCs (1.26, 0.11 to 2.42) were superior to GMSCs. The results of treatment hierarchies also demonstrated that the two highest-ranked interventions were PDLSCs and BMSCs. Conclusion PDLSCs and BMSCs were the most effective and well-documented stem cells for PTR among the five kinds of stem cells evaluated in this study, and there was no statistical significance between them. To translate the stem cell therapies for PTR successfully in the clinic, future studies should utilize robust experimental designs and reports.
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Affiliation(s)
- Qiang Li
- Department of Oral Implantology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.,Central Laboratory, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Guangwen Yang
- Department of Oral Implantology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.,Central Laboratory, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Jialing Li
- Central Laboratory, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.,Department of Orthodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Meng Ding
- Central Laboratory, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Na Zhou
- Department of Oral Implantology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Heng Dong
- Department of Oral Implantology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China. .,Central Laboratory, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.
| | - Yongbin Mou
- Department of Oral Implantology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.
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21
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Granz CL, Gorji A. Dental stem cells: The role of biomaterials and scaffolds in developing novel therapeutic strategies. World J Stem Cells 2020; 12:897-921. [PMID: 33033554 PMCID: PMC7524692 DOI: 10.4252/wjsc.v12.i9.897] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 06/05/2020] [Accepted: 08/16/2020] [Indexed: 02/06/2023] Open
Abstract
Dental stem cells (DSCs) are self-renewable cells that can be obtained easily from dental tissues, and are a desirable source of autologous stem cells. The use of DSCs for stem cell transplantation therapeutic approaches is attractive due to their simple isolation, high plasticity, immunomodulatory properties, and multipotential abilities. Using appropriate scaffolds loaded with favorable biomolecules, such as growth factors, and cytokines, can improve the proliferation, differentiation, migration, and functional capacity of DSCs and can optimize the cellular morphology to build tissue constructs for specific purposes. An enormous variety of scaffolds have been used for tissue engineering with DSCs. Of these, the scaffolds that particularly mimic tissue-specific micromilieu and loaded with biomolecules favorably regulate angiogenesis, cell-matrix interactions, degradation of extracellular matrix, organized matrix formation, and the mineralization abilities of DSCs in both in vitro and in vivo conditions. DSCs represent a promising cell source for tissue engineering, especially for tooth, bone, and neural tissue restoration. The purpose of the present review is to summarize the current developments in the major scaffolding approaches as crucial guidelines for tissue engineering using DSCs and compare their effects in tissue and organ regeneration.
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Affiliation(s)
- Cornelia Larissa Granz
- Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Münster 48149, Germany
| | - Ali Gorji
- Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Münster 48149, Germany
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22
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Diomede F, Marconi GD, Fonticoli L, Pizzicanella J, Merciaro I, Bramanti P, Mazzon E, Trubiani O. Functional Relationship between Osteogenesis and Angiogenesis in Tissue Regeneration. Int J Mol Sci 2020; 21:E3242. [PMID: 32375269 PMCID: PMC7247346 DOI: 10.3390/ijms21093242] [Citation(s) in RCA: 250] [Impact Index Per Article: 50.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 04/30/2020] [Accepted: 05/01/2020] [Indexed: 12/18/2022] Open
Abstract
Bone tissue renewal can be outlined as a complicated mechanism centered on the interaction between osteogenic and angiogenic events capable of leading to bone formation and tissue renovation. The achievement or debacle of bone regeneration is focused on the primary role of vascularization occurrence; in particular, the turning point is the opportunity to vascularize the bulk scaffolds, in order to deliver enough nutrients, growth factors, minerals and oxygen for tissue restoration. The optimal scaffolds should ensure the development of vascular networks to warrant a positive suitable microenvironment for tissue engineering and renewal. Vascular Endothelial Growth Factor (VEGF), a main player in angiogenesis, is capable of provoking the migration and proliferation of endothelial cells and indirectly stimulating osteogenesis, through the regulation of the osteogenic growth factors released and through paracrine signaling. For this reason, we concentrated our attention on two principal groups involved in the renewal of bone tissue defects: the cells and the scaffold that should guarantee an effective vascularization process. The application of Mesenchymal Stem Cells (MSCs), an excellent cell source for tissue restoration, evidences a crucial role in tissue engineering and bone development strategies. This review aims to provide an overview of the intimate connection between blood vessels and bone formation that appear during bone regeneration when MSCs, their secretome-Extracellular Vesicles (EVs) and microRNAs (miRNAs) -and bone substitutes are used in combination.
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Affiliation(s)
- Francesca Diomede
- Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy; (F.D.); (G.D.M.); (L.F.); (I.M.); (O.T.)
| | - Guya Diletta Marconi
- Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy; (F.D.); (G.D.M.); (L.F.); (I.M.); (O.T.)
| | - Luigia Fonticoli
- Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy; (F.D.); (G.D.M.); (L.F.); (I.M.); (O.T.)
| | - Jacopo Pizzicanella
- ASL02 Lanciano-Vasto-Chieti, “Ss. Annunziata” Hospital, 66100 Chieti, Italy;
| | - Ilaria Merciaro
- Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy; (F.D.); (G.D.M.); (L.F.); (I.M.); (O.T.)
| | | | - Emanuela Mazzon
- IRCCS Centro Neurolesi “Bonino-Pulejo”, 98124 Messina, Italy;
| | - Oriana Trubiani
- Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy; (F.D.); (G.D.M.); (L.F.); (I.M.); (O.T.)
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Redox Control of IL-6-Mediated Dental Pulp Stem-Cell Differentiation on Alginate/Hydroxyapatite Biocomposites for Bone Ingrowth. NANOMATERIALS 2019; 9:nano9121656. [PMID: 31766398 PMCID: PMC6955885 DOI: 10.3390/nano9121656] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 11/13/2019] [Accepted: 11/19/2019] [Indexed: 12/12/2022]
Abstract
Composites and porous scaffolds produced with biodegradable natural polymers are very promising constructs which show high biocompatibility and suitable mechanical properties, with the possibility to be functionalized with growth factors involved in bone formation. For this purpose, alginate/hydroxyapatite (Alg/HAp) composite scaffolds using a novel production design were successfully developed and tested for their biocompatibility and osteoconductive properties in vitro. Redox homeostasis is crucial for dental pulp stem cell (DPSC) differentiation and mineralized matrix deposition, and interleukin-6 (IL-6) was found to be involved not only in immunomodulation but also in cell proliferation and differentiation. In the present study, we evaluated molecular pathways underlying the intracellular balance between redox homeostasis and extracellular matrix mineralization of DPSCs in the presence of composite scaffolds made of alginate and nano-hydroxyapatite (Alg/HAp). Prostaglandin-2 (PGE2) and IL-6 secretion was monitored by ELISA assays, and protein expression levels were quantified by Western blotting. This work aims to demonstrate a relationship between DPSC capacity to secrete a mineralized matrix in the presence of Alg/HAp scaffolds and their immunomodulatory properties. The variation of the molecular axis Nrf2 (nuclear factor erythroid 2-related factor 2)/PGE2/IL-6 suggests a tight intracellular balance between oxidative stress responses and DPSC differentiation in the presence of Alg/HAp scaffolds.
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Stuepp RT, Barros Delben P, Modolo F, Trentin AG, Garcez RC, Biz MT. Human Dental Pulp Stem Cells in Rat Mandibular Bone Defects. Cells Tissues Organs 2019; 207:138-148. [PMID: 31734662 DOI: 10.1159/000502513] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Accepted: 08/06/2019] [Indexed: 11/19/2022] Open
Abstract
This study aimed to evaluate the use of human dental pulp stem cells (hDPSCs) in non-critical-sized mandibular bone defects in rats. hDPSCs from permanent teeth were isolated and engrafted in mandibular bone defects in rats for 7, 14, and 28 days; bone defects without cells formed the control group. Samples were evaluated by scanning electron microscopy (SEM), light microscopy (hematoxylin and eosin staining), and the regeneration area was measured by the Image J program. Before surgery procedures, the human dental pulp cells were characterized as dental pulp stem cells: fusiform morphology, plastic-adherent; expression of CD105, CD73, and CD90; lack of expression of CD45 and CD34, and differentiated into osteoblasts, adipocytes, and chondroblasts. The results indicated that within 7 days the control group presented a pronounced bone formation when compared with the treated group (p < 0.05). After 14 days, the treated group showed an increase in bone formation, but with no statistical difference among the groups (p > 0.05). In the final evaluated period there was no difference between the control group and the treated group (p > 0.05). There was a significant difference between 7 and 14 days (p < 0.05) and between 7 and 28 days (p < 0.05) in the treated group. In conclusion, there is no evidence that the use of hDPSCs in the conditions of this study could improve bone formation in non-critical-sized mandibular bone defects.
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Affiliation(s)
- Rubia Teodoro Stuepp
- Programa de Graduação em Odontologia, Universidade Federal de Santa Catarina, Florianópolis, Brazil
| | - Priscilla Barros Delben
- Programa de Pós-Graduação em Biologia Celular e do Desenvolvimento, Universidade Federal de Santa Catarina, Florianópolis, Brazil
| | - Filipe Modolo
- Departamento de Patologia, Universidade Federal de Santa Catarina, Florianópolis, Brazil
| | - Andrea Gonçalves Trentin
- Departamento de Biologia Celular, Embriologia e Genética, Universidade Federal de Santa Catarina, Florianópolis, Brazil
| | - Ricardo Castilho Garcez
- Departamento de Biologia Celular, Embriologia e Genética, Universidade Federal de Santa Catarina, Florianópolis, Brazil
| | - Michelle Tillmann Biz
- Departamento de Ciências Morfológicas, Universidade Federal de Santa Catarina, Florianópolis, Brazil,
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