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Mbitta Akoa D, Avril A, Hélary C, Poliard A, Coradin T. Evaluation of Silica and Bioglass Nanomaterials in Pulp-like Living Materials. ACS Biomater Sci Eng 2025; 11:891-902. [PMID: 39803670 DOI: 10.1021/acsbiomaterials.4c01898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2025]
Abstract
Although silicon is a widespread constituent in dental materials, its possible influence on the formation and repair of teeth remains largely unexplored. Here, we studied the effect of two silicic acid-releasing nanomaterials, silica and bioglass, on a living model of pulp consisting of dental pulp stem cells seeded in dense type I collagen hydrogels. Silica nanoparticles and released silicic acid had little effect on cell viability and mineralization efficiency but impacted metabolic activity, delayed matrix remodeling, and led to heterogeneous cell distribution. Bioglass improved cell metabolic activity and led to a homogeneous dispersion of cells and mineral deposits within the hydrogel. These results suggest that the presence of calcium ions in bioglass is not only favorable to cell proliferation but can also counterbalance the negative effects of silicon. Both chemical and biological processes should therefore be considered when investigating the effects of silicon-containing materials on dental tissues.
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Affiliation(s)
- Daline Mbitta Akoa
- Sorbonne Université, CNRS, Laboratoire de Chimie de la Matière Condensée de Paris, Paris 75252, France
| | - Anthony Avril
- Sorbonne Université, CNRS, Laboratoire de Chimie de la Matière Condensée de Paris, Paris 75252, France
| | - Christophe Hélary
- Sorbonne Université, CNRS, Laboratoire de Chimie de la Matière Condensée de Paris, Paris 75252, France
| | - Anne Poliard
- Université de Paris Cité, UR2496 Pathologies, Imagerie et Biothérapies Orofaciales, FHU-DDS-Net, Dental School, Montrouge 92120, France
| | - Thibaud Coradin
- Sorbonne Université, CNRS, Laboratoire de Chimie de la Matière Condensée de Paris, Paris 75252, France
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Alothman FA, Hakami LS, Alnasser A, AlGhamdi FM, Alamri AA, Almutairii BM. Recent Advances in Regenerative Endodontics: A Review of Current Techniques and Future Directions. Cureus 2024; 16:e74121. [PMID: 39712709 PMCID: PMC11662148 DOI: 10.7759/cureus.74121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/20/2024] [Indexed: 12/24/2024] Open
Abstract
Regenerative endodontics is a rapidly evolving discipline focused on biologically restoring the pulp-dentin complex to revive vitality in non-vital teeth. Unlike traditional endodontic therapies that rely on inert materials to preserve structure, regenerative techniques aim to re-establish natural structure and function by harnessing advancements in tissue engineering. This narrative review examines recent progress in stem cell applications, scaffold development, signaling molecules, and clinical protocols that contribute to successful regenerative outcomes. Advances in stem cell sources, biomimetic scaffolds, and growth factor delivery systems have shown promising results, though challenges such as variability in outcomes and the need for standardized clinical protocols remain. This review also highlights future directions, including gene therapy and three-dimensional bioprinting, which hold the potential to overcome current limitations and pave the way for effective and reliable biologically restorative dental treatments.
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Affiliation(s)
| | - Lamia S Hakami
- Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, SAU
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Bae KB, Kim HM, Son JW, Ryu JY, Hwang YC, Koh JT, Oh WM, Park C, Lee BN. Effect of 3D-printed polycaprolactone/osteolectin scaffolds on the odontogenic differentiation of human dental pulp cells. Biomed Mater 2024; 19:045027. [PMID: 38740059 DOI: 10.1088/1748-605x/ad4ad9] [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: 01/25/2024] [Accepted: 05/13/2024] [Indexed: 05/16/2024]
Abstract
Cell-based tissue engineering often requires the use of scaffolds to provide a three-dimensional (3D) framework for cell proliferation and tissue formation. Polycaprolactone (PCL), a type of polymer, has good printability, favorable surface modifiability, adaptability, and biodegradability. However, its large-scale applicability is hindered by its hydrophobic nature, which affects biological properties. Composite materials can be created by adding bioactive materials to the polymer to improve the properties of PCL scaffolds. Osteolectin is an odontogenic factor that promotes the maintenance of the adult skeleton by promoting the differentiation of LepR+ cells into osteoblasts. Therefore, the aim of this study was to evaluate whether 3D-printed PCL/osteolectin scaffolds supply a suitable microenvironment for the odontogenic differentiation of human dental pulp cells (hDPCs). The hDPCs were cultured on 3D-printed PCL scaffolds with or without pores. Cell attachment and cell proliferation were evaluated using EZ-Cytox. The odontogenic differentiation of hDPCs was evaluated by alizarin red S staining and alkaline phosphatase assays. Western blot was used to evaluate the expression of the proteins DSPP and DMP-Results: The attachment of hDPCs to PCL scaffolds with pores was significantly higher than to PCL scaffolds without pores. The odontogenic differentiation of hDPCs was induced more in PCL/osteolectin scaffolds than in PCL scaffolds, but there was no statistically significant difference. 3D-printed PCL scaffolds with pores are suitable for the growth of hDPCs, and the PCL/osteolectin scaffolds can provide a more favorable microenvironment for the odontogenic differentiation of hDPCs.
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Affiliation(s)
- Kkot-Byeol Bae
- Department of Conservative Dentistry, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea
| | - Hae-Mi Kim
- Private practice, Local Dental Clinic, Seoul, Republic of Korea
| | - Ji-Won Son
- Researcher, Department of Conservative Dentistry, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea
| | - Jae-Young Ryu
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea
| | - Yun-Chan Hwang
- Department of Conservative Dentistry, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea
| | - Jeong-Tae Koh
- Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea
| | - Won-Mann Oh
- Department of Conservative Dentistry, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea
| | - Chan Park
- Department of Prosthodontics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea
| | - Bin-Na Lee
- Department of Conservative Dentistry, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea
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Alsalhi A. Applications of selected polysaccharides and proteins in dentistry: A review. Int J Biol Macromol 2024; 260:129215. [PMID: 38185301 DOI: 10.1016/j.ijbiomac.2024.129215] [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: 06/13/2023] [Revised: 12/18/2023] [Accepted: 01/02/2024] [Indexed: 01/09/2024]
Abstract
In the last ten years, remarkable characteristics and a variety of functionalities have been created in biopolymeric materials for clinical dental applications. This review gives an overview of current knowledge of natural biopolymers (biological macromolecules) in terms of structural, functional, and property interactions. Natural biopolymers such as polysaccharides (chitosan, bacterial cellulose, hyaluronic acid, and alginate) and polypeptides (collagen and silk fibroin) have been discussed for dental uses. These biopolymers exhibit excellent properties alone and when employed with other composite molecules making them ideal for treatment of periodontitis, endodontics, dental pulp regeneration and oral wound healing. These biopolymers together with the composite materials exhibit better biocompatibility, inertness, elasticity and flexibility which makes them a leading candidate to be used for other dental applications like caries management, oral appliances, dentures, dental implants and oral surgeries.
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Affiliation(s)
- Abdullah Alsalhi
- Department of Pharmaceutics, College of Pharmacy, Jazan University, P.O. Box 114, Jazan 45142, Saudi Arabia.
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Abo-Heikal MM, El-Shafei JM, Shouman SA, Roshdy NN. Evaluation of the efficacy of injectable platelet-rich fibrin versus platelet-rich plasma in the regeneration of traumatized necrotic immature maxillary anterior teeth: A randomized clinical trial. Dent Traumatol 2024; 40:61-75. [PMID: 37612879 DOI: 10.1111/edt.12881] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 07/25/2023] [Accepted: 07/26/2023] [Indexed: 08/25/2023]
Abstract
BACKGROUND/AIM This study aimed at comparing the regenerative potential of injectable platelet-rich fibrin (i-PRF) (Group 1) and platelet-rich plasma (Group 2) scaffolds. MATERIALS AND METHODS Twenty-three patients, aged from 9 to 24 years, having 24 immature traumatized necrotic maxillary anterior teeth, were enrolled. Teeth trauma was confirmed by patients' history. Preoperative three-dimensional scans were done. In the first visit, canals were irrigated with 1.5% sodium hypochlorite then medicated with calcium hydroxide. After 2 weeks, patients were randomly assigned into one of the treatment groups (n = 12). The platelet concentrate was applied after centrifuging 10 mL of autologous venous blood with respect to the centrifugation protocol for each platelet concentrate. Patients were recalled at 6 and 12 months posttreatment, during which clinical and radiographic examinations and assessment of pulp sensitivity were done. Three-dimensional scanning was done after 12 months. The increase in root length and decrease in root canal diameters were calculated at three canal levels. Statistical analysis was done using the paired t-test and the independent t-test. The significance level was set at p < .05. RESULTS There was no statistically significant difference between both groups regarding the increase in root length, decrease in coronal and middle canal diameters and the response to the electric pulp tester. Group (1) showed significantly greater decrease in apical canal diameter than Group (2) (p = .008). CONCLUSION I-PRF can be considered as a valid regenerative scaffold for clinical use and with regards to the easier preparation technique, it is more recommended than platelet-rich plasma.
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Qiu M, Bae KB, Liu G, Jang JH, Koh JT, Hwang YC, Lee BN. Osteolectin Promotes Odontoblastic Differentiation in Human Dental Pulp Cells. J Endod 2023; 49:1660-1667. [PMID: 37774945 DOI: 10.1016/j.joen.2023.09.010] [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: 06/27/2023] [Revised: 09/08/2023] [Accepted: 09/20/2023] [Indexed: 10/01/2023]
Abstract
INTRODUCTION Osteolectin is a secreted glycoprotein of the C-type lectin domain superfamily, expressed in bone tissues and is reported as a novel osteogenic factor that promotes bone regeneration. However, the effect of osteolectin on human dental pulp cells (hDPCs) has not been reported. Therefore, we aimed to investigate the odontoblastic differentiation of osteolectin in hDPCs and further attempt to reveal its underlying mechanism. METHODS Cytotoxicity assays were used to detect the cytotoxicity of osteolectin. The odontoblastic differentiation of hDPCs and its underlying mechanisms were measured by the alkaline phosphatase (ALP) activity, mineralized spots formation, and the gene and protein expression of odontoblastic differentiation through ALP staining, Alizarin red S staining, quantitative real-time polymerase chain reaction, and Western blot analysis, respectively. RESULTS WST-1 assay showed osteolectin at concentrations below 300 ng/ml was noncytotoxic and safe for hDPCs. The following experiment demonstrated that osteolectin could increase ALP activity, accelerate the mineralization process, and up-regulate the odontogenic differentiation markers in both gene and protein levels (P < .05). Osteolectin stimulated the phosphorylation of ERK, JNK, and Protein kinase B (AKT) in hDPCs. Extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK), and AKT inhibitors decreased ALP activity and mineralization capacity and suppressed the expression of dentin sialophosphoprotein and dentin matrix protein-1. CONCLUSION Osteolectin can promote odontoblastic differentiation of hDPCs, and the whole process may stimulate ERK, JNK, and AKT signaling pathways by increasing p-ERK, p-JNK, and p-AKT signals.
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Affiliation(s)
- Manfei Qiu
- Department of Conservative Dentistry, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, Republic of Korea
| | - Kkot-Byeol Bae
- Department of Conservative Dentistry, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, Republic of Korea
| | - Guo Liu
- Department of Conservative Dentistry, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, Republic of Korea; Department of Endodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China
| | - Ji-Hyun Jang
- Department of Conservative Dentistry, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea
| | - Jeong-Tae Koh
- Department of Pharmacology and Dental Therapeutics, School of Dentistry, Dental Science Research, Institute, Chonnam National University, Gwangju, Republic of Korea; Research Center for Biomineralization Disorders, Chonnam National University, Gwangju, Republic of Korea
| | - Yun-Chan Hwang
- Department of Conservative Dentistry, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, Republic of Korea
| | - Bin-Na Lee
- Department of Conservative Dentistry, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, Republic of Korea.
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Liu Y, Liu H, Guo S, Qi J, Zhang R, Liu X, Sun L, Zong M, Cheng H, Wu X, Li B. Applications of Bacterial Cellulose-Based Composite Materials in Hard Tissue Regenerative Medicine. Tissue Eng Regen Med 2023; 20:1017-1039. [PMID: 37688748 PMCID: PMC10645761 DOI: 10.1007/s13770-023-00575-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 07/05/2023] [Accepted: 07/09/2023] [Indexed: 09/11/2023] Open
Abstract
BACKGROUND Cartilage, bone, and teeth, as the three primary hard tissues in the human body, have a significant application value in maintaining physical and mental health. Since the development of bacterial cellulose-based composite materials with excellent biomechanical strength and good biocompatibility, bacterial cellulose-based composites have been widely studied in hard tissue regenerative medicine. This paper provides an overview of the advantages of bacterial cellulose-based for hard tissue regeneration and reviews the recent progress in the preparation and research of bacterial cellulose-based composites in maxillofacial cartilage, dentistry, and bone. METHOD A systematic review was performed by searching the PubMed and Web of Science databases using selected keywords and Medical Subject Headings search terms. RESULTS Ideal hard tissue regenerative medicine materials should be biocompatible, biodegradable, non-toxic, easy to use, and not burdensome to the human body; In addition, they should have good plasticity and processability and can be prepared into materials of different shapes; In addition, it should have good biological activity, promoting cell proliferation and regeneration. Bacterial cellulose materials have corresponding advantages and disadvantages due to their inherent properties. However, after being combined with other materials (natural/ synthetic materials) to form composite materials, they basically meet the requirements of hard tissue regenerative medicine materials. We believe that it is worth being widely promoted in clinical applications in the future. CONCLUSION Bacterial cellulose-based composites hold great promise for clinical applications in hard tissue engineering. However, there are still several challenges that need to be addressed. Further research is needed to incorporate multiple disciplines and advance biological tissue engineering techniques. By enhancing the adhesion of materials to osteoblasts, providing cell stress stimulation through materials, and introducing controlled release systems into matrix materials, the practical application of bacterial cellulose-based composites in clinical settings will become more feasible in the near future.
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Affiliation(s)
- Yingyu Liu
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Haiyan Liu
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Susu Guo
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Jin Qi
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Ran Zhang
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Xiaoming Liu
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Lingxiang Sun
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Mingrui Zong
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Huaiyi Cheng
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China
| | - Xiuping Wu
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China.
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China.
| | - Bing Li
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China.
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, China.
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Li Y, Liu C, Han G. Research progress of odontogenic extracellular vesicles in regeneration of dental pulp. Oral Dis 2023; 29:2565-2577. [PMID: 36415913 DOI: 10.1111/odi.14451] [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: 07/11/2022] [Revised: 10/26/2022] [Accepted: 11/15/2022] [Indexed: 11/24/2022]
Abstract
It is well understood that maintaining viable pulp is critical for tooth retention. This review focused on cell-free therapy based on extracellular vesicles (EVs), a novel minimally invasive treatment strategy for endodontic restoration. This study was conducted by searching mainstream electronic databases such as Web of Science and PubMed for relevant studies on the therapeutic role of odontogenic EVs in pulp healing published in the last five years. We selected 89 relevant articles and discovered that dental stem cells (DSCs) derived EVs (DSC-EVs) have become a research hotspot in oral regenerative medicine, with significant advantages over cell transplantation in terms of low immunogenicity, ease of isolation, preservation, and management. Here, we introduce in detail the therapeutic effects of DSC-EVs for pulp restoration from three perspectives: excellent odontogenic properties, clinical applications, and possible molecular mechanisms. This article contributes a new viewpoint to the field of regenerative endodontics.
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Affiliation(s)
- Yanan Li
- Department of Oral Geriatrics, Hospital of Stomatology, Jilin University, Changchun, China
| | - Chaoran Liu
- Department of Oral Geriatrics, Hospital of Stomatology, Jilin University, Changchun, China
| | - Guanghong Han
- Department of Oral Geriatrics, Hospital of Stomatology, Jilin University, Changchun, China
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Agriesti F, Landini F, Tamma M, Pacelli C, Mazzoccoli C, Calice G, Ruggieri V, Capitanio G, Mori G, Piccoli C, Capitanio N. Bioenergetic profile and redox tone modulate in vitro osteogenesis of human dental pulp stem cells: new perspectives for bone regeneration and repair. Stem Cell Res Ther 2023; 14:215. [PMID: 37608350 PMCID: PMC10463344 DOI: 10.1186/s13287-023-03447-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 08/10/2023] [Indexed: 08/24/2023] Open
Abstract
BACKGROUND Redox signaling and energy metabolism are known to be involved in controlling the balance between self-renewal and proliferation/differentiation of stem cells. In this study we investigated metabolic and redox changes occurring during in vitro human dental pulp stem cells (hDPSCs) osteoblastic (OB) differentiation and tested on them the impact of the reactive oxygen species (ROS) signaling. METHODS hDPSCs were isolated from dental pulp and subjected to alkaline phosphatase and alizarin red staining, q-RT-PCR, and western blotting analysis of differentiation markers to assess achievement of osteogenic/odontogenic differentiation. Moreover, a combination of metabolic flux analysis and confocal cyto-imaging was used to profile the metabolic phenotype and to evaluate the redox tone of hDPSCs. RESULTS In differentiating hDPSCs we observed the down-regulation of the mitochondrial respiratory chain complexes expression since the early phase of the process, confirmed by metabolic flux analysis, and a reduction of the basal intracellular peroxide level in its later phase. In addition, dampened glycolysis was observed, thereby indicating a lower energy-generating phenotype in differentiating hDPSCs. Treatment with the ROS scavenger Trolox, applied in the early-middle phases of the process, markedly delayed OB differentiation of hDPSCs assessed as ALP activity, Runx2 expression, mineralization capacity, expression of stemness and osteoblast marker genes (Nanog, Lin28, Dspp, Ocn) and activation of ERK1/2. In addition, the antioxidant partly prevented the inhibitory effect on cell metabolism observed following osteogenic induction. CONCLUSIONS Altogether these results provided evidence that redox signaling, likely mediated by peroxide species, influenced the stepwise osteogenic expansion/differentiation of hDPSCs and contributed to shape its accompanying metabolic phenotype changes thus improving their efficiency in bone regeneration and repair.
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Affiliation(s)
- Francesca Agriesti
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
- Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy
| | - Francesca Landini
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Mirko Tamma
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Consiglia Pacelli
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Carmela Mazzoccoli
- Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy
| | - Giovanni Calice
- Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy
| | - Vitalba Ruggieri
- Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy
- Clinical Pathology Unit, “Madonna delle Grazie’’ Hospital, Matera, Italy
| | - Giuseppe Capitanio
- Department of Translational Biomedicine and Neuroscience “DiBraiN”, University of Bari “Aldo Moro”, 70124 Bari, Italy
| | - Giorgio Mori
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Claudia Piccoli
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Nazzareno Capitanio
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
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Ramli H, Yusop N, Ramli R, Berahim Z, Peiris R, Ghani N. Application of neurotransmitters and dental stem cells for pulp regeneration: A review. Saudi Dent J 2023; 35:387-394. [PMID: 37520592 PMCID: PMC10373085 DOI: 10.1016/j.sdentj.2023.05.004] [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: 12/30/2022] [Revised: 05/07/2023] [Accepted: 05/07/2023] [Indexed: 08/01/2023] Open
Abstract
INTRODUCTION Although there have been many studies on stem cells, few have investigated how neurotransmitters and stem cell proliferation interact to regenerate dental pulp. Dental pulp regeneration is an innovative procedure for reviving dental pulp, if feasible for the entire tooth. Upon tooth injury, activated platelets release serotonin and dopamine in bulk to mobilize dental pulp stem cells to mediate natural dental repair. This has induced research on the role of neurotransmitters in increasing the proliferation rate of stem cells. This review also covers prospective future treatments for dental pulp regeneration. METHODS A literature search was performed via PubMed and ScienceDirect from 2001 to 2022, using the keywords "neurotransmitter," "stem cell," "tooth regeneration," "tooth repair," "regenerative dentistry," and "dental pulp." Different inclusion/exclusion criteria were used, and the search was restricted to English articles. RESULTS Nine publications reporting neurotransmitter interactions with stem cells for tooth and pulp regeneration were selected. CONCLUSION Neurotransmitters were found to interact with dental stem cells. Evidence pointing to neurotransmitters as a factor in the increased proliferation of stem cells was found. This review thus gives hope for tooth pulp regeneration and repair.
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Affiliation(s)
- Hidayah Ramli
- Basic and Medical Sciences Unit, School of Dental Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kota Bharu, Kelantan, Malaysia
| | - Norhayati Yusop
- Basic and Medical Sciences Unit, School of Dental Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kota Bharu, Kelantan, Malaysia
| | - Rosmaliza Ramli
- Basic and Medical Sciences Unit, School of Dental Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kota Bharu, Kelantan, Malaysia
| | - Zurairah Berahim
- Periodontic Unit, School of Dental Sciences, Health Campus, Universiti Sains Malaysia, Kelantan 16150, Kota Bharu, Malaysia
| | - Roshan Peiris
- Department of Basic Sciences, Faculty of Dental Sciences, University of Peradeniya, 20400 Peradeniya, Sri Lanka
| | - Nurhafizah Ghani
- Basic and Medical Sciences Unit, School of Dental Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kota Bharu, Kelantan, Malaysia
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Piglionico SS, Pons C, Romieu O, Cuisinier F, Levallois B, Panayotov IV. In vitro, ex vivo, and in vivo models for dental pulp regeneration. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2023; 34:15. [PMID: 37004591 PMCID: PMC10067643 DOI: 10.1007/s10856-023-06718-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 03/13/2023] [Indexed: 05/03/2023]
Abstract
Based on the concept of tissue engineering (Cells-Scaffold-Bioactive molecules), regenerative endodontics appeared as a new notion for dental endodontic treatment. Its approaches aim to preserve dental pulp vitality (pulp capping) or to regenerate a vascularized pulp-like tissue inside necrotic root canals by cell homing. To improve the methods of tissue engineering for pulp regeneration, numerous studies using in vitro, ex vivo, and in vivo models have been performed. This review explores the evolution of laboratory models used in such studies and classifies them according to different criteria. It starts from the initial two-dimensional in vitro models that allowed characterization of stem cell behavior, through 3D culture matrices combined with dental tissue and finally arrives at the more challenging ex vivo and in vivo models. The travel which follows the elaboration of such models reveals the difficulty in establishing reproducible laboratory models for dental pulp regeneration. The development of well-established protocols and new laboratory ex vivo and in vivo models in the field of pulp regeneration would lead to consistent results, reduction of animal experimentation, and facilitation of the translation to clinical practice.
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Affiliation(s)
- Sofia Silvia Piglionico
- LBN, Univ. Montpellier, Montpellier, France.
- Centro de Investigaciones Odontológicas, National University of Cuyo, Mendoza, Argentina.
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Singer L, Fouda A, Bourauel C. Biomimetic approaches and materials in restorative and regenerative dentistry: review article. BMC Oral Health 2023; 23:105. [PMID: 36797710 PMCID: PMC9936671 DOI: 10.1186/s12903-023-02808-3] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 02/10/2023] [Indexed: 02/18/2023] Open
Abstract
Biomimetics is a branch of science that explores the technical beauty of nature. The concept of biomimetics has been brilliantly applied in famous applications such as the design of the Eiffel Tower that has been inspired from the trabecular structure of bone. In dentistry, the purpose of using biomimetic concepts and protocols is to conserve tooth structure and vitality, increase the longevity of restorative dental treatments, and eliminate future retreatment cycles. Biomimetic dental materials are inherently biocompatible with excellent physico-chemical properties. They have been successfully applied in different dental fields with the advantages of enhanced strength, sealing, regenerative and antibacterial abilities. Moreover, many biomimetic materials were proven to overcome significant limitations of earlier available generation counterpart. Therefore, this review aims to spot the light on some recent developments in the emerging field of biomimetics especially in restorative and regenerative dentistry. Different approaches of restoration, remineralisation and regeneration of teeth are also discussed in this review. In addition, various biomimetic dental restorative materials and tissue engineering materials are discussed.
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Affiliation(s)
- Lamia Singer
- Oral Technology, University Hospital Bonn, 53111, Bonn, North Rhine-Westphalia, Germany. .,Department of Orthodontics, University Hospital Bonn, 53111, Bonn, North Rhine-Westphalia, Germany.
| | - Ahmed Fouda
- grid.15090.3d0000 0000 8786 803XOral Technology, University Hospital Bonn, 53111 Bonn, North Rhine-Westphalia Germany ,grid.33003.330000 0000 9889 5690Department of Fixed Prosthodontics, Suez Canal University, Ismailia, Egypt
| | - Christoph Bourauel
- grid.15090.3d0000 0000 8786 803XOral Technology, University Hospital Bonn, 53111 Bonn, North Rhine-Westphalia Germany
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Yu L, Zeng L, Zhang Z, Zhu G, Xu Z, Xia J, Weng J, Li J, Pathak JL. Cannabidiol Rescues TNF-α-Inhibited Proliferation, Migration, and Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells. Biomolecules 2023; 13:biom13010118. [PMID: 36671503 PMCID: PMC9856031 DOI: 10.3390/biom13010118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 12/29/2022] [Accepted: 01/02/2023] [Indexed: 01/11/2023] Open
Abstract
Strategies to promote dental pulp stem cells (DPSCs) functions including proliferation, migration, pro-angiogenic effects, and odontogenic/osteogenic differentiation are in urgent need to restore pulpitis-damaged dentin/pulp regeneration and DPSCs-based bone tissue engineering applications. Cannabidiol (CBD), an active component of Cannabis sativa has shown anti-inflammation, chemotactic, anti-microbial, and tissue regenerative potentials. Based on these facts, this study aimed to analyze the effect of CBD on DPSCs proliferation, migration, and osteogenic/odontogenic differentiation in basal and inflammatory conditions. Highly pure DPSCs with characteristics of mesenchymal stem cells (MSCs) were successfully isolated, as indicated by the results of flowcytometry and multi-lineage (osteogenic, adipogenic, and chondrogenic) differentiation potentials. Among the concentration tested (0.1-12.5 µM), CBD (2.5 μM) showed the highest anabolic effect on the proliferation and osteogenic/odontogenic differentiation of DPSCs. Pro-angiogenic growth factor VEGF mRNA expression was robustly higher in CBD-treated DPSCs. CBD also prompted the migration of DPSCs and CBD receptor CB1 and CB2 expression in DPSCs. TNF-α inhibited the viability, migration, and osteogenic/odontogenic differentiation of DPSCs and CBD reversed these effects. CBD alleviated the TNF-α-upregulated expression of pro-inflammatory cytokines TNF-α, interleukin (IL)-1β, and IL-6 in DPSCs. In conclusion, our results indicate the possible application of CBD on DPSCs-based dentin/pulp and bone regeneration.
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Affiliation(s)
- Lina Yu
- Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Department of Preventive Dentistry, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou 510182, China
- School and Hospital of Stomatology, Guangzhou Medical University, Guangzhou 510182, China
| | - Liting Zeng
- Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Department of Preventive Dentistry, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou 510182, China
- School and Hospital of Stomatology, Guangzhou Medical University, Guangzhou 510182, China
| | - Zeyu Zhang
- Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Department of Preventive Dentistry, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou 510182, China
- School and Hospital of Stomatology, Guangzhou Medical University, Guangzhou 510182, China
| | - Guanxiong Zhu
- Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Department of Preventive Dentistry, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou 510182, China
- School and Hospital of Stomatology, Guangzhou Medical University, Guangzhou 510182, China
| | - Zidan Xu
- Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Department of Preventive Dentistry, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou 510182, China
- School and Hospital of Stomatology, Guangzhou Medical University, Guangzhou 510182, China
| | - Junyi Xia
- Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Department of Preventive Dentistry, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou 510182, China
- School and Hospital of Stomatology, Guangzhou Medical University, Guangzhou 510182, China
| | - Jinlong Weng
- Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Department of Preventive Dentistry, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou 510182, China
- School and Hospital of Stomatology, Guangzhou Medical University, Guangzhou 510182, China
| | - Jiang Li
- Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Department of Preventive Dentistry, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou 510182, China
- School and Hospital of Stomatology, Guangzhou Medical University, Guangzhou 510182, China
- Correspondence: (J.L.); (J.L.P.); Tel.: +(020)-8050-0893 (J.L.); +(020)-8192-7729 (J.L.P.)
| | - Janak Lal Pathak
- Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Department of Preventive Dentistry, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou 510182, China
- Correspondence: (J.L.); (J.L.P.); Tel.: +(020)-8050-0893 (J.L.); +(020)-8192-7729 (J.L.P.)
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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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15
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Effect of Long-Term Cryopreservation on the Stemness of Stem Cells of Apical Papilla. Int J Dent 2022; 2022:6004350. [PMID: 36606134 PMCID: PMC9810390 DOI: 10.1155/2022/6004350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 11/29/2022] [Accepted: 12/06/2022] [Indexed: 12/29/2022] Open
Abstract
Stem cells of apical papilla (SCAPs) are considered a subpopulation of dental stem cells with unique properties. They originate from a developing tissue, the apical papilla of developing teeth, a characteristic that enhances their stemness. Banking of these stem cells can offer a source of dental stem cells for future regenerative therapies. Until now, only the effect of six months' cryopreservation on SCAPs has been studied. In this study, the long-term (19 months) effect of cryopreservation on SCAPs was examined by means of estimation of their differentiation's capacity, flow cytometry immunophenotypical characterization, and molecular characterization of the main transcriptional factors that coincide with pluripotency. As was indicated from our results, 19-month cryopreservation of SCAPs did not affect negatively their stemness; since no significant difference was observed on their typical fibroblast-like morphology, they retained their differentiation capacity, and no discrepancies were found either on immunophenotypical level or molecular level.
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16
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Li Z, Wu M, Liu S, Liu X, Huan Y, Ye Q, Yang X, Guo H, Liu A, Huang X, Yang X, Ding F, Xu H, Zhou J, Liu P, Liu S, Jin Y, Xuan K. Apoptotic vesicles activate autophagy in recipient cells to induce angiogenesis and dental pulp regeneration. Mol Ther 2022; 30:3193-3208. [PMID: 35538661 PMCID: PMC9552912 DOI: 10.1016/j.ymthe.2022.05.006] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 04/19/2022] [Accepted: 05/07/2022] [Indexed: 11/16/2022] Open
Abstract
Extracellular vesicles (EVs) derived from living cells play important roles in donor cell-induced recipient tissue regeneration. Although numerous studies have found that cells undergo apoptosis after implantation in an ischemic-hypoxic environment, the roles played by the EVs released by apoptotic cells are largely unknown. In this study, we obtained apoptotic vesicles (apoVs) derived from human deciduous pulp stem cells and explored their effects on the dental pulp regeneration process. Our work showed that apoVs were ingested by endothelial cells (ECs) and elevated the expression of angiogenesis-related genes, leading to pulp revascularization and tissue regeneration. Furthermore, we found that, at the molecular level, apoV-carried mitochondrial Tu translation elongation factor was transported and regulated the angiogenic activation of ECs via the transcription factor EB-autophagy pathway. In a beagle model of dental pulp regeneration in situ, apoVs recruited endogenous ECs and facilitated the formation of dental-pulp-like tissue rich in blood vessels. These findings revealed the significance of apoptosis in tissue regeneration and demonstrated the potential of using apoVs to promote angiogenesis in clinical applications.
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Affiliation(s)
- Zihan Li
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China; State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China
| | - Meiling Wu
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China
| | - Siying Liu
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China
| | - Xuemei Liu
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China; State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China
| | - Yu Huan
- Department of Neurosurgery, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, China
| | - Qingyuan Ye
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China; State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Xiaoxue Yang
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China
| | - Hao Guo
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China
| | - Anqi Liu
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China
| | - Xiaoyao Huang
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China
| | - Xiaoshan Yang
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China; Stomatology Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Feng Ding
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China
| | - Haokun Xu
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China
| | - Jun Zhou
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China
| | - Peisheng Liu
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China
| | - Shiyu Liu
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China.
| | - Yan Jin
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China.
| | - Kun Xuan
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China.
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Sugiaman VK, Djuanda R, Pranata N, Naliani S, Demolsky WL. Tissue Engineering with Stem Cell from Human Exfoliated Deciduous Teeth (SHED) and Collagen Matrix, Regulated by Growth Factor in Regenerating the Dental Pulp. Polymers (Basel) 2022; 14:polym14183712. [PMID: 36145860 PMCID: PMC9503223 DOI: 10.3390/polym14183712] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 08/25/2022] [Accepted: 09/02/2022] [Indexed: 11/16/2022] Open
Abstract
Maintaining dental pulp vitality and preventing tooth loss are two challenges in endodontic treatment. A tooth lacking a viable pulp loses its defense mechanism and regenerative ability, making it more vulnerable to severe damage and eventually necessitating extraction. The tissue engineering approach has drawn attention as an alternative therapy as it can regenerate dentin-pulp complex structures and functions. Stem cells or progenitor cells, extracellular matrix, and signaling molecules are triad components of this approach. Stem cells from human exfoliated deciduous teeth (SHED) are a promising, noninvasive source of stem cells for tissue regeneration. Not only can SHEDs regenerate dentin-pulp tissues (comprised of fibroblasts, odontoblasts, endothelial cells, and nerve cells), but SHEDs also possess immunomodulatory and immunosuppressive properties. The collagen matrix is a material of choice to provide structural and microenvironmental support for SHED-to-dentin pulp tissue differentiation. Growth factors regulate cell proliferation, migration, and differentiation into specific phenotypes via signal-transduction pathways. This review provides current concepts and applications of the tissue engineering approach, especially SHEDs, in endodontic treatment.
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Affiliation(s)
- Vinna K Sugiaman
- Department of Oral Biology, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
| | - Rudy Djuanda
- Department of Conservative Dentistry and Endodontic, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
| | - Natallia Pranata
- Department of Oral Biology, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
| | - Silvia Naliani
- Department of Prosthodontics, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
| | - Wayan L Demolsky
- Department of Oral Biology, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
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18
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Liang C, Liang Q, Xu X, Liu X, Gao X, Li M, Yang J, Xing X, Huang H, Tang Q, Liao L, Tian W. Bone morphogenetic protein 7 mediates stem cells migration and angiogenesis: therapeutic potential for endogenous pulp regeneration. Int J Oral Sci 2022; 14:38. [PMID: 35858911 PMCID: PMC9300630 DOI: 10.1038/s41368-022-00188-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 06/17/2022] [Accepted: 06/19/2022] [Indexed: 02/05/2023] Open
Abstract
Pulp loss is accompanied by the functional impairment of defense, sensory, and nutrition supply. The approach based on endogenous stem cells is a potential strategy for pulp regeneration. However, endogenous stem cell sources, exogenous regenerative signals, and neovascularization are major difficulties for pulp regeneration based on endogenous stem cells. Therefore, the purpose of our research is to seek an effective cytokines delivery strategy and bioactive materials to reestablish an ideal regenerative microenvironment for pulp regeneration. In in vitro study, we investigated the effects of Wnt3a, transforming growth factor-beta 1, and bone morphogenetic protein 7 (BMP7) on human dental pulp stem cells (h-DPSCs) and human umbilical vein endothelial cells. 2D and 3D culture systems based on collagen gel, matrigel, and gelatin methacryloyl were fabricated to evaluate the morphology and viability of h-DPSCs. In in vivo study, an ectopic nude mouse model and an in situ beagle dog model were established to investigate the possibility of pulp regeneration by implanting collagen gel loading BMP7. We concluded that BMP7 promoted the migration and odontogenic differentiation of h-DPSCs and vessel formation. Collagen gel maintained the cell adhesion, cell spreading, and cell viability of h-DPSCs in 2D or 3D culture. The transplantation of collagen gel loading BMP7 induced vascularized pulp-like tissue regeneration in vivo. The injectable approach based on collagen gel loading BMP7 might exert promising therapeutic application in endogenous pulp regeneration. BMP7 as a regenerative signaling molecule mediates stem cell migration and odontoblastic differentiation (a) and as a pro-angiogenic factor promotes revascularization of endothelial cells (b). Collagen gel supports cell adhesion, spreading, and viability (c). ![]()
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Affiliation(s)
- Cheng Liang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Qingqing Liang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xun Xu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xiaojing Liu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xin Gao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Maojiao Li
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Jian Yang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xiaotao Xing
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Haisen Huang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Qi Tang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Li Liao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
| | - Weidong Tian
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
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19
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Fu T, Liu Y, Huang X, Guo Y, Shen J, Shen H. lncRNA SNHG1 regulates odontogenic differentiation of human dental pulp stem cells via miR-328-3p/Wnt/β-catenin pathway. Stem Cell Res Ther 2022; 13:311. [PMID: 35841022 PMCID: PMC9284872 DOI: 10.1186/s13287-022-02979-w] [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: 12/26/2021] [Accepted: 04/17/2022] [Indexed: 12/03/2022] Open
Abstract
Background Elucidating the mechanism of odontogenic differentiation of human dental pulp stem cells (hDPSCs) is the key to in-depth mastery and development of regenerative endodontic procedures (REPs). In odontogenic differentiation, lncRNAs have a regulatory role. The goal of this research is to determine the involvement of short nucleolar RNA host gene 1 (SNHG1) in hDPSCs’ odontogenic differentiation and the mechanism that underpins it. Methods hDPSCs were isolated from the dental pulp tissue of healthy immature permanent teeth. Follow-up experiments were performed when the third generation of primary cells were transfected. The proliferation ability was measured by CCK-8. The biological effects of SNHG1 and miR-328-3p were determined by real-time quantitative polymerase chain reaction (qRT-PCR), western blot (WB), alkaline phosphatase (ALP) staining and activity, alizarin red S staining (ARS) and quantification, and immunofluorescence staining. The binding of SNHG1 and miR-328-3p was confirmed using a dual-luciferase reporter assay. qRT-PCR and WB were used to determine whether the canonical Wnt/β-catenin pathway was activated. Results On the 0th, 3rd, and 7th days of odontogenic differentiation of hDPSCs, SNHG1 showed a gradual up-regulation trend. SNHG1 overexpression enhanced the mRNA and protein expression of dentin sialophosphoprotein (DSPP), dentine matrix protein 1 (DMP-1) and ALP. We found that SNHG1 could bind to miR-328-3p. miR-328-3p inhibited the odontogenic differentiation of hDPSCs. Therefore, miR-328-3p mimics rescued the effect of SNHG1 overexpression on promoting odontogenic differentiation. In addition, SNHG1 inhibited Wnt/β-catenin pathway via miR-328-3p in odontogenic differentiation of hDPSCs. Conclusion lncRNA SNHG1 inhibits Wnt/β-catenin pathway through miR-328-3p and then promotes the odontogenic differentiation of hDPSCs. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-02979-w.
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Affiliation(s)
- Tingting Fu
- Department of Pediatric and Preventive Dentistry, Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China
| | - Yiran Liu
- Department of Pediatric and Preventive Dentistry, Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China
| | - Xin Huang
- Department of Pediatric and Preventive Dentistry, Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China
| | - Yan Guo
- Department of Pediatric and Preventive Dentistry, Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China
| | - Jiaping Shen
- Department of Pediatric and Preventive Dentistry, Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China.
| | - Hong Shen
- Department of Pediatric and Preventive Dentistry, Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China.
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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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21
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Enamel Matrix Derivative Enhances the Odontoblastic Differentiation of Dental Pulp Stem Cells via Activating MAPK Signaling Pathways. Stem Cells Int 2022; 2022:2236250. [PMID: 35530415 PMCID: PMC9071913 DOI: 10.1155/2022/2236250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 03/27/2022] [Accepted: 04/05/2022] [Indexed: 12/03/2022] Open
Abstract
The odontoblastic differentiation of dental pulp stem cells (DPSCs) contributes to pulp-dentin regeneration. Enamel matrix derivative (EMD) is considered to be a critical epithelial signal to induce cell differentiation during odontogenesis and has been widely applied to clinical periodontal tissue regeneration. The purpose of this study was to explore the effect of EMD on DPSCs proliferation and odontoblastic differentiation, as well as the underlying mechanisms. We conducted in vitro and in vivo researches to get a comprehensive understanding of EMD. In vitro phase: cell proliferation was assessed by a cell counting kit-8 (CCK-8) assay; then, alkaline phosphatase (ALP) activity and staining, alizarin red staining, real-time RT-PCR, and western blot analysis were conducted to determine the odontoblastic potential and involvement of MAPK signaling pathways. In vivo phase: after ensuring the biocompatibility of VitroGel 3D-RGD via scanning electron microscopy (SEM), the hydrogel mixture was subcutaneously injected into nude mice followed by histological and immunohistochemical analyses. The results revealed that EMD did not interfere with DPSCs proliferation but promoted the odontoblastic differentiation of DPSCs in vitro and in vivo. Furthermore, blocking the MAPK pathways suppressed the EMD-enhanced differentiation of DPSCs. Finally, VitroGel 3D-RGD could well support the proliferation, differentiation, and regeneration of DPSCs. Overall, this study demonstrates that EMD enhances the odontoblastic differentiation of DPSCs through triggering MAPK signaling pathways. The findings provide a new insight into the mechanism by which EMD affects DPSCs differentiation and proposes EMD as a promising candidate for future stem cell therapy in endodontics.
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22
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Anjali S, Resmi R, Saravana RP, Joseph R, Saraswathy M. Ferulic acid incorporated anti-microbial self cross-linking hydrogel: A promising system for moderately exudating wounds. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103446] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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23
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Liang X, Xie L, Zhang Q, Wang G, Zhang S, Jiang M, Zhang R, Yang T, Hu X, Yang Z, Tian W. Gelatin methacryloyl-alginate core-shell microcapsules as efficient delivery platforms for prevascularized microtissues in endodontic regeneration. Acta Biomater 2022; 144:242-257. [PMID: 35364321 DOI: 10.1016/j.actbio.2022.03.045] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 03/17/2022] [Accepted: 03/24/2022] [Indexed: 02/06/2023]
Abstract
Combined injectable cell-laden microspheres and angiogenesis approaches are promising for functional vascularized endodontic regeneration. However, advanced microsphere designs and production techniques that benefit practical applications are rarely developed. Herein, gelatin methacryloyl (GelMA)-alginate core-shell microcapsules were fabricated to co-encapsulate human dental pulp stem cells (hDPSCs) and human umbilical vein endothelial cells (HUVECs) based on a coaxial electrostatic microdroplet technique. This technique enables high-throughput production, convenient collection, and minimal material waste. The average diameter of core-shell microcapsules was ∼359 µm, and that of GelMA cores was ∼278 µm. There were higher proliferation rates for hDPSCs and HUVECs co-encapsulated in the GelMA cores than for hDPSCs or HUVECs monoculture group. HUVECs assembled to form 3D capillary-like networks in co-culture microcapsules. Moreover, HUVECs promoted the osteo/odontogenic differentiation of hDPSCs in microcapsules. After 14 days of cultivation, prevascularized microtissues formed in microcapsules that contained abundant deposited extracellular matrix (ECM); no microcapsule aggregation occurred. In vivo studies confirmed that better microvessel formation and pulp-like tissue regeneration occurred in the co-culture group than in hDPSCs group. Thus, an effective platform for prevascularization microtissue preparation was proposed and showed great promise in endodontic regeneration and tissue engineering applications. STATEMENT OF SIGNIFICANCE: Cell-laden microspheres combined with the proangiogenesis approach are promising in endodontic regeneration. We proposed GelMA-alginate core-shell microcapsules generated via the coaxial electrostatic microdroplet (CEM) method, which utilizes a double-lumen needle to allow for core-shell structures to form. The microcapsules were used for co-culturing hDPSCs and HUVECs to harvest large amounts of prevascularized microtissues, which further showed improved vascularization and pulp-like tissue regeneration in vivo. This CEM method and the microcapsule system have advantages of high-throughput generation, convenient collection, and avoid aggregation during long-term culturing. We proposed a high-effective platform for mass production of prevascularized microtissues, which exhibit great promise in the clinical transformation of endodontic regeneration and other applications in regenerative medicine.
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Affiliation(s)
- Xi Liang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Li Xie
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
| | - Qingyuan Zhang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Ge Wang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Siyuan Zhang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Mingyan Jiang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Ruitao Zhang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Ting Yang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Xingyu Hu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Ziyang Yang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of Stomatology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China
| | - Weidong Tian
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
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24
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Paul K, Islam A, Volponi AA. Future horizons: embedding the evolving science of regenerative dentistry in a modern, sustainable dental curriculum. Br Dent J 2022; 232:207-210. [PMID: 35217737 DOI: 10.1038/s41415-022-3981-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 11/02/2021] [Indexed: 11/09/2022]
Abstract
Regenerative dentistry is an emerging field promising to revolutionise the way we approach and perform clinical therapies. This multidisciplinary field, integrating cellular biology, material science and tissue engineering, aims to restore and maintain biological vitality unlike conventional dental therapies, providing a new approach in achieving sustainability within dentistry. Although this emerging field in dentistry seems futuristic and a distant reality, it is closer than we perceive it, as rapid scientific advances contribute to novel technologies. In this opinion piece we share our views on the emerging field and the need of embedding the scientific knowledge and sustainability within the dental curriculum. We critically discuss challenges and quests ahead of our dental profession facing the future.
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Affiliation(s)
- Kiri Paul
- Centre for Dental Education, Faculty of Dentistry, Oral and Craniofacial Sciences, King´s College University of London, Guy´s Hospital Tower, Floor 27, London, SE1 9RT, UK
| | - Abida Islam
- Centre for Dental Education, Faculty of Dentistry, Oral and Craniofacial Sciences, King´s College University of London, Guy´s Hospital Tower, Floor 27, London, SE1 9RT, UK
| | - Ana Angelova Volponi
- Centre for Dental Education, Faculty of Dentistry, Oral and Craniofacial Sciences, King´s College University of London, Guy´s Hospital Tower, Floor 27, London, SE1 9RT, UK; Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral and Craniofacial Sciences, King´s College University of London, Guy´s Hospital Tower, Floor 27, London, SE1 9RT, UK.
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25
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Zhang Q, Yang T, Zhang R, Liang X, Wang G, Tian Y, Xie L, Tian W. Platelet lysate functionalized gelatin methacrylate microspheres for improving angiogenesis in endodontic regeneration. Acta Biomater 2021; 136:441-455. [PMID: 34551330 DOI: 10.1016/j.actbio.2021.09.024] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 09/13/2021] [Accepted: 09/14/2021] [Indexed: 02/06/2023]
Abstract
Rapid angiogenesis is one of the challenges in endodontic regeneration. Recently, tailored polymeric microsphere system that loaded pro-angiogenic growth factors (GFs) is promising in facilitating vascularization in dental pulp regeneration. In addition, the synergistic effect of multiple GFs is considered more beneficial, but combination usage of them is rather complex and costly. Herein, we aimed to incorporate human platelet lysate (PL), a natural-derived pool of multiple GFs, into gelatin methacrylate (GelMA) microsphere system (GP), which was further modified by Laponite (GPL), a nanoclay with efficient drug delivery ability. These hybrid microspheres were successfully fabricated by electrostatic microdroplet technique with suitable size range (180∼380 µm). After incorporation of the PL and Laponite with GelMA, the Young's modulus of the hybrid hydrogel increased up to about 3-fold and the swelling and degradation rate decreased simultaneously. The PL-derived GFs continued to release up to 28 days from both the GP and GPL microspheres, while the latter released relatively more slowly. What's more, the released GFs could effectively induce tubule formation of human umbilical endothelial cells (HUVECs) and also promote human dental pulp stem cells (hDPSCs) migration. Additionally, the PL component in the GelMA microspheres significantly improved the proliferation, spreading, and odontogenic differentiation of the encapsulated hDPSCs. As further verified by the subcutaneous implantation results, both of the GP and GPL groups enhanced microvascular formation and pulp-like tissue regeneration. This work demonstrated that PL-incorporating GelMA microsphere system was a promising functional vehicle for promoting vascularized endodontic regeneration. STATEMENT OF SIGNIFICANCE: Polymeric microsphere system loaded with pro-angiogenic growth factors (GFs) shows great promise for regeneration of vascularized dental pulp. Herein, we prepared a functional GelMA microsphere system incorporated with human platelet lysates (PL) and nanoclay Laponite by the electrostatic microdroplet method. The results demonstrated that the GelMA/PL/Laponite microspheres significantly improved the spreading, proliferation, and odontogenic differentiation of the encapsulated hDPSCs compared with pure GelMA microspheres. Moreover, they also enhanced microvascular formation and pulp-like tissue regeneration in vivo. This hybrid microsphere system has great potential to accelerate microvessel formation in regenerated dental pulp and other tissues.
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26
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Kukreja BJ, Bhat KG, Kukreja P, Kumber VM, Balakrishnan R, Govila V. Isolation and immunohistochemical characterization of periodontal ligament stem cells: A preliminary study. J Indian Soc Periodontol 2021; 25:295-299. [PMID: 34393399 PMCID: PMC8336774 DOI: 10.4103/jisp.jisp_442_20] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Revised: 12/12/2020] [Accepted: 12/15/2020] [Indexed: 01/04/2023] Open
Abstract
Context: It is a known fact that periodontal tissue regeneration can be achieved by the use of periodontal ligament stem cells (PDLSCs). Current mainstay of periodontal treatment is focusing on stem cell tissue engineering as an effective therapy, making it important to isolate PDLSCs from periodontal tissues. Aims: The present research endeavor was undertaken to elucidate a technique for isolating PDLSCs for in vivo reconstructing the natural PDL tissue. Settings and Design: The study design involves In vitro prospective study. Materials and Methods: Premolar teeth were extracted from 12 patients who were under orthodontic treatment. PDL cells were scraped from their roots. Using 10 ml of Dulbecco's modified Eagle's medium with pH 7.2, the specimens of the periodontal tissue were transferred to laboratory where cell culture was done. Isolated stem cells were grown on 24-well microtiter plates-containing cover slips. They were incubated overnight at approximately 37°C in 95% air and 5% humidification. Anti-CD 45, CD73, CD90, CD105, and CD146 antibodies were used. After staining, cells were observed under phase-contrast microscopy and in inverted microscope. Results: The cells showed a marked growth and 90% confluence at day 6. Cells presented thin and long fibroblastic spindle morphology. Isolated PDLSCs showed colony-forming ability at the 14th day after seeding. Immunohistochemical staining of PDLSCs showed positive uptake for CD146, CD90, CD73, CD105, and negative uptake for CD45. Conclusions: The human PDLSCs can be clearly isolated and characterized by using CD90, CD73, CD146, and CD105 markers of stem cells.
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Affiliation(s)
- Bhavna Jha Kukreja
- Department of Periodontology, Babu Banarasi Das College of Dental Sciences, Babu Banarasi Das University, Lucknow, Uttar Pradesh, India
| | - Kishore Gajanan Bhat
- Department of Microbiology, Maratha Mandal's Nathajirao G. Halgekar Institute of Dental Sciences and Research Centre, Belagavi, Karnataka, India
| | - Pankaj Kukreja
- Department of Biomedical Dental Sciences, Faculty of Dentistry, Al Baha University, Al Baha, Kingdom of Saudi Arabia
| | - Vijay Mahadev Kumber
- Maratha Mandal's Nathajirao G. Halgekar Institute of Dental Sciences and Research Centre, Maratha Mandal's Central Research Laboratory, Belagavi, Karnataka, India
| | - Rajkumar Balakrishnan
- Department of Conservative Dentistry and Endodontics, Babu Banarasi Das College of Dental Sciences, Babu Banarasi Das University, Lucknow, Uttar Pradesh, India
| | - Vivek Govila
- Department of Periodontology, Saraswati Dental College and Hospital, Lucknow, Uttar Pradesh, India
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27
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Mangione F, Salmon B, EzEldeen M, Jacobs R, Chaussain C, Vital S. Characteristics of Large Animal Models for Current Cell-Based Oral Tissue Regeneration. TISSUE ENGINEERING PART B-REVIEWS 2021; 28:489-505. [PMID: 33882717 DOI: 10.1089/ten.teb.2020.0384] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
The recent advances in the field of cell-based therapeutics open promising perspectives for oral tissue regeneration. The development of large animal models, which overcome the limits of the rodent models and allow to emulate clinical situations, is crucial for the validation of regenerative strategies to move toward clinical application. Currently, porcine, canine, and ovine models are mainly developed for oral regeneration and their specific characteristics have an impact on the outcomes of the studies. Thus, this systematic review investigates the application of porcine, canine, and ovine models in present cell-based oral regeneration, according to the species characteristics and the targeted tissue to regenerate. A customized search of PubMed, EMBASE, Scopus, and Web of Science databases from January 2015 to March 2020 was conducted. Relevant articles about cell-based oral tissues engineering in porcine, canine, and ovine models were evaluated. Among the evaluated articles, 58 relevant studies about cell-based oral regeneration in porcine, canine, and ovine models matched the eligibility criteria and were selected for full analysis. Porcine models, the most similar species with humans, were mostly used for bone and periodontium regeneration; tooth regeneration was reported only in pig, except for one study in dog. Canine models were the most transversal models, successfully involved for all oral tissue regeneration and notably in implantology. However, differences with humans and ethical concerns affect the use of these models. Ovine models, alternative to porcine and canine ones, were mainly used for bone and, scarcely, periodontium regeneration. The anatomy and physiology of these animals restrain their involvement. If consistency was found in defect specificities and cell trends among different species animal models of bone, dentin-pulp complex, or tooth regeneration, variability appeared in periodontium. Regeneration assessment methods were more elaborate in porcines and canines than in ovines. Risk of bias was low for selection, attrition and reporting, but unclear for performance and detection. Overall, if none of the large animal models can be considered an ideal one, they are of deemed importance for oral cell-based tissue engineering and researchers should consider their relevance to establish favorable conditions for a given preclinical cell-based therapeutics.
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Affiliation(s)
- Francesca Mangione
- URP 2496 Laboratory Orofacial Pathologies, Imaging and Biotherapies, Life Imaging Platform (PIV), UFR Odontology, Université de Paris, Montrouge, France.,Henri Mondor Hospital, AP-HP, Créteil, France
| | - Benjamin Salmon
- URP 2496 Laboratory Orofacial Pathologies, Imaging and Biotherapies, Life Imaging Platform (PIV), UFR Odontology, Université de Paris, Montrouge, France.,Bretonneau Hospital, AP-HP, Paris, France.,Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, Filière OSCAR, AP-HP, Paris, France
| | - Mostafa EzEldeen
- OMFS-IMPATH Research Group, Department of Imaging and Pathology, Faculty of Medicine, University of Leuven, Leuven, Belgium.,Maxillofacial Surgery Department, University Hospitals Leuven, Leuven, Belgium.,Department of Oral Health Sciences, KU Leuven and Paediatric Dentistry and Special Dental Care, University Hospitals Leuven, Leuven, Belgium
| | - Reinhilde Jacobs
- OMFS-IMPATH Research Group, Department of Imaging and Pathology, Faculty of Medicine, University of Leuven, Leuven, Belgium.,Maxillofacial Surgery Department, University Hospitals Leuven, Leuven, Belgium.,Department of Dental Medicine, Karolinska Institute, Stockholm, Sweden
| | - Catherine Chaussain
- URP 2496 Laboratory Orofacial Pathologies, Imaging and Biotherapies, Life Imaging Platform (PIV), UFR Odontology, Université de Paris, Montrouge, France.,Bretonneau Hospital, AP-HP, Paris, France.,Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, Filière OSCAR, AP-HP, Paris, France
| | - Sibylle Vital
- URP 2496 Laboratory Orofacial Pathologies, Imaging and Biotherapies, Life Imaging Platform (PIV), UFR Odontology, Université de Paris, Montrouge, France.,AP-HP, Hôpital Louis Mourier, DMU ESPRIT, Colombes, France
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28
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Liu Y, Su YY, Yang Q, Zhou T. Stem cells in the treatment of renal fibrosis: a review of preclinical and clinical studies of renal fibrosis pathogenesis. Stem Cell Res Ther 2021; 12:333. [PMID: 34112221 PMCID: PMC8194041 DOI: 10.1186/s13287-021-02391-w] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 05/14/2021] [Indexed: 02/05/2023] Open
Abstract
Renal fibrosis commonly leads to glomerulosclerosis and renal interstitial fibrosis and the main pathological basis involves tubular atrophy and the abnormal increase and excessive deposition of extracellular matrix (ECM). Renal fibrosis can progress to chronic kidney disease. Stem cells have multilineage differentiation potential under appropriate conditions and are easy to obtain. At present, there have been some studies showing that stem cells can alleviate the accumulation of ECM and renal fibrosis. However, the sources of stem cells and the types of renal fibrosis or renal fibrosis models used in these studies have differed. In this review, we summarize the pathogenesis (including signaling pathways) of renal fibrosis, and the effect of stem cell therapy on renal fibrosis as described in preclinical and clinical studies. We found that stem cells from various sources have certain effects on improving renal function and alleviating renal fibrosis. However, additional clinical studies should be conducted to confirm this conclusion in the future.
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Affiliation(s)
- Yiping Liu
- Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, No. 69 Dongsha Road, Shantou, 515041, China
| | - Yan-Yan Su
- Department of Nephrology, Huadu District People's Hospital of Guangzhou, Southern Medical University, Guangzhou, China
| | - Qian Yang
- Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, No. 69 Dongsha Road, Shantou, 515041, China
| | - Tianbiao Zhou
- Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, No. 69 Dongsha Road, Shantou, 515041, China.
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29
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Bekhouche M, Bolon M, Charriaud F, Lamrayah M, Da Costa D, Primard C, Costantini A, Pasdeloup M, Gobert S, Mallein-Gerin F, Verrier B, Ducret M, Farges JC. Development of an antibacterial nanocomposite hydrogel for human dental pulp engineering. J Mater Chem B 2021; 8:8422-8432. [PMID: 32804177 DOI: 10.1039/d0tb00989j] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Hydrogel-based regenerative endodontic procedures (REPs) are considered to be very promising therapeutic strategies to reconstruct the dental pulp (DP) tissue in devitalized human teeth. However, the success of the regeneration process is limited by residual bacteria that may persist in the endodontic space after the disinfection step and contaminate the biomaterial. The aim of this work was to develop an innovative fibrin hydrogel incorporating clindamycin (CLIN)-loaded Poly (d,l) Lactic Acid (PLA) nanoparticles (NPs) to provide the hydrogel with antibacterial properties. CLIN-PLA-NPs were synthesized by a surfactant-free nanoprecipitation method and their microphysical properties were assessed by dynamic light scattering, electrophoretic mobility and scanning electron microscopy. Their antimicrobial efficacy was evaluated on Enteroccocus fæcalis by the determination of the minimal inhibitory concentration (MIC) and the minimal biofilm inhibition and eradication concentrations (MBIC and MBEC). Antibacterial properties of the nanocomposite hydrogel were verified by agar diffusion assays. NP distribution into the hydrogel and release from it were evaluated using fluorescent PLA-NPs. NP cytotoxicity was assessed on DP mesenchymal stem cells (DP-MSCs) incorporated into the hydrogel. Type I collagen synthesis was investigated after 7 days of culture by immunohistochemistry. We found that CLIN-PLA-NPs displayed a drug loading of 10 ± 2 μg per mg of PLA polymer and an entrapment efficiency of 43 ± 7%. Antibiotic loading did not affect NP size, polydispersity index and zeta potential. The MIC for Enterococcus fæcalis was 32 μg mL-1. MBIC50 and MBEC50 were 4 and 16 μg mL-1, respectively. CLIN-PLA-NPs appeared homogenously distributed throughout the hydrogel. CLIN-PLA-NP-loaded hydrogels clearly inhibited E. faecalis growth. DP-MSC viability and type I collagen synthesis within the fibrin hydrogel were not affected by CLIN-PLA-NPs. In conclusion, CLIN-PLA-NP incorporation into the fibrin hydrogel gave the latter antibacterial and antibiofilm properties without affecting cell viability and function. This formulation could help establish an aseptic environment supporting DP reconstruction and, accordingly, might be a valuable tool for REPs.
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Affiliation(s)
- M Bekhouche
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France and Faculté d'Odontologie, Université de Lyon, Université Lyon 1, Lyon, France
| | - M Bolon
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France
| | - F Charriaud
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France
| | - M Lamrayah
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France
| | - D Da Costa
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France and Adjuvatis®, Lyon, France
| | | | - A Costantini
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France
| | - M Pasdeloup
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France
| | - S Gobert
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France
| | - F Mallein-Gerin
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France
| | - B Verrier
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France
| | - M Ducret
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France and Faculté d'Odontologie, Université de Lyon, Université Lyon 1, Lyon, France and Hospices Civils de Lyon, Service de Consultations et Traitements Dentaires, Lyon, France
| | - J-C Farges
- Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR5305 CNRS/Université Lyon 1, Lyon, France and Faculté d'Odontologie, Université de Lyon, Université Lyon 1, Lyon, France and Hospices Civils de Lyon, Service de Consultations et Traitements Dentaires, Lyon, France
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Deng Z, Yan W, Dai X, Chen M, Qu Q, Wu B, Zhao W. N-Cadherin Regulates the Odontogenic Differentiation of Dental Pulp Stem Cells via β-Catenin Activity. Front Cell Dev Biol 2021; 9:661116. [PMID: 33859987 PMCID: PMC8042212 DOI: 10.3389/fcell.2021.661116] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Accepted: 03/11/2021] [Indexed: 12/22/2022] Open
Abstract
Dental pulp stem cell (DPSC) transplantation has shown new prospects in dental pulp regeneration, and is of great significance in the treatment of pulpitis and pulp necrosis. The fate and regenerative potential of stem cells are dependent, to a great extent, on their microenvironment, which is composed of various tissue components, cell populations, and soluble factors. N-cadherin-mediated cell–cell interaction has been implicated as an important factor in controlling the cell-fate commitment of mesenchymal stem cells. In this study, the effect of N-cadherin on odontogenic differentiation of DPSCs and the potential underlying mechanisms, both in vitro and in vivo, was investigated using a cell culture model and a subcutaneous transplantation mouse model. It was found that the expression of N-cadherin was reversely related to the expression of odontogenic markers (dentin sialophosphoprotein, DSPP, and runt-related transcription factor 2, Runx2) during the differentiation process of DPSCs. Specific shRNA-mediated knockdown of N-cadherin expression in DPSCs significantly increased the expression of DSPP and Runx2, alkaline phosphatase (ALP) activity, and the formation of mineralized nodules. Notably, N-cadherin silencing promoted nucleus translocation and accumulation of β-catenin. Inhibition of β-catenin by a specific inhibitor XAV939, reversed the facilitating effects of N-cadherin downregulation on odontogenic differentiation of DPSCs. In addition, knockdown of N-cadherin promoted the formation of odontoblast-like cells and collagenous matrix in β-tricalcium phosphate/DPSCs composites transplanted into mice. In conclusion, N-cadherin acted as a negative regulator via regulating β-catenin activity during odontogenic differentiation of DPSCs. These data may help to guide DPSC behavior by tuning the N-cadherin-mediated cell–cell interactions, with implications for pulp regeneration.
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Affiliation(s)
- Zilong Deng
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Wenjuan Yan
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xingzhu Dai
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ming Chen
- Stomatological Hospital, Southern Medical University, Guangzhou, China
| | - Qian Qu
- Stomatology Healthcare Center, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen, China
| | - Buling Wu
- Shenzhen Stomatology Hospital (Pingshan), Southern Medical University, Shenzhen, China
| | - Wanghong Zhao
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Campos Y, Sola FJ, Fuentes G, Quintanilla L, Almirall A, Cruz LJ, Rodríguez-Cabello JC, Tabata Y. The Effects of Crosslinking on the Rheology and Cellular Behavior of Polymer-Based 3D-Multilayered Scaffolds for Restoring Articular Cartilage. Polymers (Basel) 2021; 13:907. [PMID: 33809430 PMCID: PMC7999668 DOI: 10.3390/polym13060907] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/11/2021] [Accepted: 03/12/2021] [Indexed: 01/10/2023] Open
Abstract
Polymer-based tri-layered (bone, intermediate and top layers) scaffolds used for the restoration of articular cartilage were prepared and characterized in this study to emulate the concentration gradient of cartilage. The scaffolds were physically or chemically crosslinked. In order to obtain adequate scaffolds for the intended application, the impact of the type of calcium phosphate used in the bone layer, the polymer used in the intermediate layer and the interlayer crosslinking process were analyzed. The correlation among SEM micrographs, physical-chemical characterization, swelling behavior, rheological measurements and cell studies were examined. Storage moduli at 1 Hz were 0.3-1.7 kPa for physically crosslinked scaffolds, and 4-5 kPa (EDC/NHS system) and 15-20 kPa (glutaraldehyde) for chemically crosslinked scaffolds. Intrinsic viscoelasticity and poroelasticity were considered in discussing the physical mechanism dominating in different time/frequency scales. Cell evaluation showed that all samples are available as alternatives to repair and/or substitute cartilage in articular osteoarthritis.
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Affiliation(s)
- Yaima Campos
- Centro de Biomateriales, Universidad de La Habana, ave Universidad e/G y Ronda, Vedado, Plaza, La Habana CP 10400, Cuba; (Y.C.); (F.J.S.); (A.A.)
- TNI Group, Department of Radiology, LUMC, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;
| | - Francisco J. Sola
- Centro de Biomateriales, Universidad de La Habana, ave Universidad e/G y Ronda, Vedado, Plaza, La Habana CP 10400, Cuba; (Y.C.); (F.J.S.); (A.A.)
| | - Gastón Fuentes
- Centro de Biomateriales, Universidad de La Habana, ave Universidad e/G y Ronda, Vedado, Plaza, La Habana CP 10400, Cuba; (Y.C.); (F.J.S.); (A.A.)
- TNI Group, Department of Radiology, LUMC, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;
- 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;
- Bioforge Group, Campus Miguel Delibes, CIBER-BBN, Universidad de Valladolid, Edificio LUCIA, Paseo Belén 19, 47011 Valladolid, Spain; (L.Q.); (J.C.R.-C.)
| | - Luis Quintanilla
- Bioforge Group, Campus Miguel Delibes, CIBER-BBN, Universidad de Valladolid, Edificio LUCIA, Paseo Belén 19, 47011 Valladolid, Spain; (L.Q.); (J.C.R.-C.)
| | - Amisel Almirall
- Centro de Biomateriales, Universidad de La Habana, ave Universidad e/G y Ronda, Vedado, Plaza, La Habana CP 10400, Cuba; (Y.C.); (F.J.S.); (A.A.)
- 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;
| | - Luis J. Cruz
- TNI Group, Department of Radiology, LUMC, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;
| | - José C. Rodríguez-Cabello
- Bioforge Group, Campus Miguel Delibes, CIBER-BBN, Universidad de Valladolid, Edificio LUCIA, Paseo Belén 19, 47011 Valladolid, Spain; (L.Q.); (J.C.R.-C.)
| | - 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;
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Contessi Negrini N, Angelova Volponi A, Higgins C, Sharpe P, Celiz A. Scaffold-based developmental tissue engineering strategies for ectodermal organ regeneration. Mater Today Bio 2021; 10:100107. [PMID: 33889838 PMCID: PMC8050778 DOI: 10.1016/j.mtbio.2021.100107] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 02/15/2021] [Accepted: 02/27/2021] [Indexed: 12/12/2022] Open
Abstract
Tissue engineering (TE) is a multidisciplinary research field aiming at the regeneration, restoration, or replacement of damaged tissues and organs. Classical TE approaches combine scaffolds, cells and soluble factors to fabricate constructs mimicking the native tissue to be regenerated. However, to date, limited success in clinical translations has been achieved by classical TE approaches, because of the lack of satisfactory biomorphological and biofunctional features of the obtained constructs. Developmental TE has emerged as a novel TE paradigm to obtain tissues and organs with correct biomorphology and biofunctionality by mimicking the morphogenetic processes leading to the tissue/organ generation in the embryo. Ectodermal appendages, for instance, develop in vivo by sequential interactions between epithelium and mesenchyme, in a process known as secondary induction. A fine artificial replication of these complex interactions can potentially lead to the fabrication of the tissues/organs to be regenerated. Successful developmental TE applications have been reported, in vitro and in vivo, for ectodermal appendages such as teeth, hair follicles and glands. Developmental TE strategies require an accurate selection of cell sources, scaffolds and cell culture configurations to allow for the correct replication of the in vivo morphogenetic cues. Herein, we describe and discuss the emergence of this TE paradigm by reviewing the achievements obtained so far in developmental TE 3D scaffolds for teeth, hair follicles, and salivary and lacrimal glands, with particular focus on the selection of biomaterials and cell culture configurations.
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Affiliation(s)
| | - A. Angelova Volponi
- Centre for Craniofacial and Regenerative Biology, King's College London, London, UK
| | - C.A. Higgins
- Department of Bioengineering, Imperial College London, London, UK
| | - P.T. Sharpe
- Centre for Craniofacial and Regenerative Biology, King's College London, London, UK
| | - A.D. Celiz
- Department of Bioengineering, Imperial College London, London, UK
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Regeneration of pulp-dentin complex using human stem cells of the apical papilla: in vivo interaction with two bioactive materials. Clin Oral Investig 2021; 25:5317-5329. [PMID: 33630165 DOI: 10.1007/s00784-021-03840-9] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 02/15/2021] [Indexed: 12/15/2022]
Abstract
OBJECTIVES To compare the regenerative properties of human stem cells of the apical papilla (SCAPs) embedded in a platelet-rich plasma (PRP) scaffold, when implanted in vivo using an organotypic model composed of human root segments, with or without the presence of the bioactive cements - ProRoot MTA or Biodentine. MATERIAL AND METHODS SCAPs were isolated from third molars with incomplete rhizogenesis and expanded and characterized in vitro using stem cell and surface markers. The pluripotency of these cells was also assessed using adipogenic, chondrogenic, and osteogenic differentiation protocols. SCAPs together with a scaffold of PRP were added to the root segment lumen and the organotypic model implanted on the dorsal region of immunodeficient rats for a period of 4 months. RESULTS Presence of SCAPs induced de novo formation of dentin-like and pulp-like tissue. A barrier of either ProRoot MTA or Biodentine did not significantly affect the fraction of sections from roots segments observed to contain deposition of hard material (P > 0.05). However, the area of newly deposited dentin was significantly greater in segments containing a barrier of Biodentine compared with ProRoot MTA (P < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE SCAPs offer a viable alternative to other dental stem cells (DSCs) in their regenerative properties when enclosed in the microenvironment of human tooth roots. The present study also suggests that the presence of bioactive materials does not hinder or impede the formation of new hard tissues, but the presence of Biodentine may promote greater mineralized tissue deposition.
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Different Approaches to the Regeneration of Dental Tissues in Regenerative Endodontics. APPLIED SCIENCES-BASEL 2021. [DOI: 10.3390/app11041699] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
(1) Background: The regenerative procedure has established a new approach to root canal therapy, to preserve the vital pulp of the tooth. This present review aimed to describe and sum up the different approaches to regenerative endodontic treatment conducted in the last 10 years; (2) Methods: A literature search was performed in the PubMed and Cochrane Library electronic databases, supplemented by a manual search. The search strategy included the following terms: “regenerative endodontic protocol”, “regenerative endodontic treatment”, and “regenerative endodontics” combined with “pulp revascularization”. Only studies on humans, published in the last 10 years and written in English were included; (3) Results: Three hundred and eighty-six potentially significant articles were identified. After exclusion of duplicates, and meticulous analysis, 36 case reports were selected; (4) Conclusions: The pulp revascularization procedure may bring a favorable outcome, however, the prognosis of regenerative endodontics (RET) is unpredictable. Permanent immature teeth showed greater potential for positive outcomes after the regenerative procedure. Further controlled clinical studies are required to fully understand the process of the dentin–pulp complex regeneration, and the predictability of the procedure.
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iRoot SP Promotes Osteo/Odontogenesis of Bone Marrow Mesenchymal Stem Cells via Activation of NF- κB and MAPK Signaling Pathways. Stem Cells Int 2021; 2020:6673467. [PMID: 33424977 PMCID: PMC7775135 DOI: 10.1155/2020/6673467] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Revised: 11/11/2020] [Accepted: 11/18/2020] [Indexed: 12/11/2022] Open
Abstract
The regeneration of bone and tooth tissues, and related cellular therapies, has attracted widespread attention. Bone marrow mesenchymal stem cells (BMSCs) are potential candidates for such regeneration. iRoot SP is a premixed bioceramic root canal sealer widely used in clinical settings. However, the effect of iRoot SP on the biological features of BMSCs has not been elucidated. In the present study, we found that 0.2 mg/ml iRoot SP conditioned medium promoted osteo/odontogenic differentiation and enhanced mineralization of BMSCs without affecting the proliferative ability. Mechanistically, the NF-κB and MAPK signaling pathways were activated in SP-treated BMSCs, and differentiation was inhibited when cultured with the specific inhibitor. Taken together, these findings demonstrate that iRoot SP promotes osteo/odontogenic differentiation of BMSCs via the NF-κB and MAPK signaling pathways, which could provide a new theoretical basis for clinical applications of iRoot SP and a new therapeutic target for the regeneration of bone and tooth tissue in the future.
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hDPSC-laden GelMA microspheres fabricated using electrostatic microdroplet method for endodontic regeneration. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 121:111850. [PMID: 33579484 DOI: 10.1016/j.msec.2020.111850] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 12/22/2020] [Accepted: 12/28/2020] [Indexed: 02/05/2023]
Abstract
The microsphere system has attracted considerable attention as a stem-cell delivery vehicle in regeneration medicine owing to its injectability, fast substance transfer ability, and mimicry of the three-dimensional native environment. However, suitable biomaterials for preparation of microspheres optimal for endodontic regeneration are still being explored. Owing to its excellent bioactivity and biodegradability, gelatin methacryloyl (GelMA) was used to fabricate hydrogel microspheres by the electrostatic microdroplet method, and the potential of GelMA microspheres applied in endodontic regeneration was studied. The average size of GelMA microspheres encapsulating human dental pulp stem cells (hDPSCs) was ~200 μm, and the Young's modulus was approximately 582.8 ± 66.0 Pa, which was close to that of the natural human dental pulp. The encapsulated hDPSCs could effectively adhere, spread, proliferate, and secrete extracellular matrix proteins in the microspheres, and tended to occupy the outer layer. Moreover, the cell-laden GelMA microsphere system could withstand cryopreservation, and the thawed cells exhibited normal functions. After subcutaneous implantation in a nude mouse model, more vascularized pulp-like tissues were generated in the cell-laden GelMA microsphere group compared with that in the cell-laden bulk GelMA group, and this was accompanied by a suitable degradation rate. The GelMA microspheres showed remarkable performances and great potential as cell delivery vehicles in endodontic regeneration.
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Lin CC, Chiu JY. A novel γ-PGA composite gellan membrane containing glycerol for guided bone regeneration. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 118:111404. [PMID: 33255007 DOI: 10.1016/j.msec.2020.111404] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 08/03/2020] [Accepted: 08/11/2020] [Indexed: 11/19/2022]
Abstract
An ideal barrier membrane design should incorporate the function of a delivery vehicle for transporting drugs and osteoinductive factors to where the body is under inflammation. In the present study, a functional hydrogel-based barrier membrane is fabricated using calcium-form poly-γ-glutamic acid (γ-PGA) and glycerol blending into gellan gum. The concentration of the calcium-form poly-γ-glutamic acid (γ-PGA) and the glycerol ratio are studied for improving practicability in easy-handling and expanding the coverage area. Gellan gum-based membranes with uniformly distributed calcium aggregates are not only successfully manufactured but also providing excellent characteristics for protein adsorption, bioactivity, and bone cell maturation. Our composite gellan gum-based membranes were tested including to their morphology, mechanical properties, swelling behavior, protein adsorption, drug diffusion, and lysozyme degradation. The biocompatibility, proliferation, and osteoblastic response of membranes were examined by osteoblast-like (MG63) cells. Our results indicate that adequate physical cross-linking with γ-PGA improves the original mechanical properties and delays degradation. Growing glycerol ratio not only enhances the elongation at break and diffusion rate, but it also changes the tensile strength and the remaining weight. In vitro biocompatibility tests, an adequate ratio of γ-PGA modification significantly enhances the proliferation, the secretion of alkaline phosphatase (ALP) and mineralization. However, worth noting is the glycerol-modified membrane cannot bear a close resemblance with the non-glycerol group in the high level of osteoblastic response. In general, these tunable materials with biocompatibility, biodegradability, and positive osteoblastic responses were poised to be possible candidates for bone defect repair.
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Affiliation(s)
- Chi-Chang Lin
- Department of Chemical and Material Engineering, Tunghai University, Taichung 40704, Taiwan.
| | - Jiun-Yan Chiu
- Department of Chemical and Material Engineering, Tunghai University, Taichung 40704, Taiwan
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Diana R, Ardhani R, Kristanti Y, Santosa P. Dental pulp stem cells response on the nanotopography of scaffold to regenerate dentin-pulp complex tissue. Regen Ther 2020; 15:243-250. [PMID: 33426225 PMCID: PMC7770425 DOI: 10.1016/j.reth.2020.09.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 08/05/2020] [Accepted: 09/16/2020] [Indexed: 12/13/2022] Open
Abstract
The study of regenerative dentistry receives a fast growing interest. The potential ability of the dentin-pulp complex to regenerate is both promising and perplexing. To answer the challenging nature of the dental environment, scientists have developed various combinations of biomaterial scaffolds, stem cells, and incorporation of several growth factors. One of the crucial elements of this tissue engineering plan is the selection and fabrication of scaffolds. However, further findings suggest that cell behavior hugely depends on mechanical signaling. Nanotopography modifies scaffolds to alter cell migration and differentiation. However, to the best of the author's knowledge, there are very few studies addressing the correlation between nanotopography and dentin-pulp complex regeneration. Therefore, this article presents a comprehensive review of these studies and suggests a direction for future developments, particularly in the incorporation of nanotopography design for dentin-pulp complex regeneration.
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Key Words
- BDNF, brain-derived neurotrophic factor
- BMP, bone morphogenetic protein
- DPSC, dental pulp stem cell
- Dental pulp stem cell
- Dentin-pulp complex tissue
- ECM, extracellular matrix
- FGF2, fibroblast growth factor-2
- GDNF, glial cell line-derived neurotrophic factor
- GO, graphene oxide
- GelMA, methacrylated gelatin
- IGF, insulin-like growth factor
- ION-CPC, iron oxide nanoparticle-incorporating calcium phosphate cement
- LPS, lipopolysaccharide
- NGF, nerve growth factor
- Nanotopography
- PCL, polycaprolactone
- PDGF, platelet-derived growth factor
- PEGMA, poly(ethylene glycol) dimethacrylate
- PGA, polyglycolic acid
- PHMS, polyhydroxymethylsiloxane
- PLGA, poly-dl-lactic-co-glycolic acid
- PLLA, poly-l-lactic acid
- RGO, reduced graphene oxide
- Regenerative dentistry
- SACP, stem cells from apical papilla
- SDF-1, stromal cell-derived factor-1
- SHED, stem cells from human exfoliated deciduous teeth
- Scaffold
- TGF-β, transforming growth factor-β
- TNF-α, t umour necrosis factor-alpha
- VEGF, vascular endothelial growth factor
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Affiliation(s)
- Rasda Diana
- Department of Conservative Dentistry, Faculty of Dentistry Universitas Gadjah Mada, Jl Denta Sekip Utara, Yogyakarta, 55281, Indonesia
| | - Retno Ardhani
- Department of Dental Biomedical Sciences, Faculty of Dentistry Universitas Gadjah Mada, Jl Denta Sekip Utara, Yogyakarta, 55281, Indonesia
- Corresponding author. Fax: +62274 515307.
| | - Yulita Kristanti
- Department of Conservative Dentistry, Faculty of Dentistry Universitas Gadjah Mada, Jl Denta Sekip Utara, Yogyakarta, 55281, Indonesia
| | - Pribadi Santosa
- Department of Conservative Dentistry, Faculty of Dentistry Universitas Gadjah Mada, Jl Denta Sekip Utara, Yogyakarta, 55281, Indonesia
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Zeb Khan S, Mirza S, Karim S, Inoue T, Bin-Shuwaish MS, Al Deeb L, Al Ahdal K, Al-Hamdan RS, Maawadh AM, Vohra F, Abduljabbar T. Immunohistochemical study of dental pulp cells with 3D collagen type I gel in demineralized dentin tubules in vivo. Bosn J Basic Med Sci 2020; 20:438-444. [PMID: 32216743 PMCID: PMC7664783 DOI: 10.17305/bjbms.2020.4614] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 03/27/2020] [Indexed: 11/16/2022] Open
Abstract
Dental pulp cells (DPCs) represent good candidates for the regeneration of dental tissue. This study aimed to evaluate the growth and differentiation potential of DPCs cultured inside demineralized dentin tubules in vivo. Six green fluorescent protein-transgenic rats (body weight 100 g each) and thirty-two Sprague-Dawley (SD) male rats (body weight 250 g each) were used for DPC collection and dentin tubules preparation and transplantation, respectively. Third-passage DPCs with or without collagen gels were loaded into demineralized dentin tubules. Both types of grafts were transplanted into the rectus abdominis muscles of SD rats and were harvested after 21 days. The expression of alkaline phosphatase (ALP), bone sialoprotein (BSP), osteopontin (OPN), nestin, and dentin sialoprotein (DSP) was analyzed by immunohistochemistry. Histological analysis showed that DPCs in the collagen gel formed an osteodentin-like hard tissue matrix after 21 days. Increased positive immunoreactivity for ALP, BSP, OPN, nestin, and DSP was observed in experimental groups compared with control. Our results demonstrate that DPCs in collagen gel inside demineralized dentin tubules show increased growth and differentiation.
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Affiliation(s)
- Sultan Zeb Khan
- Department of Clinical Pathophysiology, Graduate School of Tokyo Dental College, Tokyo, Japan
| | - Sana Mirza
- Department of Oral Pathology, Faculty of Dentistry, Ziauddin University, Karachi, Pakistan
| | - Samina Karim
- Department of Ophthalmology, Hayatabad Medical Complex, Khyber Girls Medical College, Peshawar, Pakistan
| | - Takashi Inoue
- Department of Clinical Pathophysiology, Graduate School of Tokyo Dental College, Tokyo, Japan
| | - Mohammed S Bin-Shuwaish
- Department of Restorative Dentistry, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Laila Al Deeb
- Department of Restorative Dentistry, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Khold Al Ahdal
- Department of Restorative Dentistry, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Rana S Al-Hamdan
- Department of Restorative Dentistry, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Ahmed M Maawadh
- Department of Restorative Dentistry, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Fahim Vohra
- Department of Prosthetic Dental Sciences, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Tariq Abduljabbar
- Department of Prosthetic Dental Sciences, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
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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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Qi Y, Zou T, Dissanayaka WL, Wong HM, Bertassoni LE, Zhang C. Fabrication of Tapered Fluidic Microchannels Conducive to Angiogenic Sprouting within Gelatin Methacryloyl Hydrogels. J Endod 2020; 47:52-61. [PMID: 33045266 DOI: 10.1016/j.joen.2020.08.026] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 08/10/2020] [Accepted: 08/13/2020] [Indexed: 12/23/2022]
Abstract
INTRODUCTION The transplantation of stem cells/tissue constructs into root canal space is a promising strategy for regenerating lost pulp tissue. However, the root canal system, which is cone shaped with a taper from the larger coronal end to the smaller apical end, limits the vascular supply and, therefore, the regenerative capacity. The current study aimed to fabricate built-in microchannels with different tapers to explore various approaches to endothelialize these microchannels. METHODS The fluidic microchannels with varying tapers (parallel, 0.04, and 0.06) were fabricated within gelatin methacryloyl (GelMA) hydrogel (with or without stem cell from the apical papilla [SCAP] encapsulation) of different concentrations (5%, 7.5%, and 10% [w/v]). Green fluorescent protein-expressing human umbilical vein endothelial cells (HUVECs-GFP) were seeded alone or with SCAPs in coculture into these microchannels. Angiogenic sprouting was assessed by fluorescence and a confocal microscope and ImageJ software (National Institutes of Health, Bethesda, MD). Immunostaining was conducted to illustrate monolayer formation. Data were statistically analyzed by 1-way/2-way analysis of variance. RESULTS HUVEC-only inoculation formed an endothelial monolayer inside the microchannel without angiogenic sprouting. HUVECs-GFP/SCAPs cocultured at a 1:1 ratio produced the longest sprouting compared with the other 3 ratios. The average length of the sprouting in the 0.04 taper microchannel was significantly longer compared with that in the parallel and 0.06 taper microchannels. Significant differences in HUVEC-GFP sprouting were observed in 5% GelMA hydrogel. Encapsulation of SCAPs within hydrogel further stimulated the sprouting of HUVECs. CONCLUSIONS The coculture of SCAPs and HUVECs-GFP at a ratio of 1:1 in 0.04 taper fluidic microchannels fabricated with 5% (w/v) GelMA hydrogel with SCAPs encapsulated was found to be the optimal condition to enhance angiogenesis inside tapered microchannels.
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Affiliation(s)
- Yubingqing Qi
- Department of Endodontology, Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Ting Zou
- Department of Endodontology, Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Waruna Lakmal Dissanayaka
- Department of Endodontology, Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Hai Ming Wong
- Department of Paediatric Dentistry and Orthodontics, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Luiz E Bertassoni
- Department of Biomaterials and Biomechanics, School of Dentistry Center for Regenerative Medicine, Oregon Health and Science University, Portland, Oregon
| | - Chengfei Zhang
- Department of Endodontology, Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, China.
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Xia K, Chen Z, Chen J, Xu H, Xu Y, Yang T, Zhang Q. RGD- and VEGF-Mimetic Peptide Epitope-Functionalized Self-Assembling Peptide Hydrogels Promote Dentin-Pulp Complex Regeneration. Int J Nanomedicine 2020; 15:6631-6647. [PMID: 32982223 PMCID: PMC7495350 DOI: 10.2147/ijn.s253576] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Accepted: 07/15/2020] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Cell-based tissue engineering is a promising method for dentin-pulp complex (DPC) regeneration. The challenges associated with DPC regeneration include the generation of a suitable microenvironment that facilitates the complete odontogenic differentiation of dental pulp stem cells (DPSCs) and the rapid induction of angiogenesis. Thus, the survival and subsequent differentiation of DPSCs are limited. Extracellular matrix (ECM)-like biomimetic hydrogels composed of self-assembling peptides (SAPs) were developed to provide an appropriate microenvironment for DPSCs. For functional DPC regeneration, the most important considerations are to provide an environment that promotes the adequate attachment of DPSCs and rapid vascularization of the regenerating pulp. Morphogenic signals in the form of growth factors (GFs) have been incorporated into SAPs to promote productive DPSC behaviors. However, the use of GFs has several drawbacks. We envision using a scaffold with SAPs coupled with long-term factors to increase DPSC attachment and vascularization as a method to address this challenge. METHODS In this study, we developed synthetic material for an SAP-based scaffold with RGD- and vascular endothelial growth factor (VEGF)-mimetic peptide epitopes with the dual functions of dentin and pulp regeneration. DPSCs and human umbilical vein endothelial cells (HUVECs) were used to evaluate the biological effects of SAP-based scaffolds. Furthermore, the pulpotomized molar rat model was employed to test the reparative and regenerative effects of SAP-based scaffolds. RESULTS This scaffold simultaneously presented RGD- and VEGF-mimetic peptide epitopes and provided a 3D microenvironment for DPSCs. DPSCs grown on this composite scaffold exhibited significantly improved survival and angiogenic and odontogenic differentiation in the multifunctionalized group in vitro. Histological and functional evaluations of a partially pulpotomized rat model revealed that the multifunctionalized scaffold was superior to other options with respect to stimulating pulp recovery and dentin regeneration in vivo. CONCLUSION Based on our data obtained with the functionalized SAP scaffold, a 3D microenvironment that supports stem cell adhesion and angiogenesis was generated that has great potential for dental pulp tissue engineering and regeneration.
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Affiliation(s)
- Kun Xia
- Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai200072, People’s Republic of China
- Department of Preventive Dentistry, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou325027, People’s Republic of China
| | - Zhuo Chen
- Department of Endodontics, The Affiliated Stomatology Hospital, Zhejiang University School of Medicine, Hangzhou310006, People’s Republic of China
- Key Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang University School of Stomatology, Hangzhou310006, People’s Republic of China
| | - Jie Chen
- Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai200072, People’s Republic of China
| | - Huaxing Xu
- Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai200072, People’s Republic of China
| | - Yunfei Xu
- Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai200072, People’s Republic of China
| | - Ting Yang
- Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai200072, People’s Republic of China
| | - Qi Zhang
- Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai200072, People’s Republic of China
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Sui B, Wu D, Xiang L, Fu Y, Kou X, Shi S. Dental Pulp Stem Cells: From Discovery to Clinical Application. J Endod 2020; 46:S46-S55. [DOI: 10.1016/j.joen.2020.06.027] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Sasaki J, Zhang Z, Oh M, Pobocik A, Imazato S, Shi S, Nör J. VE-Cadherin and Anastomosis of Blood Vessels Formed by Dental Stem Cells. J Dent Res 2020; 99:437-445. [PMID: 32028818 PMCID: PMC7088203 DOI: 10.1177/0022034520902458] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
It is known that dental pulp stem cells (DPSCs) can be induced to differentiate into vasculogenic endothelial (VE) cells. However, the process that results in sprouting and anastomosis of DPSC-derived vessels remains unclear. Here, we performed studies to understand the mechanisms underpinning the anastomosis of the host vasculature with blood vessels generated by DPSCs (a model for mesenchymal stem cells). VE-cadherin-silenced primary human DPSCs seeded in tooth slice/scaffolds and transplanted into the subcutaneous space of immunodeficient mice generated fewer functional blood vessels (i.e., anastomosed with the host vasculature) than control DPSCs transduced with scrambled sequences. Both VE-cadherin-silenced and mitogen-activated protein kinase kinase 1 (MEK1)-silenced cells showed a decrease in the number of capillary sprouts in vitro. Interestingly, DPSC stably transduced with a VE-cadherin reporter demonstrated that vascular endothelial growth factor (VEGF) induces VE-cadherin expression in sprouting DPSCs undergoing anastomosis, but not in quiescent DPSCs. To begin to understand the mechanisms regulating VE-cadherin, we stably silenced MEK1 and observed that VEGF was no longer able to induce VE-cadherin expression and capillary sprout formation. Notably ERG, a transcriptional factor downstream from MEK/ERK, binds to the promoter region of VE-cadherin (chip assay) and is induced by VEGF in DPSCs. Collectively, these data defined a signaling pathway triggered by VEGF that results in phosphorylation of MEK1/ERK and activation of ERG leading to expression of VE-cadherin, which is required for anastomosis of DPSC-derived blood vessels. In conclusion, these results unveiled a signaling pathway that enables the generation of functional blood vessels upon vasculogenic differentiation of DPSCs.
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Affiliation(s)
- J.I. Sasaki
- Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA
- Department of Biomaterials Science, Osaka University Graduate School of Dentistry, Suita City, Osaka, Japan
| | - Z. Zhang
- Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA
| | - M. Oh
- Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA
| | - A.M. Pobocik
- Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA
| | - S. Imazato
- Department of Biomaterials Science, Osaka University Graduate School of Dentistry, Suita City, Osaka, Japan
| | - S. Shi
- Department of Anatomy and Cell Biology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA, USA
| | - J.E. Nör
- Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA
- Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI, USA
- Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, MI, USA
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Xu J, Gou L, Zhang P, Li H, Qiu S. Platelet-rich plasma and regenerative dentistry. Aust Dent J 2020; 65:131-142. [PMID: 32145082 PMCID: PMC7384010 DOI: 10.1111/adj.12754] [Citation(s) in RCA: 166] [Impact Index Per Article: 33.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/27/2020] [Indexed: 11/30/2022]
Abstract
Regenerative dentistry is an emerging field of medicine involving stem cell technology, tissue engineering and dental science. It exploits biological mechanisms to regenerate damaged oral tissues and restore their functions. Platelet‐rich plasma (PRP) is a biological product that is defined as the portion of plasma fraction of autologous blood with a platelet concentration above that of the original whole blood. A super‐mixture of key cytokines and growth factors is present in platelet granules. Thus, the application of PRP has gained unprecedented attention in regenerative medicine. The rationale underlies the utilization of PRP is that it acts as a biomaterial to deliver critical growth factors and cytokines from platelet granules to the targeted area, thus promoting regeneration in a variety of tissues. Based on enhanced understanding of cell signalling and growth factor biology, researchers have begun to use PRP treatment as a novel method to regenerate damaged tissues, including liver, bone, cartilage, tendon and dental pulp. To enable better understanding of the regenerative effects of PRP in dentistry, this review describes different methods of preparation and application of this biological product, and provides detailed explanations of the controversies and future prospects related to the use of PRP in dental regenerative medicine.
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Affiliation(s)
- J Xu
- Shenzhen Longgang Institute of Stomatology, Shenzhen, Guangdong, China.,Department of Otolaryngology, Longgang E.N.T. Hospital & Shenzhen Key Laboratory of E.N.T., Institute of E.N.T, Shenzhen, Guangdong, China
| | - L Gou
- Center for Genetic Medicine, Xuzhou Maternity and Child Health Care Hospital, Xuzhou, Jiangsu, China
| | - P Zhang
- Shenzhen Longgang Institute of Stomatology, Shenzhen, Guangdong, China.,Department of Otolaryngology, Longgang E.N.T. Hospital & Shenzhen Key Laboratory of E.N.T., Institute of E.N.T, Shenzhen, Guangdong, China
| | - H Li
- Shenzhen Longgang Institute of Stomatology, Shenzhen, Guangdong, China.,Department of Otolaryngology, Longgang E.N.T. Hospital & Shenzhen Key Laboratory of E.N.T., Institute of E.N.T, Shenzhen, Guangdong, China
| | - S Qiu
- Department of Otolaryngology, Longgang E.N.T. Hospital & Shenzhen Key Laboratory of E.N.T., Institute of E.N.T, Shenzhen, Guangdong, China
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Raddall G, Mello I, Leung BM. Biomaterials and Scaffold Design Strategies for Regenerative Endodontic Therapy. Front Bioeng Biotechnol 2019; 7:317. [PMID: 31803727 PMCID: PMC6874017 DOI: 10.3389/fbioe.2019.00317] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 10/25/2019] [Indexed: 12/21/2022] Open
Abstract
Challenges with traditional endodontic treatment for immature permanent teeth exhibiting pulp necrosis have prompted interest in tissue engineering approaches to regenerate the pulp-dentin complex and allow root development to continue. These procedures are known as regenerative endodontic therapies. A fundamental component of the regenerative endodontic process is the presence of a scaffold for stem cells from the apical papilla to adhere to, multiply and differentiate. The aim of this review is to provide an overview of the biomaterial scaffolds that have been investigated to support stem cells from the apical papilla in regenerative endodontic therapy and to identify potential biomaterials for future research. An electronic search was conducted using Pubmed and Novanet databases for published studies on biomaterial scaffolds for regenerative endodontic therapies, as well as promising biomaterial candidates for future research. Using keywords "regenerative endodontics," "scaffold," "stem cells" and "apical papilla," 203 articles were identified after duplicate articles were removed. A second search using "dental pulp stem cells" instead of "apical papilla" yielded 244 articles. Inclusion criteria included the use of stem cells from the apical papilla or dental pulp stem cells in combination with a biomaterial scaffold; articles using other dental stem cells or no scaffolds were excluded. The investigated scaffolds were organized in host-derived, naturally-derived and synthetic material categories. It was found that the biomaterial scaffolds investigated to date possess both desirable characteristics and issues that limit their clinical applications. Future research investigating the scaffolds presented in this article may, ultimately, point to a protocol for a consistent, clinically-successful regenerative endodontic therapy.
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Affiliation(s)
- Gavin Raddall
- Faculty of Dentistry, Dalhousie University, Halifax, NS, Canada
| | - Isabel Mello
- Department of Dental Clinical Sciences, Faculty of Dentistry, Dalhousie University, Halifax, NS, Canada
| | - Brendan M. Leung
- Department of Applied Oral Sciences, Faculty of Dentistry, Dalhousie University, Halifax, NS, Canada
- School of Biomedical Engineering, Faculties of Medicine and Engineering, Dalhousie University, Halifax, NS, Canada
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Mandakhbayar N, El-Fiqi A, Lee JH, Kim HW. Evaluation of Strontium-Doped Nanobioactive Glass Cement for Dentin–Pulp Complex Regeneration Therapy. ACS Biomater Sci Eng 2019; 5:6117-6126. [DOI: 10.1021/acsbiomaterials.9b01018] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Nandin Mandakhbayar
- Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, South Korea
| | - Ahmed El-Fiqi
- Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, South Korea
- Glass Research Department, National Research Centre, Cairo 12622, Egypt
| | - Jung-Hwan Lee
- Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, South Korea
- Glass Research Department, National Research Centre, Cairo 12622, Egypt
- Department of Biomaterials Science, School of Dentistry, Dankook University, Cheonan 330-714, South Korea
| | - Hae-Won Kim
- Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, South Korea
- Department of Biomaterials Science, School of Dentistry, Dankook University, Cheonan 330-714, South Korea
- UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan 31116, Republic of Korea
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Electrical Stimulation through Conductive Substrate to Enhance Osteo-Differentiation of Human Dental Pulp-Derived Stem Cells. APPLIED SCIENCES-BASEL 2019. [DOI: 10.3390/app9183938] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Human dental pulp-derived stem cells (hDPSCs) are promising cellular sources for bone healing. The acceleration of their differentiation should be beneficial to their clinical application. Therefore, a conductive polypyrrole (PPy)-made electrical stimulation (ES) device was fabricated to provide direct-current electric field (DCEF) treatment, and its effect on osteo-differentiation of hDPSCs was investigated in this study. To determine the optimal treating time, electrical field of 0.33 V/cm was applied to hDPSCs once for 4 h on different days after the osteo-induction. The alizarin red S staining results suggested that ES accelerated the mineralization rates of hDPSCs. The quantification analysis results revealed a nearly threefold enhancement in calcium deposition by ES at day 0, 2, and 4, whereas the promotion effect in later stages was in vain. To determine the ES-mediated signaling pathway, the expression of genes in the bone morphogenetic protein (BMP) family and related receptors were quantified using qPCR. In the early stages of osteo-differentiation, the mRNA levels of BMP2, BMP3, BMP4, and BMP5 were increased significantly in the ES groups, indicating that these genes were involved in the specific signaling routes induced by ES. We are the first using DCEF to improve the osteo-differentiation of hDPSCs, and our results promise the therapeutic applications of hDPSCs on cell-based bone tissue engineering.
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El Gezawi M, Wölfle UC, Haridy R, Fliefel R, Kaisarly D. Remineralization, Regeneration, and Repair of Natural Tooth Structure: Influences on the Future of Restorative Dentistry Practice. ACS Biomater Sci Eng 2019; 5:4899-4919. [PMID: 33455239 DOI: 10.1021/acsbiomaterials.9b00591] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Currently, the principal strategy for the treatment of carious defects involves cavity preparations followed by the restoration of natural tooth structure with a synthetic material of inferior biomechanical and esthetic qualities and with questionable long-term clinical reliability of the interfacial bonds. Consequently, prevention and minimally invasive dentistry are considered basic approaches for the preservation of sound tooth structure. Moreover, conventional periodontal therapies do not always ensure predictable outcomes or completely restore the integrity of the periodontal ligament complex that has been lost due to periodontitis. Much effort and comprehensive research have been undertaken to mimic the natural development and biomineralization of teeth to regenerate and repair natural hard dental tissues and restore the integrity of the periodontium. Regeneration of the dentin-pulp tissue has faced several challenges, starting with the basic concerns of clinical applicability. Recent technologies and multidisciplinary approaches in tissue engineering and nanotechnology, as well as the use of modern strategies for stem cell recruitment, synthesis of effective biodegradable scaffolds, molecular signaling, gene therapy, and 3D bioprinting, have resulted in impressive outcomes that may revolutionize the practice of restorative dentistry. This Review covers the current approaches and technologies for remineralization, regeneration, and repair of natural tooth structure.
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Affiliation(s)
- Moataz El Gezawi
- Department of Restorative Dental Sciences, Imam Abdulrahman Bin Faisal University, Dammam 34221, Saudi Arabia
| | - Uta Christine Wölfle
- Department of Conservative Dentistry and Periodontology, University Hospital, LMU Munich, 80336 Munich, Germany
| | - Rasha Haridy
- Department of Clinical Dental Sciences, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia.,Department of Conservative Dentistry, Faculty of Oral and Dental Medicine, Cairo University, Cairo 11553, Egypt
| | - Riham Fliefel
- Experimental Surgery and Regenerative Medicine (ExperiMed), University Hospital, LMU Munich, 80336 Munich, Germany.,Department of Oral and Maxillofacial Surgery, University Hospital, LMU Munich, 80337 Munich, Germany.,Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Alexandria University, Alexandria 21526, Egypt
| | - Dalia Kaisarly
- Department of Conservative Dentistry and Periodontology, University Hospital, LMU Munich, 80336 Munich, Germany.,Biomaterials Department, Faculty of Oral and Dental Medicine, Cairo University, Cairo 11553, Egypt
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Lu J, Li Z, Wu X, Chen Y, Yan M, Ge X, Yu J. iRoot BP Plus promotes osteo/odontogenic differentiation of bone marrow mesenchymal stem cells via MAPK pathways and autophagy. Stem Cell Res Ther 2019; 10:222. [PMID: 31358050 PMCID: PMC6664598 DOI: 10.1186/s13287-019-1345-3] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 06/30/2019] [Accepted: 07/15/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND iRoot BP Plus is a novel bioceramic endodontic material. Recently, it has been considered as an alternative to MTA which is the most popular scaffold cover during regenerative endodontic therapy. This study aimed to evaluate the effects of iRoot BP Plus on the osteo/odontogenic capacity of bone marrow mesenchymal stem cells (BMMSCs), including the underlying mechanisms. METHODS BMMSCs were collected by a whole marrow method and treated with iRoot BP Plus-conditioned medium (BP-CM). The proliferation ability was evaluated by cell counting kit 8 and flow cytometry. Complete medium was used as a blank control, and 2 mg/ml MTA-conditioned medium was served as a positive control. Alkaline phosphatase (ALP) activity assay, ALP staining, western blot, real-time RT-PCR, Alizarin Red S staining, and immunofluorescence staining were performed to explore the osteo/odontogenic potential and the involvement of MAPK pathways. Besides, autophagy was investigated by western blot, immunofluorescence staining, and transmission electron microscopy. RESULTS
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Affiliation(s)
- Jiamin Lu
- Key Laboratory of Oral Diseases of Jiangsu Province, Institute of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, 210029, Jiangsu, China
| | - Zehan Li
- Key Laboratory of Oral Diseases of Jiangsu Province, Institute of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, 210029, Jiangsu, China
| | - Xiao Wu
- Key Laboratory of Oral Diseases of Jiangsu Province, Institute of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, 210029, Jiangsu, China
| | - Yan Chen
- Nanjing Stomatological Hospital, Medical School of Nanjing University, 30 Zhongyang Road, Nanjing, 210008, Jiangsu, China
| | - Ming Yan
- Key Laboratory of Oral Diseases of Jiangsu Province, Institute of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, 210029, Jiangsu, China.,Endodontic Department, School of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, 210029, Jiangsu, China
| | - Xingyun Ge
- Key Laboratory of Oral Diseases of Jiangsu Province, Institute of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, 210029, Jiangsu, China
| | - Jinhua Yu
- Key Laboratory of Oral Diseases of Jiangsu Province, Institute of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, 210029, Jiangsu, China. .,Endodontic Department, School of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, 210029, Jiangsu, China.
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