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Tissue Engineering Updates and Perspective in Dentistry

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Biomedical Engineering and Materials".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 44289

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Dr. Federico Mussano

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CIR Dental School, Department of Surgical Sciences, University of Turin, Turin, Italy
Interests: bone regeneration; biomaterials; dental implants; MSCs differentiation; bone substitute materials; biological interfaces
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Giulio Preti

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Department of Surgical Sciences, University of Torino, Via Nizza 230, 10126 Torino, Italy
Interests: dentistry; bone tissue engineering; dental implants; dental materials; oral rehabilitation
Special Issues, Collections and Topics in MDPI journals

Dr. Davide Cavagnetto

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Guest Editor

CIR Dental School, Department of Surgical Sciences, University of Torino, Torino, Italy
Interests: bone regeneration; biomaterials; dental implants; MSCs differentiation; bone substitute materials; biological interfaces
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The remarkable advancements of stem cell biology and the progress in biomaterial research are prompting an impressive development of protocols based on regenerative techniques in dentistry. Clinical applications range between pulp revitalization procedures, guided tissue regeneration and stem cell implantation for hard and soft tissue repair. While in the past, grafts and membranes were used for guided tissue regeneration, technological advancements are now constantly pushing the boundaries further. Thus, new dental techniques are continuously bridging the gap between research and clinical application. As the guest editor of the Special Issue on these topics, which will be published in the Biomedicine journal (Publisher MDPI, St Alban-Anlage 66, Basel, Switzerland; IF 2019: 4.717), I would like to invite colleagues who have experience in both the dental and biological fields and who are experts in dental tissue engineering to participate.

This Special Issue aims to be a report on the state of the art of basic, translational, and clinical research in the tissue engineering field that can provide fellow dentists and researchers of various specialties with information on regenerative techniques.

The Special Issue will cover but not be limited to the following topics:

Bases of bone physiology;

Wound healing;

Biomaterials in use in dentistry;

Growth factors for dental use;

Implant surface treatment;

Surgical techniques of bone regeneration;

Regeneration aspects in conservative dentistry;

Regeneration aspects in periodontal therapy;

Regeneration aspects in implantology;

Mesenchymal stem cells;

State of the art of clinical applications of stem cells in bone regeneration.

It is my pleasure to invite you to submit a manuscript for this Special Issue. Full papers, communications, and reviews are welcome.

Prof. Dr. Federico Mussano
Prof. Dr. Giulio Preti
Dr. Davide Cavagnetto
Guest Editors

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Published Papers (11 papers)

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Research

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22 pages, 5335 KiB

Open AccessArticle

Analysis of the Influence of Jaw Periosteal Cells on Macrophages Phenotype Using an Innovative Horizontal Coculture System

by Fang He, Felix Umrath, Christiane von Ohle, Siegmar Reinert and Dorothea Alexander

Biomedicines 2021, 9(12), 1753; https://doi.org/10.3390/biomedicines9121753 - 24 Nov 2021

Cited by 4 | Viewed by 2158

Abstract

Jaw periosteum-derived mesenchymal stem cells (JPCs) represent a promising cell source for bone tissue engineering in oral and maxillofacial surgery due to their high osteogenic potential and good accessibility. Our previous work demonstrated that JPCs are able to regulate THP-1-derived macrophage polarization in a direct coculture model. In the present study, we used an innovative horizontal coculture system in order to understand the underlying paracrine effects of JPCs on macrophage phenotype polarization. Therefore, JPCs and THP-1-derived M1/M2 macrophages were cocultured in parallel chambers under the same conditions. After five days of horizontal coculture, flow cytometric, gene and protein expression analyses revealed inhibitory effects on costimulatory and proinflammatory molecules/factors as well as activating effects on anti-inflammatory factors in M1 macrophages, originating from multiple cytokines/chemokines released by untreated and osteogenically induced JPCs. A flow cytometric assessment of DNA synthesis reflected significantly decreased numbers of proliferating M1/M2 cells when cocultured with JPCs. In this study, we demonstrated that untreated and osteogenically induced JPCs are able to switch macrophage polarization from a classical M1 to an alternative M2-specific phenotype by paracrine secretion, and by inhibition of THP-1-derived M1/M2 macrophage proliferation. Full article

(This article belongs to the Special Issue Tissue Engineering Updates and Perspective in Dentistry)

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15 pages, 4712 KiB

Open AccessArticle

Increasing Odontoblast-like Differentiation from Dental Pulp Stem Cells through Increase of β-Catenin/p-GSK-3β Expression by Low-Frequency Electromagnetic Field

by Han-Moi Lim, Myeong-Hyun Nam, Yu-Mi Kim and Young-Kwon Seo

Biomedicines 2021, 9(8), 1049; https://doi.org/10.3390/biomedicines9081049 - 19 Aug 2021

Cited by 12 | Viewed by 3115

Abstract

Odontoblasts produce proteins that form the dentinal extracellular matrix, which can protect the dental pulp from external stimuli and is required for tooth regeneration. This study showed that a pulsed electromagnetic field (PEMF) can regulate cell metabolism and induce cell differentiation. This study determined the frequency of PEMF that is effective for odontoblast differentiation. Human dental pulp stem cells (hDPSCs) were cultured in odontoblast differentiation medium containing dexamethasone, BMP2, TGF-β1, and FGF-2, and then exposed to 10 mT intensity of PEMF at 40, 60, 70, and 150 Hz for 15 min/day. The MTT assay, LDH assay, flow cytometry, protein and gene expression, and immunofluorescence were performed to check if hDPSCs differentiated into odontoblast-like cells. The hDPSCs showed frequency-dependent differences in protein and gene expression. The mesenchymal stem cell markers were reduced to a greater extent at 60 and 70 Hz than at other frequencies, and odontoblast-related markers, particularly β-catenin, p-GSK-3β, and p-p38, were increased at 60 and 70 Hz. Exposure to 10 mT intensity of PEMF at 70 Hz influenced the differentiation of hDPSCs considerably. Taken together, PEMF treatment can promote differentiation of hDPSCs into odontoblast-like cells by increasing p-GSK-3β and β-catenin expression. Full article

(This article belongs to the Special Issue Tissue Engineering Updates and Perspective in Dentistry)

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17 pages, 4396 KiB

Open AccessArticle

Bidirectional Differentiation of Human-Derived Stem Cells Induced by Biomimetic Calcium Silicate-Reinforced Gelatin Methacrylate Bioink for Odontogenic Regeneration

by Yi-Ting Lin, Tuan-Ti Hsu, Yu-Wei Liu, Chia-Tze Kao and Tsui-Hsien Huang

Biomedicines 2021, 9(8), 929; https://doi.org/10.3390/biomedicines9080929 - 31 Jul 2021

Cited by 24 | Viewed by 4197

Abstract

Tooth loss or damage is a common problem affecting millions of people worldwide, and it results in significant impacts on one’s quality of life. Dental regeneration with the support of stem cell-containing scaffolds has emerged as an alternative treatment strategy for such cases. With this concept in mind, we developed various concentrations of calcium silicate (CS) in a gelatin methacryloyl (GelMa) matrix and fabricated human dental pulp stem cells (hDPSCs)-laden scaffolds via the use of a bioprinting technology in order to determine their feasibility in promoting odontogenesis. The X-ray diffraction and Fourier transform-infrared spectroscopy showed that the incorporation of CS increased the number of covalent bonds in the GelMa hydrogels. In addition, rheological analyses were conducted for the different concentrations of hydrogels to evaluate their sol–gel transition temperature. It was shown that incorporation of CS improved the printability and printing quality of the scaffolds. The printed CS-containing scaffolds were able to release silicate (Si) ions, which subsequently significantly enhanced the activation of signaling-related markers such as ERK and significantly improved the expression of odontogenic-related markers such as alkaline phosphatase (ALP), dentin matrix protein-1 (DMP-1), and osteocalcin (OC). The calcium deposition assays were also significantly enhanced in the CS-containing scaffold. Our results demonstrated that CS/GelMa scaffolds were not only enhanced in terms of their physicochemical behaviors but the odontogenesis of the hDPSCs was also promoted as compared to GelMa scaffolds. These results demonstrated that CS/GelMa scaffolds can serve as cell-laden materials for future clinical applications and use in dentin regeneration. Full article

(This article belongs to the Special Issue Tissue Engineering Updates and Perspective in Dentistry)

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13 pages, 25123 KiB

Open AccessArticle

Osteoconductive Properties of a Volume-Stable Collagen Matrix in Rat Calvaria Defects: A Pilot Study

by Karol Alí Apaza Alccayhuaman, Stefan Tangl, Stéphane Blouin, Markus A. Hartmann, Patrick Heimel, Ulrike Kuchler, Jung-Seok Lee and Reinhard Gruber

Biomedicines 2021, 9(7), 732; https://doi.org/10.3390/biomedicines9070732 - 25 Jun 2021

Cited by 2 | Viewed by 2540

Abstract

Volume-stable collagen matrices (VSCM) are conductive for the connective tissue upon soft tissue augmentation. Considering that collagen has osteoconductive properties, we have investigated the possibility that the VSCM also consolidates with the newly formed bone. To this end, we covered nine rat calvaria circular defects with a VSCM. After four weeks, histology, histomorphometry, quantitative backscattered electron imaging, and microcomputed tomography were performed. We report that the overall pattern of mineralization inside the VSCM was heterogeneous. Histology revealed, apart from the characteristic woven bone formation, areas of round-shaped hypertrophic chondrocyte-like cells surrounded by a mineralized extracellular matrix. Quantitative backscattered electron imaging confirmed the heterogenous mineralization occurring within the VSCM. Histomorphometry found new bone to be 0.7 mm² (0.01 min; 2.4 max), similar to the chondrogenic mineralized extracellular matrix with 0.7 mm² (0.0 min; 4.2 max). Microcomputed tomography showed the overall mineralized tissue in the defect to be 1.6 mm³ (min 0.0; max 13.3). These findings suggest that in a rat cranial defect, VSCM has a limited and heterogeneous capacity to support intramembranous bone formation but may allow the formation of bone via the endochondral route. Full article

(This article belongs to the Special Issue Tissue Engineering Updates and Perspective in Dentistry)

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18 pages, 3904 KiB

Open AccessEditor’s ChoiceArticle

Biofabrication of Gingival Fibroblast Cell-Laden Collagen/Strontium-Doped Calcium Silicate 3D-Printed Bi-Layered Scaffold for Osteoporotic Periodontal Regeneration

by Chen-Ying Wang, Yung-Cheng Chiu, Alvin Kai-Xing Lee, Yun-An Lin, Ping-Yi Lin and Ming-You Shie

Biomedicines 2021, 9(4), 431; https://doi.org/10.3390/biomedicines9040431 - 16 Apr 2021

Cited by 43 | Viewed by 4480

Abstract

Periodontal disease is a chronic disease that can lead to lose teeth and even tooth loss if left untreated. Osteoporosis and periodontal disease share similar characteristics and associated factors. Current regenerative techniques for periodontal diseases are ineffective in restoring complete function and structural integrity of periodontium due to unwanted migration of cells. In this study, we applied the concept of guided tissue regeneration (GTR) and 3D fabricated gingival fibroblast cell-laden collagen/strontium-doped calcium silicate (SrCS) bi-layer scaffold for periodontal regeneration. The results revealed that the bioactive SrCS had a hydroxyapatite formation on its surface after 14 days of immersion and that SrCS could release Sr and Si ions even after 6 months of immersion. In addition, in vitro results showed that the bi-layer scaffold enhanced secretion of FGF-2, BMP-2, and VEGF from human gingival fibroblasts and increased secretion of osteogenic-related proteins ALP, BSP, and OC from WJMSCs. In vivo studies using animal osteoporotic models showed that the 3D-printed cell-laden collagen/SrCS bi-layer scaffold was able to enhance osteoporotic bone regeneration, as seen from the increased Tb.Th and BV/TV ratio and the histological stains. In conclusion, it can be seen that the bi-layer scaffolds enhanced osteogenesis and further showed that guided periodontal regeneration could be achieved using collagen/SrCS scaffolds, thus making it a potential candidate for future clinical applications. Full article

(This article belongs to the Special Issue Tissue Engineering Updates and Perspective in Dentistry)

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12 pages, 1908 KiB

Open AccessArticle

Isolation and Characterization of Buccal Fat Pad and Dental Pulp MSCs from the Same Donor

by Tullio Genova, Davide Cavagnetto, Fabio Tasinato, Sara Petrillo, Federico Alessandro Ruffinatti, Luca Mela, Massimo Carossa, Luca Munaron, Ilaria Roato and Federico Mussano

Biomedicines 2021, 9(3), 265; https://doi.org/10.3390/biomedicines9030265 - 7 Mar 2021

Cited by 14 | Viewed by 2407

Abstract

Mesenchymal stem cells (MSCs) can be harvested from different sites in the oral cavity, representing a reservoir of cells useful for regenerative purposes. As direct comparisons between at least two types of MSCs deriving from the same patient are surprisingly rare in scientific literature, we isolated and investigated the osteoinductive potential of dental pulp stem cells (DPSCs) and buccal fat pad stem cells (BFPSCs). MSCs were isolated from the third molar dental pulp and buccal fat pads of 12 patients. The number of viable cells was quantified through manual count. Proliferation and osteodifferentiation assays, flow cytometry analysis of cell phenotypes, and osteocalcin release in vitro were performed. The isolation of BFPSCs and DPSCs was successful in 7 out of 12 (58%) and 3 out of 12 (25%) of retrieved samples, respectively. The yield of cells expressing typical stem cell markers and the level of proliferation were higher in BFPSCs than in DPSCs. Both BFP-SCs and DPSCs differentiated into osteoblast-like cells and were able to release a mineralized matrix. The release of osteocalcin, albeit greater for BFPSCs, did not show any significant difference between BFPSCs and DPSCs. The yield of MSCs depends on their site of origin as well as on the protocol adopted for their isolation. Our data show that BFP is a valuable source for the derivation of MSCs that can be used for regenerative treatments. Full article

(This article belongs to the Special Issue Tissue Engineering Updates and Perspective in Dentistry)

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18 pages, 4393 KiB

Open AccessArticle

Incorporation of Calcium Sulfate Dihydrate into a Mesoporous Calcium Silicate/Poly-ε-Caprolactone Scaffold to Regulate the Release of Bone Morphogenetic Protein-2 and Accelerate Bone Regeneration

by Kuo-Hao Huang, Chen-Ying Wang, Cheng-Yu Chen, Tuan-Ti Hsu and Chun-Pin Lin

Biomedicines 2021, 9(2), 128; https://doi.org/10.3390/biomedicines9020128 - 29 Jan 2021

Cited by 19 | Viewed by 3697

Abstract

Tissue engineering and scaffolds play an important role in tissue regeneration by supporting cell adhesion, proliferation, and differentiation. The design of a scaffold is critical in determining its feasibility, and it is critical to note that each tissue is unique in terms of its morphology and composition. However, calcium-silicate-based scaffolds are undegradable, which severely limits their application in bone regeneration. In this study, we developed a biodegradable mesoporous calcium silicate (MS)/calcium sulfate (CS)/poly-ε-caprolactone (PCL) composite and fabricated a composite scaffold with 3D printing technologies. In addition, we were able to load bone morphogenetic protein-2 (BMP-2) into MS powder via a one-step immersion procedure. The results demonstrated that the MS/CS scaffold gradually degraded within 3 months. More importantly, the scaffold exhibited a gradual release of BMP-2 throughout the test period. The adhesion and proliferation of human dental pulp stem cells on the MS/CS/BMP-2 (MS/CS/B) scaffold were significantly greater than that on the MS/CS scaffold. It was also found that cells cultured on the MS/CS/B scaffold had significantly higher levels of alkaline phosphatase activity and angiogenic-related protein expression. The MS/CS/B scaffold promoted the growth of new blood vessels and bone regeneration within 4 weeks of implantation in rabbits with induced critical-sized femoral defects. Therefore, it is hypothesized that the 3D-printed MS/CS/B scaffold can act both as a conventional BMP-2 delivery system and as an ideal osteoinductive biomaterial for bone regeneration. Full article

(This article belongs to the Special Issue Tissue Engineering Updates and Perspective in Dentistry)

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Review

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23 pages, 1084 KiB

Open AccessReview

Materials for Dentoalveolar Bioprinting: Current State of the Art

by Mehdi Salar Amoli, Mostafa EzEldeen, Reinhilde Jacobs and Veerle Bloemen

Biomedicines 2022, 10(1), 71; https://doi.org/10.3390/biomedicines10010071 - 30 Dec 2021

Cited by 12 | Viewed by 3187

Abstract

Although current treatments can successfully address a wide range of complications in the dentoalveolar region, they often still suffer from drawbacks and limitations, resulting in sub-optimal treatments for specific problems. In recent decades, significant progress has been made in the field of tissue engineering, aiming at restoring damaged tissues via a regenerative approach. Yet, the translation into a clinical product is still challenging. Novel technologies such as bioprinting have been developed to solve some of the shortcomings faced in traditional tissue engineering approaches. Using automated bioprinting techniques allows for precise placement of cells and biological molecules and for geometrical patient-specific design of produced biological scaffolds. Recently, bioprinting has also been introduced into the field of dentoalveolar tissue engineering. However, the choice of a suitable material to encapsulate cells in the development of so-called bioinks for bioprinting dentoalveolar tissues is still a challenge, considering the heterogeneity of these tissues and the range of properties they possess. This review, therefore, aims to provide an overview of the current state of the art by discussing the progress of the research on materials used for dentoalveolar bioprinting, highlighting the advantages and shortcomings of current approaches and considering opportunities for further research. Full article

(This article belongs to the Special Issue Tissue Engineering Updates and Perspective in Dentistry)

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15 pages, 1198 KiB

Open AccessReview

Plant-Derived Substances with Antibacterial, Antioxidant, and Flavoring Potential to Formulate Oral Health Care Products

by Marco A. Lugo-Flores, Karen P. Quintero-Cabello, Patricia Palafox-Rivera, Brenda A. Silva-Espinoza, Manuel Reynaldo Cruz-Valenzuela, Luis Alberto Ortega-Ramirez, Gustavo Adolfo Gonzalez-Aguilar and Jesus Fernando Ayala-Zavala

Biomedicines 2021, 9(11), 1669; https://doi.org/10.3390/biomedicines9111669 - 11 Nov 2021

Cited by 10 | Viewed by 4548

Abstract

Bacterial diseases and reactive oxygen species can cause dental caries and oral cancer. Therefore, the present review analyzes and discusses the antibacterial and antioxidant properties of synthetic and plant-derived substances and their current and future patents to formulate dental products. The reviewed evidence indicates that chlorhexidine, fluorides, and hydrogen peroxide have adverse effects on the sensory acceptability of oral care products. As an alternative, plant-derived substances have antimicrobial and antioxidant properties that can be used in their formulation. Also, adding plant metabolites favors the sensory acceptability of dental products compared with synthetic compounds. Therefore, plant-derived substances have antibacterial, antioxidant, and flavoring activity with the potential to be used in the formulation of toothpaste, mouth rinses, dentures cleansers-fixatives, and saliva substitutes. Full article

(This article belongs to the Special Issue Tissue Engineering Updates and Perspective in Dentistry)

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38 pages, 3595 KiB

Open AccessReview

Pre-Clinical Models in Implant Dentistry: Past, Present, Future

by Nicolas Blanc-Sylvestre, Philippe Bouchard, Catherine Chaussain and Claire Bardet

Biomedicines 2021, 9(11), 1538; https://doi.org/10.3390/biomedicines9111538 - 26 Oct 2021

Cited by 27 | Viewed by 6345

Abstract

Biomedical research seeks to generate experimental results for translation to clinical settings. In order to improve the transition from bench to bedside, researchers must draw justifiable conclusions based on data from an appropriate model. Animal testing, as a prerequisite to human clinical exposure, is performed in a range of species, from laboratory mice to larger animals (such as dogs or non-human primates). Minipigs appear to be the animal of choice for studying bone surgery around intraoral dental implants. Dog models, well-known in the field of dental implant research, tend now to be used for studies conducted under compromised oral conditions (biofilm). Regarding small animal models, research studies mostly use rodents, with interest in rabbit models declining. Mouse models remain a reference for genetic studies. On the other hand, over the last decade, scientific advances and government guidelines have led to the replacement, reduction, and refinement of the use of all animal models in dental implant research. In new development strategies, some in vivo experiments are being progressively replaced by in vitro or biomaterial approaches. In this review, we summarize the key information on the animal models currently available for dental implant research and highlight (i) the pros and cons of each type, (ii) new levels of decisional procedures regarding study objectives, and (iii) the outlook for animal research, discussing possible non-animal options. Full article

(This article belongs to the Special Issue Tissue Engineering Updates and Perspective in Dentistry)

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18 pages, 1068 KiB

Open AccessReview

Oral Cavity as a Source of Mesenchymal Stem Cells Useful for Regenerative Medicine in Dentistry

by Ilaria Roato, Giorgia Chinigò, Tullio Genova, Luca Munaron and Federico Mussano

Biomedicines 2021, 9(9), 1085; https://doi.org/10.3390/biomedicines9091085 - 25 Aug 2021

Cited by 20 | Viewed by 5608

Abstract

The use of mesenchymal stem cells (MSCs) for regenerative purposes has become common in a large variety of diseases. In the dental and maxillofacial field, there are emerging clinical needs that could benefit from MSC-based therapeutic approaches. Even though MSCs can be isolated from different tissues, such as bone marrow, adipose tissue, etc., and are known for their multilineage differentiation, their different anatomical origin can affect the capability to differentiate into a specific tissue. For instance, MSCs isolated from the oral cavity might be more effective than adipose-derived stem cells (ASCs) for the treatment of dental defects. Indeed, in the oral cavity, there are different sources of MSCs that have been individually proposed as promising candidates for tissue engineering protocols. The therapeutic strategy based on MSCs can be direct, by using cells as components of the tissue to be regenerated, or indirect, aimed at delivering local growth factors, cytokines, and chemokines produced by the MSCs. Here, the authors outline the major sources of mesenchymal stem cells attainable from the oral cavity and discuss their possible usage in some of the most compelling therapeutic frontiers, such as periodontal disease and dental pulp regeneration. Full article

(This article belongs to the Special Issue Tissue Engineering Updates and Perspective in Dentistry)

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