Cell-Free Approaches for Dental Pulp Tissue Engineering

Galler, Kerstin M.; Widbiller, Matthias

doi:10.1016/j.joen.2020.06.034

Cited by 31 publications

(41 citation statements)

References 45 publications

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“…2013, Huang & Godoy 2014, Galler et al . 2014). However, the terms ‘revascularization’ and ‘revitalization’ continue to be used instead of the term CF‐RET.…”

Section: Clarification Of the Concept – A Specific Definition Of Regenerative Endodonticsmentioning

confidence: 99%

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Clinical cell‐based versus cell‐free regenerative endodontics: clarification of concept and term

et al. 2021

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There is no consensus on the true meaning of clinical regenerative endodontics, and there is confusion over the concept and the term. Commonly used terms include revitalization and revascularization. The clinical methods for endodontic revitalization procedures and the tissue engineering concept differ depending on whether there is exogenous delivery of cells – called cell therapy, or not. Here, in this review, the difference is clarified by emphasizing the correct terminology: cell‐free versus cell‐based regenerative endodontic therapy (CF‐RET versus CB‐RET). The revitalization procedures practised clinically do not fit into the modern tissue engineering concepts of pulp regeneration but can be categorized as CF‐RET. The modern tissue engineering concept in pulp regeneration is a CB‐RET, which so far is at the clinical trial stage. However, histological examination of teeth following regenerative endodontic treatments reveals healing with repair derived from stem cells that originate from the periodontal, bone and other tissues. The aim of regenerative endodontics is regeneration of the pulp–dentine complex. This review discusses why CF‐RET is unlikely to regenerate a pulp–dentine complex with current protocols. The American Association of Endodontists and the European Society of Endodontology have not yet recommended autologous stem cell transplantation (CB‐RERT) which aspires for regeneration. Therefore, an understanding of the concept, term, difficulties and differences in current protocols is important for the clinician. However, rather than being discouraged that ideal regeneration has not been achieved to date, repair can be an acceptable outcome in clinical regenerative endodontics as it has also been accepted in medicine. Repair should also be considered in the context that resolution of the clinical signs/symptoms of pulp necrosis/apical periodontitis is generally reliably obtained in clinical regenerative endodontics.

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“…2013, Huang & Godoy 2014, Galler et al . 2014). However, the terms ‘revascularization’ and ‘revitalization’ continue to be used instead of the term CF‐RET.…”

Section: Clarification Of the Concept – A Specific Definition Of Regenerative Endodonticsmentioning

confidence: 99%

“…2013, Huang & Godoy 2014, Galler et al . 2014) but not yet widely adopted. This review extends our understanding by adding specific definitions, concepts, the limitations and advantages of the different approaches which have not been emphasized in prior reviews.…”

Section: Introductionmentioning

confidence: 99%

Clinical cell‐based versus cell‐free regenerative endodontics: clarification of concept and term

et al. 2021

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“…To overcome the limitations related to current pulp capping materials, tissue engineering has become a promising strategy for pulp-dentin complex regeneration. This research field applied to Dentistry has established different biological therapies that use biomaterials, such as scaffolds, to act as temporary substitutes of extracellular matrix (ECM) and to modulate tissue regeneration with no toxic effects to pulp cells (3). The processes of adhesion, proliferation and differentiation of human dental pulp cells (HDPCs) seeded on natural polymers scaffolds have been widely assessed due to the similarity of the polymeric matrix with glycosaminoglycans (GAG), which are the main constituent of mineralized ECM (1,4).…”

Section: Introductionmentioning

confidence: 99%

“…Another strategy to promote deposition of mineralized tissue is adding to the scaffold bioactive substances and molecules capable of signaling the differentiation of MSCs and attracting cells to the injured site (1,3). The association of simvastatin to scaffolds has been proven to enhance the osteogenic and odontogenic potential of HDPCs and to accelerate mineralized tissue formation by activating the ERK1/2 and Smad1/2/3 signaling pathways, up-regulating the expression of alkaline phosphatase (ALP), dentin sialophosphoprotein (DSPP), and dentin matrix acidic phosphoprotein 1 (DMP-1) (5,10-14).…”

Section: Introductionmentioning

confidence: 99%

Simvastatin-Enriched Macro-Porous Chitosan-Calcium-Aluminate Scaffold for Mineralized Tissue Regeneration

et al. 2020

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The present study evaluated the odontogenic potential of human dental pulp cells (HDPCs) exposed to chitosan scaffolds containing calcium aluminate (CHAlCa) associated or not with low doses of simvastatin (SV). Chitosan scaffolds received a suspension of calcium aluminate (AlCa) and were then immersed into solutions containing SV. The following groups were established: chitosan-calcium-aluminate scaffolds (CHAlCa - Control), chitosan calcium-aluminate with 0.5 µM SV (CHAlCa-SV0.5), and chitosan calcium-aluminate with 1.0 µM SV (CHAlCa-SV1.0). The morphology and composition of the scaffolds were evaluated by SEM and EDS, respectively. After 14 days of HDPCs culture on scaffolds, cell viability, adhesion and spread, mineralized matrix deposition as well as gene expression of odontogenic markers were assessed. Calcium aluminate particles were incorporated into the chitosan matrix, which exhibited regular pores homogeneously distributed throughout its structure. The selected SV dosages were biocompatible with HDPCs. Chitosan-calcium-aluminate scaffolds with 1 µM SV induced the odontoblastic phenotype in the HDPCs, which showed enhanced mineralized matrix deposition and up-regulated ALP, Col1A1, and DMP-1 expression. Therefore, one can conclude that the incorporation of calcium aluminate and simvastatin in chitosan scaffolds had a synergistic effect on HDPCs, favoring odontogenic cell differentiation and mineralized matrix deposition.

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“…In regenerative endodontics, 2 main concepts have emerged, cell-based and cell-free approaches (Galler et al 2014). The cell-based approach requires cells from dental populations alone (Syed-Picard et al 2014) or combined with a carrier scaffold (Huang et al 2010) with or without growth factors (GFs) (Vo et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Decellularized Swine Dental Pulp Tissue for Regenerative Root Canal Therapy

et al. 2018

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In the current theme of dental pulp regeneration, biological and synthetic scaffolds are becoming a potential therapy for pulp revitalization. The goal is to provide a suitable environment for cellular infiltration, proliferation, and differentiation. The extracellular matrix (ECM) represents a natural scaffold material resembling the native tissue chemical and mechanical properties. In the past few years, ECM-based scaffolds have shown promising results in terms of progenitor cells recruitment, promotion of constructive remodeling, and modulation of host response. These properties make ECM-derived scaffolds an ideal candidate for pulp regenerative therapy. Development of strategies for clinically relevant tissue engineering using dental pulp extracellular matrix (DP-ECM) can provide an alternative to conventional root canal treatment. In this work, we successfully decellularized ECM derived from porcine dental pulp. The resulting scaffold was characterized using immunostaining (collagen type I, dentin matrix protein 1, dentin sialoprotein, and Von Willebrand factor) and enzyme-linked immunosorbent assay (transforming growth factor β, vascular endothelial growth factor, and basic fibroblast growth factor) for extracellular proteins where the ECM retained its proteins and significant amount of growth factors. Furthermore, a pilot in vivo study was conducted where the matrix was implanted for 8 wk in a dog root canal model. Our in vitro and preliminary in vivo data show that the decellularized ECM supports cellular infiltration together with the expression of pulp-dentin and vascular markers (DSP and CD31) compared to the controls. Herein, we show the feasibility to produce a decellularized ECM scaffold and validate the concept of using ECM-based scaffolds for pulp regeneration.

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Cell-Free Approaches for Dental Pulp Tissue Engineering

Cited by 31 publications

References 45 publications

Clinical cell‐based versus cell‐free regenerative endodontics: clarification of concept and term

Clinical cell‐based versus cell‐free regenerative endodontics: clarification of concept and term

Simvastatin-Enriched Macro-Porous Chitosan-Calcium-Aluminate Scaffold for Mineralized Tissue Regeneration

Decellularized Swine Dental Pulp Tissue for Regenerative Root Canal Therapy

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