Advanced in Vitro Experimental Models for Tissue Engineering-based Reconstruction of a 3D Dentin/pulp Complex: a Literat

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Advanced in Vitro Experimental Models for Tissue Engineering-based Reconstruction of a 3D Dentin/pulp Complex: a Literature Review Christina Hadjichristou 1

&

Imad About 2 & Petros Koidis 1 & Athina Bakopoulou 1

Accepted: 25 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Objective Experimental procedures have been used to monitor cellular responses at the dentin/pulp interface. Aiming to divert from in vivo studies and oversimplified two-dimensional assays, three-dimensional (3D) models have been developed. This review provides an overview of existing literature, regarding 3D in vitro dentin/pulp reconstruction. Material & Methods PubMed, Scopus, Cochrane Library and Web of Science- were systematically searched for attributes between 1998 and 2020. The search focused on articles on the development of three-dimensional tools for the reconstruction of a dentin/pulp complex under in vitro conditions, which were then screened and qualitatively assessed. Article grouping according to mode of implementation, resulted in five categories: the customised cell perfusion chamber (CPC) (n = 8), the tooth bud model (TBM) (n = 3), the 3D dentin/pulp complex manufactured by tissue engineering (DPC) (n = 6), the entire tooth culture (ETC) (n = 4) and the tooth slice culture model (TSC) (n = 5). Results A total of 26 publications, applying nine and eight substances for pulp and dentin representation respectively, were included. Natural materials and dentin components were the most widely utilized. The most diverse category was the DPC, while the CPC group was the test with the highest longevity. The most consistent categories were the ETC and TSC models, while the TBM presented as the most complete de novo approach. Conclusions All studies presented with experimental protocols with potential upgrades. Solving the limitations of each category will provide a complete in vitro testing and monitoring tool of dental responses to exogenous inputs. Clinical Relevance The 3D dentin/pulp complexes are valid supplementary tools for in vivo studies and clinical testing.

Keywords Dentin pulp complex . Three-dimensional . Tissue engineering . Tissue manufacturing . Regeneration . Bioengineering

Introduction * Christina Hadjichristou [email protected] Imad About [email protected] Petros Koidis [email protected] Athina Bakopoulou [email protected] 1

Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki (A.U.Th), GR-54124 Thessaloniki, Greece

2

Centre National de la Recherche Scientifique, Institute of Movement Sciences, Aix Marseille University, Marseille, France

Dentin and the dental pulp are two components of the dental tissue, which function as a complex. Odontoblasts, lining the circumference of the pulp, give rise to predentin and eventually to dentin and in turn dentin -being more robust- protects the dental pulp [1]. Stimuli from the external environment are transferred from dentin to the pulp and in return