Bioactivity of bioceramic materials used in the dentin-pulp complex therapy : a systematic review

Abstract

Dentistry-applied bioceramic materials are ceramic materials that are categorized asbioinert, bioactive and biodegradable. They share a common characteristic of being specificallydesigned to fulfil their function; they are able to act as root canal sealers, cements, root repair or fillingmaterials. Bioactivity is only attributed to those materials which are capable of inducing a desiredtissue response from the host. The aim of this study is to present a systematic review of availableliterature investigating bioactivity of dentistry-applied bioceramic materials towards dental pulp stemcells, including a bibliometric analysis of such a group of studies and a presentation of the parametersused to assess bioactivity, materials studied and a summary of results. The research question, based onthe PICO model, aimed to assess the current knowledge on dentistry-based bioceramic materials byexploring to what extent they express bioactive properties inin vitroassays and animal studies whenexposed to dental pulp stem cells, as opposed to a control or compared to different bioceramic materialcompositions, for their use in the dentin-pulp complex therapy. A systematic search of the literaturewas performed in six databases, followed by article selection, data extraction, and quality assessment.Studies assessing bioactivity of one or more bioceramic materials (both commercially available ornovel/experimental) towards dental pulp stem cells (DPSCs) were included in our review. A total of37 articles were included in our qualitative review. Quantification of osteogenic, odontogenic andangiogenic markers using reverse transcriptase polymerase chain reaction (RT-PCR) is the prevailingmethod used to evaluate bioceramic material bioactivity towards DPSCs in the current investigativestate, followed by alkaline phosphatase (ALP) enzyme activity assays and Alizarin Red Staining(ARS) to assess mineralization potential. Mineral trioxide aggregate and Biodentine are the prevalentreference materials used to compare with newly introduced bioceramic materials. Available literaturecompares a wide range of bioceramic materials for bioactivity, consisting mostly ofin vitroassays.The desirability of this property added to the rapid introduction of new material compositions makesthis subject a clear candidate for future research.Keywords:bioactivity; bioceramic materials; dental pulp stem cells; systematic reviewMaterials2019,12, 1015; doi:10.3390/ma12071015www.mdpi.com/journal/materials Materials2019,12, 10152 of 301. IntroductionWithin the field of biomedical therapeutics, we can highlight the concept of tissue engineeringto refer to the development of procedures and biomaterials that aim to devise new tissues to replacethose damaged, following the principles of cellular and molecular biology and taking as a premise thesearch for “biological solutions for biological problems” [1].In 2007, the American Association of Endodontists adopted the term “regenerative endodontics”to refer to the concept of tissue engineering applied to the restoration of root canal health, in a waythat continuous development of the root and tissues surrounding it is promoted [2].The introduction of the so-called bioceramic materials meant a great advance for this newparadigm in endodontic therapy [3], given their biocompatible nature and excellent physicochemicalproperties [4]. Categorized as bioinert, bioactive and biodegradable [5], dentistry-applied bioceramicmaterials are ceramic materials which share a common characteristic of being specifically designed tofulfil their function; they are able to act as root canal sealers, cements, root repair or filling materials [4].Applied to vital pulp therapy, bioceramic materials can be used in cases of pulp exposition fromtrauma, caries or other mechanical causes, as direct pulp cappers [6].Properties like biocompatibility and bioactivity are to be expected in dentistry-applied bioceramicmaterials for their use in vital pulp therapy [7]. The first one refers to the “ability to perform as asubstrate that will support the appropriate cellular activity, including the facilitation of molecularand mechanical signaling systems, in order to optimize tissue regeneration, without eliciting anyundesirable local or systemic responses in the eventual host” [8], while bioactivity goes even further,and is only attributed to those materials which are capable of inducing a desired tissue responsefrom the host [9] by the use of biomimetic approaches [10]. The term differs depending on the fieldin which it is implemented, being related to the cellular effects induced by biologically active ionsand substances released from biomaterials in the field of tissue engineering, but referred to as thebiomaterial’s capability of forming hydroxyl apatite mineral on its surface bothin vitroandin vivointhe field of biomaterial science [11].Considering these desirable characteristics of bioceramic materials, it seems convenient to analyzethe interaction between human dental pulp stem cells (hDPSCs), which are post-natal stem cellswith mesenchymal stem cell (MSCs)-like characteristics, like auto-renewal ability and multilineagedifferentiation potential [12], and them; as their combined use could mean and advancement in thefield of regenerative endodontics.Cytotoxicity and biocompatibility of a wide range of bioceramic materials towards dental stemcells (DSCs) have been investigated in numerous studies [13–17]; among others. The well-knownPro-Root MTA (Dentsply Tulsa Dental Specialties, Tulsa, OK, USA) has been shown to increaseosteoblast, fibroblast, cementoblast, odontoblast and pulp cell differentiation, but its handling difficultyamong other limitations encourages for a search for alternative materials [13]. Materials like Biodentine(Septodont, Saint Maurdes-Fosses, France) and TheraCal LC (Bisco Inc., Schaumburg, IL, USA) areexamples of bioceramic materials introduced posteriorly in dentistry for their use in vital pulp therapyas blood clot protectors in pulpal revascularization procedures, standing out for their consistency,easier manipulation and tricalcium silicate composition [16].However, to the best of the authors’ knowledge, there has been no effort to sort and summarizestudies analyzing bioactivity of such materials into more homogenous subgroups that would allow foran easier analysis of the evidence.