A critical analysis of research methods and experimental models to study biocompatibility of endodontic materials

Abstract

Materials used for endodontics and with direct contact to tissues have a wide range of indications, from vital pulpal treatments to root filling materials and those used in endodontic surgery. In principle, interaction with dental materials may result in damage to tissues locally or systemically. Thus, a great variety of test methods are applied to evaluate a materials' potential risk of adverse biological effects to ensure their biocompatibility before commercialization. However, the results of biocompatibility evaluations are dependent on not only the tested materials but also the test methods due to the diversity of these effects and numerous variables involved. In addition, diverse biological effects require equally diverse assessments on a structured and planned approach. Such a structured assessment of the materials consists of four phases: general toxicity, local tissue irritation, pre‐clinical tests and clinical evaluations. Various types of screening assays are available; it is imperative to understand their advantages and limitations to recognize their appropriateness and for an accurate interpretation of their results. Recent scientific advances are rapidly introducing new materials to endodontics including nanomaterials, gene therapy and tissue engineering biomaterials. These new modalities open a new era to restore and regenerate dental tissues; however, all these new technologies can also present new hazards to patients. Before any clinical usage, new materials must be proven to be safe and not hazardous to health. Certain international standards exist for safety evaluation of dental materials (ISO 10993 series, ISO 7405 and ISO 14155‐1), but researchers often fail to follow these standards due to lack of access to standards, limitation of the guidelines and complexity of new experimental methods, which may cause technical errors. Moreover, many laboratories have developed their testing strategy for biocompatibility, which makes any comparison between findings more difficult. The purpose of this review was to discuss the concept of biocompatibility, structured test programmes and international standards for testing the biocompatibility of endodontic material biocompatibility. The text will further detail current test methods for evaluating the biocompatibility of endodontic materials, and their advantages and limitations.

Cytotoxicity and Genotoxicity of Epoxy Resin-Based Root Canal Sealers before and after Setting Procedures

“…Discrepancies between the agar overlay test and MTT assay demonstrate the different properties of each experiment. Agar overlay tests quantitatively evaluate decolorized zones and lysis indices [25], whereas the MTT assay analyzes the mitochondrial activity of the cells [26]. The use of the agar overlay test for unset sealers is considered an improper experimental method because of unclear boundaries, according to the current results.…”

Bioactivity analysis of calcium silicate‐based sealers and repair cements on the phenotype and cytokine secretion profile of CD14+ monocytes: An ex vivo study

“…The effects of TM obtained from TotalFill BC Sealer, BioRoot‐RCS, Biodentine and TotalFill BC RRM Fast‐Set Putty on cell morphology, phenotype and cytokine secretion of CD14 + monocytes were evaluated. Different in vitro studies were used as tools to evaluate the safety and efficacy of a new material, and a standardization of these first phase studies is necessary (Hosseinpour et al, 2022). The advantages of evaluating cell viability by LIVEDEAD flow cytometry are that it allows the analysis of a large number of cells in a short period of time.…”

“…In addition, it can be used very easily to differentiate cell populations and to determine differences in cell size and/or complexity (Robinson, 2018). Also, different cell cultures are used for biocompatibility evaluation (Hosseinpour et al, 2022). In the present study, the immunological activity produced by primary cultures of isolated diploid cells present in periapical tissues in contact with calcium silicate‐based materials was investigated.…”

Algal-derived macromolecules and their composites: From synthetic biology to biomedical applications in bone and cardiovascular tissue engineering

“…One success indicator for biomaterials is their acceptability by the human body, known as biocompatibility. It is crucial for biomaterials to cause the least injury, cytotoxicity, genotoxicity, carcinogenicity, and immunogenicity in their recipients (De Jong et al, 2020;Raut et al, 2020;Hosseinpour et al, 2022). Marine macroalgae Ulva sp.…”