Immunohistochemical Expression of Non-collagenous Extracellular Matrix Molecules Involved in Tertiary Dentinogenesis Following Direct Pulp Capping: a Systematic Review

Background: Extracellular matrix molecules (ECMM) expression during tertiary dentinogenesis provides useful information for regenerative applications and efficacy of pulp capping materials.

Aim: To identify and review the expression and roles of non-collagenous ECMM after successful direct pulp capping (DPC), following mechanical pulp exposures, via immunohistochemistry (IHC). The study addressed the question of where will successful DPC impact the IHC expression of these molecules.

Data Sources: In vivo animal and human original clinical studies reporting on ECMM in relation to different follow-up periods were screened and evaluated via descriptive analysis. The electronic literature search was carried out in three databases (MEDLINE/PubMed, Web of Science, Scopus), followed by manual screening of relevant journals and cross-referencing, up to December 2018.

Study Eligibility Criteria, Participants, And Interventions: Randomized and non-randomized controlled trials, conducted in humans and animals, were selected. Histological evidence for tertiary dentine formation was a prerequisite for IHC evaluation.

Study Appraisal And Synthesis Methods: The methodological quality of the included articles was independently assessed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) and the Cochrane risk of bias tool (RoB 1), respectively.

Results: From a total of 1534 identified studies, 18 were included. Thirteen papers evaluated animal subjects and five studies were carried out on humans. In animals and humans, fibronectin and tenascin expressions were detected in pulp and odontoblast-like cells (OLC); dentine sialoprotein was expressed in both soft and newly-formed mineralized tissue. In animals, bone sialoprotein was early expressed, in association with OLC and predentin; the immunoreactivity for dentine sialophosphoprotein and dentine matrix protein-1 was associated with the OLC and dentine bridge; osteopontin was expressed in OLC, predentine and reparative dentine. A considerable heterogeneity was found in the methodologies of the included studies, as well as interspecies variability of results in terms of time.

Conclusions And Implications Of Key Findings: Within the limited scientific evidence, all non-collagenous ECMM expressions during tertiary dentinogenesis are active and related to soft and hard tissues. There is a shortage of human studies, and future research directions should focus more on them. PROSPERO Protocol: CRD42019121304.