Bone morphogenetic proteins in dentinogenesis and their potential role in pulp tissue regeneration: a scoping review

To map and categorize the existing literature on the use of bone morphogenetic proteins (BMPs) in dentinogenesis and pulp tissue regeneration, identifying research trends, experimental approaches, and knowledge gaps to inform future studies and potential clinical translation.

Studies investigating tooth-derived stem or progenitor cells (Population), under the direct application of bone morphogenetic proteins (BMPs) (Concept), employing in vitro and/or animal experimental models to assess dentinogenesis and pulp tissue regeneration-such as cellular differentiation, mineralization, or pulp tissue repair (Context)-were included. A systematic search without restrictions was conducted in August 2025 across PubMed/MEDLINE, Scopus, Web of Science, Embase, LILACS, and the Cochrane Library, complemented by grey literature searches. Findings were summarized by BMP type and main biological outcomes related to dentinogenesis and pulp tissue regeneration.

Databases searches retrieved 2497 records and a total of 42 studies were included. BMP-2 was the most investigated (66%), across diverse experimental models using dental pulp stem cells, stem cells from the apical papilla, odontoblast-like cell lines, and dental papilla cells. Reported BMP-2 concentrations varied from 10 to 50 ng/mL. BMP-4 was studied in 19% of the studies, most in vitro models, using dental-derived mesenchymal and epithelial-mesenchymal interaction systems, with concentrations ranging from 10 to 100 ng/mL. BMP-7 was investigated in 14% of the studies, in dose-response in vitro studies, most often using dental pulp stem cells, with concentrations ranging from 2 to 250 ng/mL. BMP-9 was evaluated in a single in vitro study using stem cells from the apical papilla. Positive odontoblastic differentiation outcomes were reported in 90% of BMP-2 studies, 100% of BMP-4 studies, 40% of BMP-7 studies, and in the BMP-9 study. Mineralization outcomes were reported in 60% of BMP-2 studies, 62.5% of BMP-4 studies, and 60% of BMP-7 studies, while no mineralization assessment was reported for BMP-9. In vivo evidence of pulp repair and hard tissue formation was limited but suggested potential benefits of BMP-based strategies, particularly for BMP-2 and BMP-7, in promoting reparative dentin formation and pulp-like tissue regeneration.

Exogenous BMPs-particularly BMP-2, followed by BMP-4 and BMP-7-promote odontoblastic differentiation and mineralized tissue formation in dental-derived cells. Evidence is largely based on heterogeneous in vitro models using diverse scaffold-based delivery systems. Despite consistent odontogenic potential, the lack of standardized protocols and clinically relevant models limits comparability and hinders translation to regenerative endodontic practice.

Regenerative endodontic procedures (REPs) aim to promote pulp tissue repair and continued root development through stem/progenitor cell differentiation and dentin matrix production. Bone morphogenetic proteins (BMPs) show promise as biological adjuncts, yet clinical translation remains limited. This scoping review maps evidence, identifies translational approaches, and highlights key knowledge gaps.