Cellular and molecular response of dental stem cells to decellularized extracellular matrix scaffolds in regenerative endodontics: a systematic review

Background Decellularized extracellular matrices (dECMs) have gained increasing attention in regenerative dentistry due to their ability to replicate aspects of the native cellular microenvironment while reducing immunogenicity. Dental-derived stem cells exhibit regenerative and immunomodulatory properties, making them promising candidates for tissue repair when combined with biologically derived scaffolds such as dECMs. Objective This systematic review aimed to evaluate the cellular and molecular responses of dental-derived stem cells exposed to decellularized extracellular matrix scaffolds in experimental in vitro models. Methods A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science to identify relevant in vitro studies investigating interactions between dental stem cells and decellularized extracellular matrix scaffolds. Ten studies published between 2015 and 2024 met the eligibility criteria and were included. Data on cell viability, adhesion, proliferation, migration, differentiation, and gene or protein expression were extracted. Due to heterogeneity in stem cell sources, scaffold origins, and decellularization protocols, a qualitative synthesis was performed. Risk of bias was assessed using the Quality Assessment Tool for In Vitro studies tool. Results Across the included studies, dECM scaffolds were generally associated with favorable cellular responses, including improved cell attachment, survival, and proliferation. Molecular analyses frequently reported increased expression of markers related to odontogenic and osteogenic differentiation, extracellular matrix remodeling, and cell–matrix interactions. However, the magnitude and consistency of these responses varied according to the dECM source and decellularization methodology. The majority of the studies demonstrated a medium risk of bias, reflecting limitations in methodological reporting and experimental design. Conclusion The current in vitro evidence suggests that dECM scaffolds may support beneficial cellular and molecular responses in dental-derived stem cells. Nevertheless, confidence in these findings is constrained by methodological heterogeneity, the lack of standardized protocols, and a predominance of studies with medium risk of bias. Consequently, these findings should be interpreted as preliminary, underscoring the need for rigorously designed and standardized preclinical investigations prior to clinical translation to regenerative dental therapies. Systematic Review Registration https://doi.org/10.17605/OSF.IO/Z25HR , identifier Z25HR.