The Role of Lasers in Enhancing Growth Factor-Mediated Regenerative Endodontic Procedures: A Systematic Review

Regenerative endodontics focuses on biologically restoring the pulp-dentin complex in immature permanent teeth affected by necrosis. Endogenous growth factors (GFs) such as vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and bone morphogenetic proteins (BMPs) play a key role in regulating cellular processes involved in tissue repair and regeneration. Recently, laser technologies have emerged as promising adjuncts for enhancing regenerative outcomes by stimulating cellular activity and GF release. This systematic review aimed to evaluate the influence of laser applications on GF expression and related regenerative outcomes in human dental tissues. The review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included human-based in vitro, ex vivo, and in vivo studies that investigated the effects of laser energy on GF activity during regenerative endodontic procedures (REPs). Risk of bias was assessed using the Quality Assessment Tool for In Vitro Studies (QUIN). 15 studies fulfilled the inclusion criteria. Diode lasers with wavelengths ranging from 450-980 nm were the most commonly used, while two studies evaluated Er:YAG lasers. Most studies demonstrated increased expression of GFs such as VEGF, TGF-β1, PDGF, and BMPs, along with enhanced markers of odontogenic, osteogenic, and neurogenic differentiation. However, heterogeneity in laser parameters and experimental designs limited direct comparison across studies. Within the limitations of predominantly preclinical evidence, laser therapy appears to enhance biological signaling pathways associated with pulp-dentin regeneration. Nevertheless, well-designed clinical trials are required to establish standardized protocols and confirm long-term clinical outcomes in regenerative endodontics.