Light-Based Therapies for Metabolic Modulation of Mesenchymal Stem Cells in Regenerative Dentistry

Abstract

Abstract Periodontal diseases and temporomandibular disorders are characterized by chronic inflammation and progressive destruction of supporting tissues, leading to functional and aesthetic impairments. In this context, regenerative dentistry has increasingly focused on minimally invasive strategies capable of restoring tissue structure and function. Mesenchymal stem cells (MSCs) have emerged as central elements of regenerative approaches due to their multilineage differentiation potential, immunomodulatory properties, and paracrine activity. Concurrently, low-level laser therapy (LLLT), also known as photobiomodulation (PBM), has gained relevance as a non-invasive modality capable of modulating cellular behavior, inflammation, and tissue repair. This scoping review synthesizes current evidence on the combined application of MSCs and light-based therapies, emphasizing how laser-mediated metabolic modulation influences MSC fate and regenerative outcomes. Overall, the findings demonstrate that PBM enhances MSC proliferation, viability, migration, and lineage-specific differentiation, osteogenic, chondrogenic, angiogenic, and adipogenic, in a wavelength-, energy-, and dose-dependent manner. Emerging evidence indicates that the mitochondrial function represents a critical mechanistic link between laser irradiation and MSC responses. Photobiomodulation modulates mitochondrial bioenergetics primarily through activation of cytochrome c oxidase, resulting in increased ATP production, controlled reactive oxygen species signaling, and regulation of key transcription factors such as RUNX2, Sox9, and PPARγ. These mitochondrial-mediated effects act as metabolic checkpoints that integrate microenvironmental cues with lineage commitment and tissue-specific regeneration. Collectively, the data support the concept that precise modulation of mitochondrial activity by PBM optimizes the regenerative potential of MSCs. A deeper understanding of the interplay between laser strategies and parameters, mitochondrial metabolism, MSC source, and the cellular microenvironment is essential for the development of safe, effective, and reproducible regenerative protocols in dentistry and regenerative medicine.