Synergistic enhancement of tenogenic differentiation in adipose-derived stem cells via TGF-β and laser therapy.

Adipose-derived stem cells (ADSCs) are increasingly explored for tendon regeneration owing to their accessibility and multipotency. Low-level laser therapy (LLLT), also referred to as Photobiomodulation (PBM), has emerged as a promising non-invasive approach for modulating cellular behavior. However, directing their differentiation into tenocytes remains an ongoing focus of optimization. This study investigates the synergistic effects of transforming growth factor-beta (TGF-β) and PBM on the tenogenic differentiation of ADSCs. ADSCs were cultured and exposed to specific PBM wavelengths (525 nm, 825 nm, and consecutive irradiation) at 5 and 10 J/cm2, both in the presence and absence of TGF-β. Tenogenic differentiation was evaluated using morphological assessments, gene expression analysis of key tenogenic markers (SCX, TNC, COL1A1, COL3A1, and DCN), morphology changes, and biochemical assays. The results reveal that PBM, especially at 525 nm and 5 J/cm2, in conjunction with TGF-β, significantly enhances tenogenic gene expression, ECM protein deposition, and cellular alignment indicative of tenocyte phenotype. These findings support a promising dual-modality approach to enhance ADSC tenogenic commitment and inform future tendon tissue engineering strategies.