Photobiomodulation in Periodontitis: Targeting Matrix Metalloproteinases, Tissue Inhibitors of Metalloproteinases, and Extracellular Matrix Remodeling

Periodontitis is an inflammation-driven disease caused by dysbiosis, in which excessive host proteolytic activity contributes to connective tissue destruction and alveolar bone loss. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are key regulators of extracellular matrix turnover and potential molecular targets of photobiomodulation (PBM). This review summarizes the biological basis of MMP/TIMP regulation and critically evaluates the available clinical evidence on the effects of adjunctive PBM on these biomarkers in periodontitis. Ten clinical studies published between 2005 and 2023 were identified, together with one systematic review. The included studies used PBM-compatible protocols or mixed laser studies with a PBM-related arm. Irradiation parameters, treatment schedules, comparator therapies, follow-up duration, and biomarker assessment varied considerably. MMP-8 was the most studied marker, and its levels tended to decrease following periodontal therapy regardless of PBM application. Some studies reported greater decrease with PBM while others reported clinical improvement with no further reductions in MMP-8. Evidence for MMP-1, MMP-9, TIMP-1, and MMP/TIMP ratios was limited and heterogeneous. Changes in biomarker levels did not always correlate with clinical improvements in probing depth, clinical attachment level, gingival inflammation, bleeding indices, and early wound healing. In conclusion, PBM may influence MMP-related responses during periodontal healing, but a definite consistent additional effect beyond conventional periodontal therapy has not been established. Future randomized trials should use well-defined non-thermal PBM protocols, identical background periodontal treatment in test and control groups, quantitative assessment of active MMPs and their corresponding TIMPs, and standardized long-term clinical and biochemical follow-up.