From concept to practice: intra-articular photobiomodulation for knee osteoarthritis.

Knee osteoarthritis (KOA) is a prevalent degenerative joint disease worldwide. Current treatments primarily offer only symptomatic relief and lack disease-modifying efficacy. Photobiomodulation therapy (PBMT) has shown potential in modulating cellular metabolism and inflammation to alleviate KOA symptoms; however, its conventional transcutaneous delivery is significantly limited by inadequate tissue penetration and energy attenuation, leading to inconsistent clinical outcomes. To overcome these limitations, this review proposes an innovative therapeutic paradigm: intra-articular PBM. This approach involves the minimally invasive placement of miniaturized light sources-such as fibre-integrated acupuncture needles or micro-LEDs-directly into the joint cavity, enabling precise, in situ energy delivery to pathological tissues. Light in the 600-1000 nm range is absorbed by mitochondrial cytochrome c oxidase, initiating a cascade of biological effects including: activation of the Nrf2 pathway to enhance antioxidant capacity; suppression of the NF-κB pathway to reduce inflammation; promotion of analgesia via peripheral and central mechanisms; induction of autophagy; and inhibition of apoptosis. Together, these mechanisms contribute to chondroprotection and improvement of subchondral bone structure. Both short-term interventional and long-term implantable strategies are discussed, with emerging preclinical and early clinical evidence supporting the feasibility and efficacy of this targeted approach. Intra-articular PBM represents a significant shift from palliative symptom management to targeted, mechanism-based tissue repair. Although challenges remain in device durability, biocompatibility, and clinical translation pathways, this strategy holds considerable promise as a potential disease-modifying therapy for KOA and may offer a novel, minimally invasive treatment option for patients in the future.