Irisin-loaded Porous Silica Nanoparticles Enhance Bone Healing in High Cholesterol Diet-induced Medaka Fish Model

Irisin is a myokine that stimulates browning of white adipocytes and enhances cortical bone mass during physical exercise. However, its short half-life limits its therapeutic potential, making sustained delivery systems desirable for bone tissue regeneration. In this study, we evaluated the effect of irisin-loaded porous silica nanoparticles (SiNPs) on caudal fin regeneration in a cholesterol rich diet-induced obese medaka fish model, compared with irisin alone. Obese medaka were generated by feeding a 20% cholesterol diet for 2 months, followed by caudal fin amputation. Irisin formulations (free irisin or SiNP loaded by irisin at 350 ng and 700 ng) were administered via intraperitoneal injection. Cholesterol-fed medaka showed significant weight gain and fat accumulation over 30 days. Following fin amputation, bone regeneration was impaired in obese fish compared to normal controls. Notably, irisin-loaded SiNPs significantly en-hanced fin regeneration, particularly at the higher dose (700 ng), compared to free irisin. These findings demonstrate that porous silica nanoparticle-mediated irisin delivery improves bone regeneration in an obese medaka fish model more effectively than irisin alone.