Bone-Targeting Gallium–Gallic Acid Metal–Organic Framework (GGMA) for Dual Anti-Inflammation and Osteo-Regeneration Therapy of Osteoporosis

With the acceleration of global population aging, the incidence of osteoporosis continues to rise, posing a significant public health challenge. Current treatments exhibit limited efficacy and struggle to simultaneously regulate the abnormal inflammatory microenvironment within osteoporotic lesions. Consequently, there is an urgent need to develop a multimodal synergistic therapeutic strategy to more effectively restore the equilibrium between bone resorption and osteogenesis. Inspired by the natural bone tissue repair process, this study designed and constructed a bone-targeting metal-organic framework nanoparticle (GGMA) based on gallium gallate for the multifunctional synergistic treatment of osteoporosis. This material self-assembles through metal coordination and electrostatic interactions, integrating bone targeting, acid microenvironment responsiveness, and therapeutic functionality. The surface-bound alendronate ensures bone-specific accumulation; under acidic conditions at osteoporotic sites, the framework rapidly degrades, simultaneously releasing gallium ions and gallic acid. These components synergistically reverse osteoporosis pathology through bidirectional regulation (promoting bone formation while inhibiting resorption) and reactive oxygen species scavenging with anti-inflammatory mechanisms. This GGMA nanomaterial not only significantly enhances bioavailability of active components within bone tissue but also effectively treats osteoporosis via dual anti-inflammatory and osteogenic regulation, offering a promising approach for addressing metabolic bone disorders.