Metformin promotes the osseointegration of titanium implants under osteoporotic conditions by regulating BMSCs autophagy, and osteogenic differentiation

Osteoporosis is a common bone disorder with adverse effects on oral osseointegration, and the effects of metformin on bone metabolism have received increasing attention. The aim of the present study was to test the hypothesis that metformin promoted osteogenesis of bone mesenchymal stem cells (BMSCs) and osseointegration of titanium implants. BMSCs were treated with metformin to assess autophagic capacity, reactive oxygen species (ROS) production, anti-aging ability, and osteogenic differentiation. To determine its potential application in peri-implant of the maxilla, metformin was injected around the implant each day, immediately after the implant was embedded into the tooth socket. The results showed that metformin increased the autophagic capacity and decreased ROS production of osteoporotic BMSCs under hypoxia and serum deprivation (H/SD) culturing conditions. Metformin treatment significantly enhanced stemness properties and mineralized nodule formation, and increased the expression of osteogenic markers, including runt related transcription factor 2 (Runx2), osteocalcin (OCN), and alkaline phosphatase (ALP). Moreover, metformin substantially accelerated the formation of new bone, ameliorated the bone microarchitecture and promoted osseointegration of the dental implant. Collectively, metformin induces an osteogenic effect around the implant. Considering the widespread use of metformin, the results of the present study might promote a novel understanding of the positive effects of local metformin delivery on alveolar ridge defect, and have potential clinical application for the acceleration of osseointegration.