Development of a Bisphosphonate Delivering Hydrogel for the Augmentation of Impaired Peri-Implant Bone

摘要: Osteoporosis is a major health problem in our aging society. This metabolic disease, which characterized by deterioration of the bone microarchitecture and significant loss mass, affecting rising number mostly elderly patients. The main clinical consequences are typical fragility fractures resulting severe pain, morbidity, mortality for affected does not only cause fractures, but also complicates fracture treatment, as implants difficult to anchor impaired structure. Therefore, many mechanical pharmaceutical approaches have been developed over last decades target this issue improve implant anchorage osteoporotic bone. overall goal present PhD thesis was development bisphosphonate (BP) releasing hydrogel that can enhance fixation project divided into three sections: investigation BP effect on peri-implant bone, testing drug delivering biomaterial, evaluation its efficiency terms improvement. An ovariectomized rat model postmenopausal osteoporosis utilized spatio-temporal locally released Zoledronate, used study. delivered from biodegradable hyaluronic acid (HyA) matrix stock surrounding screws were implanted femoral condyles rats. Static dynamic histomorphometric parameters monitored four concentric layers around screw with time-lapsed vivo microCT scans. With study, we able demonstrate enhancement early formation rate accompanied an efficient inhibition resorption large range screw. In second incorporated Zoledronate-loaded hydroxyapatite nanoparticles HyA unexpected rapid mineralization within 10 days after implantation. Histology performed 2 months implantation revealed granule-shaped mineralized spots serving scaffolds new formation. When using particles, could strong inhibitory both degradation. Finally, scans first animal study create micro-finite element models analysis time course. We show Zoledronate improved significantly soon 17 when compared untreated control group. difference persisted until end at day 58. Taken together, studies demonstrated excellent suitability hydrogels local delivery BPs intended A triggered occurred prolonged period, important aspect considering osteosynthesis need reliable complete healing. Furthermore, it be shown addition particles resulted hydrogel, promising feature defect repair applications.