Nanofibrillated cellulose injectable implants loaded with Raloxifene hydrochloride and bioactive glass nanoparticles for bone regeneration: in-vitro and in-vivo study

Nanofibrillated cellulose (NFC) injectable implants loaded with raloxifene hydrochloride and bioactive glass (magnesium phosphate; MPh) for treating bone defects were prepared. MPh was prepared using a simple chemical precipitation method and characterized which showed its porous, amorphous nature and a particle size of 10–20 nm. Then, MPh was loaded in different concentrations in NFC/Poloxamer to formulate the implants. The flow rate values indicated acceptable injectability compared to Betolvex™. Adding MPh decreased the flow rate, with higher concentrations having slower flow rates. The drug release profiles of the formulations varied, with the addition of the highest MPh concentration (3 %w/v) sustaining the drug release up to 17 days. SEM images showed a porous dense matrix after contact with release medium. The healing power and rate of the formulation in male Albino rats with induced tibial bone defects were investigated. The macroscopic examination showed no signs of infection or osteolytic responses. The treated groups showed better healing compared to untreated group, with the double-dosed group exhibiting the fastest progress. Histopathological findings showed complete healing with the developed formulation particularly when double-dosed. Overall, the injectable implant provided enhanced bone healing through the synergistic actions of its components, especially when double-dosed.