Finely controlled bioceramic granules and sonoporation for osteogenic bone defect repair and reconstruction

Osteoporotic fractures caused by imbalance in bone homeostasis like chemotherapy, loss of ovarian function，glucocorticoid use and aging require special surgical procedure to treat and restore anatomical function. However, due to escalating bone weakness and impairment, it remains a clinical challenge to treat these types of fracture defects through conventional means. Herein, we fabricated a novel calcium silicate‑strontium (CS-Sr35) bioceramic granules with high biological properties and combined it with ultrasound aided sonoporation (sono) in augmenting osteoporotic critical-sized bone defect. The use of sonoporation mediated by microbubble was to influence efficient response for tissue permeability and delivery of bioactive ions from the bioceramic scaffold. The graded robust granule with adjustable microstructure exhibited physiochemical and biointegration properties favorable for ion release in vitro and osteogenic related activities in vivo. Herein, we compared the treatment of bone defect repair using (i) no scaffold (ii) CS-Sr35 only and (iii) CS-Sr35 + sono. The gradual bone repair process was elucidated by X-ray, histology and micro-CT analyses. Overall, our results showed that the CS-Sr35 + sono exhibited a tailored biodissolution behavior with complete defect repair and reconstruction. Meanwhile, the group with only CS-Sr35 granules had less osteoblastic healing while the blank group showed inadequate critical-sized defect repair throughout the study. Our study suggests that, the synergistic technique of combining bioceramic granule with sonoporation significantly optimizes osteogenic activity and biomineralization ability of the bioceramic granule for new bone growth in osteoporotic pathology and also this tailored technique provides versatile approach for improving the biological effect for next generation reconstruction and repair of diseased bone defect.