Nanohydroxyapatite Based Ceramic Carrier Promotes Bone Formation in a Femoral Neck Canal Defect in Osteoporotic Rats

Hip fractures are among the most common types of fracture risks in old age osteoporotic patients that often end up with immobile disabilities. Weak bones due to loss of mineral content along with an increase in the porosity of the femur neck canal in osteoporosis reduce the mechanical properties of the bone and predispose the patients to fractures. In this study, we have used calcium sulfate/nanohydroxyapatite based nanocement (NC) as carrier of recombinant human bone morphogenetic protein-2 (BMP-2), zoledronate (ZA), and bone marrow mesenchymal stromal cells (MSCs) derived exosomes (EXO) to enhance bone formation and defect healing in a femur neck canal defect model in osteoporotic rats. A cylindrical defect in the femur neck canal with dimensions of 1 mm (diameter) x 8 mm (length) starting from the lateral cortex toward the apex of the femur head was developed. The defect was impacted using NC alone or functionalized as (a) NC + ZA (systemic), (b) NC + ZA (local), (c) NC + EXO + ZA, and (d) NC + BMP + ZA to evaluate bone formation by ex vivo micro-computed tomography (micro-CT) and histological analysis 16 weeks postsurgery. Moreover, the femurs (both defect and contralateral leg) were subjected to biomechanical analysis to assess the effect of treatments on compressive mechanical properties of the bones. The treatment groups (NC + ZA (L), NC + BMP + ZA, and NC + EXO + ZA) showed enhanced bone formation with complete healing of the defect. No differences in the mechanical properties of both the defect and contralateral across the leg were observed among the groups. However, a trend was observed where NC + BMP + ZA showed enhanced biomechanical strength in the defect leg. This suggests that NC could act as a potent carrier of bioactive molecules to reduce the risks of hip fractures in osteoporotic animals. This type of treatment can be given to patients who are at higher risk of osteoporosis mediated femur neck fracture as a preventive measure or for enhanced healing in already compromised situations. Moreover, this study provided a proof of concept regarding the use of exosomes in bone regeneration therapy, which might be used as a booster dose that will eventually reduce the dosage of BMP and hence circumvent the limitations associated with the use of BMP.