A rat model of ischemic osteonecrosis for investigating local therapeutics using biomaterials.

Osteonecrosis is one of the most disabling diseases affecting pediatric and adult populations. Local application of biomaterials is a promising therapeutic strategy for osteonecrosis. Currently, there is a lack of low-cost animal models of osteonecrosis for testing and developing biomaterials-driven therapeutics. To develop a rat model of ischemic osteonecrosis (IO), the distal femoral epiphysis was selected due to its size 7.7 folds larger than the proximal femoral epiphysis (p<0.0001). The feasibility of intraosseous drillings and the local application of biomaterials were determined. Four model biomaterials were successfully applied: injectable hydrogel, microsphere, bone cement, and implant. The IO was induced by surgically cauterizing the blood vessels supplying the distal femoral epiphysis. Osteonecrosis of the whole epiphysis was achieved with a complete absence of blood flow and near 100% of apoptotic osteocytes. At eight weeks after IO, the severe bone deformity and the osteoarthritis were developed at the affected epiphysis. The histological analysis showed 50% lacunae empty in the IO group, comparing to 2% in the control group (p<0.0001). The μCT analysis showed the epiphyseal quotient decreased to 0.46 in the IO group, comparing to 0.53 in the control group (p<0.0001), and the distal femoral epiphysis in the IO group was 19% smaller than the control group (p<0.01). The Safranin O stained sections showed the articular cartilage erosions and subchondral bone fractures in the IO group. In summary, we established a clinically relevant IO model on rats that is compatible with the application of biomaterials for treatment.