Dietary Hesperidin Influences Long-Term Regeneration of Craniofacial Bone and Native Skeletal Bone of the Rat

Objectives: Based on the anti-inflammatory and osteogenic properties of the phytochemical hesperidin (HE), we investigated if its systemic administration could be a cost-effective method of improving BMP-induced bone regeneration. Our previous studies suggest HE has a significant skeletal bone sparing effect and the ability to provide a more effective BMP-induced craniofacial regeneration in the rat mandible critical-sized defect after two weeks of healing. We hypothesized that HE would significantly improve BMP-induced bone regeneration of craniofacial bone and skeletal bone quality after six weeks.
Methods: Sprague-Dawley rats were allocated into 3 groups (n = 4/group): a 5-mm critical-sized mandible defect + collagen scaffold or, scaffold + 1 µg of BMP2 with and without dietary HE at 100 mg/kg. HE was administered by oral gavage 2 weeks prior to surgeries and continued for 6 weeks post-surgery. The femur from rats were collected and processed for biochemical analysis for collagen cross-link assessment.
Results: Mandibles harvested at week 6 post-surgery were subjected to microcomputed tomography. The high-dose BMP2 alone caused cystic-like regeneration with incomplete defect closure. HE + BMP2 showed virtually complete bone fusion. Collagen non-reducible cross-link analyses showed that HE-treated rats have a higher ratio of Pyridinoline to deoxypyridinoline.
Conclusions: Our findings show that dietary HE has a remarkable modulatory role in the function of locally delivered high-dose BMP2 in bone regeneration. Based on our previous work on early bone healing, this is possibly via control of inflammation, osteogenesis, changes in osteocyte and osteoclast function. Our current study also suggests that collagen maturation is affected and thus can indicate higher crosslinking associated with dietary HE. In conclusion, HE the ability to provide a more effective BMP-induced craniofacial regeneration.