Background: Lactoferrin is an 80-kDa iron-binding glycoprotein that is produced in milk and other exocrine glands. In vitro, lactoferrin functions as a potent bone anabolic factor by increasing the proliferation, differentiation and survival of osteoblasts and by inhibiting osteoclastogenesis. In vivo, the effect of local application of lactoferrin on bone regeneration has produced conflicting results and studies thus far have only employed non-critical-sized calvarial defect or local subcutaneous injection models. The objective of this study was to assess the ability of bovine lactoferrin to increase bone regeneration in a rat critical-sized calvarial defect model.
Method: Critical-sized defects (5mm) were created over the right parietal bone in 60 sexually mature male Sprague-Dawley rats. The rats were randomised into three groups: Group 1(control) defects were left empty; Group 2 defects were filled with a 100 μl collagen gel (3 mg/ml); and Group 3 defects were filled with a 100 μl collagen gel containing 10 μg bovine lactoferrin. The rats were sacrificed at 4 or 12 weeks post-operatively and the calvaria were harvested for assessment of bone regeneration using μCT. This study was approved by the local Animal Ethics Committee.
Results: Collagen gels had completely degraded in all animals at the time of sacrifice. The percentage of new bone formation, at both 4 and 12 weeks was significantly greater in the group treated with lactoferrin compared with other groups. The percentage of new bone formation in groups 1, 2 and 3 was 42.7±4.2%, 35.9±5.9% and 63.2±2.3%, respectively, at 4 weeks (P=0.0008); and 41.1±5.2%, 45.8±4.8% and 74.6±4.3%, respectively, at 12 weeks (P<0.0001).
Conclusion: This study demonstrated that local application of lactoferrin significantly increased bone regeneration in a rat critical-sized calvarial defect model. The profound anabolic effect of lactoferrin on bone regeneration has therapeutic potential for treatment of bony defects and fracture non-union.
Disclosure: The authors declared no competing interests.