Hydroxyapatite, polycaprolactone and alendronate in bone regeneration in the olecranon of rabbits

摘要

Biomaterials development for bone regeneration is an increasing field. Association of hydroxyapatite (HAp) and polycaprolactone (PCL) in biomaterial formulations combines individual desirable properties for use in bone repair. Drugs may also be used in combination with the polymers and ceramics matrix.One of them is alendronate (ALN), which acts as an anti-resorptive agent, that is, inhibiting resorption by osteoclasts and additionally providing osteoblast proliferation and maturation, resulting in bone mass increment. This study aimed to evaluate bone regeneration of rabbits' olecranon defects treated with HAp in association with PCL and ALN. We used 36 rabbits, randomly distributed into four groups. The project was previously approved by Ethics Committee on Animal Use, #309/2011. All animals underwent surgical procedure, when a S-mm cortical defect was produced on the lateral face of the right olecranon. One group received no treatment (control group). The other groups received the biomaterial according to treatment: 1) PCL; 2) HAp+PCL (50% each); and 3) HAp+PCL+ALN (49.5%, 49.5% and 1%, respectively). The material was produced in powder and 250 mg was diluted in a sufficient amount of sterile saline solution to form a paste, which filled the bone defect. At eight, 45 and 90 days after surgery, three animals from each group were euthanized and the olecranon was harvested for histological analysis. On the eighth day, the defect edges were easily identifiable and trabecular bone formation began in all four groups. The amount of bone increased in the subsequent observations with more organized trabeculae. In treatments containing HAp, there was more bone formation around the composite. The property of HAp to confer osseointegration to the composite has already been reported.At 45 and 90 days, the defect was already filled by bone tissue in all groups, but with high porosity. Histomorphometric analysis showed that the amount of bone at 8 days was greater in all treated groups (＞ 25.0%) compared to the control (15.9%) in Kruskal-Wallis test. At 45 and 90 days, there was no statistical difference. No evidence of giant cells nor post-surgical infection were observed. Some animals that received ALN group showed periosteai reaction. This type of reaction has been reported when ALN was applied, but the significance and mechanism of this process need to be further explored. It is also important to highlight the defect size produced in this work: non-critical size defects, the ones able to regenerate spontaneously, biomaterial can promote faster repair, which is also desirable. Based on these results, we conclude that the composite of polycaprolactone and hydroxyapatite favors the regeneration of bone tissue, but the hydroxyapatite provides osseointegration to polycaprolactone composite and alendronate does not contribute in the process.