Histologic And Histomorphometric Comparison Of Bone Regeneration Between Bone Morphogenetic Protein‐2 And Platelet‐Derived Growth Factor‐BB In Guinea Pigs

Abstract

In dental implant treatment, the atrophic alveolar crest remains a challenging area for optimum rehabilitation. Growth factors have great potential for bone regeneration at the atrophied alveolar crest. Among the various growth factors, recombinant human bone morphogenic protein‐2 (rhBMP‐2) and recombinant human platelet‐derived growth factor (rhPDGF) have received a great deal of attention. This study evaluates the efficacy of rhBMP‐2 and rhPDGF‐BB delivered via absorbable collagen sponge (ACS) on bone formation in guinea pig. A total of 24 adult Dunkin‐Hartley guinea pigs aged 6–7 months, weighing 700–800 g were randomly assigned initially into two groups as 15 and 45 days of healing which have 12 animals in each group. Three‐millimeter‐circular bone defects were created on the tibias of animals as 2 defects per each tibia and totally 4 defects per each animal. The four groups in each animal corresponded to the biomaterial used to fill the created bone defects as follows: rhBMP‐2+ACS, rhPDGF‐BB+ACS, ACS only (positive control), and no treatment (empty; negative control). To prevent the possibility of growth factor interactions between two biomaterials, randomization was performed so that rhBMP‐2+ACS and rhPDGF‐BB+ACS were not applied to the same tibia consecutively. New bone formation was evaluated histologically and histomorphometrically at 15 (early healing) and 45 days (late healing). Data were subjected to statistical analysis. Quantities of new bone were analyzed with one‐way ANOVA followed by post hoc Holm‐Sidak testing. Statistical calculations were performed using Sigma Stat for Windows, version 3.0; P < 0.05 was considered to be significant. At day 15, new bone formation was seen at the peripheral portion of the defect where ACS was partly resorbed. Significant fibrous callus formation was observed in the rhBMP‐2+ACS group. The amounts of fibrous callus and newly formed bone trabeculae in the rhBMP‐2+ACS group were significantly higher than in the other groups (P < 0.05). Highest amount of new bone per defect area was seen in the rhBMP‐2+ACS group at the end of day 15. New bone formation in the rhPDGF‐BB+ACS group was lower than that observed in the rhBMP‐2+ACS group on day 15. However, the amount of newly formed bone trabeculae was significantly higher than in the control groups (ACS only and empty; P < 0.05). The ratio of new bone to total defect area increased significantly over time. At the end of day 45, a large part of the ACS had been resorbed. New bone per defect area at day 45 was significantly higher than at day 15 in the rhPDGF BB+ACS group (P ≤ 0.001). In the rhPDGF‐BB+ACS group, at the end of day 45, the defects were almost filled with new bone, and remodeling was determined. At the end of day 45, new bone formation was significantly higher in the rhPDGF‐BB+ACS group than in the control groups (P = 0.007 and P = 0.006 for empty and ACS only groups, respectively). There was no significant difference between the rhBMP‐2+ACS and rhPDGF‐BB+ACS groups at day 45. Advances in suitable carriers, coupled with the osteoinductive effects of rhBMP‐2 and rhPDGF‐BB, could ultimately create a future gold standard for bone grafting. Although further long‐term studies and clinical trials are required, the findings presented herein suggest a promising use of rhBMP‐2 and rhPDGF‐BB for bone regeneration applications.