Recombinant human bone morphogenetic protein-2 promotes wound healing in rat periodontal fenestration defects

Although there is considerable interest in the use of bone morphogenetic protein (BMP) to promote periodontal regeneration, little is known of its effects on the early stages of wound healing. The aim of this study was to investigate the effects of recombinant human bone morphogenetic protein 2 (rhBMP-2) on an early stage of post-operative wound healing and following complete healing (10 and 38 days, respectively) in a rat model of periodontal regeneration. The buccal aspects of molar roots were carefully denuded of their periodontal ligament through a bony window created in the mandibles of Wistar rats under general anesthesia. After the root surfaces were acid-conditioned, a 10-mu L quantity of 50 mu g/mL rhBMP-2 in a collagen gel solution was placed into the surgically created defect in test animals; in controls, either a 10-mu L quantity of only collagen gel was received, or the defect was untreated. Animals were killed 10 days or 38 days after surgery and the tissues processed for histological examination. Transverse 5-mu m sections were stained for the identification of new bone, cementum, and collagen fiber formation. In the 10-day study groups, new bone formation over the second molar and beyond the defect was significantly increased in the test group (p < 0.02), although there was no evidence of increased ankylosis. RhBMP-2 stimulated more than twice the area of cementum growth coronally compared with controls (712 +/- 286 mu m(2) and 258 +/- 57 mu m(2), respectively). Connective tissue attachment, including the number and width of collagen bundles, was similar in both test and controls. Complete healing without any evidence of ankylosis had occurred in all animals 38 days postoperatively, and no significant differences were observed between test and control groups. In conclusion, a single dose of rhBMP-2 increased the rate of normal intramembranous bone formation and selectively enhanced cementum formation coronally during early wound healing. However, the finding that rhBMP-2 induced bone formation at some distance from the defect suggests the importance of developing a suitable delivery system to maintain the concentration of BMP-2 at the site of implantation for potential therapeutic use.