Recombinant Human Bone Morphogenetic Protein-2 Promotes Wound Healing in Rat Periodontal Fenestration Defects

Abstract

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-microL quantity of 50 microg/mL rhBMP-2 in a collagen gel solution was placed into the surgically created defect in test animals; in controls, either a 10-microL 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-microm 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 microm2 and 258 +/- 57 microm2, 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 post-operatively, 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.

Pre-clinical Models for Oral and Periodontal Reconstructive Therapies

“…This microenvironment favors the proliferation and migration of mesenchymal progenitors which can originate from the periodontal ligament (PDL) and bone (Lekic et al, 1996a,b). After 10 days, a thin cementum layer with a connective tissue attachment can be observed, particularly on the apical side of the teeth, where the cementum is thicker compared with the narrow coronal region (King et al, 1997). Bone formation is typically initiated from the bony margins of the lesions (Rajshankar et al, 1998).…”

“…At 3, 10, 21, and 35 days postsurgery, tissue samples were harvested, and the regeneration of bone and cementum was evaluated. Adapted from King et al, 1997. usually validate a move to consideration of clinical applications. These large models include dogs, sheep, pigs, and non-human primates.…”

Periodontal regeneration using ex vivo autologous stem cells engineered to express the BMP-2 gene: an alternative to alveolaplasty

“…Those osteoblasts and their precursors might be a target of BMP-2. 35 BMP-2 may induce new cementum in addition to de novo bone formation. 32 In a previous study, the early effect of BMP-2 on cell recruitment resulted in a nearly threefold increase in cementogenesis by stimulating earlier cell recruitment.…”

BMP Receptors in Limb and Tooth Formation

“…rhBMP-2 and rhBMP-7 have been most extensively studied. In a rat model of periodontal regeneration, both rhBMP-2 (King et al, 1997) and rhBMP-7 (Rajshankar et al, 1998) stimulated regeneration of the bone and cementum, and maintained the periodontal ligament width (i.e., no ankyloses). In a furcation defect model, implants of either rhBMP-2 (Sigurdsson et al, 1995(Sigurdsson et al, , 1996 or rhBMP-7 (Ripamonti et at., 1996) have been reported to stimulate various degrees of periodontal regeneration; however, BMP-2 also induced some ankylosis which may have been due, in part, to the carrier used for delivery (Sigurdsson et al, 1996), whereas BMP-7 did not induce ankylosis.…”