Changes in Bone Regeneration by Trehalose Coating and Basic Fibroblast Growth Factor after Implantation of Tailor-Made Bone Implants in Dogs

Abstract

ABSTRACT. In this study, we aimed to determine the effect of trehalose coating and the optimal dose of basic fibroblast growth factor (bFGF), an osteoinductive protein, loaded onto tailor-made bone implants for implant-induced bone formation in vivo. We fabricated tailor-made α-tricalcium phosphate bone implants (11 mm diameter with 2 parallel cylindrical holes). bFGF 0, 1, 10, 100 or 200 µg/implant was incorporated into implants with and without a trehalose coating, and these were subsequently implanted into dogs to correct temporal bone defects of the same size and shape. Four weeks after implantation, we analyzed the bone implants and surrounding tissues by using microcomputed tomography imaging and histological analyses, as well as gross evaluation. No significant difference in new bone formation was observed between implants with and without a trehalose coating at any of the bFGF doses. Bone implants with 100 and 200 µg bFGF showed significantly more new bone formation at the implant site and within the cylindrical holes of the implants than those without bFGF (P<0.05). However, heterotopic bone formation on the skull near the implant was observed in the group that received 200 µg bFGF. These results suggest that 100 µg bFGF is the optimal dose for this implant in dogs, and that the trehalose coating may not be necessary in vivo, probably due to the presence of blood proteins and electrolytes at the implant site. KEY WORDS: bFGF, bone graft, in vivo, osteoinductive, tailor-made bone implant.

Use of Synthetic Bone Material with Osteoinductive Proteins to Promote Bone Healing in Dogs

“…However, an excessive dose of bFGF can induce ectopic bone formation. Choi et al reported that supersaturated bFGF flows out and forms new bone tissues in the heterotopic region in a canine skull defect model (2). In this study, both cases showed a callus on radiography in the early stage after the surgery without ectopic bone formation during the follow-up period.…”

“…Larger mammals tend to need larger doses to promote bone regeneration than those of rodents. We determined dose by referring to previous studies (2,6,16). However, an excessive dose of bFGF can induce ectopic bone formation.…”

“…Basic fibroblast growth factor (bFGF) plays an important role in skeletal development and fracture repair (7,14). In the skeletal system, bFGF promotes osteoblast differentiation and proliferation in vitro and bone regeneration in vivo (2,3,10). These proteins require adequate scaffolds to enhance their biological activities.…”

Porous Alpha-Tricalcium Phosphate with Immobilized Basic Fibroblast Growth Factor Enhances Bone Regeneration in a Canine Mandibular Bone Defect Model

“…A single injection of 200 μg bFGF was found to promote tibial fracture healing in Beagles [16], and 150 μg bFGF combined with collagen mini-pellets stimulated bone regeneration in dogs [17]. In addition, 100 μg bFGF was the optimal dose for α-TCP implantation in dogs [18]. In this study, mandibular defects were filled with about 70 mg of porous α-TCP particles, corresponding to about 4.2 μg (59.6 ng × 70 mg) bFGF.…”