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THE EFFECT OF CONTROL-RELEASED BASIC FIBROBLAST GROWTH FACTOR INCORPORATED IN ?-TRICALCIUM PHOSPHATE FOR CRANIAL REGENERATION IN A MURINE MODEL
Presenter: Azusa Shimizu, MD
Co-Authors: Tajima S; Tobita M; Tanaka R; Mizuno H; Tabata Y
Juntendo University School of Medicine

Introduction: Highly purified ?-tricalcium phosphate (?-TCP), a biodegradable material with prominent osteoconductive properties, has been clinically available as a bony substitute. However, there still remains a drawback of time-consuming for complete osteoinduction. Basic fibroblast growth factors (bFGF) play a crucial role in bone regeneration by promoting proliferation of osteo-progenitor cells and neovascularization. Gelatin has a capability of sustaining growth factors, which are gradually released from gelatin. The purpose of this study is to determine if control-released bFGF incorporated in ?-TCP can promote bone regeneration, aiming at clinical application as a better alternative material for bone grafting.

Materials and Methods: Bilateral cranial defects of 4mm in diameter were made in 10-weeks-old male Wistar rats. Before skin closure, each defect received the following materials; Group1: 20?l saline as control, Group2: ?-TCP disk (4mm in diameter, 1.5mm in thickness) in 20?l saline, Group3: ?-TCP disk in 50?g bFGF solution, Group4: ?-TCP disk in 50?g bFGF-incorporated gelatin hydrogel (n=6 each). After 1, 2 and 4 weeks, each cranial defect was evaluated by (1) quantitative analysis of ?-TCP with three-dimensional computed tomography, (2) hematoxylin and eosin (H&E) staining, (3) tartrate-resistant acid phosphatase (TRAP) staining and (4) immunohistochemistry for osteopontin and osteocalcin.

Results: There was an increase in radiolucency of ?-TCP and average rate of CT value were significantly lower in Group 3 and 4. H&E staining showed that new bone and new capillaries were observed in early stage in Group4 and that the average rate of bone formation was higher overtime in Group 4 compared with the other groups. TRAP staining and immunohistostaining revealed that cells positively for TRAP, osteopontin and osteocalsin expressed earlier in Group 4 than in the other groups.

Conclusions: These findings suggest that our new material can accelerate bone regeneration in murine cranial defect model. Such materials are thought to be one of the promising alternatives in the treatment of cranial defect.


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