Effect of fibrin-fibronectin sealing system in combination with ss-Tricalcium phosphate as a carrier for recombinant human bone morphogenetic protein-2 on bone formation in rat calvarial defects

Abstract

[한글]

골형성 유도 단백질 (bone morphogenetic protein, BMPs)은 치주치료와 골 재생 치료를 위한 효과적인 골 대체 물질로 평가되어왔다. BMPs 골형성 능력에도 불구하고, 아직 이상적인 전달체는 존재하지 않는다. 이 연구의 목적은 fibrin-fibronectin sealing system 과 ss-TCP (FFSS/ss-TCP) 복합체를 골형성 유도 단백질(rhBMP-2) 운반체로 사용하여 백서 두개골 결손부에 적용하였을 때, 골형성 효과를 평가하는 것이다.100마리의 웅성 백서에서 8mm 지름을 갖는 임계크기의 두개부 결손을 형성하였다. 20마리씩 5개의 군으로 나누고, 각 군은 아무것도 이식하지 않은 대조군, FFSS를 이식한 군, FFSS/ss-TCP를 이식한 군, FFSS와 FFSS/ss-TCP를 전달체로 사용하여 농도 0.025mg/ml rhBMP-2를 이식한 군으로 나누어 술 후 2주와 8주에 치유 결과를 조직학적, 조직계측학적으로 비교 관찰하였다.조직계측학적 관찰 결과, FFSS/ss-TCP군에서 FFSS군보다 2주째 신생골 형성량 (new bone area) 및 2, 8주째 총조직 형성량 (augmented area)이 유의성 있게 증가하였다. 2주째 신생골 형성량은 rhBMP-2/FFSS, rhBMP-2/FFSS/ss-TCP 군간의 유의 차는 없었다. 그러나 8주째에는 두 군간에도 유의 차가 관찰되었다 (P <0.01). 총조직 형성량은 rhBMP-2/FFSS/ss-TCP군에서 rhBMP-2/FFSS군 보다 2, 8주째 모두에서 유의 차 있는 증가 하였다 (P <0.01).백서 두개골 결손부에서 FFSS/ss-TCP 결합체를 rhBMP-2 전달체로 사용하였을 때 신생골 형성 및 총조직 형성에 유의한 효과가 있었다. 결론적으로, FFSS/ss-TCP는 rhBMP-2의 전달체로서의 가능성 있다고 사료된다.

[영문]Bone morphogenetic proteins (BMPs) are being evaluated as potential candidates for periodontal and bone regenerative therapy. In spite of good prospects for BMP applications, an ideal carrier system for BMPs has not yet been identified. The purpose of this study was to evaluate the osteogenic effect of a fibrin-fibronectin sealing system (FFSS) combined with ss-tricalcium phosphate (ss-TCP) as a carrier system for rhBMP-2 in the rat calvarial defect model.Eight-mm critical-size calvarial defects were created in 100 male Sprague-Dawley rats. The animals were divided into 5 groups of 20 animals each. The defects were treated with rhBMP-2/FFSS, rhBMP-2/FFSS/ss-TCP, FFSS and FFSS/ss-TCP carrier control or were left untreated as a sham-surgery control. Defects were evaluated by histologic and histometric parameters following a 2- and 8-week healing interval (10 animals/group/healing intervals).The FFSS/ss-TCP carrier group was significantly greater in new bone area at 2 weeks (p <0.05) and augmented area at 2 and 8 weeks (p <0.01) relative to the FFSS carrier group. New bone area and augmented area in the rhBMP-2/FFSS/ss-TCP group were significantly greater than in the rhBMP-2/FFSS group at 8 weeks (p <0.01). On histologic observation, FFSS remnants were observed at 2 weeks, but by 8 weeks, the FFSS appeared to be completely resorbed. rhBMP-2 combined with FFSS/ss-TCP produced significantly more new bone formation and augmentation in this calvarial defect model. In conclusion, FFSS/ss-TCP may be considered as an available carrier for rhBMP-2.