Tabata Y, Yamada K, Miyamoto S, Nagata I, Kikuchi H, Aoyama I, Tamura M, Ikada Y
Research Center for Biomedical Engineering, Kyoto University, Japan.
Biomaterials. 1998 Apr-May;19(7-9):807-15. doi: 10.1016/s0142-9612(98)00233-6.
The objective of this study is to enhance the bone induction activity of basic fibroblast growth factor (bFGF) for reconstruction of skull bone defects which has been clinically recognized as almost impossible. For this purpose, we prepared biodegradable hydrogels from gelatin with an isoelectric point of 4.9 which is capable of polyionic complexing with basic bFGF. When implanted in rabbit skull defects of 6 mm in diameter (6 defects per experimental group), the gelatin hydrogels incorporating 100 microg of bFGF promoted bone regeneration at the defect in marked contrast to free bFGF of the same dose, finally closing the bone defects after 12 weeks of implantation as is apparent from histological examination. In dual energy X-ray absorptometry analysis, the bone mineral density at the skull defects enhanced by the hydrogels was significantly higher than that by free bFGF at doses ranging from 2 to 200 microg/defect (P < 0.05). The extent of bone regeneration induced by gelatin hydrogels incorporating 100 microg of bFGF increased with a decrease in their water content. Histological examination indicated that more slowly degrading hydrogels of lower water content prolonged the retention period of osteoblasts in the bone defects. This led to enhanced bone regeneration compared with faster degrading hydrogels of higher water content. It was concluded that this biodegradable hydrogel system was a promising surgical tool to assist self-reconstruction of the skull bone.
本研究的目的是增强碱性成纤维细胞生长因子（bFGF）的骨诱导活性，以重建临床上被认为几乎不可能的颅骨缺损。为此，我们用等电点为4.9的明胶制备了可生物降解的水凝胶，其能够与碱性bFGF形成聚离子复合物。当将其植入直径为6毫米的兔颅骨缺损中（每个实验组6个缺损）时，含有100微克bFGF的明胶水凝胶在缺损处促进了骨再生，这与相同剂量的游离bFGF形成了显著对比，从组织学检查可以明显看出，植入12周后最终闭合了骨缺损。在双能X线吸收测定分析中，水凝胶增强的颅骨缺损处的骨矿物质密度显著高于剂量范围为2至200微克/缺损的游离bFGF（P<0.05）。含有100微克bFGF的明胶水凝胶诱导的骨再生程度随着其含水量的降低而增加。组织学检查表明，含水量较低、降解较慢的水凝胶延长了成骨细胞在骨缺损中的保留期。与含水量较高、降解较快的水凝胶相比，这导致了骨再生增强。得出的结论是，这种可生物降解的水凝胶系统是一种有前景的外科工具，可协助颅骨的自我重建。
