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Repair of massive bone defect by bone morphogenetic protein

骨形态发生蛋白修复大块骨缺损

基本信息

批准号：
04670891
负责人：
YOSHIKAWA Hideki
金额：
$ 1.34万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670891/
关键词：
bone morphogenetic protein osteosarcoma collagen bone graft biomaterial bone repair

项目摘要

1. Bone morphogenetic proteins were purified from Dunn osteosarcomas (800g) and human osteosarcomas in nude mice (800g) by guanidine extraction, acetone fractionation, ion-exchange chromatography, gel filtration and HPLC.2. We tested immunogenicity biocompatibility and biodegrability of various collagens, hydroxyapatites, and biopolymers, in order to select suitable carriers for BMP in vivo.3. We implanted the composites of BMP and each carrier substance into the back muscles of mice and examined new bone formation radiologically and histologically at 3 weeks.4. Pepsin-digested bovine skin collagen, hydroxyapatite, polylactic acid, and polylactic acid-polyethelene glycol, block copolymer proved to be suitable carriers for BMP.5. We implanted the composites of BMP and each carrier substance (collagen, polylactic acid, polylactic acid-polyethelene glycol) beneath the periosteum of rabbit tibia. New bone formation was observed by a composite of BMP/polylactic acid-polyethelene glycol at 4 weeks.6. We made a bony defect (2cm) in the rabbit tibia and implanted a composite of BMP/polylactic acid-polyethelene glycol in combination with hydroxyapatite rod into the gap of tibia. New bone formation was observed at the surface of the hydroxyapatite rod at 6 weeks and a bony bridge was obtained at 12 weeks.7. We implanted the composites of BMP and each carrier substance (collagen, polylactic acid, polylactic acid-polyethelene glycol) with and without hydroxyapatite into the back muscles of monkeys. Only BMP/collagen/hydroxyapatite induced new bone formation at 4 weeks.8. We implanted the composite of BMP/collagen/hydroxyapatite beneath the periosteum of monkey tibia. New bone formation was was observed at 4 weeks.

1.采用胍提取、丙酮分级、离子交换层析、凝胶过滤、HPLC等方法从Dunn骨肉瘤(800g)和人裸鼠骨肉瘤(800g)中纯化骨形态发生蛋白。2．我们测试了各种胶原蛋白、羟基磷灰石和生物聚合物的免疫原性、生物相容性和生物降解性，以选择合适的BMP体内载体。 3．我们将BMP与各载体物质的复合物植入小鼠背部肌肉，并在3周后通过放射学和组织学检查新骨形成。4．胃蛋白酶消化的牛皮胶原、羟基磷灰石、聚乳酸和聚乳酸-聚乙二醇嵌段共聚物被证明是BMP.5的合适载体。我们将BMP与各载体物质（胶原蛋白、聚乳酸、聚乳酸-聚乙二醇）的复合材料植入兔胫骨骨膜下。 BMP/聚乳酸-聚乙二醇复合材料在4周时观察到新骨形成。 6．我们在兔胫骨上制作了一个2cm的骨缺损，并将BMP/聚乳酸-聚乙二醇复合材料与羟基磷灰石棒结合植入胫骨间隙。 6周时在羟基磷灰石棒表面观察到新骨形成，12周时获得骨桥。7．我们将含有或不含羟基磷灰石的 BMP 和每种载体物质（胶原蛋白、聚乳酸、聚乳酸-聚乙二醇）的复合材料植入猴子的背部肌肉中。 4周时仅BMP/胶原蛋白/羟基磷灰石诱导新骨形成。8．我们将BMP/胶原/羟基磷灰石复合材料植入猴胫骨骨膜下。 4周时观察到新骨形成。