聚乳酸膜复合脱钙冻干异体骨修复下颌骨缺损

目的　探讨聚乳酸 (polylactic acid,PL A)膜复合脱钙冻干异体骨 (demineralized freeze- dried bone,DFDB)修复下颌骨缺损的可行性 ,比较单纯 PL A膜和 PL A膜复合 DFDB的骨修复能力。方法　在 2 4只日本大耳白兔双侧下颌骨下缘中份形成 1.0 cm× 0 .6 cm× 0 .4cm的矩形缺损。左侧缺损覆以 PL A膜 ,右侧缺损植入 DFDB后表面覆盖 PL A膜。术后 4、8、12周分期处死动物 ,取双侧下颌骨标本作大体观察 ,组织学观察 ,以及 X线片计算机灰度值分析。结果　 PL A膜复合 DFDB侧成骨活跃 ,成骨量高 ,计算机灰度值分析表明 ,术后 4、8周两侧缺损区内骨密度差异有显著性 (P<0 .0 1) ,复合材料侧骨密度较高。结论　 PL A/ DFDB复合材料是一种较理想的骨修复材料。     

组织工程骨修复颌骨缺损的实验研究

目的:利用组织工程骨诱导颌骨再生,修复颌骨缺损的效能评价。方法:取犬骨髓基质干细胞(BMSC)于含 100ml/L胎牛血清的DMEM培养液中培养,并向成骨细胞诱导。将细胞与可吸收性聚乳酸 (PLA)、重组人骨形成蛋白(rhBMP)复合植入右侧下颌骨 30×12mm椭圆形缺损区,左侧骨缺损区不植骨,作为空白对照,收 12只狗分为 4组,每组 3只,A组试验侧植入PLA/rhBMP/BMSCs,B组植入PLA/rhBMP,C组植入PLA/BM SCs,D组植入PLA。2、4、8周时行X线检查,取材组织行组织病理及扫描电镜检查,观察成骨情况。结果:A组实验侧 4周时,有小片状类骨质出现, 8周时新生骨形成大片状结构,PLA大部分降解,缺损由骨组织修复,成骨量明显大于B组或C组及D组,而空白对照侧仅为纤维组织修复。结论:聚乳酸、重组人骨形成蛋白、骨髓基质干细胞构建的组织工程骨,可诱导颌骨再生,能修复骨缺损,作为骨缺损修复材料,应用前景良好。     

改性后的骨形态发生蛋白-2聚乳酸纳米微球缓释系统促进下颌骨缺损修复的研究

目的 探讨改性后聚乳酸（PLA）包裹骨形态发生蛋白-2（BMP-2）制备的纳米微球缓释系统对兔下颌骨缺损的修复效果。方法 将PLA进行接枝聚合反应改性后,应用超声乳化法制备PLA纳米微球（PLA-N）、BMP-2-PLA 纳米微球（BMP-2-PLA-Ns）凝胶。将45只家兔随机分为3组：空白组、PLA-Ns凝胶组（对照组）、BMP-2-PLA-Ns凝胶组（实验组）,建立骨缺损动物模型,对照组植入PLA-Ns凝胶,实验组植入BMP-2-PLA-Ns凝胶,空白组不予特殊处理。术后第1、2、4周处死家兔,截取缺损区颌骨段,进行影像学、苏木精-伊红（HE）染色、PCNA免疫组织化学染色观察。结果 影像学观察可见：实验组骨缺损区修复良好,阴影不明显,修复效果好于对照组和空白组。HE染色观察可见：实验组和对照组有大量新生血管和继发性骨痂形成,实验组骨痂比例明显高于对照组和空白组。免疫组织化学观察可见：第1、2周,实验组PCNA阳性软骨细胞多于对照组和空白组;第4周,各组PCNA阳性细胞均罕见,PCNA阳性细胞检出率低于第1、2周。结论 BMP-2-PLA-NS缓释系统能明显促进下颌骨缺损修复。     

应用国产消旋聚乳酸载体复合rhBMP-2和hTGF-β1修复兔下颌骨缺损

目的评价国产消旋聚乳酸(PDLLA)载体材料复合重组人骨形成蛋白-2和转化生长因子-β1(rhBMP-2/hTGF-β1)整复兔下颌骨骨缺损的能力和载体材料的性能.方法建立健康成年家兔下颌骨骨缺损动物模型,分别应用PDLLA/rhBMP-2、PDLLA/rhBMP-2/hTGF-β1、PDLLA/hTGF-β1复合材料作为实验组,单纯PDLLA载体材料和空白组作为对照组,整复下颌骨缺损;通过大体解剖学观察、CT扫描和三维重建等影像学检查以及组织病理学检查等方法进行研究.结果术后2周时,各组下颌骨缺损区长度无差异;术后4周和8周时,PDLLA/rhBMP-2、PDLLA/rhBMP-2/hTGF-β1、PDLLA/haTGF-β1复合材料植入组,下颌骨缺损区长度与单纯PDLLA材料和空白组有显著性差异(P＜0.05),而复合材料各组间无差异.4～8周时,组织病理学检查显示实验组可见大量分泌旺盛的成骨细胞,并有明显的新骨形成,PDLLA材料逐步降解.结论国产消旋聚乳酸载体材料复合骨形成蛋白-2和(或)转化生长因子-β1具有促进骨缺损修复的作用,PDLLA可作良好的载体材料.     

纳米壳聚糖骨形成蛋白水凝胶修复下颌骨缺损实验研究

目的：观察可注射性纳米壳聚糖骨形成蛋白水凝胶修复颌骨缺损的效果。方法：以纳米壳聚糖为载体,加入重组人骨形成蛋白-2制备成可注射性纳米壳聚糖骨形成蛋白水凝胶（NCS／BMP-2 Gel）。取9只SD大鼠,在双侧背部皮下分别注射200μl（100μg／ml）NCS／BMP-2 Gel及单纯纳米壳聚糖水凝胶（NCS Gel）。于术后10、20、30 d分别处死3只,取材进行大体及常规病理学观察;选取54只SD大鼠,随机均分为3组（n＝18）制备下颌骨缺损模型,实验组骨缺损中注入NCS／BMP-2 Gel、对照组注入NCS Gel、空白组不注射。术后3、6、9周各组处死6只大鼠。分离下颌骨,用钼靶扫描图像,Image Pro-Plus软件比较其颌骨缺损面积;常规病理观察颌骨成骨情况。结果：实验侧、对照侧均形成皮下结节,实验侧30 d结节内可见类骨样结构;钼靶扫描检查：植入后3、6、9周时,实验组剩余骨缺损面积均低于对照组及空白组（P＜0．05）;组织学观察显示,实验组下颌骨成骨情况优于对照组及空白组。结论：NCS／BMP-2水凝胶有良好的生物相容性,能促进颌骨缺损修复。     

rhBMP-2、胶原、珊瑚复合人工骨临床研究

目的探讨 rh BMP- 2 /胶原 /珊瑚复合人工骨临床应用的骨修复能力。方法将 rh BMP- 2 /胶原 /珊瑚复合人工骨植入阻生智齿拔除后的牙槽窝内 ,并设单纯珊瑚和空白对照组 ,术后进行临床和 X线检查 ,记录邻近的第二磨牙远中牙槽嵴的高度和第二磨牙的松动度。结果术后 12周复合骨组牙槽窝骨缺损和牙槽嵴高度均得到良好的恢复 ,珊瑚骨组得到较好的恢复 ,而空白对照组结果不明显。结论 rh BMP- 2 /胶原 /珊瑚复合人工骨植入智齿牙槽窝可较好的修复牙槽窝骨缺损。这种新型的复合骨可能是临床应用的一种较理想的生物性植骨材料。     

基因重组人骨形成蛋白-2与珊瑚/聚乳酸复合修复骨质缺损的实验研究

目的　观察生物珊瑚、聚乳酸和rhBMP-2合成人工骨(复合骨)修复兔颅骨缺损后复合骨的变化情况。方法　选择24只新西兰兔,随机分成2组,每组12只,建立兔颅骨缺损标准模型。植入复合骨,用珊瑚/聚乳酸作为对照。术后4、8、12周每组各处死4只动物,取出植入体进行扫描电镜观察和机械强度测定。结果　复合骨在植入缺损后,不仅在植入体周边部有骨组织长入,而且在整个植入体内均有新骨形成,即出现多中心成骨。复合骨在同一时间点的成骨量明显多于对照组,随时间推移,成骨量递增。在植入前,两材料间的抗压强度无明显差异;在植入后,两植入体的抗压强度则差异显著,复合骨明显高于同期的对照组。结论　生物珊瑚、聚乳酸和rhBMP-2合成人工骨在体内以传导成骨和诱导成骨双重机制完成骨修复,且有良好的机械强度,作为植骨材料具有良好的应用前景。     

复合人工骨双重机制修复骨质缺损的实验研究

目的　研究生物珊瑚 /聚乳酸和rhBMP 2合成人工骨 (复合骨 )修复兔颅骨缺损的骨修复能力。方法　选择 2 4只新西兰兔 ,随机分成 2组 ,每组 1 2只 ,建立兔颅骨缺损标准模型。植入复合骨 ,用珊瑚 /聚乳酸作为对照。术后 4、8、1 2周每组各处死 4只动物。进行X线片、组织学观察。结果　复合骨在植入缺损后 ,不仅在其周边部有骨组织长入 ,而且在整个植入物内均有新骨形成 ,即出现多中心成骨。复合骨在同一时间点的成骨量明显多于对照组 ,随时间推移 ,成骨量递增。结论　生物珊瑚 /聚乳酸和rhBMP 2合成人工骨在体内以传导成骨和诱导成骨双重机制完成骨修复 ,作为植骨材料具有良好的应用前景     

新型骨组织工程支架复合BMP-2体内异位成骨的研究

目的 评价新型骨组织工程支架聚消旋乳酸与聚乳酸-聚乙二醇-聚乳酸共混物复合rhBMP-2作为组织因子载体的体内异位成骨的能力.方法 在12只成年新西兰兔背部两侧骶棘肌内各制作互不相通的2个肌袋.然后将复合rhBMP-2的材料植入一侧肌袋为实验组,未复合rhBMP-2的材料作为对照组植入另一侧肌袋.术后2、 4、 8周取材行大体标本观察、组织学观察,观察体内异位成骨情况.结果 植入体内8周,实验组见成熟骨组织形成,对照组无骨组织形成.结论 新型骨组织工程支架复合rhBMP-2后植入动物体内有较强的异位成骨能力,是BMP的良好载体.     

国际文摘

1.重组人 BMP- 2与骨髓联合移植再造灵长类下颌骨Reconstruction of the prim ate mandible with a combination graft of recom binant hum an bone m orphogenetic protein- 2 andbone m arrow.Seto I,Asahina I,oda M,et al.JOral Maxillofac Surg,2 0 0 1,5 9(1) :5 3- 6 2 .rh BMP- 2 / PGL A混合物与自体骨髓按 3.0 ,2 .5∶ 0 .5或 2∶ 1体积比混合后 ,植入日本猴的下颌骨骨段缺损 ,16周后处死动物观察。结果发现 ,rh BMP- 2 / PGL A与骨髓混合组 ,骨形成量明显增加 ;尤其是按 2∶ 1比例混合组 ,骨形成与单纯骨髓植入组相…     

聚乳酸与重组人骨形成蛋白—2复合植入块修复兔下颌骨缺损…

采用冷冻干燥法，将聚乳酸（ＰＬＡ）制成多孔成形块状，并将ＰＬＡ与重组人骨形成蛋白－２（ｒｈＢＭＰ－２）有效的复合，植入兔下颌骨缺损动物模型，在术后２，４周通过Ｘ线片、组织学观察缺损部位的骨生成情况。结果表明：ＰＬＡ－ｒｈＢＭＰ－２植入组术后２周就有部分新骨形成，术后４周骨生成明显；而单独植入ＰＬＡ组术后４周仅有少量新骨生成。钙含量测定显示ＰＬＡ－ｒｈＢＭＰ－２组高于ＰＬＡ组。结果提示：ＰＬＡ为ＢＭ     

基因重组人骨形成蛋白-2与珊瑚/聚乳酸复合异位诱导成骨的实验研究

目的 :观察基因重组人骨形成蛋白 - 2 (rhBMP - 2 )和珊瑚 /聚乳酸形成复合人工骨的异位诱导成骨活性。方法 :把rhBMP - 2和珊瑚 /聚乳酸形成复合人工骨。进行小鼠肌内种植 1、3、6周后 ,组织学观察其异位诱导成骨活性。结果 :rhBMP - 2赋予珊瑚 /聚乳酸骨诱导能力 ,珊瑚 /聚乳酸则充当rhBMP - 2的载体和释放系统 ,对BMP的活性未产生不利影响。与单纯的珊瑚 /聚乳酸相比 ,这种复合人工骨以软骨内成骨的方式诱导成骨。结论 :rhBMP - 2 /珊瑚 /聚乳酸复合人工骨具有良好的生物相容性和骨诱导活性 ,是一种较理想的骨移植替代材料     

聚乳酸与重组人骨形成蛋白-2复合植入块修复兔下颌骨缺损的早期观察

采用冷冻干燥法，将聚乳酸（ＰＬＡ）制成多孔成形块状，并将ＰＬＡ与重组人骨形成蛋白－２（ｒｈＢＭＰ－２）有效的复合，植入兔下颌骨缺损动物模型，在术后２，４周通过Ｘ线片、组织学观察缺损部位的骨生成情况。结果表明：ＰＬＡ－ｒｈＢＭＰ－２植入组术后２周就有部分新骨形成，术后４周骨生成明显；而单独植入ＰＬＡ组术后４周仅有少量新骨生成。钙含量测定显示ＰＬＡ－ｒｈＢＭＰ－２组高于ＰＬＡ组。结果提示：ＰＬＡ为ＢＭＰ的有效传递系统，ＰＬＡ－ｒｈＢＭＰ－２复合植入块是一种有应用潜能的人工骨替代物。     

The effect of rhBMP-2 around endosseous implants with and without membranes in the canine model

BACKGROUND: Bone morphogenetic protein (BMP) is a potent differentiating agent for cells of the osteoblastic lineage. It has been used in the oral cavity under a variety of indications and with different carriers. However, the optimal carrier for each indication is not known. This study examined a synthetic bioabsorbable carrier for BMP used in osseous defects around dental implants in the canine mandible. METHODS: Twelve canines had their mandibular four premolars and first molar teeth extracted bilaterally. After 5 months, four implants were placed with standardized circumferential defects around the coronal 4 mm of each implant. One-half of the defects received a polylactide/glycolide (PLGA) polymer carrier with or without recombinant human BMP-2 (rhBMP-2), and the other half received a collagen carrier with or without rhBMP-2. Additionally, one-half of the implants were covered with a non-resorbable (expanded polytetrafluoroethylene [ePTFE]) membrane to exclude soft tissues. Animals were sacrificed either 4 or 12 weeks later. Histomorphometric analysis included the percentage of new bone contact with the implant, the area of new bone, and the percentage of defect fill. This article describes results with the PLGA carrier. RESULTS: All implants demonstrated clinical and radiographic success with the amount of new bone formed dependent on the time and presence/absence of rhBMP-2 and presence/absence of a membrane. The percentage of bone-to-implant contact was greater with rhBMP-2, and after 12 weeks of healing, there was approximately one-third of the implant contacting bone in the defect site. After 4 weeks, the presence of a membrane appeared to slow new bone area formation. The percentage of fill in membrane-treated sites with rhBMP-2 rose from 24% fill to 42% after 4 and 12 weeks, respectively. Without rhBMP-2, the percentage of fill was 14% rising to 36% fill, respectively. CONCLUSIONS: After 4 weeks, the rhBMP-2-treated sites had a significantly higher percentage of contact, more new bone area, and higher percentage of defect fill than the sites without rhBMP-2. After 12 weeks, there was no significant difference in sites with or without rhBMP-2 regarding percentage of contact, new bone area, or percentage of defect fill. In regard to these three outcomes, comparing the results with this carrier to the results reported earlier with a collagen carrier in this study, only the area of new bone was significantly different with the collagen carrier resulting in greater bone than the PLGA carrier. Thus, the PLGA carrier for rhBMP-2 significantly stimulated bone formation around dental implants in this model after 1 month but not after 3 months of healing. The use of this growth factor and carrier combination appears to stimulate early bone healing events around the implants but not quite to the same degree as a collagen carrier.     

Efficacy of bone morphogenetic protein (BMP) with osteopromotive membranes – an experimental study in rat mandibular defects

The effect of bone morphogenetic protein (BMP) on healing of standardized bone defects was studied with and without the placement of osteopromotive membranes. Two different bovine BMP (bBMP) preparations were tested. These contained primarily collagen as a carrier. Standardized transosseous bone defects, 5 mro in diameter, were created in mandibles of rats. If left untreated, such "critical size defects" never heal during the lifetime of the animal, whereas covering with an osteopromotive membrane is known to cause complete healing of the defects in 6 weeks. The bBMP was implanted in defects and were either covered with an expanded polytetrafluoroethylene (e-PTFE) membrane (GORE–TEX®) or were left uncovered. Control defects did not receive any bBMP and were either covered with membrane or were left uncovered. Histological evaluation was made after 12 d and 24 d of healing, respectively. Implantation of bBMP alone was associated with formation of voluminous amounts of new bone, resulting in essentially complete defect healing at 24 d. However, the combination of membrane and bBMP was dearly less effective in stimulating bone healing, being only about as efficient as when using membranes alone. It was concluded that whereas both bBMP preparations were strongly osteoinductive, no further improvement of bone healing was seen when the membrane technique was supplemented with bBMP, compared to membrane alone. An explanation may be that the presence of an e-PTFE membrane prevents the degradation of the carrier material in the preparations, thus strongly reducing the availability of bBMP.     

Formation and resolution of ankylosis under application of recombinant human bone morphogenetic protein-2 (rhBMP-2) to class III furcation defects in cats

OBJECTIVES: Periodontal regeneration under application of bone morphogenetic protein (BMP) is compromised by ankylosis. Ankylosis disappearance following application of BMP has been observed in the case of a small defect, which might be beneficial change for periodontal regeneration. However, the histological observation of ankylosis disappearance has not been demonstrated in a large defect. The purpose of this present study was to confirm resolution of ankylosis during periodontal regeneration by recombinant human BMP-2 (rhBMP-2) applied to class III furcation defects. MATERIAL AND METHODS: Class III furcation defects were created in the premolars of six adult cats. The rhBMP-2 material, prepared by applying rhBMP-2 to a combination of polylactic acid-polygricolic copolymer and gelatin sponge (PGS; 0.33 microg rhBMP-2/mm(3) PGS) or control material containing only PGS, was implanted into each defect. The cats were killed at 3, 6 or 12 weeks after surgery and serial sections were prepared for histological and histometrical observation. RESULTS: Ankylosis was observed in some of the rhBMP-2/PGS group at 3 and 6 weeks, but not at 12 weeks. At 6 weeks, osteoclast-like cells were visible in the rhBMP-2/PGS group with ankylosis. Residual PGS was evident between the bone and root surface in the rhBMP-2/PGS group without ankylosis at 3 weeks. CONCLUSIONS: Resolution of ankylosis by osteoclast-like cells possibly occurred under application of rhBMP-2. Residual PGS might play an important role in preventing ankylosis formation.     

Effect of recombinant human bone morphogenetic protein-2 on bone formation in alveolar ridge defects in dogs

This study was designed to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with poly D, L lactic-co-glycolic acid (PLGA)/gelatin sponge complex (PGS) on the formation of bone in critically sized marginal defects of the mandible in dogs. Three months after extraction of the pre-molar teeth, rectangular bone defects (10 x 8 x 7 mm) were made in both sides of the mandible. A PGS block soaked in rhBMP-2 (400 microgram/ml) was implanted into one defect (BMP (+) group). As control, an untreated PGS block was implanted into the contralateral defect (BMP (-) group). 2, 4, 8, and 12 weeks after implantation, the defects were examined. In the BMP (+) group, newly formed bone was found in all defects from 4 weeks onward and was marked at 12 weeks. In contrast, the BMP (-) group showed no appreciable new bone formation, even at 12 weeks. Moreover, density of newly formed bone in the BMP (+) group was similar to that of the surrounding cortical bone at 12 weeks. These findings suggest that rhBMP-2/PGS is an effective bone substitute for reconstructive surgery of the dog mandible.     

Effect of polylactic acid on osteoinduction of demineralized bone: preliminary study of the usefulness of polylactic acid as a carrier of bone morphogenetic protein

To evaluate the usefulness of polylactic acid (PLA), a bioabsorbable and plastic polymer, as a carrier of bone morphogenetic protein (BMP), a preliminary study has been carried out to investigate any negative effect of PLA on osteoinduction of demineralized bone (DB). PLA (10,600mol. wt) was mixed with DB particles (1– 1.5 mm square) prepared from rat femurs and laid subcutaneously on the intercostal muscle of 4-week-old Wistar rats. The PLA/DB pellets were harvested at 2, 4, 8 and 24 weeks after the operation, and prepared for light microscopic examination. Histological examination revealed cartilage formation at 2 weeks and new bone formation at 4 weeks. Extensive bone and marrow formation were observed at 24 weeks. PLA was gradually absorbed and completely disappeared at 24 weeks to be replaced by connective tissue. These results demonstrate that PLA does not have a negative influence on the osteoinductive activity and that PLA could well be a promising bioabsorbable carrier of BMP.     

胶原膜与骨形成蛋白复合物的成骨作用研究

目的：评价rhBMP-2／胶原复合膜对大鼠颅内缺损修复的作用。方法：将rhBMP-2与胶原膜复合,在大鼠颅骨制备直径5mm的骨缺损,分别予双侧覆盖复合膜、外侧覆盖复合膜,外侧覆盖胶原膜作为空白对照,于术后2、4、6周,取标本进行X线检查、荧光显微镜检查及常规组织学观察。结果：在各组内、覆盖复合膜的缺损成骨面各百分比及新生骨面积均明显高于覆盖胶原的缺损组（P＜0．01）,术后6周,双侧覆盖复合膜的缺损已达骨性愈合。结：胶原膜与BMP的复合物不但具有机械性的阻挡作用,而且具有骨诱导性,可加速骨愈合。