PerioGlas/rhBMP-2用于兔下颌骨侧嵴扩增的初步实验评估

目的 探讨PerioGlas（bioaetive glass，BG）与重组人骨形成蛋白-2（recombinent human bone morphogenetic protein-2，rhBMP-2）在下颌骨侧嵴扩增的可行性。方法在免磨牙区唇侧骨皮质表面，球钻预备4～6个5mm的骨缺损，一侧骨皮质表面和骨缺损内放置BG／rhGBMP-2，另一侧作为空白对照。术后正常饮食，2、4、8周后大体观察、组织学检查和组织学测量。结果观测时间内所有植入体固住良好，没有炎性反应。下颌骨表面明显加厚。材料表面骨组织覆盖；组织学观察皮质骨表面和骨缺损内新骨形成，2周纤维组织分割BG颗粒，4周大量新生骨呈编织骨样结构，新骨与BG颗粒直接结合。8周部分BG颗粒已降解被新骨取代，并与植骨床骨皮质表面直接结合，极少量残留颗粒被新骨包围。rhBMP-2／BG的表面成骨作用比单一BG、rhBMP-2好，具有明显的骨诱导性和骨引导性。新骨形成百分比明显高于BG（P〈0．05）。临床操作性能佳，易于放置，有止血作用。结论rhBMP-2／13G可以用于下颌骨侧嵴扩增。     

重组rhBMP-2与生物玻璃陶瓷复合物的表面骨扩增作用研究

目的:探讨生物活性玻璃(biologically active glass,BAG)对重组人骨形成蛋白-2(recombinenthuman bone morphogenetic protein-2 rhBMP-2)诱导骨形成的的影响,评价rhBMP-2/BAG复合物在兔颅骨表面的骨扩增作用.方法:在16例兔模型的颅骨骨膜下、骨皮质表面,分别植入rhBMP-2/BAG、BAG和单纯BMP,并设空白对照组.植入后2、4、8周行组织学检查,观察植骨区的变化,并测量成骨厚度.结果:rhBMP-2/BAG的表面成骨作用比单一BAG、rhBMP-2好,其骨化过程类似于膜内化骨的直接骨形成,与骨皮质表面良好结合,新骨中可见BAG颗粒并于8周后大部分吸收,新骨形成厚度明显高于BAG组,BAG组的新骨形成厚度明显高于其他两组.结论:BAG具有骨传导性能和可吸收性,rhBMP-2/BAG复合材料将骨诱导性和骨传导性结合起来,促进骨表面的扩增,是一种有临床应用前景的骨替代材料.     

rhBMP-2在种植体周围骨缺损修复中应用的组织学观察

目的:研究rhBMP-2及不同载体在种植体周围骨缺损修复中的应用。方法:在beagle犬下颌骨植入种植体,颊侧形成裂开性骨缺损,置入复合了不同浓度rhBMP-2的珊瑚羟基磷灰石人造骨(CHA)或可吸收胶原海绵(ACS)。种植体植入后2、4、8、12周,获取含种植体骨标本,进行组织学观察。结果:2周时,rhBMP-2组可见极少量的新生骨组织。4周时,rhBMP-2/ACS组新骨组织由牙槽骨顶端向缺损区中心方向生长;rhBMP-2/CHA组人造骨颗粒内部和周围出现呈岛状生长的新生骨组织。8周时,rhBMP-2/ACS组的新骨形成大片状结构;rhBMP-2/CHA组人造骨颗粒周围较多骨岛形成。12周时,rhBMP-2组的缺损区内骨量和骨高度进一步增加,与种植体形成骨性结合。浓度为0.05 mg/ml和0.2 mg/ml,载体为CHA或ACS促进骨再生作用差异无统计学意义。结论:以CHA或ACS为载体rhBMP-2能促进种植体周围骨缺损区内的骨组织再生并与种植体表面较好地结合。     

活性纳米羟基磷灰石复合胶原／聚乳酸材料应用于牙槽嵴扩增的研究

目的:构建下颌牙槽嵴扩增的动物模型,并初步观察nHAC/PLA复合rhBMP-2在下颌皮质骨表面贴附式植骨的成骨能力。方法:制备AnHAC/PLA材料,将HAC/PLA、AnHAC/PLA材料分别植入新西兰兔下颌骨颊侧皮质骨表面,设计皮质骨颊侧制备沟槽的改良术式组,并与无沟槽的普通术式组对比,术后8周通过大体、X线、组织学观察来研究其牙槽骨加宽的能力。结果:AnHAC/PLA材料较nHAC/PLA材料更能良好的增加下颌骨的宽度,在皮质骨表面增加刻槽的改良术式能明显增加材料的成骨情况。结论:AnHAC/PLA材料可以有效地增加牙槽骨宽度。     

重组人骨形成蛋白-2促进兔下颌牵张成骨的研究

目的　研究局部应用基因重组人骨形成蛋白-2(rhBMP-2)对兔下颌牵张成骨的影响。方法　在12只成年大耳白兔的双侧下颌骨前部行骨切开术,将rhBMP-2与胶原复合植入一侧下颌骨切开处,另一侧单纯植入胶原作对照。用自行研制牵张器延长双侧下颌骨6 mm,在牵张结束后第4周处死动物,取双侧牵张区新生骨痂行组织学、扫描电镜及Ca/P元素测定。结果　下颌延长后两侧牵张间隙均有新骨形成,应用rhBMP-2的一侧牵张骨痂中的新骨组织比对照侧多而成熟,钙化程度较高。结论　基因重组人骨形成蛋白-2可能有促进兔下颌牵张成骨的作用。     

rhBMP-2复合生物活性玻璃诱导成骨的实验研究

目的：探讨生物活性玻璃(bioactive glass BG)对重组人骨形成蛋白-2(recombinant human bone morphogenetic protein-2,rhBMP-2)诱导骨形成的影响。方法：6只大鼠皮下袋植入rhBMP-2／BG,0．2mg 0．5mg rhBMP-2,并设空白对照组。植入后3周行组织学检查。结果：0．5mg组rhBMP-2／BG具有成骨作用,其骨化过程类似于膜内化骨的直接骨形成。结论：rhBMP-2／BG复合物能诱导新骨形成,表明BG适合作为rhBMP-2载体。     

羊下颌骨牵张骨形成实验

目的 观察山羊下颌骨牵拉后的新骨形成情况。方法 将8只山羊下颌骨单侧皮质骨切开后,每日2次,每天牵拉1mm,共8天,后继续以牵开器固定,行组织学、放射学观察。结果 牵拉术后颌骨成骨明显牵拉后2周,X线示骨间隙内新生骨已基本连接骨缺损,4周时骨化明显,组织学见大量新骨形成,随稳固期延长而渐成熟,部分形成板层骨。结论 山羊为一良好的下颌牵张模型动物。新骨形成以膜内成骨为主。     

rhBMP-2对兔下颌骨牵引成骨区骨保护素表达的影响

目的：通过动物实验,研究应用外源性rhBMP-2对兔下颌骨牵引成骨区骨保护素（osteoprotegerin,OPG）的影响。方法：在48只成年大耳白兔的一侧下颌骨前部行骨切开术,分别将空白胶原、rhBMP-2 1.5mg胶原复合物植入下颌骨切开处,用牵引器延长一侧下颌骨4mm,稳定期第1、3、7、14天,分别处死各组动物,取牵引区新生骨痂行组织学及OPG免疫组化染色。结果：下颌牵引延长后牵引间隙均有新骨形成,应用rhBMP-2 1.5mg效果好。免疫组化染色OPG主要定位于成骨细胞的胞浆中。在同一时间内,应用rhBMP-2组较对照组有显著性差异（P〈0.05）。结论：动物实验表明,rhBMP-2能促进兔下颌骨牵引成骨区新骨的生成。     

磷酸钙骨水泥与骨形成蛋白复合修复即刻种植牙骨缺损的实验研究

目的：探讨磷酸钙骨水泥(CPC)与人重组骨形成蛋白-2(rhBMP-2)复合修复即刻种植牙骨缺损的效果，为其临床应用于种植牙骨缺损修复的可行性奠定理论基础。方法：在兔股骨大转子上模拟即刻种植模型，种植体周围骨缺损区植入CPC／rhBMP-2及CPC进行修复，通过X线片，骨密度测量及组织学检查，观察新骨形成情况和材料的微观结构变化以及新骨与种植体的关系。结果：CPC／-rhBMP-2复合物可以有效地修复即刻种植牙骨缺损，材料被逐渐降解吸收，新骨与种植体表面更早地结合。结论：CPC／rhBMP-2是一种比较理想的新型骨移植材料.     

聚乳酸膜和脱钙冻干胚胎骨促进骨修复的比较研究

目的 比较聚乳酸（ＰＬＡ）膜和脱钙冻干胚胎骨（ＦｅｔａｌＢｏｎｅ，ＦＢ）促进骨修复的能力，方法 在１２只日本大耳白兔双侧下颌骨下缘中份作方块切除形成缺损，一侧缺损植入ＦＢ，另一侧缺损表面覆盖ＰＬＡ膜，术后４，８，１２周分期处死动物，下颌骨标示行放射学和组织学观察，结果 两种材料均能有效修复骨缺损，ＦＢ植入４Ｗ后术区内有大量新骨形成，术后８Ｗ缺损内骨形成活跃程度和骨形成量均高于ＰＬＡ膜侧，结论 ＦＢ     

Effect of recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge with space-providing biomaterials on the augmentation of chronic alveolar ridge defects

BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier has been shown to support significant bone formation in the craniofacial skeleton. When used as an onlay, however, rhBMP-2/ACS may become compressed with limited resulting bone formation. The objective of this study was to evaluate the effect of two space-providing biomaterials, bioactive glass (BG) and demineralized/mineralized bone matrix (DMB), on rhBMP-2/ACS induced alveolar ridge augmentation. METHODS: Bilateral alveolar ridge defects were produced in the mandible in six mongrel dogs. rhBMP-2/ACS with biomaterials was surgically implanted into contralateral defects in four animals. Treatments were alternated between jaw quadrants in consecutive animals. Two animals received rhBMP-2/ACS or sham-surgery in contralateral defects. The animals were injected with fluorescent bone labels to monitor bone formation. Clinical evaluations were made at ridge augmentation and 12 weeks post-implantation when the animals were euthanized and block biopsies collected for histopathologic evaluation. RESULTS: Sham-surgery produced limited horizontal alveolar augmentation (0.1 +/- 0.6 mm). Implantation of rhBMP-2/ACS resulted in alveolar augmentation amounting to 2.2 +/- 1.8 mm. Alveolar augmentation in sites receiving rhBMP-2/ACS with DMB or BG was 2-fold greater compared to rhBMP-2/ACS alone averaging 4.4 +/- 1.3 and 4.6 +/- 1.5 mm, respectively. The DMB biomaterial appeared substituted by newly formed bone. The BG particles were observed imbedded in bone or encapsulated in dense connective tissue without associated bone metabolic activity. Fluorescent light microscopy suggested that the new bone was formed within 4 weeks. CONCLUSION: The bioglass and demineralized/mineralized bone matrix biomaterials utilized in this study in combination with rhBMP-2/ACS supported clinical and histological ridge augmentation.     

Bone regeneration by recombinant human bone morphogenetic protein-2 in rat mandibular defects. An experimental model of defect filling.

BACKGROUND: Bone defects and irregularities are major problems for dental implant and periodontal therapies. METHODS: We investigated whether the application of recombinant human bone morphogenetic protein-2 (rhBMP-2) induces bone formation in through-and-through bone defects in the rat mandible. A round through-and-through bone defect (5 mm in diameter) was created in the angle of the mandible on both sides of the jaw using a steel round bur in each of 8 Long-Evans rats. In the experimental group, polylactic acid-polyglycolic acid copolymer/gelatin sponge (PGS) containing rhBMP-2 (6 microg/60 microl) was inserted in the bone defect. In the control group, the same carrier without rhBMP-2 was applied in the bone defect on the opposite side. Four weeks after application, the rats were sacrificed. Step serial sections stained with hematoxylin and eosin at intervals of 200 microm were prepared in a bucco-lingual direction. The size of the bone defects and new bone formation were evaluated histometrically. RESULTS: In all cases in the experimental group, a large quantity of newly formed bone was observed. The bone defects were completely filled with new bone in 4 of 8 rats in the experimental group. In the control group, small amounts of new bone formation were observed along the border of the original mandibular bone. Histometrical analysis revealed that the amount of new bone was significantly larger in the rhBMP-2 treated sites than in the control sites (P <0.0001; paired t-test). CONCLUSIONS: These results indicate that the rhBMP-2/PGS system induced effective bone regeneration on mandibular defects in rats. This procedure may be suitable as an experimental model for bone regeneration using various growth factors and effective for alveolar ridge augmentation followed by dental implant surgery.     

Reconstruction of the primate mandible with a combination graft of recombinant human bone morphogenetic protein-2 and bone marrow.

PURPOSE: This study evaluated whether recombinant human bone morphogenetic protein-2 (rhBMP-2) can be used to regenerate a resected part of the mandible in a primate model. MATERIALS AND METHODS: Segmental bone defects were created surgically in the mandible of Japanese monkeys. rhBMP-2 was suspended in a solution of polyglycolic co-lactic acid (PGLA) and lyophilized to make a BMP/PGLA complex. The rhBMP-2/PGLA complex and autogenous bone marrow in ratios of 3:0, 2.5:0.5, or 2:1 (vol:vol) were each implanted into the bone defects in 3 monkeys. Bone marrow or P(GLA alone were each implanted in 1 monkey as a control. The animals were killed 16 weeks after surgery, followed by radiologic and histologic evaluation. RESULTS: The implantation of bone marrow alone succeeded in reconstruction of the mandible, but the implantation of the rhBMP-2/PGLA complex showed only a small amount of bone formation. The combination graft of rhBMP-2/PGLA and bone marrow resulted in a greater degree of bone formation; especially the 2:1 combination showed the same result as only bone marrow implantation. CONCLUSION: The combination graft of rhBMP-2 and bone marrow, which requires only a small amount of bone marrow, was a reliable method for reconstruction of mandibular segmental defects in this animal model.     

可吸收性Bio-Gide膜治疗下颌角区局部骨缺损实验研究

目的 :本研究旨在探讨Bio-Gide膜治疗局部骨缺损的效果 ,评估其应用价值。方法 :在8只成年健康雄性新西兰大白兔的双侧下颌角区置备5×5mm2 大小的洞穿性骨缺损 ,一侧为实验侧 ,另一侧为对照侧 ,随机分成2组 (4周 ,8周组 ) ,进行肉眼、x线与组织学观察。结果 :肉眼及x线检查结果显示 :两组动物的对照侧骨缺损均明显存在 ,有的骨缺损内有肌肉长入 ,骨缺损面积增大 ;两组动物的实验侧骨缺损有不同程度修复 ,并测得实验侧骨缺损中央2×2mm2区域的平均骨密度高于对照侧 ,两者在统计学上有显著差异。组织学检查实验侧骨缺损骨性修复。结论 :Bio-Gide膜能有效阻挡软组织长入骨缺损区 ,作为骨细胞载体促进骨修复。     

Bone reconstruction following implantation of rhBMP-2 and guided bone regeneration in canine alveolar ridge defects

BACKGROUND: Alveolar ridge aberrations commonly require bone augmentation procedures for optimal placement of endosseous dental implants. The objective of this study was to evaluate local bone formation following implantation of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier with or without provisions for guided bone regeneration (GBR) as potential treatment modalities for alveolar augmentation. METHODS: Surgically induced, large, mandibular alveolar ridge saddle-type defects (2 defects/jaw quadrant) in seven young adult Hound dogs were assigned to receive rhBMP-2/ACS, rhBMP-2/ACS combined with GBR (rhBMP-2/GBR), GBR, and surgery controls. The animals were euthanized at 12 weeks post-surgery when block sections of the defect sites were collected for histologic analysis. RESULTS: Clinical complications included swelling for sites receiving rhBMP-2 and wound failure with exposure of the barrier device for sites receiving GBR (4/6) or rhBMP-2/GBR (3/7). The radiographic evaluation showed substantial bone fill for sites receiving rhBMP-2/ACS, rhBMP-2/GBR, and GBR. In particular, sites receiving rhBMP-2/GBR presented with seroma-like radiolucencies. The surgery control exhibited moderate bone fill. To evaluate the biologic potential of the specific protocols, sites exhibiting wound failure were excluded from the histometric analysis. Sites receiving rhBMP-2/ACS or rhBMP-2/GBR exhibited bone fill averaging 101%. Bone fill averaged 92% and 60%, respectively, for sites receiving GBR and surgery controls. Bone density ranged from 50% to 57% for sites receiving rhBMP-2/ACS, GBR, or surgery controls. Bone density for sites receiving rhBMP-2/GBR averaged 34% largely due to seroma formation encompassing 13% to 97% of the sites. CONCLUSION: rhBMP-2/ACS appears to be an effective alternative to GBR in the reconstruction of advanced alveolar ridge defects. Combining rhBMP-2/ACS with GBR appears to be of limited value due to the potential for wound failure or persistent seromas.     

The effect of a fibrin glue on the integration of Bio-Oss with bone tissue. A experimental study in labrador dogs

BACKGROUND: Bio-Oss is a deproteinized bovine mineral used in bone augmentation procedures. The particles are often mixed with a protein product (Tisseel) to form a mouldable graft material. AIM: The aim of the present experiment was to study the healing of self-contained bone defects after the placement of Bio-Oss particles alone or mixed with Tisseel in cylindrical defects in the edentulous mandibular ridge of dogs. MATERIAL AND METHODS: In 4 labrador dogs, the 2nd, 3rd and 4th mandibular premolars were extracted bilaterally. 3 months later, 3 cylindrical bone defects, 4 mm in diameter and 8 mm in depth, were produced in the right side of the mandible. Following a crestal incision, full thickness flaps were raised and the bone defects were prepared with a trephine drill. The defects were filled with Bio-Oss (Geistlich Biomaterials, Wolhuser, Switzerland) particles alone or mixed with Tisseel (Immuno AG, Vienna, Austria), or left "untreated". A collagen membrane (Bio-Gide, Geistlich Biomaterials, Wolhuser, Switzerland) was placed to cover all defects and the flaps were sutured. 2 months later, the defect preparation and grafting procedures were repeated in the left side of the mandible. After another month, the animals were sacrificed and biopsies obtained from the defect sites. RESULTS: Bio-Oss-treated defects revealed a higher percentage of contact between graft particles and bone tissue than defects treated with Bio-Oss+ Tisseel (15% and 30% at 1 and 3 months versus 0.4% and 8%, respectively). Further, the volume of connective tissue in the Bio-Oss treated defects decreased from the 1 to the 3 month interval (from 44% to 30%). This soft tissue was replaced with newly formed bone. In the Bio-Oss+ Tisseel treated defects, however, the proportion of connective tissue remained unchanged between 1 and 3 months. CONCLUSION: The adjunct of Tisseel may jeopardize the integration of Bio-Oss particles with bone tissue.     

Molded bone augmentation by a combination of barrier membrane and recombinant human bone morphogenetic protein-2

OBJECTIVES: To provide the histological background to a new method of local bone augmentation, we examined the events occurring beneath a barrier membrane applied with recombinant human bone morphogenetic protein-2 (rhBMP-2). MATERIALS AND METHODS: The effects on bone augmentation of rhBMP-2, applied with a membrane mold (BMP-Memb), over surgically-induced bone defects in rat calvaria were examined histologically, and the results compared with those from application of rhBMP-2 (BMP) alone, or of a molded membrane (Memb) alone. RESULTS: At postoperative week 2, the BMP group showed the most marked bone formation. However, the bone diminished in size by week 8. The Memb group showed slow but continuous bone formation by week 8. In the BMP-Memb group, bone filled the space in the mold at week 2, and this was maintained until week 8. Moreover, the soft tissue that had intervened between newly formed bone and the membrane in the Memb group was not evident in the BMP-Memb group, in which bone had formed directly on the membrane. CONCLUSIONS: The results suggest that the combination of rhBMP-2 and barrier membrane has advantages in producing and maintaining bone in the intended shape by inducing osteoblasts directly on the inner surface of the membrane.     

rhBMP-2、PRF和自体骨分别复合珊瑚羟基磷灰石成骨效能的比较研究

目的：通过建立动物骨缺损模型,比较重组人骨形成蛋白-2（rhBMP-2）与珊瑚羟基磷灰石（CHA）复合物、富血小板纤维蛋白（PRF）与珊瑚羟基磷灰石复合物、自体骨与珊瑚羟基磷灰石复合物以及单纯珊瑚羟基磷灰石这四种骨移植材料在骨缺损中的成骨效能。方法：在比格犬双侧胫骨干骺端制备四个相同的骨缺损区,在缺损区分别植入rhBMP-2/CHA、 PRF/CHA、自体骨/CHA及CHA （对照）;3个月后处死动物,行大体标本观察;拍牙科CT,观察各植骨区骨密度情况;制作石蜡切片、 HE染色,比较各植骨区骨组织学特点及新骨形成量。结果：大体标本见四组骨缺损间隙均完全关闭。 X线示自体骨/CHA组和PRF/CHA组骨密度较致密, rhBMP-2/CHA组致密性低于前两者, CHA组未见明显骨致密影。 HE切片见四组新生骨与宿主骨连接紧密,新生骨小梁不规则,粗细不一,排列无序;复合型骨移植材料的新生骨小梁比对照组更密集、粗大,连续性更好;四组植骨区成骨量比较：自体骨/CHA组〉PRF/CHA组〉rhBMP-2/CHA组〉CHA组。结论：复合型骨移植材料成骨效应明显优于单纯珊瑚羟基磷灰石;三种复合型材料中自体骨/CHA成骨效应最好,其次为PRF/CHA, rhBMP-2/CHA最差。     

Bone augmentation of the atrophic posterior mandible for dental implants using rhBMP-2 and titanium mesh: clinical technique and early results

The atrophic posterior mandible has unique challenges when implant placement is planned. The purpose of this case series was to evaluate the use of recombinant human bone morphogenetic protein 2÷acelluar collagen sponge (rhBMP-2÷ACS) and titanium mesh for augmentation of the atrophic posterior mandible prior to implant insertion. The case series included five patients with inadequate bone in the posterior mandible for implant placement. The residual ridges were augmented with rhBMP-2÷ACS and a small amount of bone substitute. Titanium mesh was used to protect the graft sites. Dental implants were inserted after 6 months of healing. Healing of the grafted ridges was uneventful. Dental implants were placed in all grafted sites without the need for further bone augmentation. All 10 implants integrated well and were restored with single crowns. The use of rhBMP-2÷ACS with titanium mesh was effective in this case series for augmentation of the atrophic posterior mandible prior to implant placement. This approach offers many advantages, including technical ease, no need for bone harvesting, decreased morbidity, and reduced surgical time.