BMP2/7异二聚体在诱导种植体周骨缺损区成骨的研究
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摘要
近几年来随着口腔科学的发展,口腔种植学得到了很大的发展,但是仍然面临着许多挑战,比如由外伤、老龄化、牙周病等造成的骨量不足情况下的种植。而种植体周围骨的数量和质量对种植体的长期存活起着非常重要的作用,故几种局部的骨再生技术被用来解决种植体周围骨缺损。应用生长因子、多肽、小分子来引导骨组织的再生是其中的方法之一。骨形态发生蛋白(Bone Morphogenetic Protein, BMP)对骨和软骨的生长有很强的作用,是骨组织工程中最有潜力的一群因子。虽然很多动物实验表明了BMP同源二聚体(如BMP2、BMP7)能有效引导骨的形成,但在临床上的效果不佳,其有效剂量很大。过高的剂量不仅带来昂贵的费用,也带来一系列并发症,如异位成骨,增加破骨细胞的活性,对神经系统的影响等。最近一些研究表明不同的BMP之间存在协同作用,BMP异二聚体比BMP同源二聚体有更好的诱导成骨作用。本研究的目的旨在探讨低浓度的rhBMP2/7异二聚体在种植体周围骨缺损上的诱导成骨作用。
第一部分
种植体周围骨缺损动物模型的建立
目的：
在小型猪的颅骨上建立种植体周围骨缺损的模型,来比较不同rhBMPs的诱导成骨作用。
材料和方法：
18只广西巴马小型猪,平均年龄9个月,体重16.50-19.80公斤,雌雄各半。用直径8mm的空心钻在每只猪的颅骨上制造4个深度为4mm的缺损,每个缺损间隔1Omm,缺损中心植入直径3.1mm种植体,植入深度为缺损底部下4mm,然后在种植体周围缺损内分别随机填入rhBMP2/7胶原海绵,rhBMP2胶原海绵,rhBMP7胶原海绵或者空白胶原海绵,表面覆盖Bio-Gide膜(40×50mm)后,分层缝合。
结果：
小型猪颅骨面积和厚度足以支持缺损和种植体,所有种植体固位、生长良好,未见明显松动。胶原海绵、Bio-Gide膜缓慢降解,炎症反应少,在各个观察时间点,均能观察到各组新骨形成的差异。在植入后6周,对照组、rhBMP2组及rhBMP7组均未见到完全的骨愈合。
结论：
小型猪颅骨的种植体周围骨缺损模型术野清楚,操作方便,各缺损的一致性强,受到干扰因素较少,能够将研究重点集中在比较不同rhBMP的性能上。
第二部分
RhBMP2/7异二聚体诱导形成的新骨的微结构分析
目的：
BMP同源二聚体(如BMP2、BMP7)由于其有效使用剂量过高,可能带来较大的经济负担和造成潜在的副作用,而未能在临床普遍应用。近年来有学者通过基因重组表达BMP异二聚体发现其比相应同源二聚体具有更强的诱导成骨作用,但对纯化的BMP异二聚体蛋白治疗研究很少。本实验旨在采用胶原海绵携带纯化的rhBMP2/7异二聚体以及相应的同源二聚体植入种植体周围骨缺损中,并使用Micro-CT来比较rhBMP异二聚体和同源二聚体在体内诱导成骨的质量和数量。
材料和方法：
动物模型同第一部分,分为空白胶原海绵组、胶原海绵携带rhBMP2同源二聚体组、胶原海绵携带rhBMP7同源二聚体组和胶原海绵携带rhBMP2/7异二聚体组。植入后2、3、6周分别处死6只小型猪(n=6／组／时间点),标本树脂包埋后,用Micro-CT扫描观察,在直接模式(direct model)下分析了缺损区域的相对骨量(relative bone volume (BV/TV:%))、骨小梁连接密度(connectivity density (Conn.D:1/mm3))、骨小梁数量(trabecular number (Tb.N:1/mm3))、骨小梁厚度(trabecular thickness (Tb.Th:mm))、骨小梁之间距离(trabecular separation (Tb.Sp: mm))和结构模型指数(structure mode index (SMI))六个指标。同时,我们扫描分析了猪颅骨未损伤的正常骨组织的上述6个指标作为阳性对照。
结果：
植入后2、3、6周,在BV/TV、Tb.N和Tb.Th指标上,rhBMP2/7组显著高于rhBMP2、7和对照组(p<0.05),同样rhBMP2、7组也显著高于对照组(p<0.05)；在Tb.Sp和SMI指标上,rhBMP2/7组在每个时间段均为最低,rhBMP2/7组同rhBMP2、7和对照组存在统计学上的差异(p<0.05), rhBMP2、7组和对照组也存在统计学上的差异(p<0.05)；对照组Conn.D值随着植入时间的增加而增加,其余三组的Conn.D值在植入后3周达到峰值,植入后6周明显下降。植入后6周,rhBMP2/7组的Tb.N、Tb.Th、Tb.Sp和Conn.D跟未损伤正常骨组织不存在统计学上的差别。
结论：
在30ng/mm3的浓度下,rhBMP2、7同源二聚体和rhBMP2/7异二聚体同对照组相比均能促进种植体周围骨缺损的新骨形成,但rhBMP2/7异二聚体同rhBMP2、7同源二聚体相比具有更高的诱导成骨作用,其形成的骨的质量和数量均高于rhBMP2、rhBMP7。
第三部分RhBMP2/7异二聚体诱导的新骨形成率、骨种植体结合率的研究
目的：
由于Micro-CT为无损伤的检查方法,我们对Micro-CT检查后的标本行进一步硬组织切片检查,以观察缺损区域的组织学行为、新骨形成率(bone area percentage, BAP)和骨种植体结合率(bone implant contact, BIC)。
材料和方法：
动物模型同第一部分。将树脂包埋的标本,行硬组织切片后,再磨至30μm厚度,亚甲基蓝-碱性品红法染色后,于光镜下观察组织学行为、用Image-Pro PlusR软件测量BAP和BIC。
结果：
植入后6周,rhBMP2/7组达到了完全的骨愈合。组织学观察可以发现rhBMP2/7能早期促进成骨细胞的分化聚集,在植入后2、3周即能观察到成骨细胞规则排列在新骨周围。在BAP值上,在每个观察时间点,rhBMP2/7组均为最高,对照组均为最低,rhBMP2/7组显著高于rhBMP2、7和对照组(p<0.05),同样rhBMP2、7组也高于对照组(p<0.05)。植入后2周,rhBMP2/7组的BIC增加明显,高于rhBMP2、7组(p<0.05),rhBMP2、7组也高于对照组(p<0.05)。植入后3周,各rhBMP组高于对照组(p<0.05),但各rhBMP组之间无统计学上的差别。植入后6周,各组的BIC值无统计学上的差别。
结论：
硬组织切片的结果进一步证实了Micro-CT的结果。rhBMP2、7同源二聚体在30ng/mm3的浓度下同对照组相比能诱导形成更多的新骨,rhBMP2/7异二聚体同rhBMP2、7同源二聚体相比,诱导形成了更多的新骨,并能早期促进骨种植体的结合。
The osseous restoration of voluminous bone defect remains a challenge in oral maxillofacial surgery.several method such as gene, cell, and cytokine therapies has been taken to solve this problem. Homodimeric BMPs have been shown to induce bone formation in both animal experiments and human trials.However, the effective doses of BMP homodimers for current clinical use are extremely high, which results in not only a substantial economic burden to patients and healthcare system, but also a series of potential side-effects, such as the over stimulation of osteoclastic activity. One alternative approach to overcome this dilemma is to adopt more potent forms of BMPs. Heterodimeric forms of BMPs exhibited more effects than the respective homodimers in-vitro osteoblastogenesis or in-vivo bone regeneration. This study aims to delineate the osteoinductive effects of BMP2/7heterodimer in a peri-implant bone defect model of pigs in comparison with BMP2and BMP7homodimers.
Part1:
Animal model
Objectives:
To build peri-implant bone defect model in minipigs' calvarias for compare the osteoinductive effects of the different rhBMPs.
Materials and Methods:
Round bone defects (4mm in depth and8mm in diameter) were created in18minipigs' calvarias. One dental titanium implant(3.1mm in diameter) was implanted in the centre of each defect with a4mm-fixture above the bottom of the defect. Collagen with or without different BMPs in a final concentration of30ng/mm3were filled in the bone defects. The bone defects and the implants were covered with a piece of Bio-Gide(?) membrane (40×50mm). Then the soft tissue was sutured layer by layer.
Results:
The area and thick of minipigs' calvarias were enough to support the defect and implant. All implant survived, have good retention. Collagen sponge and Bio-Gide membrane degrade slowly, few inflammations were observed.At each time point, each BMP group resulted in significantly higher new bone regeneration than control group. Six weeks after implant, there was no completely bone healing of rhBMP2,7and control group.
Conclusion:
The peri-implant bone defect model in minipigs'calvarias has clear operation field and easy to build. The consistency of defect was good and the interference factors were less. The research can be focused on the performance of the BMPs.
Part2: The micro-structure of new bone guided by rhBMP heterodimer
Objectives:
The high effective doses of BMP homodimers prevent their clinical applications. BMP heterodimers were exhibited to be more potent than homodimers. Most of previous studies were based on the BMP heterodimers that were produced by the technology of combined BMP2and BMP7gene transfer, hitherto, as a promising cytokine therapy, the effects of purified recombinant human BMP heterodimers on in-vivo osteogenesis were merely reported. This study using a peri-implant bone defect model in minipigs to delineate the dynamic micro-architectures of bone induced by low-dose rhBMP2/7heterodimer in peri-implant bone defects compared to rhBMP2and rhBMP7homodimer by Micro-CT.
Materials and Methods:
The same bone defect animal model as part one was used. Four groups were set up (n=6animals per group per time point):1) collagen without BMPs;2) collagen with rhBMP2homodimer;3) collagen with rhBMP7homodimer and4) collagen with rhBMP2/7heterodimer. Also the uninjured bone was adopted as a positive control.2,3, and6weeks after implantation, samples and surrounding tissues were explanted, dehydrated and embedded in methyl methacrylate (MMA). The samples were scanned by Micro-CT to evaluate newly formed bone by measuring the following parameters: BV/TV, Tb.N, Tb.Th, Tb.Sp, Conn.D and SMI.
Results:
At each time point, BMP2/7heterodimer resulted in significantly higher relative bone volume, trabecular thickness, trabecular number and significantly lower trabecular separation, structure mode index than the homodimers. After6weeks, BMP2/7resulted in the equivalent trabecular thickness, trabecular number, trabecular separation and the nearest relative bone volume, connectivity density, structure mode index to those of the uninjured bone in comparison to the rhBMP2and rhBMP7.
Conclusions:
In30ng/mm3concentration, all BMPs has strong bone regeneration than control at each observed time point, and recombinant human BMP2/7heterodimer induced new bone formation in a significantly higher quality and quantity in comparison to BMP2and BMP7homodimers in peri-implant bone defects.
Part3:
BAP and BIC of new bone guided by rhBMP heterodimer
Objectives:
Because Micro-CT was an uninjured method, histological and histomorphometric analysis was taken to the same specimens as part1.
Materials and Methods:
Animal model and grouping as part2.The dehydrated and embedded in methyl methacrylate specimens were analysised of histological behavior, new bone area percentage(BAP) and bone implant contact(BIC)
Results:
Consistent with2and3weeks, after6weeks post-operation, rhBMP2/7heterodimer resulted in significantly higher BAP than the homodimers, the BAP of rhBMP2,7homodimers also significantly higher than the control group. At2,3weeks,the BIC of BMP2/7heterodimer and BMP2,7homodimers was significantly higher than the control. At2weeks, the BIC of BMP2/7heterodimer was significantly higher than BMP2,7homodimers.
Conclusions:
Consistent with the Micro-CT result, rhBMP2/7heterodimer induced new bone formation in a significantly higher quality and quantity in comparison to rhBMP2and rhBMP7homodimers in peri-implant bone defects at the same low dose. And it can promote bone implant contact at early stage.
第一部分
种植体周围骨缺损动物模型的建立
目的：
在小型猪的颅骨上建立种植体周围骨缺损的模型,来比较不同rhBMPs的诱导成骨作用。
材料和方法：
18只广西巴马小型猪,平均年龄9个月,体重16.50-19.80公斤,雌雄各半。用直径8mm的空心钻在每只猪的颅骨上制造4个深度为4mm的缺损,每个缺损间隔1Omm,缺损中心植入直径3.1mm种植体,植入深度为缺损底部下4mm,然后在种植体周围缺损内分别随机填入rhBMP2/7胶原海绵,rhBMP2胶原海绵,rhBMP7胶原海绵或者空白胶原海绵,表面覆盖Bio-Gide膜(40×50mm)后,分层缝合。
结果：
小型猪颅骨面积和厚度足以支持缺损和种植体,所有种植体固位、生长良好,未见明显松动。胶原海绵、Bio-Gide膜缓慢降解,炎症反应少,在各个观察时间点,均能观察到各组新骨形成的差异。在植入后6周,对照组、rhBMP2组及rhBMP7组均未见到完全的骨愈合。
结论：
小型猪颅骨的种植体周围骨缺损模型术野清楚,操作方便,各缺损的一致性强,受到干扰因素较少,能够将研究重点集中在比较不同rhBMP的性能上。
第二部分
RhBMP2/7异二聚体诱导形成的新骨的微结构分析
目的：
BMP同源二聚体(如BMP2、BMP7)由于其有效使用剂量过高,可能带来较大的经济负担和造成潜在的副作用,而未能在临床普遍应用。近年来有学者通过基因重组表达BMP异二聚体发现其比相应同源二聚体具有更强的诱导成骨作用,但对纯化的BMP异二聚体蛋白治疗研究很少。本实验旨在采用胶原海绵携带纯化的rhBMP2/7异二聚体以及相应的同源二聚体植入种植体周围骨缺损中,并使用Micro-CT来比较rhBMP异二聚体和同源二聚体在体内诱导成骨的质量和数量。
材料和方法：
动物模型同第一部分,分为空白胶原海绵组、胶原海绵携带rhBMP2同源二聚体组、胶原海绵携带rhBMP7同源二聚体组和胶原海绵携带rhBMP2/7异二聚体组。植入后2、3、6周分别处死6只小型猪(n=6／组／时间点),标本树脂包埋后,用Micro-CT扫描观察,在直接模式(direct model)下分析了缺损区域的相对骨量(relative bone volume (BV/TV:%))、骨小梁连接密度(connectivity density (Conn.D:1/mm3))、骨小梁数量(trabecular number (Tb.N:1/mm3))、骨小梁厚度(trabecular thickness (Tb.Th:mm))、骨小梁之间距离(trabecular separation (Tb.Sp: mm))和结构模型指数(structure mode index (SMI))六个指标。同时,我们扫描分析了猪颅骨未损伤的正常骨组织的上述6个指标作为阳性对照。
结果：
植入后2、3、6周,在BV/TV、Tb.N和Tb.Th指标上,rhBMP2/7组显著高于rhBMP2、7和对照组(p<0.05),同样rhBMP2、7组也显著高于对照组(p<0.05)；在Tb.Sp和SMI指标上,rhBMP2/7组在每个时间段均为最低,rhBMP2/7组同rhBMP2、7和对照组存在统计学上的差异(p<0.05), rhBMP2、7组和对照组也存在统计学上的差异(p<0.05)；对照组Conn.D值随着植入时间的增加而增加,其余三组的Conn.D值在植入后3周达到峰值,植入后6周明显下降。植入后6周,rhBMP2/7组的Tb.N、Tb.Th、Tb.Sp和Conn.D跟未损伤正常骨组织不存在统计学上的差别。
结论：
在30ng/mm3的浓度下,rhBMP2、7同源二聚体和rhBMP2/7异二聚体同对照组相比均能促进种植体周围骨缺损的新骨形成,但rhBMP2/7异二聚体同rhBMP2、7同源二聚体相比具有更高的诱导成骨作用,其形成的骨的质量和数量均高于rhBMP2、rhBMP7。
第三部分RhBMP2/7异二聚体诱导的新骨形成率、骨种植体结合率的研究
目的：
由于Micro-CT为无损伤的检查方法,我们对Micro-CT检查后的标本行进一步硬组织切片检查,以观察缺损区域的组织学行为、新骨形成率(bone area percentage, BAP)和骨种植体结合率(bone implant contact, BIC)。
材料和方法：
动物模型同第一部分。将树脂包埋的标本,行硬组织切片后,再磨至30μm厚度,亚甲基蓝-碱性品红法染色后,于光镜下观察组织学行为、用Image-Pro PlusR软件测量BAP和BIC。
结果：
植入后6周,rhBMP2/7组达到了完全的骨愈合。组织学观察可以发现rhBMP2/7能早期促进成骨细胞的分化聚集,在植入后2、3周即能观察到成骨细胞规则排列在新骨周围。在BAP值上,在每个观察时间点,rhBMP2/7组均为最高,对照组均为最低,rhBMP2/7组显著高于rhBMP2、7和对照组(p<0.05),同样rhBMP2、7组也高于对照组(p<0.05)。植入后2周,rhBMP2/7组的BIC增加明显,高于rhBMP2、7组(p<0.05),rhBMP2、7组也高于对照组(p<0.05)。植入后3周,各rhBMP组高于对照组(p<0.05),但各rhBMP组之间无统计学上的差别。植入后6周,各组的BIC值无统计学上的差别。
结论：
硬组织切片的结果进一步证实了Micro-CT的结果。rhBMP2、7同源二聚体在30ng/mm3的浓度下同对照组相比能诱导形成更多的新骨,rhBMP2/7异二聚体同rhBMP2、7同源二聚体相比,诱导形成了更多的新骨,并能早期促进骨种植体的结合。
The osseous restoration of voluminous bone defect remains a challenge in oral maxillofacial surgery.several method such as gene, cell, and cytokine therapies has been taken to solve this problem. Homodimeric BMPs have been shown to induce bone formation in both animal experiments and human trials.However, the effective doses of BMP homodimers for current clinical use are extremely high, which results in not only a substantial economic burden to patients and healthcare system, but also a series of potential side-effects, such as the over stimulation of osteoclastic activity. One alternative approach to overcome this dilemma is to adopt more potent forms of BMPs. Heterodimeric forms of BMPs exhibited more effects than the respective homodimers in-vitro osteoblastogenesis or in-vivo bone regeneration. This study aims to delineate the osteoinductive effects of BMP2/7heterodimer in a peri-implant bone defect model of pigs in comparison with BMP2and BMP7homodimers.
Part1:
Animal model
Objectives:
To build peri-implant bone defect model in minipigs' calvarias for compare the osteoinductive effects of the different rhBMPs.
Materials and Methods:
Round bone defects (4mm in depth and8mm in diameter) were created in18minipigs' calvarias. One dental titanium implant(3.1mm in diameter) was implanted in the centre of each defect with a4mm-fixture above the bottom of the defect. Collagen with or without different BMPs in a final concentration of30ng/mm3were filled in the bone defects. The bone defects and the implants were covered with a piece of Bio-Gide(?) membrane (40×50mm). Then the soft tissue was sutured layer by layer.
Results:
The area and thick of minipigs' calvarias were enough to support the defect and implant. All implant survived, have good retention. Collagen sponge and Bio-Gide membrane degrade slowly, few inflammations were observed.At each time point, each BMP group resulted in significantly higher new bone regeneration than control group. Six weeks after implant, there was no completely bone healing of rhBMP2,7and control group.
Conclusion:
The peri-implant bone defect model in minipigs'calvarias has clear operation field and easy to build. The consistency of defect was good and the interference factors were less. The research can be focused on the performance of the BMPs.
Part2: The micro-structure of new bone guided by rhBMP heterodimer
Objectives:
The high effective doses of BMP homodimers prevent their clinical applications. BMP heterodimers were exhibited to be more potent than homodimers. Most of previous studies were based on the BMP heterodimers that were produced by the technology of combined BMP2and BMP7gene transfer, hitherto, as a promising cytokine therapy, the effects of purified recombinant human BMP heterodimers on in-vivo osteogenesis were merely reported. This study using a peri-implant bone defect model in minipigs to delineate the dynamic micro-architectures of bone induced by low-dose rhBMP2/7heterodimer in peri-implant bone defects compared to rhBMP2and rhBMP7homodimer by Micro-CT.
Materials and Methods:
The same bone defect animal model as part one was used. Four groups were set up (n=6animals per group per time point):1) collagen without BMPs;2) collagen with rhBMP2homodimer;3) collagen with rhBMP7homodimer and4) collagen with rhBMP2/7heterodimer. Also the uninjured bone was adopted as a positive control.2,3, and6weeks after implantation, samples and surrounding tissues were explanted, dehydrated and embedded in methyl methacrylate (MMA). The samples were scanned by Micro-CT to evaluate newly formed bone by measuring the following parameters: BV/TV, Tb.N, Tb.Th, Tb.Sp, Conn.D and SMI.
Results:
At each time point, BMP2/7heterodimer resulted in significantly higher relative bone volume, trabecular thickness, trabecular number and significantly lower trabecular separation, structure mode index than the homodimers. After6weeks, BMP2/7resulted in the equivalent trabecular thickness, trabecular number, trabecular separation and the nearest relative bone volume, connectivity density, structure mode index to those of the uninjured bone in comparison to the rhBMP2and rhBMP7.
Conclusions:
In30ng/mm3concentration, all BMPs has strong bone regeneration than control at each observed time point, and recombinant human BMP2/7heterodimer induced new bone formation in a significantly higher quality and quantity in comparison to BMP2and BMP7homodimers in peri-implant bone defects.
Part3:
BAP and BIC of new bone guided by rhBMP heterodimer
Objectives:
Because Micro-CT was an uninjured method, histological and histomorphometric analysis was taken to the same specimens as part1.
Materials and Methods:
Animal model and grouping as part2.The dehydrated and embedded in methyl methacrylate specimens were analysised of histological behavior, new bone area percentage(BAP) and bone implant contact(BIC)
Results:
Consistent with2and3weeks, after6weeks post-operation, rhBMP2/7heterodimer resulted in significantly higher BAP than the homodimers, the BAP of rhBMP2,7homodimers also significantly higher than the control group. At2,3weeks,the BIC of BMP2/7heterodimer and BMP2,7homodimers was significantly higher than the control. At2weeks, the BIC of BMP2/7heterodimer was significantly higher than BMP2,7homodimers.
Conclusions:
Consistent with the Micro-CT result, rhBMP2/7heterodimer induced new bone formation in a significantly higher quality and quantity in comparison to rhBMP2and rhBMP7homodimers in peri-implant bone defects at the same low dose. And it can promote bone implant contact at early stage.
引文
Aono, A., M. Hazama, et al. (1995). "Potent Ectopic Bone-Inducing Activity of Bone Morphogenetic Protein-4/7 Heterodimer." Biochemical and Biophysical Research Communications 210(3):670-677.
Barboza, E. P., R. O. de Souza, et al. (2002). "Bone regeneration of localized chronic alveolar defects utilizing cell binding peptide associated with anorganic bovine-derived bone mineral:A clinical and histological study." Journal of Periodontology 73(10):1153-1159.
Carson, J. S. and M. P. G. Bostrom (2007). "Synthetic bone scaffolds and fracture repair." Injury-International Journal of the Care of the Injured 38:S33-S37.
Finkemeier, C. G. (2002). "Bone-grafting and bone-graft substitutes." Journal of Bone and Joint Surgery-American Volume 84A(3):454-464.
Franceschi, R. T. (2005). "Biological approaches to bone regeneration by gene therapy.' Journal of Dental Research 84(12):1093-1103.
Gautschi, O. P., S. P. Frey, et al. (2007). "Bone morphogenetic proteins in clinical applications." Anz Journal of Surgery 77(8):626-631.
Israel, D. I., J. Nove, et al. (1996). "Heterodimeric bone morphogenetic proteins show enhanced activity in vitro and in vivo." Growth Factors 13(3-4):291-300.
Liu, Y., K. de Groot, et al. (2005). "BMP-2 liberated from biomimetic implant coatings induces and sustains direct ossification in an ectopic rat model." Bone 36(5): 745-757.
Liu, Y., L. Enggist, et al. (2007). "The influence of BMP-2 and its mode of delivery on the osteoconductivity of implant surfaces during the early phase of osseointegration." Biomaterials 28(16):2677-2686.
McKay, W. F., S. M. Peckham, et al. (2007). "A comprehensive clinical review of recombinant human bone morphogenetic protein-2 (INFUSE Bone Graft)." International Orthopaedics 31(6):729-734.
Toth, J. M., S. D. Boden, et al. (2009). "Short-term osteoclastic activity induced by locally high concentrations of recombinant human bone morphogenetic protein-2 in a cancellous bone environment." Spine (Phila Pa 1976) 34(6):539-550.
Urist, M. R. (1965). "Bone:formation by autoinduction." Science 150(698):893-899.
White, A. P., A. R. Vaccaro, et al. (2007). "Clinical applications of BMP-7/OP-1 in fractures, nonunions and spinal fusion." International Orthopaedics 31(6):735-741.
Zhao, M., Z. Zhao, et al. (2005). "Combinatorial gene therapy for bone regeneration: Cooperative interactions between adenovirus vectors expressing bone morphogenetic proteins 2,4, and 7." Journal of Cellular Biochemistry 95(1):1-16.
Zheng, Y. N., G. Wu, et al. (2010). "rhBMP2/7 Heterodimer:An Osteoblastogenesis Inducer of Not Higher Potency but Lower Effective Concentration Compared with rhBMP2 and rhBMP7 Homodimers." Tissue Engineering Part A 16(3):879-887.
Zhu, W., B. A. Rawlins, et al. (2004). "Combined bone morphogenetic protein-2 and -7 gene transfer enhances osteoblastic differentiation and spine fusion in a rodent model." Journal of Bone and Mineral Research 19(12):2021-2032.
Aono, A., M. Hazama, et al. (1995). "Potent Ectopic Bone-Inducing Activity of Bone Morphogenetic Protein-4/7 Heterodimer." Biochemical and Biophysical Research Communications 210(3):670-677.
Barboza, E. P., M. E. Duarte, et al. (2000). "Ridge augmentation following implantation of recombinant human bone morphogenetic protein-2 in the dog." J Periodontol 71(3):488-496.
Barr, T., A. J. McNamara, et al. (2010). "Comparison of the osteoinductivity of bioimplants containing recombinant human bone morphogenetic proteins 2 (Infuse) and 7 (OP-1)." Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109(4): 531-540.
Becker, D., U. Geissler, et al. (2002). "Proliferation and differentiation of rat calvarial osteoblasts on type I collagen-coated titanium alloy." J Biomed Mater Res 59(3): 516-527.
Boden, S. D., J. Kang, et al. (2002). "Use of recombinant human bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans:a prospective, randomized clinical pilot trial:2002 Volvo Award in clinical studies." Spine (Phila Pa 1976) 27(23):2662-2673.
Carson, J. S. and M. P. G. Bostrom (2007). "Synthetic bone scaffolds and fracture repair." Injury-International Journal of the Care of the Injured 38:S33-S37.
Cochran, D. L., A. A. Jones, et al. (2000). "Evaluation of recombinant human bone morphogenetic protein-2 in oral applications including the use of endosseous implants:3-year results of a pilot study in humans." J Periodontol 71(8): 1241-1257.
Cochran, D. L., P. V. Nummikoski, et al. (1997). "Radiographic analysis of regenerated bone around endosseous implants in the canine using recombinant human bone morphogenetic protein-2." Int J Oral Maxillofac Implants 12(6):739-748.
Cook, S. D., M. W. Wolfe, et al. (1995). "Effect of recombinant human osteogenic protein-1 on healing of segmental defects in non-human primates." J Bone Joint Surg Am 77(5):734-750.
Finkemeier, C. G. (2002). "Bone-grafting and bone-graft substitutes." Journal of Bone and Joint Surgery-American Volume 84A(3):454-464.
Fiorellini, J. P., T. H. Howell, et al. (2005). "Randomized study evaluating recombinant human bone morphogenetic protein-2 for extraction socket augmentation." J Periodontol 76(4):605-613.
Franceschi, R. T. (2005). "Biological approaches to bone regeneration by gene therapy.' Journal of Dental Research 84(12):1093-1103.
Gautschi, O. P., S. P. Frey, et al. (2007). "Bone morphogenetic proteins in clinical applications." Anz Journal of Surgery 77(8):626-631.
Geiger, M., R. H. Li, et al. (2003). "Collagen sponges for bone regeneration with rhBMP-2." Adv Drug Deliv Rev 55(12):1613-1629.
Gosain, A. K., L. S. Song, et al. (2000). "Osteogenesis in cranial defects:Reassessment of the concept of critical size and the expression of TGF-beta isoforms." Plastic and Reconstructive Surgery 106(2):360-371.
Govender, S., C. Csimma, et al. (2002). "Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures:a prospective, controlled, randomized study of four hundred and fifty patients." Journal of Bone and Joint Surgery-American Volume 84-A(12):2123-2134.
Howell, T. H., J. Fiorellini, et al. (1997). "A feasibility study evaluating rhBMP-2/absorbable collagen sponge device for local alveolar ridge preservation or augmentation." Int J Periodontics Restorative Dent 17(2):124-139.
Israel, D. I., J. Nove, et al. (1996). "Heterodimeric bone morphogenetic proteins show enhanced activity in vitro and in vivo." Growth Factors 13(3-4):291-300.
Jung, R. E., R. Glauser, et al. (2003). "Effect of rhBMP-2 on guided bone regeneration in humans." Clin Oral Implants Res 14(5):556-568.
Liu, Y., L. Enggist, et al. (2007). "The influence of BMP-2 and its mode of delivery on the osteoconductivity of implant surfaces during the early phase of osseointegration." Biomaterials 28(16):2677-2686.
McKay, W. F., S. M. Peckham, et al. (2007). "A comprehensive clinical review of recombinant human bone morphogenetic protein-2 (INFUSE Bone Graft)." International Orthopaedics 31(6):729-734.
Nagao, H., N. Tachikawa, et al. (2002). "Effect of recombinant human bone morphogenetic protein-2 on bone formation in alveolar ridge defects in dogs.1 International Journal of Oral and Maxillofacial Surgery 31(1):66-72.
Ono, I., T. Yamashita, et al. (2004). "Combination of porous hydroxyapatite and cationic liposomes as a vector for BMP-2 gene therapy." Biomaterials 25(19):4709-4718.
Park, J., R. Lutz, et al. (2007). "The effect on bone regeneration of a liposomal vector to deliver BMP-2 gene to bone grafts in peri-implant bone defects." Biomaterials 28(17):2772-2782.
Schlegel, K. A., F. J. Lang, et al. (2006). "The monocortical critical size bone defect as an alternative experimental model in testing bone substitute materials." Oral Surg Oral Med Oral Pathol Oral Radiol Endod 102(1):7-13.
Schmitz, J. P. and J. O. Hollinger (1986). "The Critical Size Defect as an Experimental-Model for Craniomandibulofacial Nonunions." Clinical Orthopaedics and Related Research(205):299-308.
Sigurdsson, T. J., E. Fu, et al. (1997). "Bone morphogenetic protein-2 for peri-implant bone regeneration and osseointegration." Clin Oral Implants Res 8(5):367-374.
Starr, A. J. (2003). "Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures." J Bone Joint Surg Am 85-A(10):2049; author replies 2049-2050.
Toth, J. M., S. D. Boden, et al. (2009). "Short-term osteoclastic activity induced by locally high concentrations of recombinant human bone morphogenetic protein-2 in a cancellous bone environment." Spine (Phila Pa 1976) 34(6):539-550.
White, A. P., A. R. Vaccaro, et al. (2007). "Clinical applications of BMP-7/OP-1 in fractures, nonunions and spinal fusion." International Orthopaedics 31(6):735-741.
Wikesjo, U. M., M. Qahash, et al. (2003). "Space-providing expanded polytetrafluoroethylene devices define alveolar augmentation at dental implants induced by recombinant human bone morphogenetic protein 2 in an absorbable collagen sponge carrier." Clin Implant Dent Relat Res 5(2):112-123.
Wikesjo, U. M., M. Qahash, et al. (2004). "rhBMP-2 significantly enhances guided bone regeneration." Clin Oral Implants Res 15(2):194-204.
Wiltfang, J., F. R. Kloss, et al. (2004). "Effects of platelet-rich plasma on bone healing in combination with autogenous bone and bone substitutes in critical-size defects-An animal experiment." Clinical Oral Implants Research 15(2):187-193.
Yoshikawa, T., H. Ohgushi, et al. (2000). "In vivo osteogenic durability of cultured bone in porous ceramics:a novel method for autogenous bone graft substitution." Transplantation 69(1):128-134.
Zhao, M., Z. Zhao, et al. (2005). "Combinatorial gene therapy for bone regeneration: Cooperative interactions between adenovirus vectors expressing bone morphogenetic proteins 2,4, and 7." Journal of Cellular Biochemistry 95(1):1-16.
Zheng, Y. N., G. Wu, et al. (2010). "rhBMP2/7 Heterodimer:An Osteoblastogenesis Inducer of Not Higher Potency but Lower Effective Concentration Compared with rhBMP2 and rhBMP7 Homodimers." Tissue Engineering Part A 16(3):879-887.
Zhu, W., J. Kim, et al. (2006). "Noggin regulation of bone morphogenetic protein (BMP) 2/7 heterodimer activity in vitro." Bone 39(1):61-71.
Zhu, W., B. A. Rawlins, et al. (2004). "Combined bone morphogenetic protein-2 and -7 gene transfer enhances osteoblastic differentiation and spine fusion in a rodent model." Journal of Bone and Mineral Research 19(12):2021-2032.
何复明.纯钛种植体氟改性多孔表面的制备及生物学效应评价.浙江大学博士学位论文,杭州,浙江大学2011：51-53.
Borah, B., G. J. Gross, et al. (2001). "Three-dimensional microimaging (MR mu I and mu CT), finite element modeling, and rapid prototyping provide unique insights into bone architecture in osteoporosis." Anatomical Record 265(2):101-110.
Carbonare, L. D., M. T. Valenti, et al. (2005). "Bone microarchitecture evaluated by histomorphometry." Micron 36(7-8):609-616.
Cowan, C. M., T. Aghaloo, et al. (2007). "MicroCT evaluation of three-dimensional mineralization in response to BMP-2 doses in vitro and in critical sized rat calvarial defects." Tissue Engineering 13(3):501-512.
Efeoglu, C., J. L. Burke, et al. (2009). "Analysis of calvarial bone defects in rats using microcomputed tomography:potential for a novel composite material and a new quantitative measurement." British Journal of Oral & Maxillofacial Surgery 47(8): 616-621.
Haidar, Z. S., R. C. Hamdy, et al. (2009). "Delivery of recombinant bone morphogenetic proteins for bone regeneration and repair. Part B:Delivery systems for BMPs in orthopaedic and craniofacial tissue engineering." Biotechnol Lett 31(12): 1825-1835.
Hildebrand, T., A. Laib, et al. (1999). "Direct three-dimensional morphometric analysis of human cancellous bone:Microstructural data from spine, femur, iliac crest, and calcaneus." Journal of Bone and Mineral Research 14(7):1167-1174.
Hildebrand, T. and P. Ruegsegger (1997). "Quantification of Bone Microarchitecture with the Structure Model Index." Comput Methods Biomech Biomed Engin 1(1): 15-23.
Jiang, Y. B., J. Zhao, et al. (2005). "Application of micro-CT assessment of 3-D bone microstructure in preclinical and clinical studies." Journal of Bone and Mineral Metabolism 23:122-131.
Kang, Q., M. H. Sun, et al. (2004). "Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery." Gene Therapy 11(17):1312-1320.
Koh, J. T., Z. Zhao, et al. (2008). "Combinatorial gene therapy with BMP2/7 enhances cranial bone regeneration." Journal of Dental Research 87(9):845-849.
Link, T. M. and J. S. Bauer (2002). "Imaging of trabecular bone structure." Semin Musculoskelet Radiol 6(3):253-261.
Mosekilde, L. (1988). "Age-Related-Changes in Vertebral Trabecular Bone Architecture-Assessed by a New Method." Bone 9(4):247-250.
Odgaard, A. and H. J. G. Gundersen (1993). "Quantification of Connectivity in Cancellous Bone, with Special Emphasis on 3-D Reconstructions." Bone 14(2): 173-182.
Parfitt, A. M. (1987). "Trabecular Bone Architecture in the Pathogenesis and Prevention of Fracture." American Journal of Medicine 82(1B):68-72.
Reddi, A. H. (2001). "Bone morphogenetic proteins:From basic science to clinical applications." Journal of Bone and Joint Surgery-American Volume 83A:S1-S6.
Thomsen, J. S., A. Laib, et al. (2005). "Stereological measures of trabecular bone structure:comparison of 3D micro computed tomography with 2D histological sections in human proximal tibial bone biopsies." Journal of Microscopy-Oxford 218:171-179.
Yu, N. Y., A. Schindeler, et al. (2010). "In vivo local co-delivery of recombinant human bone morphogenetic protein-7 and pamidronate via poly-D, L-lactic acid." Eur Cell Mater 20:431-441; discussion 441-432.
Zhao, M., Z. Zhao, et al. (2005). "Combinatorial gene therapy for bone regeneration: Cooperative interactions between adenovirus vectors expressing bone morphogenetic proteins 2,4, and 7." Journal of Cellular Biochemistry 95(1):1-16.
Zheng, Y. N., G. Wu, et al. (2010). "rhBMP2/7 Heterodimer:An Osteoblastogenesis Inducer of Not Higher Potency but Lower Effective Concentration Compared with rhBMP2 and rhBMP7 Homodimers." Tissue Engineering Part A 16(3):879-887.
Zhu, W., B. A. Rawlins, et al. (2004). "Combined bone morphogenetic protein-2 and-7 gene transfer enhances osteoblastic differentiation and spine fusion in a rodent model." Journal of Bone and Mineral Research 19(12):2021-2032.
何复明.纯钛种植体氟改性多孔表面的制备及生物学效应评价.浙江大学博士学位论文,杭州,浙江大学2011：51-53.
Akca, K., T. L. Chang, et al. (2006). "Biomechanical aspects of initial intraosseous stability and implant design: a quantitative micro-morphometric analysis." Clinical Oral Implants Research 17(4): 465-472.
Davies, J. E. (2003). "Understanding peri-implant endosseous healing." J Dent Educ 67(8): 932-949.
Freilich, M., M. P. C, et al. (2008). "Growth of new bone guided by implants in a murine calvarial model." Bone 43(4): 781-788.
Kawai, M., H. Maruyama, et al. (2009). "Simple strategy for bone regeneration with a BMP-2/7 gene expression cassette vector." Biochemical and Biophysical Research Communications 390(3): 1012-1017.
Koh, J. T., Z. Zhao, et al. (2008). "Combinatorial gene therapy with BMP2/7 enhances cranial bone regeneration." Journal of Dental Research 87(9): 845-849.
Lavery, K., P. Swain, et al. (2008). "BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells." Journal of Biological Chemistry 283(30): 20948-20958.
Link, T. M. and J. S. Bauer (2002). "Imaging of trabecular bone structure." Semin Musculoskelet Radiol 6(3): 253-261.
Little, S. C. and M. C. Mullins (2009). "Bone morphogenetic protein heterodimers assemble heteromeric type I receptor complexes to pattern the dorsoventral axis." Nature Cell Biology 11(5): 637-U439.
Lutz, R., J. Park, et al. (2008). "Bone regeneration after topical BMP-2-gene delivery in circumferential peri-implant bone defects." Clinical Oral Implants Research 19(6): 590-599.
Meredith, N. (1998). "Assessment of implant stability as a prognostic determinant." International Journal of Prosthodontics 11(5):491-501.
Nohe, A., S. Hassel, et al. (2002). "The mode of bone morphogenetic protein (BMP) receptor oligomerization determines different BMP-2 signaling pathways." Journal of Biological Chemistry 277(7):5330-5338.
Pan Qiuhui., Y. S., Dong Qunwei.,Sun Fenyong. (2007). "Relationship between the bioactivity of BMP2/7 heterodimers and its regulation of CIZ expression." China Biotechnology 27(9):14-18.
Shen, Z. J., T. Nakamoto, et al. (2002). "Negative regulation of bone morphogenetic protein/Smad signaling by cas-interacting zinc finger protein in osteoblasts. Journal of Biological Chemistry 277(33):29840-29846.
Sykaras, N., R. G. Triplett, et al. (2001). "Effect of recombinant human bone morphogenetic protein-2 on bone regeneration and osseointegration of dental implants." Clin Oral Implants Res 12(4):339-349.
Thomsen, J. S., A. Laib, et al. (2005). "Stereological measures of trabecular bone structure:comparison of 3D micro computed tomography with 2D histological sections in human proximal tibial bone biopsies." Journal of Microscopy-Oxford 218:171-179.
Yang, G. L., F. M. He, et al. (2008). "Bone responses to titanium implants surface-roughened by sandblasted and double etched treatments in a rabbit model.' Oral Surg Oral Med Oral Pathol Oral Radiol Endod 106(4):516-524.
Zarb, G. A. (1983). "Introduction to Osseointegration in Clinical Dentistry." Journal of Prosthetic Dentistry 49(6):824-824.
Zhao, M., Z. Zhao, et al. (2005). "Combinatorial gene therapy for bone regeneration: Cooperative interactions between adenovirus vectors expressing bone morphogenetic proteins 2,4, and 7." Journal of Cellular Biochemistry 95(1):1-16.
Zheng, Y. N., G. Wu, et al. (2010). "rhBMP2/7 Heterodimer:An Osteoblastogenesis Inducer of Not Higher Potency but Lower Effective Concentration Compared with rhBMP2 and rhBMP7 Homodimers." Tissue Engineering Part A 16(3):879-887.
Zhu, W., J. Kim, et al. (2006). "Noggin regulation of bone morphogenetic protein (BMP) 2/7 heterodimer activity in vitro." Bone 39(1):61-71.
Aono, A., M. Hazama, et al. (1995). "Potent Ectopic Bone-Inducing Activity of Bone Morphogenetic Protein-4/7 Heterodimer." Biochemical and Biophysical Research Communications 210(3):670-677.
Baltzer, A. W., C. Lattermann, et al. (2000). "Genetic enhancement of fracture repair: healing of an experimental segmental defect by adenoviral transfer of the BMP-2 gene." Gene Ther 7(9):734-739.
Barboza, E. P., A. L. Caula, et al. (2004). "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." J Periodontol 75(5):702-708.
Barboza, E. P., M. E. Duarte, et al. (2000). "Ridge augmentation following implantation of recombinant human bone morphogenetic protein-2 in the dog." J Periodontol 71(3):488-496.
Bessho, K., D. L. Carnes, et al. (1999). "BMP stimulation of bone response adjacent to titanium implants in vivo." Clin Oral Implants Res 10(3):212-218.
Blumenthal, N. M., G. Koh-Kunst, et al. (2002). "Effect of surgical implantation of recombinant human bone morphogenetic protein-2 in a bioabsorbable collagen sponge or calcium phosphate putty carrier in intrabony periodontal defects in the baboon." J Periodontol 73(12):1494-1506.
Celeste, A. J., J. A. Iannazzi, et al. (1990). "Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone.' Proc Natl Acad Sci U S A 87(24):9843-9847.
Cochran, D. L., A. A. Jones, et al. (2000). "Evaluation of recombinant human bone morphogenetic protein-2 in oral applications including the use of endosseous implants:3-year results of a pilot study in humans." J Periodontol 71(8): 1241-1257.
Cochran, D. L., P. V. Nummikoski, et al. (1997). "Radiographic analysis of regenerated bone around endosseous implants in the canine using recombinant human bone morphogenetic protein-2." Int J Oral Maxillofac Implants 12(6):739-748.
Fiorellini, J. P., T. H. Howell, et al. (2005). "Randomized study evaluating recombinant human bone morphogenetic protein-2 for extraction socket augmentation." J Periodontol 76(4):605-613.
Franceschi, R. T., D. Wang, et al. (2000). "Gene therapy for bone formation:in vitro and in vivo osteogenic activity of an adenovirus expressing BMP7." J Cell Biochem 78(3):476-486.
Franceschi, R. T., S. Y. Yang, et al. (2004). "Gene therapy approaches for bone regeneration." Cells Tissues Organs 176(1-3):95-108.
Freilich, M., M. P. C, et al. (2008). "Growth of new bone guided by implants in a murine calvarial model." Bone 43(4):781-788.
Giannobile, W. V., S. Ryan, et al. (1998). "Recombinant human osteogenic protein-1 (OP-1) stimulates periodontal wound healing in class Ⅲ furcation defects." J Periodontol 69(2):129-137.
Hall, J., R. G. Sorensen, et al. (2007). "Bone formation at rhBMP-2-coated titanium implants in the rat ectopic model." J Clin Periodontol 34(5):444-451.
Hanisch, O., D. N. Tatakis, et al. (1997). "Bone formation and reosseointegration in peri-implantitis defects following surgical implantation of rhBMP-2." Int J Oral Maxillofac Implants 12(5):604-610.
Howell, T. H., J. Fiorellini, et al. (1997). "A feasibility study evaluating rhBMP-2/absorbable collagen sponge device for local alveolar ridge preservation or augmentation." Int J Periodontics Restorative Dent 17(2):124-139.
Israel, D. I., J. Nove, et al. (1996). "Heterodimeric bone morphogenetic proteins show enhanced activity in vitro and in vivo." Growth Factors 13(3-4):291-300.
Jovanovic, S. A., D. R. Hunt, et al. (2003). "Long-term functional loading of dental implants in rhBMP-2 induced bone-A histologic study in the canine ridge augmentation model." Clinical Oral Implants Research 14(6):793-803.
Jovanovic, S. A., D. R. Hunt, et al. (2007). "Bone reconstruction following implantation of rhBMP-2 and guided bone regeneration in canine alveolar ridge defects." Clin Oral Implants Res 18(2):224-230.
Jung, R. E., R. Glauser, et al. (2003). "Effect of rhBMP-2 on guided bone regeneration in humans." Clin Oral Implants Res 14(5):556-568.
Koh, J. T., Z. Zhao, et al. (2008). "Combinatorial gene therapy with BMP2/7 enhances cranial bone regeneration." J Dent Res 87(9):845-849.
Krebsbach, P. H., K. Gu, et al. (2000). "Gene therapy-directed osteogenesis: BMP-7-transduced human fibroblasts form bone in vivo." Hum Gene Ther 11(8): 1201-1210.
Liu, Y., K. de Groot, et al. (2005). "BMP-2 liberated from biomimetic implant coatings induces and sustains direct ossification in an ectopic rat model." Bone 36(5): 745-757.
Liu, Y., L. Enggist, et al. (2007). "The influence of BMP-2 and its mode of delivery on the osteoconductivity of implant surfaces during the early phase of osseointegration." Biomaterials 28(16):2677-2686.
Lutz, R., J. Park, et al. (2008). "Bone regeneration after topical BMP-2-gene delivery in circumferential peri-implant bone defects." Clinical Oral Implants Research 19(6): 590-599.
Marukawa, E., I. Asahina, et al. (2001). "Bone regeneration using recombinant human bone morphogenetic protein-2 (rhBMP-2) in alveolar defects of primate mandibles." Br J Oral Maxillofac Surg 39(6):452-459.
Miranda, D. A., N. M. Blumenthal, et al. (2005). "Evaluation of recombinant human bone morphogenetic protein-2 on the repair of alveolar ridge defects in baboons." J Periodontol 76(2):210-220.
Okubo, Y, K. Bessho, et al. (2000). "Osteoinduction by bone morphogenetic protein-2 via adenoviral vector under transient immunosuppression." Biochem Biophys Res Commun 267(1):382-387.
Park, J., R. Lutz, et al. (2007). "The effect on bone regeneration of a liposomal vector to deliver BMP-2 gene to bone grafts in peri-implant bone defects." Biomaterials 28(17):2772-2782.
Rutherford, R. B. (2001). "BMP-7 gene transfer to inflamed ferret dental pulps." Eur J Oral Sci 109(6):422-424.
Saito, E., A. Saito, et al. (2003). "Favorable healing following space creation in rhBMP-2-induced periodontal regeneration of horizontal circumferential defects in dogs with experimental periodontitis." J Periodontol 74(12):1808-1815.
Schliephake, H., A. Aref, et al. (2005). "Effect of immobilized bone morphogenic protein 2 coating of titanium implants on peri-implant bone formation." Clinical Oral Implants Research 16(5):563-569.
Selvig, K. A., R. G. Sorensen, et al. (2002). "Bone repair following recombinant human bone morphogenetic protein-2 stimulated periodontal regeneration." J Periodontol 73(9):1020-1029.
Seto, I., N. Tachikawa, et al. (2002). "Restoration of occlusal function using osseointegrated implants in the canine mandible reconstructed by rhBMP-2." Clin Oral Implants Res 13(5):536-541.
Sigurdsson, T. J., E. Fu, et al. (1997). "Bone morphogenetic protein-2 for peri-implant bone regeneration and osseointegration." Clin Oral Implants Res 8(5):367-374.
Sigurdsson, T. J., S. Nguyen, et al. (2001). "Alveolar ridge augmentation with rhBMP-2 and bone-to-implant contact in induced bone." Int J Periodontics Restorative Dent 21(5):461-473.
Stenport, V. F., C. Johansson, et al. (2003). "Titanium implants and BMP-7 in bone:an experimental model in the rabbit." J Mater Sci Mater Med 14(3):247-254.
Stenport, V. F., A. M. Roos-Jansaker, et al. (2003). "Failure to induce supracrestal bone growth between and around partially inserted titanium implants using bone morphogenetic protein (BMP):an experimental study in dogs." Clin Oral Implants Res 14(2):219-225.
Sykaras, N., R. G. Triplett, et al. (2001). "Effect of recombinant human bone morphogenetic protein-2 on bone regeneration and osseointegration of dental implants." Clin Oral Implants Res 12(4):339-349.
Tatakis, D. N., A. Koh, et al. (2002). "Peri-implant bone regeneration using recombinant human bone morphogenetic protein-2 in a canine model:a dose-response study." J Periodontal Res 37(2):93-100.
Urist, M. R. (1965). "Bone:formation by autoinduction." Science 150(698):893-899.
Urist, M. R. (1970). "The substratum for bone morphogenesis." Symp Soc Dev Biol (Suppl) 1970(4):125-163.
Urist, M. R., Y. K. Huo, et al. (1984). "Purification of bovine bone morphogenetic protein by hydroxyapatite chromatography." Proc Natl Acad Sci U S A 81(2): 371-375.
Wang, E. A., V. Rosen, et al. (1988). "Purification and characterization of other distinct bone-inducing factors." Proc Natl Acad Sci U S A 85(24):9484-9488.
Wikesjo, U. M., M. Qahash, et al. (2003). "Space-providing expanded polytetrafluoroethylene devices define alveolar augmentation at dental implants induced by recombinant human bone morphogenetic protein 2 in an absorbable collagen sponge carrier." Clin Implant Dent Relat Res 5(2):112-123.
Wikesjo, U. M., M. Qahash, et al. (2004). "rhBMP-2 significantly enhances guided bone regeneration." Clin Oral Implants Res 15(2):194-204.
Wikesjo, U. M., R. G. Sorensen, et al. (2002). "RhBMP-2/alphaBSM induces significant vertical alveolar ridge augmentation and dental implant osseointegration." Clin Implant Dent Relat Res 4(4):174-182.
Wozney, J. M., V. Rosen, et al. (1988). "Novel regulators of bone formation:molecular clones and activities." Science 242(4885):1528-1534.
Zhao, M., Z. Zhao, et al. (2005). "Combinatorial gene therapy for bone regeneration: Cooperative interactions between adenovirus vectors expressing bone morphogenetic proteins 2,4, and 7." Journal of Cellular Biochemistry 95(1):1-16.
Zhu, W., B. A. Rawlins, et al. (2004). "Combined bone morphogenetic protein-2 and -7 gene transfer enhances osteoblastic differentiation and spine fusion in a rodent model." Journal of Bone and Mineral Research 19(12):2021-2032.
Barboza, E. P., R. O. de Souza, et al. (2002). "Bone regeneration of localized chronic alveolar defects utilizing cell binding peptide associated with anorganic bovine-derived bone mineral:A clinical and histological study." Journal of Periodontology 73(10):1153-1159.
Carson, J. S. and M. P. G. Bostrom (2007). "Synthetic bone scaffolds and fracture repair." Injury-International Journal of the Care of the Injured 38:S33-S37.
Finkemeier, C. G. (2002). "Bone-grafting and bone-graft substitutes." Journal of Bone and Joint Surgery-American Volume 84A(3):454-464.
Franceschi, R. T. (2005). "Biological approaches to bone regeneration by gene therapy.' Journal of Dental Research 84(12):1093-1103.
Gautschi, O. P., S. P. Frey, et al. (2007). "Bone morphogenetic proteins in clinical applications." Anz Journal of Surgery 77(8):626-631.
Israel, D. I., J. Nove, et al. (1996). "Heterodimeric bone morphogenetic proteins show enhanced activity in vitro and in vivo." Growth Factors 13(3-4):291-300.
Liu, Y., K. de Groot, et al. (2005). "BMP-2 liberated from biomimetic implant coatings induces and sustains direct ossification in an ectopic rat model." Bone 36(5): 745-757.
Liu, Y., L. Enggist, et al. (2007). "The influence of BMP-2 and its mode of delivery on the osteoconductivity of implant surfaces during the early phase of osseointegration." Biomaterials 28(16):2677-2686.
McKay, W. F., S. M. Peckham, et al. (2007). "A comprehensive clinical review of recombinant human bone morphogenetic protein-2 (INFUSE Bone Graft)." International Orthopaedics 31(6):729-734.
Toth, J. M., S. D. Boden, et al. (2009). "Short-term osteoclastic activity induced by locally high concentrations of recombinant human bone morphogenetic protein-2 in a cancellous bone environment." Spine (Phila Pa 1976) 34(6):539-550.
Urist, M. R. (1965). "Bone:formation by autoinduction." Science 150(698):893-899.
White, A. P., A. R. Vaccaro, et al. (2007). "Clinical applications of BMP-7/OP-1 in fractures, nonunions and spinal fusion." International Orthopaedics 31(6):735-741.
Zhao, M., Z. Zhao, et al. (2005). "Combinatorial gene therapy for bone regeneration: Cooperative interactions between adenovirus vectors expressing bone morphogenetic proteins 2,4, and 7." Journal of Cellular Biochemistry 95(1):1-16.
Zheng, Y. N., G. Wu, et al. (2010). "rhBMP2/7 Heterodimer:An Osteoblastogenesis Inducer of Not Higher Potency but Lower Effective Concentration Compared with rhBMP2 and rhBMP7 Homodimers." Tissue Engineering Part A 16(3):879-887.
Zhu, W., B. A. Rawlins, et al. (2004). "Combined bone morphogenetic protein-2 and -7 gene transfer enhances osteoblastic differentiation and spine fusion in a rodent model." Journal of Bone and Mineral Research 19(12):2021-2032.
Aono, A., M. Hazama, et al. (1995). "Potent Ectopic Bone-Inducing Activity of Bone Morphogenetic Protein-4/7 Heterodimer." Biochemical and Biophysical Research Communications 210(3):670-677.
Barboza, E. P., M. E. Duarte, et al. (2000). "Ridge augmentation following implantation of recombinant human bone morphogenetic protein-2 in the dog." J Periodontol 71(3):488-496.
Barr, T., A. J. McNamara, et al. (2010). "Comparison of the osteoinductivity of bioimplants containing recombinant human bone morphogenetic proteins 2 (Infuse) and 7 (OP-1)." Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109(4): 531-540.
Becker, D., U. Geissler, et al. (2002). "Proliferation and differentiation of rat calvarial osteoblasts on type I collagen-coated titanium alloy." J Biomed Mater Res 59(3): 516-527.
Boden, S. D., J. Kang, et al. (2002). "Use of recombinant human bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans:a prospective, randomized clinical pilot trial:2002 Volvo Award in clinical studies." Spine (Phila Pa 1976) 27(23):2662-2673.
Carson, J. S. and M. P. G. Bostrom (2007). "Synthetic bone scaffolds and fracture repair." Injury-International Journal of the Care of the Injured 38:S33-S37.
Cochran, D. L., A. A. Jones, et al. (2000). "Evaluation of recombinant human bone morphogenetic protein-2 in oral applications including the use of endosseous implants:3-year results of a pilot study in humans." J Periodontol 71(8): 1241-1257.
Cochran, D. L., P. V. Nummikoski, et al. (1997). "Radiographic analysis of regenerated bone around endosseous implants in the canine using recombinant human bone morphogenetic protein-2." Int J Oral Maxillofac Implants 12(6):739-748.
Cook, S. D., M. W. Wolfe, et al. (1995). "Effect of recombinant human osteogenic protein-1 on healing of segmental defects in non-human primates." J Bone Joint Surg Am 77(5):734-750.
Finkemeier, C. G. (2002). "Bone-grafting and bone-graft substitutes." Journal of Bone and Joint Surgery-American Volume 84A(3):454-464.
Fiorellini, J. P., T. H. Howell, et al. (2005). "Randomized study evaluating recombinant human bone morphogenetic protein-2 for extraction socket augmentation." J Periodontol 76(4):605-613.
Franceschi, R. T. (2005). "Biological approaches to bone regeneration by gene therapy.' Journal of Dental Research 84(12):1093-1103.
Gautschi, O. P., S. P. Frey, et al. (2007). "Bone morphogenetic proteins in clinical applications." Anz Journal of Surgery 77(8):626-631.
Geiger, M., R. H. Li, et al. (2003). "Collagen sponges for bone regeneration with rhBMP-2." Adv Drug Deliv Rev 55(12):1613-1629.
Gosain, A. K., L. S. Song, et al. (2000). "Osteogenesis in cranial defects:Reassessment of the concept of critical size and the expression of TGF-beta isoforms." Plastic and Reconstructive Surgery 106(2):360-371.
Govender, S., C. Csimma, et al. (2002). "Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures:a prospective, controlled, randomized study of four hundred and fifty patients." Journal of Bone and Joint Surgery-American Volume 84-A(12):2123-2134.
Howell, T. H., J. Fiorellini, et al. (1997). "A feasibility study evaluating rhBMP-2/absorbable collagen sponge device for local alveolar ridge preservation or augmentation." Int J Periodontics Restorative Dent 17(2):124-139.
Israel, D. I., J. Nove, et al. (1996). "Heterodimeric bone morphogenetic proteins show enhanced activity in vitro and in vivo." Growth Factors 13(3-4):291-300.
Jung, R. E., R. Glauser, et al. (2003). "Effect of rhBMP-2 on guided bone regeneration in humans." Clin Oral Implants Res 14(5):556-568.
Liu, Y., L. Enggist, et al. (2007). "The influence of BMP-2 and its mode of delivery on the osteoconductivity of implant surfaces during the early phase of osseointegration." Biomaterials 28(16):2677-2686.
McKay, W. F., S. M. Peckham, et al. (2007). "A comprehensive clinical review of recombinant human bone morphogenetic protein-2 (INFUSE Bone Graft)." International Orthopaedics 31(6):729-734.
Nagao, H., N. Tachikawa, et al. (2002). "Effect of recombinant human bone morphogenetic protein-2 on bone formation in alveolar ridge defects in dogs.1 International Journal of Oral and Maxillofacial Surgery 31(1):66-72.
Ono, I., T. Yamashita, et al. (2004). "Combination of porous hydroxyapatite and cationic liposomes as a vector for BMP-2 gene therapy." Biomaterials 25(19):4709-4718.
Park, J., R. Lutz, et al. (2007). "The effect on bone regeneration of a liposomal vector to deliver BMP-2 gene to bone grafts in peri-implant bone defects." Biomaterials 28(17):2772-2782.
Schlegel, K. A., F. J. Lang, et al. (2006). "The monocortical critical size bone defect as an alternative experimental model in testing bone substitute materials." Oral Surg Oral Med Oral Pathol Oral Radiol Endod 102(1):7-13.
Schmitz, J. P. and J. O. Hollinger (1986). "The Critical Size Defect as an Experimental-Model for Craniomandibulofacial Nonunions." Clinical Orthopaedics and Related Research(205):299-308.
Sigurdsson, T. J., E. Fu, et al. (1997). "Bone morphogenetic protein-2 for peri-implant bone regeneration and osseointegration." Clin Oral Implants Res 8(5):367-374.
Starr, A. J. (2003). "Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures." J Bone Joint Surg Am 85-A(10):2049; author replies 2049-2050.
Toth, J. M., S. D. Boden, et al. (2009). "Short-term osteoclastic activity induced by locally high concentrations of recombinant human bone morphogenetic protein-2 in a cancellous bone environment." Spine (Phila Pa 1976) 34(6):539-550.
White, A. P., A. R. Vaccaro, et al. (2007). "Clinical applications of BMP-7/OP-1 in fractures, nonunions and spinal fusion." International Orthopaedics 31(6):735-741.
Wikesjo, U. M., M. Qahash, et al. (2003). "Space-providing expanded polytetrafluoroethylene devices define alveolar augmentation at dental implants induced by recombinant human bone morphogenetic protein 2 in an absorbable collagen sponge carrier." Clin Implant Dent Relat Res 5(2):112-123.
Wikesjo, U. M., M. Qahash, et al. (2004). "rhBMP-2 significantly enhances guided bone regeneration." Clin Oral Implants Res 15(2):194-204.
Wiltfang, J., F. R. Kloss, et al. (2004). "Effects of platelet-rich plasma on bone healing in combination with autogenous bone and bone substitutes in critical-size defects-An animal experiment." Clinical Oral Implants Research 15(2):187-193.
Yoshikawa, T., H. Ohgushi, et al. (2000). "In vivo osteogenic durability of cultured bone in porous ceramics:a novel method for autogenous bone graft substitution." Transplantation 69(1):128-134.
Zhao, M., Z. Zhao, et al. (2005). "Combinatorial gene therapy for bone regeneration: Cooperative interactions between adenovirus vectors expressing bone morphogenetic proteins 2,4, and 7." Journal of Cellular Biochemistry 95(1):1-16.
Zheng, Y. N., G. Wu, et al. (2010). "rhBMP2/7 Heterodimer:An Osteoblastogenesis Inducer of Not Higher Potency but Lower Effective Concentration Compared with rhBMP2 and rhBMP7 Homodimers." Tissue Engineering Part A 16(3):879-887.
Zhu, W., J. Kim, et al. (2006). "Noggin regulation of bone morphogenetic protein (BMP) 2/7 heterodimer activity in vitro." Bone 39(1):61-71.
Zhu, W., B. A. Rawlins, et al. (2004). "Combined bone morphogenetic protein-2 and -7 gene transfer enhances osteoblastic differentiation and spine fusion in a rodent model." Journal of Bone and Mineral Research 19(12):2021-2032.
何复明.纯钛种植体氟改性多孔表面的制备及生物学效应评价.浙江大学博士学位论文,杭州,浙江大学2011：51-53.
Borah, B., G. J. Gross, et al. (2001). "Three-dimensional microimaging (MR mu I and mu CT), finite element modeling, and rapid prototyping provide unique insights into bone architecture in osteoporosis." Anatomical Record 265(2):101-110.
Carbonare, L. D., M. T. Valenti, et al. (2005). "Bone microarchitecture evaluated by histomorphometry." Micron 36(7-8):609-616.
Cowan, C. M., T. Aghaloo, et al. (2007). "MicroCT evaluation of three-dimensional mineralization in response to BMP-2 doses in vitro and in critical sized rat calvarial defects." Tissue Engineering 13(3):501-512.
Efeoglu, C., J. L. Burke, et al. (2009). "Analysis of calvarial bone defects in rats using microcomputed tomography:potential for a novel composite material and a new quantitative measurement." British Journal of Oral & Maxillofacial Surgery 47(8): 616-621.
Haidar, Z. S., R. C. Hamdy, et al. (2009). "Delivery of recombinant bone morphogenetic proteins for bone regeneration and repair. Part B:Delivery systems for BMPs in orthopaedic and craniofacial tissue engineering." Biotechnol Lett 31(12): 1825-1835.
Hildebrand, T., A. Laib, et al. (1999). "Direct three-dimensional morphometric analysis of human cancellous bone:Microstructural data from spine, femur, iliac crest, and calcaneus." Journal of Bone and Mineral Research 14(7):1167-1174.
Hildebrand, T. and P. Ruegsegger (1997). "Quantification of Bone Microarchitecture with the Structure Model Index." Comput Methods Biomech Biomed Engin 1(1): 15-23.
Jiang, Y. B., J. Zhao, et al. (2005). "Application of micro-CT assessment of 3-D bone microstructure in preclinical and clinical studies." Journal of Bone and Mineral Metabolism 23:122-131.
Kang, Q., M. H. Sun, et al. (2004). "Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery." Gene Therapy 11(17):1312-1320.
Koh, J. T., Z. Zhao, et al. (2008). "Combinatorial gene therapy with BMP2/7 enhances cranial bone regeneration." Journal of Dental Research 87(9):845-849.
Link, T. M. and J. S. Bauer (2002). "Imaging of trabecular bone structure." Semin Musculoskelet Radiol 6(3):253-261.
Mosekilde, L. (1988). "Age-Related-Changes in Vertebral Trabecular Bone Architecture-Assessed by a New Method." Bone 9(4):247-250.
Odgaard, A. and H. J. G. Gundersen (1993). "Quantification of Connectivity in Cancellous Bone, with Special Emphasis on 3-D Reconstructions." Bone 14(2): 173-182.
Parfitt, A. M. (1987). "Trabecular Bone Architecture in the Pathogenesis and Prevention of Fracture." American Journal of Medicine 82(1B):68-72.
Reddi, A. H. (2001). "Bone morphogenetic proteins:From basic science to clinical applications." Journal of Bone and Joint Surgery-American Volume 83A:S1-S6.
Thomsen, J. S., A. Laib, et al. (2005). "Stereological measures of trabecular bone structure:comparison of 3D micro computed tomography with 2D histological sections in human proximal tibial bone biopsies." Journal of Microscopy-Oxford 218:171-179.
Yu, N. Y., A. Schindeler, et al. (2010). "In vivo local co-delivery of recombinant human bone morphogenetic protein-7 and pamidronate via poly-D, L-lactic acid." Eur Cell Mater 20:431-441; discussion 441-432.
Zhao, M., Z. Zhao, et al. (2005). "Combinatorial gene therapy for bone regeneration: Cooperative interactions between adenovirus vectors expressing bone morphogenetic proteins 2,4, and 7." Journal of Cellular Biochemistry 95(1):1-16.
Zheng, Y. N., G. Wu, et al. (2010). "rhBMP2/7 Heterodimer:An Osteoblastogenesis Inducer of Not Higher Potency but Lower Effective Concentration Compared with rhBMP2 and rhBMP7 Homodimers." Tissue Engineering Part A 16(3):879-887.
Zhu, W., B. A. Rawlins, et al. (2004). "Combined bone morphogenetic protein-2 and-7 gene transfer enhances osteoblastic differentiation and spine fusion in a rodent model." Journal of Bone and Mineral Research 19(12):2021-2032.
何复明.纯钛种植体氟改性多孔表面的制备及生物学效应评价.浙江大学博士学位论文,杭州,浙江大学2011：51-53.
Akca, K., T. L. Chang, et al. (2006). "Biomechanical aspects of initial intraosseous stability and implant design: a quantitative micro-morphometric analysis." Clinical Oral Implants Research 17(4): 465-472.
Davies, J. E. (2003). "Understanding peri-implant endosseous healing." J Dent Educ 67(8): 932-949.
Freilich, M., M. P. C, et al. (2008). "Growth of new bone guided by implants in a murine calvarial model." Bone 43(4): 781-788.
Kawai, M., H. Maruyama, et al. (2009). "Simple strategy for bone regeneration with a BMP-2/7 gene expression cassette vector." Biochemical and Biophysical Research Communications 390(3): 1012-1017.
Koh, J. T., Z. Zhao, et al. (2008). "Combinatorial gene therapy with BMP2/7 enhances cranial bone regeneration." Journal of Dental Research 87(9): 845-849.
Lavery, K., P. Swain, et al. (2008). "BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells." Journal of Biological Chemistry 283(30): 20948-20958.
Link, T. M. and J. S. Bauer (2002). "Imaging of trabecular bone structure." Semin Musculoskelet Radiol 6(3): 253-261.
Little, S. C. and M. C. Mullins (2009). "Bone morphogenetic protein heterodimers assemble heteromeric type I receptor complexes to pattern the dorsoventral axis." Nature Cell Biology 11(5): 637-U439.
Lutz, R., J. Park, et al. (2008). "Bone regeneration after topical BMP-2-gene delivery in circumferential peri-implant bone defects." Clinical Oral Implants Research 19(6): 590-599.
Meredith, N. (1998). "Assessment of implant stability as a prognostic determinant." International Journal of Prosthodontics 11(5):491-501.
Nohe, A., S. Hassel, et al. (2002). "The mode of bone morphogenetic protein (BMP) receptor oligomerization determines different BMP-2 signaling pathways." Journal of Biological Chemistry 277(7):5330-5338.
Pan Qiuhui., Y. S., Dong Qunwei.,Sun Fenyong. (2007). "Relationship between the bioactivity of BMP2/7 heterodimers and its regulation of CIZ expression." China Biotechnology 27(9):14-18.
Shen, Z. J., T. Nakamoto, et al. (2002). "Negative regulation of bone morphogenetic protein/Smad signaling by cas-interacting zinc finger protein in osteoblasts. Journal of Biological Chemistry 277(33):29840-29846.
Sykaras, N., R. G. Triplett, et al. (2001). "Effect of recombinant human bone morphogenetic protein-2 on bone regeneration and osseointegration of dental implants." Clin Oral Implants Res 12(4):339-349.
Thomsen, J. S., A. Laib, et al. (2005). "Stereological measures of trabecular bone structure:comparison of 3D micro computed tomography with 2D histological sections in human proximal tibial bone biopsies." Journal of Microscopy-Oxford 218:171-179.
Yang, G. L., F. M. He, et al. (2008). "Bone responses to titanium implants surface-roughened by sandblasted and double etched treatments in a rabbit model.' Oral Surg Oral Med Oral Pathol Oral Radiol Endod 106(4):516-524.
Zarb, G. A. (1983). "Introduction to Osseointegration in Clinical Dentistry." Journal of Prosthetic Dentistry 49(6):824-824.
Zhao, M., Z. Zhao, et al. (2005). "Combinatorial gene therapy for bone regeneration: Cooperative interactions between adenovirus vectors expressing bone morphogenetic proteins 2,4, and 7." Journal of Cellular Biochemistry 95(1):1-16.
Zheng, Y. N., G. Wu, et al. (2010). "rhBMP2/7 Heterodimer:An Osteoblastogenesis Inducer of Not Higher Potency but Lower Effective Concentration Compared with rhBMP2 and rhBMP7 Homodimers." Tissue Engineering Part A 16(3):879-887.
Zhu, W., J. Kim, et al. (2006). "Noggin regulation of bone morphogenetic protein (BMP) 2/7 heterodimer activity in vitro." Bone 39(1):61-71.
Aono, A., M. Hazama, et al. (1995). "Potent Ectopic Bone-Inducing Activity of Bone Morphogenetic Protein-4/7 Heterodimer." Biochemical and Biophysical Research Communications 210(3):670-677.
Baltzer, A. W., C. Lattermann, et al. (2000). "Genetic enhancement of fracture repair: healing of an experimental segmental defect by adenoviral transfer of the BMP-2 gene." Gene Ther 7(9):734-739.
Barboza, E. P., A. L. Caula, et al. (2004). "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." J Periodontol 75(5):702-708.
Barboza, E. P., M. E. Duarte, et al. (2000). "Ridge augmentation following implantation of recombinant human bone morphogenetic protein-2 in the dog." J Periodontol 71(3):488-496.
Bessho, K., D. L. Carnes, et al. (1999). "BMP stimulation of bone response adjacent to titanium implants in vivo." Clin Oral Implants Res 10(3):212-218.
Blumenthal, N. M., G. Koh-Kunst, et al. (2002). "Effect of surgical implantation of recombinant human bone morphogenetic protein-2 in a bioabsorbable collagen sponge or calcium phosphate putty carrier in intrabony periodontal defects in the baboon." J Periodontol 73(12):1494-1506.
Celeste, A. J., J. A. Iannazzi, et al. (1990). "Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone.' Proc Natl Acad Sci U S A 87(24):9843-9847.
Cochran, D. L., A. A. Jones, et al. (2000). "Evaluation of recombinant human bone morphogenetic protein-2 in oral applications including the use of endosseous implants:3-year results of a pilot study in humans." J Periodontol 71(8): 1241-1257.
Cochran, D. L., P. V. Nummikoski, et al. (1997). "Radiographic analysis of regenerated bone around endosseous implants in the canine using recombinant human bone morphogenetic protein-2." Int J Oral Maxillofac Implants 12(6):739-748.
Fiorellini, J. P., T. H. Howell, et al. (2005). "Randomized study evaluating recombinant human bone morphogenetic protein-2 for extraction socket augmentation." J Periodontol 76(4):605-613.
Franceschi, R. T., D. Wang, et al. (2000). "Gene therapy for bone formation:in vitro and in vivo osteogenic activity of an adenovirus expressing BMP7." J Cell Biochem 78(3):476-486.
Franceschi, R. T., S. Y. Yang, et al. (2004). "Gene therapy approaches for bone regeneration." Cells Tissues Organs 176(1-3):95-108.
Freilich, M., M. P. C, et al. (2008). "Growth of new bone guided by implants in a murine calvarial model." Bone 43(4):781-788.
Giannobile, W. V., S. Ryan, et al. (1998). "Recombinant human osteogenic protein-1 (OP-1) stimulates periodontal wound healing in class Ⅲ furcation defects." J Periodontol 69(2):129-137.
Hall, J., R. G. Sorensen, et al. (2007). "Bone formation at rhBMP-2-coated titanium implants in the rat ectopic model." J Clin Periodontol 34(5):444-451.
Hanisch, O., D. N. Tatakis, et al. (1997). "Bone formation and reosseointegration in peri-implantitis defects following surgical implantation of rhBMP-2." Int J Oral Maxillofac Implants 12(5):604-610.
Howell, T. H., J. Fiorellini, et al. (1997). "A feasibility study evaluating rhBMP-2/absorbable collagen sponge device for local alveolar ridge preservation or augmentation." Int J Periodontics Restorative Dent 17(2):124-139.
Israel, D. I., J. Nove, et al. (1996). "Heterodimeric bone morphogenetic proteins show enhanced activity in vitro and in vivo." Growth Factors 13(3-4):291-300.
Jovanovic, S. A., D. R. Hunt, et al. (2003). "Long-term functional loading of dental implants in rhBMP-2 induced bone-A histologic study in the canine ridge augmentation model." Clinical Oral Implants Research 14(6):793-803.
Jovanovic, S. A., D. R. Hunt, et al. (2007). "Bone reconstruction following implantation of rhBMP-2 and guided bone regeneration in canine alveolar ridge defects." Clin Oral Implants Res 18(2):224-230.
Jung, R. E., R. Glauser, et al. (2003). "Effect of rhBMP-2 on guided bone regeneration in humans." Clin Oral Implants Res 14(5):556-568.
Koh, J. T., Z. Zhao, et al. (2008). "Combinatorial gene therapy with BMP2/7 enhances cranial bone regeneration." J Dent Res 87(9):845-849.
Krebsbach, P. H., K. Gu, et al. (2000). "Gene therapy-directed osteogenesis: BMP-7-transduced human fibroblasts form bone in vivo." Hum Gene Ther 11(8): 1201-1210.
Liu, Y., K. de Groot, et al. (2005). "BMP-2 liberated from biomimetic implant coatings induces and sustains direct ossification in an ectopic rat model." Bone 36(5): 745-757.
Liu, Y., L. Enggist, et al. (2007). "The influence of BMP-2 and its mode of delivery on the osteoconductivity of implant surfaces during the early phase of osseointegration." Biomaterials 28(16):2677-2686.
Lutz, R., J. Park, et al. (2008). "Bone regeneration after topical BMP-2-gene delivery in circumferential peri-implant bone defects." Clinical Oral Implants Research 19(6): 590-599.
Marukawa, E., I. Asahina, et al. (2001). "Bone regeneration using recombinant human bone morphogenetic protein-2 (rhBMP-2) in alveolar defects of primate mandibles." Br J Oral Maxillofac Surg 39(6):452-459.
Miranda, D. A., N. M. Blumenthal, et al. (2005). "Evaluation of recombinant human bone morphogenetic protein-2 on the repair of alveolar ridge defects in baboons." J Periodontol 76(2):210-220.
Okubo, Y, K. Bessho, et al. (2000). "Osteoinduction by bone morphogenetic protein-2 via adenoviral vector under transient immunosuppression." Biochem Biophys Res Commun 267(1):382-387.
Park, J., R. Lutz, et al. (2007). "The effect on bone regeneration of a liposomal vector to deliver BMP-2 gene to bone grafts in peri-implant bone defects." Biomaterials 28(17):2772-2782.
Rutherford, R. B. (2001). "BMP-7 gene transfer to inflamed ferret dental pulps." Eur J Oral Sci 109(6):422-424.
Saito, E., A. Saito, et al. (2003). "Favorable healing following space creation in rhBMP-2-induced periodontal regeneration of horizontal circumferential defects in dogs with experimental periodontitis." J Periodontol 74(12):1808-1815.
Schliephake, H., A. Aref, et al. (2005). "Effect of immobilized bone morphogenic protein 2 coating of titanium implants on peri-implant bone formation." Clinical Oral Implants Research 16(5):563-569.
Selvig, K. A., R. G. Sorensen, et al. (2002). "Bone repair following recombinant human bone morphogenetic protein-2 stimulated periodontal regeneration." J Periodontol 73(9):1020-1029.
Seto, I., N. Tachikawa, et al. (2002). "Restoration of occlusal function using osseointegrated implants in the canine mandible reconstructed by rhBMP-2." Clin Oral Implants Res 13(5):536-541.
Sigurdsson, T. J., E. Fu, et al. (1997). "Bone morphogenetic protein-2 for peri-implant bone regeneration and osseointegration." Clin Oral Implants Res 8(5):367-374.
Sigurdsson, T. J., S. Nguyen, et al. (2001). "Alveolar ridge augmentation with rhBMP-2 and bone-to-implant contact in induced bone." Int J Periodontics Restorative Dent 21(5):461-473.
Stenport, V. F., C. Johansson, et al. (2003). "Titanium implants and BMP-7 in bone:an experimental model in the rabbit." J Mater Sci Mater Med 14(3):247-254.
Stenport, V. F., A. M. Roos-Jansaker, et al. (2003). "Failure to induce supracrestal bone growth between and around partially inserted titanium implants using bone morphogenetic protein (BMP):an experimental study in dogs." Clin Oral Implants Res 14(2):219-225.
Sykaras, N., R. G. Triplett, et al. (2001). "Effect of recombinant human bone morphogenetic protein-2 on bone regeneration and osseointegration of dental implants." Clin Oral Implants Res 12(4):339-349.
Tatakis, D. N., A. Koh, et al. (2002). "Peri-implant bone regeneration using recombinant human bone morphogenetic protein-2 in a canine model:a dose-response study." J Periodontal Res 37(2):93-100.
Urist, M. R. (1965). "Bone:formation by autoinduction." Science 150(698):893-899.
Urist, M. R. (1970). "The substratum for bone morphogenesis." Symp Soc Dev Biol (Suppl) 1970(4):125-163.
Urist, M. R., Y. K. Huo, et al. (1984). "Purification of bovine bone morphogenetic protein by hydroxyapatite chromatography." Proc Natl Acad Sci U S A 81(2): 371-375.
Wang, E. A., V. Rosen, et al. (1988). "Purification and characterization of other distinct bone-inducing factors." Proc Natl Acad Sci U S A 85(24):9484-9488.
Wikesjo, U. M., M. Qahash, et al. (2003). "Space-providing expanded polytetrafluoroethylene devices define alveolar augmentation at dental implants induced by recombinant human bone morphogenetic protein 2 in an absorbable collagen sponge carrier." Clin Implant Dent Relat Res 5(2):112-123.
Wikesjo, U. M., M. Qahash, et al. (2004). "rhBMP-2 significantly enhances guided bone regeneration." Clin Oral Implants Res 15(2):194-204.
Wikesjo, U. M., R. G. Sorensen, et al. (2002). "RhBMP-2/alphaBSM induces significant vertical alveolar ridge augmentation and dental implant osseointegration." Clin Implant Dent Relat Res 4(4):174-182.
Wozney, J. M., V. Rosen, et al. (1988). "Novel regulators of bone formation:molecular clones and activities." Science 242(4885):1528-1534.
Zhao, M., Z. Zhao, et al. (2005). "Combinatorial gene therapy for bone regeneration: Cooperative interactions between adenovirus vectors expressing bone morphogenetic proteins 2,4, and 7." Journal of Cellular Biochemistry 95(1):1-16.
Zhu, W., B. A. Rawlins, et al. (2004). "Combined bone morphogenetic protein-2 and -7 gene transfer enhances osteoblastic differentiation and spine fusion in a rodent model." Journal of Bone and Mineral Research 19(12):2021-2032.