新型仿生BMP-BG-COL-HYA-PS复合支架的实验研究
|
摘要
当前各种原因造成的难治性骨缺损是临床上面临的一大难题,为了避免传统的自体骨及同种异体骨移植所带来的问题,人们开发了许多种类的人工骨修复材料,时至今日,这一领域已成为创伤骨科和骨组织工程学研究的一个热点。在这些材料中,58s生物玻璃以其良好的生物相容性引起人们的广泛重视。为了研制一种理想的仿生型骨修复材料,本课题在综合分析大量文献的基础上,选用化学组成与生物体的自然骨骼相似、容易与周围的骨骼形成紧密牢固的化学键合、经生物降解形成新的骨骼成分、具有良好生物相容性和骨传导性的生物活性玻璃(Bioactive glass,BG)作为复合支架的基体,与天然骨基质主要成分中的I型胶原(Collagen,COL)、透明质酸(Hyaluronicacid,HYA)、磷酸丝氨酸(Phosphatidylserine,PS)交联,并与骨形态发生蛋白(Bone morphogenetic protein.BMP)复合,利用冷冻干燥技术,制备BMP-BG-COL-HYA-PS复合支架,通过体内外系列实验研究观察其理化性能、生物相容性及其诱导、传导成骨能力。
实验分四个部分进行观察研究:
1.仿生型BMP-BG-COL-HYA-PS复合支架材料的制备及性能表征研究。
58s生物活性玻璃(58s BG)采用了溶胶凝胶技术制备工艺。BG-COL-HYA-PS(nano-bioactive glass(BG),collagen(COL),hyaluronic acid(HYA) and phosphatidylserine(PS),BG-COL-HYA-PS)与BMP根据不同的比率,采用了交联和冷冻干燥进行复合。SEM显微形貌显示BMP-BG-COL-HYA-PS复合支架均具有相互交错、连续的不规则多孔结构。孔径大小在100微米到400um间分布。冷冻干燥后孔隙率为80%。BMP-BG-COL-HYA-PS网络支架具有紧密的结构,生物玻璃颗粒包裹在胶原蛋白-透明质酸-磷酸丝氨酸复合聚合物中,颗粒间通过纤维状的有机大分子相连。采用三点弯曲试验法分析BMP-BG-COL-HYA-PS复合支架的机械性能,测试结果显示BMP-BG-COL-HYA-PS复合支架的断裂强度(Strength at break)为1.406±0.019MPa;弹性模量(Elastic modulus)为35.812±0.016kPa。说明BG-COL-HYA-PS复合支架具有较高的韧性。
2.仿生型BMP-BG-COL-HYA-PS复合支架材料的生物相容性检测
倒置显微镜、扫描电镜显示骨髓基质干细胞在BMP-BG-COL-HYA-PS材料上能良好粘附、增殖,并向支架孔内生长,用倒置相差显微镜观察骨髓基质干细胞与支架联合培养时的动力学生长情况可以观察到细胞具有明显向材料聚集的生长趋势。BMP-BG-COL-HYA-PS材料浸提液注入动物体内的急性毒性反应试验结果依据规定的判定标准判定为无毒性。制备材料体外浸泡第1天、第7天的浸提液,将材料及其浸提液分别与人骨髓基质干细胞(MSCs)体外共培养,通过SEM观察、MTT测定,探讨复合材料的细胞粘附能力及其浸提液对于人MSCs增殖的影响。SEM结果显示:复合材料与MSCs细胞可良好粘附、增殖,细胞形态正常。体外培养时复合材料不同时间的浸提液对MSCs细胞的增殖具有促进作用。说明仿生复合材料BMP-BG-COL-HYA-PS具有良好的骨细胞相容性和生物安全性。
3.BMP-BG-COL-HYA-PS复合人工骨的异位成骨活性研究
将制备的BMP-BG-COL-HYA-PS,BG-COL-HYA-PS块分别植入小鼠两侧股部肌袋内,术后2周、4周取材,进行大体观察、X线、组织学检测,观察成骨状况和组织学反应,以评价载体材料的组织相容性及异位成骨能力。X线检查示材料植入4周在复合材料周围有高密度影出现,组织学观察两种植入物在植入初期周围均有轻度非特异性炎症反应,材料周围有软骨细胞出现。4周后炎症消失,材料周围出现新骨,BMP-BG-COL-HYA-PS组成骨量明显。表明复合材料具有较强的异位诱导成骨能力。
4.仿生型BMP-BG-COL-HYA-PS复合支架修复兔挠骨缺损的实验研究
将52只兔子随机分成3组,BMP-BG-COL-HYA-PS组、BG-COL-HYA-PS组和空白对照组。左右两侧桡骨制造15mm骨缺损,分别植入相应材料。②在植入材料后2,4,8,12周观察动物饮食、活动及伤口愈合等大体情况,以及缺损部位X射线变化,并取材分别进行组织形态学、扫描电镜、以及骨密度的检测。结果分析:①兔大体观察结果:术后所有动物伤口愈合良好,未发生骨折,活动、进食情况和精神状态基本正常。②兔桡骨缺损区X射线检查结果:术后2周,BMP-BG-COL-HYA-PS组两截骨端有明显致密影,外层有少量骨痂形成;术后8周骨皮质连接完整;12周缺损完全修复,髓腔基本再通。③兔桡骨缺损区组织形态学观察结果:术后2周BMP-BG-COL-HYA-PS组即可见成骨细胞沿支架材料爬行并分泌骨基质;4周可见大量新生骨小梁向缺损中心生长;12周缺损区内基本看不到支架材料,完全由新生骨组织替代,髓腔已再通。④各组兔桡骨缺损区骨密度测定结果:BMP-BG-COL-HYA-PS组术后4,12周骨密度分别是BG-COL-HYA-PS组的4.71倍和1.675倍,析因设计方差分析不同实验组F=1262.398,P＜0.01;LSD-t两两比较差异均有显著性意义,P＜0.01。
从以上试验结果表明:BMP-BG-COL-HYA-PS复合支架具有与天然骨组织及细胞外基质相似的组成成分、良好的生物相容性和可降解性,在诱导成骨和促进矿化方面性能优越,作为骨缺损修复替代材料应用前景广阔。
Nowadays complex bone defects from various injuries have become a great challenge to orthopedists.To deal with complications associated with autogenous and allogenous bone grafting,people developed various kinds of artificial bone repairing materials(bone substitute),which has become a focus of intensive research in traumaology and tissue engineering.Of all materials available,58s BG has received considerable attention.
To develop an optimal bio-mimetic material for bone repair,this study,based on thorough analysis of literature data,selected bioactive glass(BG) as the principal constituent of the scaffold composite, considering that its chemical components are similar to natural bones and it readily integrates with surrounding bone tissues through tight chemical bond formation.It induces bone formation through biodegradation and has good biocompatibility and osteoconductivity.The composite scaffold BG-COL-HYA-PS was fabricated by crosslinking BG with the major components of natural matrix TypeⅠcollagen(COL),hyaluronic acid(HYA) and phosphatidylserine(PS) and then combined with bone morphogenetic protein(BMP),using the freeze-drying technology.The composite scaffold was evaluated by a series of in vitro and in vivo experiments,for its physical-chemical properties,biocompatibility, osteoinductivity and osteoconductivity.
The experiments were divided into four parts:
1.Fabrication and characterization of the biomimetic BMP-BG-COL-HYA-PS composite material.
The 58S bioactive glass(58SBG) was prepared by solvent-casting process.The BMP-BG-COL-HYA-PS scaffold composites were prepared by mixing nano powders of the bioactive glass,TypeⅠcollagen, hyaluronic acid(HYA),BMP and phosphatidylserine according to different ratios,using a technology of cross-linking followed by freeze-drying.The morphology,porous size and porosity of the composite scaffolds were examined by scanning electron microscopy(SEM). Mechanical strength and characteristics were evaluated by three-point bending tests.Inflation dynamics was examined using phosphate-buffered saline(PBS) as the immersion media.Strength at break is 1.406士0.019MPa;Elastic modulus is 35.812士0.016kPa.
2.Biocompatibility evaluation of the biomimetic BMP-BG-COL-HYA-PS composite material.
Using in vitro cell culture technique,the MSCs were seeded onto composites BMP-BG-COL-HYA-PS.Cell growth and reciprocity were monitored using MTT assay,inversion phase contrast microscope and SEM.Biocompatibility studies were performed on healthy Kunming mice selected according to the evaluation criteria for medical implant materials and the recommended biological and animal tests in GB/T16886.5-1997-ISO 10993-5:1992.These results were used for the evaluation of biological compatibility and safety of the composite materials.
3.Ectopic osteogenic activity of BMP-BG-COL-HYA-PS composite.
To investigate the ectopic osteoinduction and biocompatibility of BMP-BG-COL-HYA-PS composite and BG-COL-HYA-PS composite,they were synthesized and implanted into the muscle pouches in the right and left thigh of mice,respectively.At 2 and 4 week after implantation,the rats were killed,the samples were harvested,and the ectopic new bone formation was detected by X-ray analysis and histologic examination.X-ray analysis revealed that more callus-like shadow appeared adjacent to the implant of BMP-BG-COL-HYA-PS after 4 weeks.Histologically,there was slight acute inflammation in the surrounding tissue of both types of implants at the early stage.With new chondrocytes being evident at all BMP-BG-COL-HYA-PS implanted sites within 2 weeks after implantation.In 4 weeks,all of the implants with BMP-BG-COL-HYA-PS showed new bone formation with characteristics hematopoietic marrow and osseous trabeculae,and the amount of new bone as a result of the use of BMP-BG-COL-HYA-PS was significantly higher than that obtained with BG-COL-HYA-PS.The biocompatibility of composite samples was assessed by cell adhesion,proliferation,and differentiation assays using MSCs cells.MSCs were cultured with the 24h extraction medium of 1st,7th day of BMP-BG-COL-HYA-PS and BG-COL-HYA-PS samples.Cell-material interaction on the surface of the composites was observed by SEM.Cell proliferation and differentiation were measured by MTT.The effects of BMP-BG-COL-HYA-PS on the behavior of MSCs ceils were evaluated in comparison with those of BG-COL-HYA-PS.Morphology investigation of adhered cells by SEM indicated that MSCs cells could adhere,proliferate on the surface of the composite presenting normal morphology.MSCs cells,cultured in the presence of BMP-BG-COL-HYA-PS composite extract samples had a higher proliferation rate as compared to the control sample after 7 days of incubation.All these results suggest that the composite is biocompatible, nontoxic,and in some cases shows an increase in the proliferation rate of the cells as compared to the control.These results indicate that BMP-BG-COL-HYA-PS is more effective in inducing ectopic osteogenesis,that would be useful for repair bone defects.
4.Biomimetic scaffold composite BMP-BG-COL-HYA-PS in the repair of rabbit radius defect
In vivo studies of the biomimetic BMP-BG-COL-HYA-PS composite scaffold for the repair of rabbit radius defects.52 Healthy adult New Zealand rabbits were used as model to create radius defects (center-section belt periosteum 15mm bone damage)on both sides.The defects were implanted with various grafts:BG-COL-HYA-PS and BMP-BG-COL-HYA-PS composites,no implant as the control group. X-Ray radiophotography was taken at weeks 2,4,8 and 12 after operation,and tissue samples were taken for histomorphological and SEM examination.Bone density,mineral apposition rate and bone formation rate were determined at weeks 4 and 12 after operation to evaluate the effectiveness of BMP-BG-COL-HYA-PS composite scaffold for repair of the bone defects.RESULTS:①Gross observation results: The wounds healed by first intention after operation,no fracture occurred. The activity,eating and mental state of the animals were normal basically.②Results of X-ray examination in the defect region:two weeks after the operation,there was significant dense shadow and a degree of porosity at ends of the oseotomy in the BMP-BG-COL-PS-HYA group.At week 8 after operation,cortical bone was fully connected.At week 12 defects were fully repaired and medullary cavity was recanalized basically.③Findings of histomorphologic observation in defect region of rabbits:In the BMP-BG-COL-PS-HYA group,two weeks after operation,osteoblasts were found along the scaffold material and excreted matrix.At weeks 4 it was found that a mass of new bone trabecula grew towards defect center. At week 12 there was no scaffold material in the defect region,which was replaced by new bone tissue fully,and the medullary cavity was recanalized.④Determination results of BMD in defect region of each group:The BMD in the BMP-BG-COL-PS-HYA group was 4.71 times and 1.675 times that in the BG-COL-PS-HYA group at weeks 4 and 12 after operation.F value was equal to 1262.398,P＜0.01 in different experimental groups detected with factorial design and variance analysis. There was significant difference in the LSD-t pair wise comparison P＜0.01.
On the basis of these observations.We can conclude that the biomimetic BMP-BG-COL-PS-HYA composites scaffold has similar composition and structure to the natural bone and extracellular matrix,as well as good biocompatibility and biodegradability.It holds promise in induction of bone formation and mineralization,and should have broad applications as a bone substitute material.
实验分四个部分进行观察研究:
1.仿生型BMP-BG-COL-HYA-PS复合支架材料的制备及性能表征研究。
58s生物活性玻璃(58s BG)采用了溶胶凝胶技术制备工艺。BG-COL-HYA-PS(nano-bioactive glass(BG),collagen(COL),hyaluronic acid(HYA) and phosphatidylserine(PS),BG-COL-HYA-PS)与BMP根据不同的比率,采用了交联和冷冻干燥进行复合。SEM显微形貌显示BMP-BG-COL-HYA-PS复合支架均具有相互交错、连续的不规则多孔结构。孔径大小在100微米到400um间分布。冷冻干燥后孔隙率为80%。BMP-BG-COL-HYA-PS网络支架具有紧密的结构,生物玻璃颗粒包裹在胶原蛋白-透明质酸-磷酸丝氨酸复合聚合物中,颗粒间通过纤维状的有机大分子相连。采用三点弯曲试验法分析BMP-BG-COL-HYA-PS复合支架的机械性能,测试结果显示BMP-BG-COL-HYA-PS复合支架的断裂强度(Strength at break)为1.406±0.019MPa;弹性模量(Elastic modulus)为35.812±0.016kPa。说明BG-COL-HYA-PS复合支架具有较高的韧性。
2.仿生型BMP-BG-COL-HYA-PS复合支架材料的生物相容性检测
倒置显微镜、扫描电镜显示骨髓基质干细胞在BMP-BG-COL-HYA-PS材料上能良好粘附、增殖,并向支架孔内生长,用倒置相差显微镜观察骨髓基质干细胞与支架联合培养时的动力学生长情况可以观察到细胞具有明显向材料聚集的生长趋势。BMP-BG-COL-HYA-PS材料浸提液注入动物体内的急性毒性反应试验结果依据规定的判定标准判定为无毒性。制备材料体外浸泡第1天、第7天的浸提液,将材料及其浸提液分别与人骨髓基质干细胞(MSCs)体外共培养,通过SEM观察、MTT测定,探讨复合材料的细胞粘附能力及其浸提液对于人MSCs增殖的影响。SEM结果显示:复合材料与MSCs细胞可良好粘附、增殖,细胞形态正常。体外培养时复合材料不同时间的浸提液对MSCs细胞的增殖具有促进作用。说明仿生复合材料BMP-BG-COL-HYA-PS具有良好的骨细胞相容性和生物安全性。
3.BMP-BG-COL-HYA-PS复合人工骨的异位成骨活性研究
将制备的BMP-BG-COL-HYA-PS,BG-COL-HYA-PS块分别植入小鼠两侧股部肌袋内,术后2周、4周取材,进行大体观察、X线、组织学检测,观察成骨状况和组织学反应,以评价载体材料的组织相容性及异位成骨能力。X线检查示材料植入4周在复合材料周围有高密度影出现,组织学观察两种植入物在植入初期周围均有轻度非特异性炎症反应,材料周围有软骨细胞出现。4周后炎症消失,材料周围出现新骨,BMP-BG-COL-HYA-PS组成骨量明显。表明复合材料具有较强的异位诱导成骨能力。
4.仿生型BMP-BG-COL-HYA-PS复合支架修复兔挠骨缺损的实验研究
将52只兔子随机分成3组,BMP-BG-COL-HYA-PS组、BG-COL-HYA-PS组和空白对照组。左右两侧桡骨制造15mm骨缺损,分别植入相应材料。②在植入材料后2,4,8,12周观察动物饮食、活动及伤口愈合等大体情况,以及缺损部位X射线变化,并取材分别进行组织形态学、扫描电镜、以及骨密度的检测。结果分析:①兔大体观察结果:术后所有动物伤口愈合良好,未发生骨折,活动、进食情况和精神状态基本正常。②兔桡骨缺损区X射线检查结果:术后2周,BMP-BG-COL-HYA-PS组两截骨端有明显致密影,外层有少量骨痂形成;术后8周骨皮质连接完整;12周缺损完全修复,髓腔基本再通。③兔桡骨缺损区组织形态学观察结果:术后2周BMP-BG-COL-HYA-PS组即可见成骨细胞沿支架材料爬行并分泌骨基质;4周可见大量新生骨小梁向缺损中心生长;12周缺损区内基本看不到支架材料,完全由新生骨组织替代,髓腔已再通。④各组兔桡骨缺损区骨密度测定结果:BMP-BG-COL-HYA-PS组术后4,12周骨密度分别是BG-COL-HYA-PS组的4.71倍和1.675倍,析因设计方差分析不同实验组F=1262.398,P＜0.01;LSD-t两两比较差异均有显著性意义,P＜0.01。
从以上试验结果表明:BMP-BG-COL-HYA-PS复合支架具有与天然骨组织及细胞外基质相似的组成成分、良好的生物相容性和可降解性,在诱导成骨和促进矿化方面性能优越,作为骨缺损修复替代材料应用前景广阔。
Nowadays complex bone defects from various injuries have become a great challenge to orthopedists.To deal with complications associated with autogenous and allogenous bone grafting,people developed various kinds of artificial bone repairing materials(bone substitute),which has become a focus of intensive research in traumaology and tissue engineering.Of all materials available,58s BG has received considerable attention.
To develop an optimal bio-mimetic material for bone repair,this study,based on thorough analysis of literature data,selected bioactive glass(BG) as the principal constituent of the scaffold composite, considering that its chemical components are similar to natural bones and it readily integrates with surrounding bone tissues through tight chemical bond formation.It induces bone formation through biodegradation and has good biocompatibility and osteoconductivity.The composite scaffold BG-COL-HYA-PS was fabricated by crosslinking BG with the major components of natural matrix TypeⅠcollagen(COL),hyaluronic acid(HYA) and phosphatidylserine(PS) and then combined with bone morphogenetic protein(BMP),using the freeze-drying technology.The composite scaffold was evaluated by a series of in vitro and in vivo experiments,for its physical-chemical properties,biocompatibility, osteoinductivity and osteoconductivity.
The experiments were divided into four parts:
1.Fabrication and characterization of the biomimetic BMP-BG-COL-HYA-PS composite material.
The 58S bioactive glass(58SBG) was prepared by solvent-casting process.The BMP-BG-COL-HYA-PS scaffold composites were prepared by mixing nano powders of the bioactive glass,TypeⅠcollagen, hyaluronic acid(HYA),BMP and phosphatidylserine according to different ratios,using a technology of cross-linking followed by freeze-drying.The morphology,porous size and porosity of the composite scaffolds were examined by scanning electron microscopy(SEM). Mechanical strength and characteristics were evaluated by three-point bending tests.Inflation dynamics was examined using phosphate-buffered saline(PBS) as the immersion media.Strength at break is 1.406士0.019MPa;Elastic modulus is 35.812士0.016kPa.
2.Biocompatibility evaluation of the biomimetic BMP-BG-COL-HYA-PS composite material.
Using in vitro cell culture technique,the MSCs were seeded onto composites BMP-BG-COL-HYA-PS.Cell growth and reciprocity were monitored using MTT assay,inversion phase contrast microscope and SEM.Biocompatibility studies were performed on healthy Kunming mice selected according to the evaluation criteria for medical implant materials and the recommended biological and animal tests in GB/T16886.5-1997-ISO 10993-5:1992.These results were used for the evaluation of biological compatibility and safety of the composite materials.
3.Ectopic osteogenic activity of BMP-BG-COL-HYA-PS composite.
To investigate the ectopic osteoinduction and biocompatibility of BMP-BG-COL-HYA-PS composite and BG-COL-HYA-PS composite,they were synthesized and implanted into the muscle pouches in the right and left thigh of mice,respectively.At 2 and 4 week after implantation,the rats were killed,the samples were harvested,and the ectopic new bone formation was detected by X-ray analysis and histologic examination.X-ray analysis revealed that more callus-like shadow appeared adjacent to the implant of BMP-BG-COL-HYA-PS after 4 weeks.Histologically,there was slight acute inflammation in the surrounding tissue of both types of implants at the early stage.With new chondrocytes being evident at all BMP-BG-COL-HYA-PS implanted sites within 2 weeks after implantation.In 4 weeks,all of the implants with BMP-BG-COL-HYA-PS showed new bone formation with characteristics hematopoietic marrow and osseous trabeculae,and the amount of new bone as a result of the use of BMP-BG-COL-HYA-PS was significantly higher than that obtained with BG-COL-HYA-PS.The biocompatibility of composite samples was assessed by cell adhesion,proliferation,and differentiation assays using MSCs cells.MSCs were cultured with the 24h extraction medium of 1st,7th day of BMP-BG-COL-HYA-PS and BG-COL-HYA-PS samples.Cell-material interaction on the surface of the composites was observed by SEM.Cell proliferation and differentiation were measured by MTT.The effects of BMP-BG-COL-HYA-PS on the behavior of MSCs ceils were evaluated in comparison with those of BG-COL-HYA-PS.Morphology investigation of adhered cells by SEM indicated that MSCs cells could adhere,proliferate on the surface of the composite presenting normal morphology.MSCs cells,cultured in the presence of BMP-BG-COL-HYA-PS composite extract samples had a higher proliferation rate as compared to the control sample after 7 days of incubation.All these results suggest that the composite is biocompatible, nontoxic,and in some cases shows an increase in the proliferation rate of the cells as compared to the control.These results indicate that BMP-BG-COL-HYA-PS is more effective in inducing ectopic osteogenesis,that would be useful for repair bone defects.
4.Biomimetic scaffold composite BMP-BG-COL-HYA-PS in the repair of rabbit radius defect
In vivo studies of the biomimetic BMP-BG-COL-HYA-PS composite scaffold for the repair of rabbit radius defects.52 Healthy adult New Zealand rabbits were used as model to create radius defects (center-section belt periosteum 15mm bone damage)on both sides.The defects were implanted with various grafts:BG-COL-HYA-PS and BMP-BG-COL-HYA-PS composites,no implant as the control group. X-Ray radiophotography was taken at weeks 2,4,8 and 12 after operation,and tissue samples were taken for histomorphological and SEM examination.Bone density,mineral apposition rate and bone formation rate were determined at weeks 4 and 12 after operation to evaluate the effectiveness of BMP-BG-COL-HYA-PS composite scaffold for repair of the bone defects.RESULTS:①Gross observation results: The wounds healed by first intention after operation,no fracture occurred. The activity,eating and mental state of the animals were normal basically.②Results of X-ray examination in the defect region:two weeks after the operation,there was significant dense shadow and a degree of porosity at ends of the oseotomy in the BMP-BG-COL-PS-HYA group.At week 8 after operation,cortical bone was fully connected.At week 12 defects were fully repaired and medullary cavity was recanalized basically.③Findings of histomorphologic observation in defect region of rabbits:In the BMP-BG-COL-PS-HYA group,two weeks after operation,osteoblasts were found along the scaffold material and excreted matrix.At weeks 4 it was found that a mass of new bone trabecula grew towards defect center. At week 12 there was no scaffold material in the defect region,which was replaced by new bone tissue fully,and the medullary cavity was recanalized.④Determination results of BMD in defect region of each group:The BMD in the BMP-BG-COL-PS-HYA group was 4.71 times and 1.675 times that in the BG-COL-PS-HYA group at weeks 4 and 12 after operation.F value was equal to 1262.398,P＜0.01 in different experimental groups detected with factorial design and variance analysis. There was significant difference in the LSD-t pair wise comparison P＜0.01.
On the basis of these observations.We can conclude that the biomimetic BMP-BG-COL-PS-HYA composites scaffold has similar composition and structure to the natural bone and extracellular matrix,as well as good biocompatibility and biodegradability.It holds promise in induction of bone formation and mineralization,and should have broad applications as a bone substitute material.
引文
1 李玉宝主编.纳米生物医药材料.北京:化学工业出版社,2004.
2 Tracy W.The Use of an Injectable Bone Graft Substitute in Tibial Metaphysical Fractures Orthopedics,2004,1:S103-107.
3 Kelly CM,Wilkins RM.Treatment of benign bone lesion with an injectablecalcium sulphate-based bone graft substitute.Orthopedics,2004,27(1):131-135.
4 胡蕴玉.把握契机加快我国组织工程学的应用研究.中华骨科杂志,2000,20:517.
5 Joseph M L LTnT'e,Mathias PGB.Biosynthetic bone crafting.Clin Orthop,1999,367S:107-5117.
6 L,clwrcl.Bone morphogenetic protest-2.Clip Orthop,1996,324:39
7 Loin iMU V icki R.Bone morphogenetic protein bone morpho-genetic protein gene fimilv in bone formation end repair.Clin Ortbop,1999,346,26-37
8 Urist MR.Bone formation by auto induetion.Seienee,1965;150:893-899.
9 Urist MR,StratesBS.Bone morphogenetie Protein.JDentRes,1971:50(6):1392-1406.
10 Urist MR et al.A bovine low molecular weight bone morphogenetie Protein(BMP) fraction Clin Orthrop,1982:162:219-227.
11 Riley EA,LaneJM,Urist MR et aI.Bone morphogenetie Protein -2:Biology and application Clinic Orthrop,1996:324:39-6.
12 Iwasaki S,Hattori A,Sato M,et al.Characterization of the bone morphogenetic Protein-2 as a neurotrophic factor.Induction of neuronal differenation of PCI2 cells in the absence ofmitogen-activated Protein kinase activation.J Biol Chem,1996;271(29):17360-17365.
13 Mishina Y,Suzuki A,Gilbert DJ,et al.Genomic organization and chromososmal location ofthe mouse type I BMP-2 receptor.Biochem Biophys Res Commun,1995:206(1):310-317.
14 吴祖尧.诱导成骨与骨形态发生蛋白.中华骨科杂志,1988:(3):23卜234。
15 Nilsson OS,Urist MR,Dawson EG,et al.Bone repair induced by bone mophogenetic Protein in ulnar defects.J Bone Joint Surg(Br),1986:68:635-642.
16 R Osen V,Cox K,Hattersley G.Bone morphogenetic Protein.Princioles of bone biology.New York,Academic Press,1996:661-671.
17 Yatita H,oritno H,Shirai Y,et al.Expression of bone morphogenetie Proteins and rat distal-less homolog genes following gratfe moral fracture.J Bone Miner,2000;18(2):63-70.
18 Bostrom MP,Lane JM,Berberian WS,et al.Immunoloea lization and expression of bone Morphogenetic proteins-2 and 4 infracture healing.J Orthop Res,1995:13(3):357-367.
19 JI X, Chen D, Xu C, et al. Patterns of gene expression as sociated with BMP-2 induced osteo blast and adipocyte differentiation of mesenehymal Progenitor cell 3T3F442A.J Bone MinerMetab, 2000;18(3): 132-139
20 Okubo Y, Bessho K, Fujimura K, et al. osteoinduetion by reeombinant human bone morphogenetic Protein-2 at intrmuseular, intermuseular, subcutaneous and intrafat tysites, Int J Oral Maxillofac Su, 2000;29(1):62-66.
21 Haaijman A.Kerien M,Lanske B,et al. Inhibition of terminal chondroeyte differentiation by bone morphogenetic Protein-7 in vitro depends on the Periartcle region but is indendent Of parathyroid hormone-related Peptide. Bone.1999;25(4):397-04.
22 I.EIgayar, A.E. A lieu, A.R. Boccaccini. Structural analysis of bioacaive glasses. Journal of NonK-Crystalline Solids, 2005, (351):173-183.
23 Na Li, Qing Jic, Sumin Zhu. A new route to prepare macroporous bioactive sol-gel glasses with high meachanical strength [J]. Materials Letters, 2004, (5):2747-2750
24 Mlichela Bosetti, Mario Canvas. The effect of bioactive glasses on bone marrow stromal cell differentiation.Biomaterials, 2005, (26):3873-3879.
25 Richard M. Day, Aldo R. Boccaccini. Assessment of polyglycolic acid mesh and bioactiveglass for soft-tissue engineering scaffolds.Biomaterials. 2004, (25):5857-5866.
26 G. Jiang, M.E. Evans. Preparation of poly(e-caprolactone)/continuous bioglass fibre composite using monomer transfer moulding for bone implant.2004,(8):18.
27 C. Char, I. Thompson. Evaluation of Bioglass/dextran composite as a bone graft substitute. [J].lnt. J. Oral Maxillofac. Surg, 2002,(31):7377
28 Huc A.Collagen biomaterials characteristics and applications [J].J American Leather Chemists Association,1985,80(7):195}212.
29 Santin M, Motta A,Cannas M.Changes in serum conditioning profiles of glutaraldehyde-crosslinked collagen sponges after their treat-ment with calcification inhibition[J].J Biomed Res, 1998, 40(3): 434441
30 Laurent TC, Biochemistry of hyaluronan. Acta Otolaryngol(Strockh), 1987,442(1):724
31 Hunter G K, Hauschka P V, Poole A R et al. Nucleation and inhibition of hydroxyapatite formation by mineralized tissue proteins. J. of Biochem., 1996,317:59-64
32 Hulbert SF, Hench LL, Forbes D, Bowman LS.History of bioceramics. In: Ceramics in Surgery, Ed.P.Vincenzini, 1983, Elsevier Scientific Company, Amsterdam, and Netherlands.3-25.
33 Bieber EJ, Wood MB.Bone reconstruction.Clin Plast Surg.1986; 13:645-55.
34 Bos KE.Bone scintigraphy of experimental composite bone grafts revascularized by microvascular anastomoses.Plast Reconstr Surg.1979; 64:353-60.
35 Doi K, Tominaga S, Shibata T.Bone grafts with microvascular anastomoses ofvascular pedicles: an experimental study in dogs.J Bone Joint Surg Am. 1977; 59:809-15.
36 Enneking WF,Burchardt H,Puhl JJ,Piotrowski G.Physical and biologicalaspects of repair in dog cortical-bone transplants. J Bone Joint Surg Am.1975;57:237-52.
37 Lane JM, Tomin E, Bostrom MPG.Biosynthetic bone grafting.Clin Orthop.1999; 367S:107-17.
38 Mellonig JT, Prewett AB, Moyer MP.HIV inactivation in a bone allograft.J Periodontol.1992; 63:979-83.
39 Mizutani A,Fujita T,Watanabe S,Sakakida K,Okada Y.Experiments onantigenicity in allotransplanted cancellous bone.Int Orthop.1990;14:243-48.
40 Buck BE,Malinin TI,Brown MD.Bone transplantation and humanimmunodeficiency virus.An estimate of risk of acquired immuno deficiencysyndrome(AIDS).Clin Orthop.1989;240:129-36.
41 Bucholz RW, Carlton A, Holmes R.lnterporous hydroxyapatite as a bone graft substitute in tibial plateau fractures.Clin.Orthop.1989; 240:53-62.
42 Hench LL, Polak JM.Third-generation biomedical materials. Science. 2002; 295:1014-16.
43 Jacobs JJ,Skipor AK,Patterson LM,Hallab NJ,Paprosky WG,Black J,GalanteJO.Metal release in patients who have had a primary total hip arthroplasty:Aprospective, controlled,longitudinal study.J Bone Joint Surg Series A.1998;80:1447-58.
44 Okazaki Y,Gotoh E,Manabe T,Kobayashi K.Comparison of metalconcentrations in rat tibia tissues with various metallic implants.Biomaterials.2004;25:5913-20.
45Heinmann RB.Application of plasma sprayed ceramic coatings.Key Eng Mater.1996; 122-124:399-442.
46 Hamaouche M,Meunier A,Greenspan DC,Blanchat C,Zhong JP,La Torre GP,Sedel L.Bioactive of sol-gel bioactive glass coated alumina implants.J BiomedMater Res.2000;52:422-29.
47 Hench LL,Splinter RJ,Allen WC,Greenlee TK.Bonding mechanism at theinterface of ceramic prosthetic materials.J Biomed Mater Res Symp.1971:2:117-41.
48 钟吉平,Hench LL．生物玻璃的研究与进展．无机材料学报．1995;10：129-38.
49 Wang M.Dveloping bioactive composite materials for tissue replacement. Biomaterials.2003; 24:2133-51.
50 Kokubo T, Kim HM, Kawashita M.Novel bioactive materials with different mechanical properties.Biomaterials.2003; 24:2161-75.
51 ItlA,Koort J,Ylnen O,Hupa M,Aro HT.Biological significance of surface microroughing in bone incorporation of porous bioactive glass implants.JBiomed Mater Res.2003;67A:496-503.
52 Ducheyne P,Radin S,King L.The effect of calcium phosphate ceramic composition and structure on in vitro behavior. I .Dissolution.J Biomed MaterRes. 1993:27:25-34.
53 Radin SR,Ducheyne P.Ducheyne P.Radin S,King L.The effect of calciumphosphate ceramic composition and structure On in vitro behavior.Ⅱ.Precipitation.J Biomed Mater Res.1993;27:35-45.
54 李玉宝,生物医用材料,化学工业出版社,2003.80-122.
55 Peltier LF.The use of plaster of Paris to fill defects in bone.Clin Orthop.1961;21:1-31.
56 Peltier LF.Treatment of unicameral bone cyst by curettage and packing withplaster of Paris pellets.J Bone Joint Surg.1978;70:820-22.
57 Oesini G,Ricci J,Scarano A,Pecora G,Petrone G,Lezzi G,Piattelli A.Bone-defect healing with calcium-sulphate particles and cement:Anexperimental study in rabbit.J Biomed Mater Res.2004;68B:199-208.
58 Lu J,Descaps M,Dejou J.Koubi G,Hardouin P,Lemaitre J,Prout JP.Thebiodegradatiob mechanism of calcium phosphate biomaterials in bone.J BiomedMater Res.2002;63B:408-12.
59 Behravesh E,Zygourakis K.Adhesion and migration of marrow-derivedosteoblasts on injectable in situ crosslinkable poly(propylene fumarate-co-ethyleneglycol)-based hydrogels with a covalently linked RGDS peptide.Journal ofBiomedical Materials Research PartA,2003,65A:260-270.
60 Xu YH,Shi XY,Hu WY,et al.Osteogenic activity in vivo of true bone ceramicwith osteoblast compound substances.Journal of the fourth military medicaluniversity,2002,23:223-226.Chinese.
61 张阳德,顾红,李晓莉等.骨组织工程中的支架材料.中国医学工程,2005,13:199-202.
62 Greenspan DC,Zhong JP,Wheeler D.Bioactivity and biodegradability:melt vs.sol-gel-derived bioglass in vitro and in vivo.Bioceramics.1998;11:345-48.
63 Jones JR,Sepulveda P,Hench LL.Dose-dependent behavior of bioactive glassdissolution.J Biomed Mater Res.2002;59B:720-26.
64 Hamadouche M,Meunier A,Greespan DC,Blanchat C,Zhong JP,Torre GPL.Long-term in vivo bioactivity and degradability of bulk sol-gel bioactive glasses.J Biomed Mater Res.2001;54:560-66.
65 Laqueeiere P,Jallot E,Kilian L,Benhayoune H,Balossier G.Effects of bioactiveglass particles and their ionic product on intracellular concentrations.J BiomedMater Res.2003;65A:441-46.
66 Gough JE,Jones JR,Hench LL.Nodule formation and mineralisation of humanprimary osteoblasts cultured on a porous bioactive glass scaffold.Biomaterials.2004;25:2039-46.
67 Silver lA,Erecinska M.Interactions of osteoblastic and other cells with bioactiveglasses and silica in vitro and in vivo.Mat-wiss u Werksofftech.2003;34:1069-75.
68 Bielby R,Christodoulou IS,Pryce RS,Radford WJP,Hench LL,Polak JM.Time-and concentration-dependent effect of dissolution products of 58S sol-gelbioactive glass on proliferation and differentiation of murine and humanosteoblasts.Tiss Engin.2004;10:1018-26.
69 李沁华.天然大分子及其生物材料在组织工程中的应用.现代康复.2001: 5:21-23.
70 郑磊,王前,裴国献.骨组织工程中细胞外基质材料的选择.中华外科杂志.2000;38:745-48.
71 刘彦春,王炜,曹谊林等.卵磷脂、多聚赖氨酸和PLA包埋PGA与软骨细胞体外培养的实验研究.实用美容整形外科杂志.1997;8:225-27.
72 Verrier S,Blaker JJ,Maquet V,Hench LL,Boccaccini AR.PDLLA/Bioglass?composites for soft-tissue and hard-tissue engineering:an in vitro cell biologyassement.Biomaterials.2004;25:3013-21.
73 Kellom?ki M,Niiranen H,Puumanen K,Ashammakhi N,Waris T,Trml P。Bioabsorbable scaffolds for guided bone regeneration and generation.Biomaterials.2000;21:2495-505.
74 Wang XJ,Li YB.Development of biomimetic nano-hydroxyl-apatite /poly(hexamethylene adipamide) composites.Biomaterials,2002,23:4787-4791.
75 Yan YG,Li YB.Synthesis and properties of a copolymer of poly(1,4-phenylene sulfide)-poly(2,4-phenylene sulfide acid) and its HA reinforcedcomposite.European Polymer Journal.2003.39:411-416.
76 沈序辉,宋晨路,等.有机-羟基磷灰石复合骨替代材料.材料科学与工程,1999,17(4):85-90.
77 Bai MH,Liu XY,GE BF et al.An implant of a composite of bovine bonemorphogenetic protein and Plaster of Paris for treatment of femoral shaft nonunion,Int Surg,1996,81:390-392.
78 Takaoka K,Nakahara H,Yoshikawa H,et al.Ectopic bone induction on and in porous Hydroxyapatite combined with collagen and bone morphogenetic protein.Clin Orthop,1988;234:250-254.
79 King GN,King N,Hughes FJ.Effect of two delivery systems for recombinant human bone Morphogenetic protein-2 on periodontal regeneration in vivo.J Periodontal Res,1998;33(4):226-236.
80 Omura S,Mizuki N,Kawabe R.et al.A carrier for clinical use of recombinant human BMP-2:dehydrothermally cross-linked composite of fibrillar and denatured ateloeollagensponge.Int J Oral Maxillofac Surg,1998;27(2):129-134.
81 Mattioli Belmonte M,Gigante A,Muzzarelli RA,et al.N,N-dicarboxymethyl chitosan as delivery agent for bone morphogenetic protein in the repair of articular cartilage.Med BiolEng Comput,1999;37(1):130-134.
82 Schwartz Z,Somers A,Mellonig Jof,et al.Addition of human recombinant boneMorphogenetic protein-2 to inactive commercial human demineralized freeze-dried boneAllograft makes an effective composite bone inductive implant material.J Periodoniol,1998;69(12):1337-1345.
83 Ike M,Urist MR.Recycled dentin root matrix for a carrier of recombinant human boneMorphogenetic protein.J Oral Implantol,1998;24(3):124-132.
84 Katoh T,Sato K,Kawamura M,et al.Osteogenesis in sintered bone combined with bovineBone morphogenetic protein.Clin Orthop, 1993;(287):266-275.
85 胡蕴玉,陆裕朴,刘玮,等.异种骨移植修复骨缺损的实验研究.中华骨科杂志,1990;10(1):33-37.
86 刘玮.陆裕朴,胡蕴玉,等.重组合异种骨的研制及其生物学活性分析.中华医学杂志,1991;71(7):38-42.
87 李亚非,胡蕴玉,宋海燕,等.重组合异种骨在小鼠体内诱导成骨活性的剂量依赖性研究.中华骨科杂志,1995;15(7):447-53.
88 Mattioli Belmonte M,Gigante A,Muzzarelli RA,et al.N,N-dicarboxymethyl chitosan as delivery agent for bone morphogenetic protein in the repair of articular cartilage.Med BiolEng Comput,1999;37(1):130-134.
89 Kubler NR,Moser M,Berr K,et al.Biological activity of E.coli expressed BMp-4.MundKiefer Gesichtschir,1998:S149-S152.
90 Kawakami T,Kawai T,Takei N,et al.Evaluation of heterotopic bone formation inducedby squalane and bone morphogenetic protein composite.Clin Orthop,1997;337:261-266.
91 Kuboki Y,Saito T,Murata M,et al.Two distinctive BMP-carriers induce zonal chondrogenesis and membranous ossification,respectively;geometrical factors of matricesFor cell-differentiation.Connect Tissue Res,1995;32:219-226.
92 Kawakami T,Uji H,Antoh M,Squalane as a possible carrier of bone morphogeneticprotein.Biomaterials,1993;14(8):575-577.
93 Hedner E,Linde A.Efficacy of bone morphogenetic protein(BMP) with osteopromotive.Membranes-an experimental study in rat mandibular defects.Eur J Oral Sci,1995;103(4):236-241.
94 Hayashi K,Inadome T,Tsumura H,et al.Bone-implant interface mechanics of in vivoBioinert ceramics.Biomed Mater Res,1993;14:1173-1179.
95,Christel PS.Biocompatibility of surgical-grade dense polycrystalline alumina.Clin orthop,1992;282:10-18.
96 Gross U,Sehmitz HJ,Strunz V.Surface activities of bioactive glass,aluminum oxide,andTitanium in a living environment.Ann NY Acad Sci,1988;523:211-226.
97 Barbon F,Locardi B,Verita M,et al.Biocompatibility and osteogenetic characteristics of newBiocompatible glass.Biomaterials,1991;12:565-568.
98 Santos EM,Radin S,Shenker BJ,et aI.Si-Ca-P xerogels and bone morphogenetic protein actSynergistically on rat stromal marrow cell differentiation in vitro.J Biomed Mater Res,1998;41:87-94.
99 Ijiri S,Nakamura T,Fujisawa Y,et al.Ectopic bone induction in porous apatite-wollastonite-Containing glass ceramic combined with bone morphogenetic protein.J Biomed Mater Res,1997;35(4):421-432.
100 Kawai T,Mieki A,Ohno Y,et al.Osteoinduective activity of composites of boneMorphogenetic protein and pure titanium.Clin OrthoP,1993;290:296-305.
101 Peppas HA, Lanser R. New challenges in biomaterial、Science, 1994;263:1715-1720.
102 Lam K, Esselburge H, SchakenraadJ, et al. Biodegradable of porous versus non-porouspoly (L-lactic acid) films. J Mater Sci: Mater Med, 1994;5:101-110.
103 Uganuma J, Alexander H. Biological response of intermedullary bone to poly-L-lactic acid.JAppl Biomat, 1993;4:13-16.
104 Agrawal C, Achanasion KA.Technique to control PH in vicinity of biodegrading PLA-PAGimplants. J Biomed Mater Res, 1997:38:105-114.
105 Strunz V,Bunte M,Stellmach R,Gross U,Kuhl K,Newesely H,Bromer H,Deutscher K.Glass ceramics as a bioactive implantation material.DtschZahnarztl Z.1976;31(1):69-70
106 Kokubo T,Ito S.Sakka S.Formation of a high-strength bioactive glass-ceramicin the system MgO-CaO-SiO2-P2O5.J Mater Sci. 1986;21:536-40.
107 W.Vogel and W.HIand.Development,structure,properties and application ofglass-ceramics for medicine.J Non-Crys Sol. 1990; 123:349-53.
108 Zhong JP, Greenspan DC.Processing and properties of sol-gel bioactive glasses.J Biomed Mater Res.2000; 53A:694-701.
109 Li Rclark AE, Hench LL.An investigation of bioactive glass powders by sol-gelprocessing.J Appl Biomater.1999; 2:231-39.
110 Sepulveda P, Jones JR, Hench LL.Characterization of melt-derived 45S5 andsol-gel derived 58S bioactive glasses.J Biomed Mater Res.2001; 58A.734-40.
111 Perez-Pariente J, Balas F, Vallet-RegiM.Surface and chemical study ofSiO2·P2O5·CaO (MgO) bioactive glasses.Chem Mater.2000; 12:750-55.
112 Balas F, Perez-Pariente J, Vallet-RegiM.Relationship between bioactivity andtextural parameters in glasses.Bioceramics.1998; 11:125-28.
113 Arcos D, Greenspan DC, Vallet-Regf.lnfluence of the stabilization temperatureon textural and structural features and ion release in SiO2-CaO-P2O5 sol-gelglasses.Chem Mater.2002; 14:1515-22.
114 Gatti AM,Hench LL,Gonella F,Caccavale F.Test of bioactivity in four differentglasses.Bioceramics.1997;10:287-90
115 Ramila M, Vallet-RegiM.Static and dynamic in vitro study of a sol-gel glassbioactivity.Biomaterials.2001; 22:2301-06.
116 Izquierdo-Barba I, Salinas AJ, Vallet-Regi.ln vitro calcium phosphate layerformation on sol-gel glasses of the CaO-SiO2 system.J Biomed Mater Res.1999; 47:243-50.
117 Miyaji F,Kim HM,Handa S,Kokubo T,Nakamura T.Bonelike apatite coatingon organic polymers:novel nucleation process using sodium silicate solution.Biomaterials.1999;20:913-19.
118 Zhu P, Masuda Y, Koumoto K.The effect of surface charge on hydroxyapatite nucleation.Biomaterials.2004; 25:3915-21.
119 Hench LL, Wilson J.Bioactive glasses: present and future. Bioceramics.1998; 11:31-36.
120 Greenspan DC, Zhong JP, Chen XF, LaTorre GP.The evaluation of degradablityof melt and sol-gel derived bioglass in-vitro.Bioceramics.1997;10:391-94.
121 Huang ZJ,Yang YP,Guo X,Li CJ,Yang LH.Biodegradation of crystalline glasscontaining calcium phosphate.Bioceramics.1996;9:147-50.
122 Webster TJ,Ergun C,Doremus RH,et al.Enhanced osteoclast-like cell functionon nanophase ceramics.Biomatedals,2001,22:1327-1333.
123 王身国,杨健,蔡晴,石桂欣,贝建中.组织工程用生物材料及细胞支架研究进展.中华整形外科杂志.2000;16:328-30.
124 Zhong JP,Greenspan DC.Processing and propertiew of sol-gel bioactive glasses.J Biomed Mater Res A.2000;53:694-701.
125 Hench LL,Splinter RJ,Allen WC,Greenlee TK.Bonding mechanism at theinterface of ceramic prosthetic materials.J Biomed Mater Res Symp.1971;2:117-41
126 Kojubo T,Shigematsu M,Nagashima Y.Bull Inst Chem Res.Kyoto Univ.1982;60:260-68.
127 Kokubo T,Ito S,Yamamuro T.Formation of a high-strength bioactive glass-ceramic in the system MgO-CaO-SiO2-P2O5.J Mater Sci.1986;21:536-40.
128 Bromer H,Pfeil E,Kas HH.German Patent 2323100,1973.
129 Vogel W.玻璃科学技术前沿.1984年北京国际玻璃讨论会议论文集.1984,44.
130 Li R,Clark AE,Hench LL.An investigation of bioactive glass powders by sol-gel processing.J Appl Biomater.1991;2:231-39.
131 扬志明.组织工程 北京:化学工业出版社,2002.1-3
132 Bauer TW,Muschler GF.Bone graft materials.An overview of the basic science.Ciin Orthop Relat Res 2000[(371):10-27
133 Thomas J.Webster,Celaletd in Ergun,Robert H.Doremus,et al.Specific proteins mediate enhanced osteoblast adhesion on nanophase ceramics.J Biomed Mater Res.2000 Sep.5;51(3):475-83.
134 Thomas J.Webster,Richard W.Siegel,Rena Bizios.Osteoblast adhesion on nanophase ceramics.Biomaterials.1999 Ju1;20(13):1221-7.
135 王身国,贝建中.组织工程细胞支架及其相关技术的研究[J].中国创伤骨科杂志,2000,2(4):277-9
136 Houseman BT,Mrksich M.The microenvironment of immobilized Arg-Gly-Asppeptides is an important determinant of cell adhesion.Biomaterials 2001[22(9):943-55
137 付静.陈晓峰.张梅梅,等.医用生物活性玻璃的红外光谱分析及其生物活性探讨[J].生物医学工程杂志,1999,16(增刊):22-4
138 Termine JD,Belcourt AB,Conn KM,et al.Mineral and collagen-bindingproteins of fetal calf bone.J Biol Chem 1981[256(20):10403-8
139 Damien CJ,Ricci JL,Christel P,et al.Formation of a calcium phosphate-richlayer on absorbable calcium carbonate bone graft substitutes.Calcif Tissue Int1994[55(2):151-8
140 Saito N,Takaoka K.New synthetic biodegradable polymers as BMP carriers forbone tissue engineering.Biomaterials 2003,24:2287-93.
141 S.D.Putney,P.A.Burke,Improving protein therapeutics with sustained-releaseformulations.Nat.Biotechnol.1998,16:153 - 157.
142 Miyamoto S,Takaoka K,Okada T,Yoshikawa H,Hashimoto J,Suzuki S,Ono K.Evaluation of polylactic acid homopolymers as carriers for bone morphogeneticprotein.Clin Orthop 1992;278:274-85.
143 C.A.Kirker-Head,Potential applications and delivery strategies for bone morphogenetic proteins,Adv.Drug Deliv.2000 43(12):65-92.
144 Y.Tabata,Tissue regeneration based on growth factor release,Tissue Eng.2003,9(Suppl.l) S5-S 15.
145 Douglas S.Musgrave,Patrick Bosch,Joon Y.Lee.Ex Vivo Gene Therapy to Produce Bone Using Different CELL Types.Clin Orthop,2000,378:290-305.
146 R.Z.LeGeros,Properties of osteoconductive biomaterials:calcium phosphates,Clin.2002,(10):81-98.
147 L.Meinel,V.Kareourgiou,R.Fajardo,B.Snyder,V.Shinde-Patil,L.Zichner,D.Kaplan,R.Langer,G.Vunjak-Novakovic,Bone tissue engineering using humanmesenchymal stem cells:effects of scaffold material and medium flow,Ann.Biomed.Eng.2004,32:112-122.
148 Petite H,Viateau V,Bensaid W,Meunier A,Pollak C,Bourguignon M,Oudina K,Sedel L,Guillemin G.Tissueengineered bone regeneration.Nat Biotechnol2000;18:959-63.
149 T.W.Bauer,G.F.Muschler,Bone graft materials.An overview of the basic science.Clin.2000(10):10-27.
150 Filho OP,LaTorre GP,Hench LL.Effect of crystallization on apatite-layerformation of bioactive glass 45S5.J Biomed Mater Res.1996;30:509-14.
151 Rajendran V,Nishaa Begum A,Azooz MA,Batal FH.Microstructure aldependence on relevant physical-mechanical properties on SiO2-Na2O-CaO-P2O5 biological glasses.Biomaterials.2002;23:4263-75.
152 Lee YK,Kim KN,Choi SY,Kim CS.Effect of iron state on crystallization anddissolution in Fe2O3-CaO-SiO2 glasses.J Mater Sci:Mater Meal.2000;11:511-15.
153 Vallet-RegiM,Izquierdo-Barba I,Salinas AJ.Influence of P2O5 on crystallinityof apatite formed in vitro on surface of bioactive glasses.J Biomed Mater Res.1999;46:560-65.
154 中华人民共和国国家标准.多孔陶瓷性能测试方法.GB/T 1996.
155 Wake MC,Patrick CW,Mikos AG.Pore morphology affects on the fibrovasculartissue growth in porous polymer subst rates.Cell Transplant,1994,3:339-343.
156 Ishaug SL,Crane GM,Misser MJ.Bone formation by thrcc dimentional stromalosteoblast culture in biodegradable polymer scaffolds.J Biomed Mater Res,1997,36:17-28.
157 Cook AD,Hrkach JS,Gao NN,et al.Characterization and development ofRGD-peptide-modified poly(lactic acid-co-lysine)as an interactive,resorbablebiomatedals.J B iomed Mater Res,1997,35:513-523.
158 Zheng J,Northrup SR,Homsby PJ.Modification of materials formed formpoly (L-lactic-co-glycolic acid) to enable covalent binding of biopolymers:application to high-density three-dimensional cell culture in foams with attachedcollagen.In Vitro Cell Der Biol Anim,1998,34:679-684.
159 R.A.A.Muzzarelli,C.Zucchii,P.Llari,et al.Osteoconductive properties ofmethylpyrrolidinone chitosan in an animal model.Biomaterials.1993April 14(12):925-929.
160 K.A.HING,S.M.BEST,K.E.TANNER,et al.Quantification of boneingrowth within bone-derived porous hydroxyapatite implants of varyingdensity.J Mater Sci Mater Med.1999 Oct-Nov;10(10/11):663-70.
161 Flautre B,Descamps M,Delecourt C,et al.Porous HA ceramic for bonereplacement:role of the pores and interconnections -- experimental studyin the rabbit.Mater Sci Mater Med.2001 Aug;12(8):679-82.
162 Wei J,Li YB.Tissue engineering scaffold material of nanoapatite rystals and polyamide composite.Eur Polymer J,2004,40:509 -- 515.
163 Biomaterial aspects of Interpore-200 poroushydroxyapatite.Dent Clin North Am.1986 Jan;30(1):49-67.
164 柴本浦,汤学明,李慧.骼部骨折患者中股骨肋颈松质的破骨细胞性骨吸收.中华骨科杂志,1995,15(5):291-296.
165 Walsh W R,Labrador D P,Kim H K.Ultrasonic properties of cortical bone following fluorideion treatment.Am.Biomed.Eng.,1994,22:404-414.
166 Walsh W R,Ohno M,Guzelsu N.Bone composite behavior:effects of mineral organic bonding.J.Mater.Sci.Mater.Med.,1994,5:72-79.
167 薛庆善.体外培养的原理与技术.(第一版).北京.科学出版社.2001:p53.
168 Lin HR,Yeh YJ.Porous alginate/hydroxyapatite composite scaffolds for bonetissue engineering:preparation,characterization,and in vitro studies.J BiomedMater Res.2004;71B:52-65.
169 Kokubo T,Kushitani H,Sakka S,Kitsugi T,Yamamuro T.Solutions able toreproduce in vivo surfaces-tructure changes in bioactive glass-ceramic A-W.JBiomed Mater Res 1990;24:721-34.
170 Greenspan DC,Zhong JP,LaTorre GP.Effect of surface area to volume ratio onin vitro surface reactions of bioactive glass particulates.Bioceramics.1994;7:55-60.
171 涂杰等,生物玻璃矿化性能及其离子溶出对成骨细胞功能的影响。无机材料学报 2007,2。3-7。
172 Wang JS,Goodman S,Aspenberg P.Bone formation in the presence ofphagocytosable hydroxyapatite particles.Clin Orthop,1994,304:272-279.
173 Li JG.Characterization of calcium phosphates precipitated from simulated bodyfluid of different buffering capacities.Biomatedals,1997,18:743-747.
174 Tertinnikov ON.In vitro hydroxyapatite deposition onto a film surface-graftedwith organophosphate polymer.J Biomed Mater Res,1994,28:1365-1373.
175 Kokubo T.Apatite formation on organic polymers by a biomimetic process.EurJ Solid State Inorg Chem,1995,32:819-827.
176 Hats K,Kokubo T.Growth bone like apatite Layer on a substrate by abiomimetic process.J Am Ceram Soc,1995,78:1049-530.
177 Hench LL,Splinter RJ,Allen WC,Greenlee TK.Bonding mechanism at theinterface of ceramic prosthetic materials.J Biomed Mater Res Symp.1971;2:117-41
178 Hench LL.Bioceramics(Andersson,Happonen and Yli-Urpo Oxford:Butterworth-Heinemann).1990;7:241.
179 Kokubo T,Kushitani H,Sakka S,Kitsugi T,Yamamuro T.Solutions able toreproduce in vivo surfaces-tructure changes in bioactive glass-ceramic A-W.JBiomed Mater Res 1990;24:721-34.
180 Rizkalla AS,Jones QW,Routledge T,Hall GC,Langman M.Chemical reactivityof experimental bioactive glasses.Bioceramics.1998;11:133-40.
181 Ylnen H,Karlsson KH,Aro HT.Effect of immersion in SBF on porousbioactive bodies made by sintering bioactive glass microapheres.J Non-CrysSolids.2000;47:107-15.
182 Perez-Pariente J,Balas F,Roman J,Salinas AJ,Vallet-RegiM.Influence ofcomposition and surface characteristics on the in vitro bioactivity ofSiO2-CaO-P2O5-MgO sol-gel glasses.J Biomed Mater Res.1999;47:170-75.
183 李玉宝.生物医用材料.化学工业出版社.2003.5.p80-122.
184 Jones JR,Sepulveda P,Hench LL.Dose-dependent behavior of bioactive glassdissolution.J Biomed Mater Res.2002;59B:720-26.
185 Hamadouche M,Meunier A,Greenspan DC,Blanchat C,Zhong JP,Torre GPL.Long-term in vivo bioactivity and degradability of bulk sol-gel bioactive glasses.J Biomed Mater Res.2001;54:560-66.
186 Hench LL.Bioceramics:from concept to clinic.J Am Ceramics Soc,1991,74:1487.
187 Hench LL,Wilson H.An Introduction to Bioceramics,world Scientific,London,1993.
188 Kokubo T.Recent progress in.glass-based materials for biomedicalapplications.J Ceram Soc,Japan,1991,99:965-973.
189 Kokubo T.Bioactive glass ceramics:properties and application.Biomaterials,1991,12:155-163.
190 Khor KA,Li H,Cheang P,et al.In vitro behavior of HVOF sprayed calciumphosphate splats and coatings.Biomaterials,2003,24:723-735.
191 Gu YW,Khor KA,Cheang P.In vitro studies of plasma-sprayed hydroxyapatite/Ti-6Al-4V composite coatings in simulated body fluid(SBF).Biomaterials,2003,24:1603-1611.
192 彭雪林,李玉宝,王学江,等.医用纳米羟基磷灰石/聚酰胺66复合材料体外浸泡行为研究.功能材料,2004,35:253-256.
193 滕勇,胡蕴玉,王臻等。成人骨髓基质干细胞体外定向诱导分化为软骨细胞的实验研究。中国实验外科杂志,2005,22:17-19。
194 邓小明,朱科明主编:常用实验动物麻醉,上海:第二军医大学出版社,2001.
195 Kasten Griensven M,et al.Comparison of human bone marrow stromal cell seeded on calcium-deficient hydroxyap-antite,beta-tricalcium phosphate and demineralized bone matrix.Biomaterials,2003,24:2593-2603.
196 ISO 10993(ISO/TC 194):Biological evaluation of medical devices.
197 张真,卢晓风等.生物材料有效性和安全性评价的现状与趋势,生物医学工程杂 志,2002,19(1):117-121.
198 郝和平,奚廷斐,卜长生主编:医疗器械监督管理和评价,北京:中国医药科技出版社,2001.
199 杨晓芳,奚廷斐.生物材料生物相容性评价研究进展.生物医学工程杂志,2001,18(1):123-128.
200 Johson HJ.Biocompatibility test procedures for materials evalation invitro:comparative test system sensitivity.J Biomed Mater Res,1983,17:571-575.
201 张彩霞,闻学雷等.生物材料体内外试验相关性研究-细胞与软组织毒性.中国生物医学工程学报,2002,21(4):122-127.
202 郝和平主编:生物医学材料生物学评价标准实施指南,北京,中国标准出版社,2000.
203 BS 5736(United Kingdom):Evaluation of medical devices for biological harzards,1989
204 ASTM F748-95,Annual Book of ASTM Standards,1998,13(1)193-197
205 Sabita S.Screening of in vitro cytotoxicity by the adhecive test.Biomaterials,1990,11(3):133-136.
206 R.Yang,Y.J.Wang,X.F.Chen,N.R.Zhao.Biomimetic fabrication of BCP/COL/HCA scaffolds for bone tissue engineering.Materials Letters,2005,59:3635-3640.
207 张晓凯,陈晓峰.BG PHBV复合多孔组织工程支架材料的动物植入实验观察.电子显微学报,2004,6:169-172.
208 任耀彬,郑裕东.用于骨组织工程的羟基丁酸-戊酸共聚物生物活性玻璃复合多孔支架材料.高分子材料科学与工程,2003,20:193-199.
209 Yingjun Wang,Chunrong Yang,Xiaofeng Chen,Naru Zhao.Development and Characterization of NovelBiomimetic Composite Scaffolds Based on Bioglass-Collagen-Hyaluronic Acid-Phosphatidylserine for Tissue Engineering Applications.Macromolecular Material and Engineering,2005,10:1-8.
210 Cole BJ,Bostrom MP,Pritchard TL.et al.Use of bone morphogenetic protein 2 on ectopic porous coated implants in the rat.Clin Orthop Relat Res.1997:219-228.
211 Whang k.tsai DC,Nam EK.et al.Ectopic bone formation via rhBMP-2delivery from porous bioabsorbable polymer scaffolds.J Biomed Mater Res.1998,42:491-499.
212 Tsurga E,Takita H,Itoh H.et al.Pore size of porous hydroxyapatite as the cell-substratum controls BMP-induced osteogenesis.J Biochem 1997,121:317-324.
213 Ekelund A,Brosjo O,Nilsson OS.Experimental induction of heterotopic bone.Clin Orthop Relat Res,1991:102-112.
214 Hollinger JO,Schmitt JM,Buck DC.et al.Recombinant human bone morphogenetic protein-2 and collagen for bone regeneration.J Biomed Mater Res.1998,43:356-364.
215 K.A.HNIG,5.M.BEST,K.E.TANNER,etal.Quantification of bone ingrowth within bone-derived Porous hydroxyapatitc implants of varying density.J MaterSci Mater Med.1999Oet-Nov:10(10/11):663-70.
216 Kim HW,Kim HE,Salih V.Stimulation of osteoblast responses to biomimetic nanocomposites of gelatin-hydroxyapatite for tissue engineering scaffolds.Biomaterials 2005[26(25):5221-30
217 Liao SS,Cui FZ,Zhang W,et al.Hierarchically biomimetic bone scaffoldmaterials:nano-HA/collagen/PLA composite.Biomed Mater Res B ApplBiomater 2004[69(2):158-65Bauer TW,Muschler GF.Bone
218 Arrington ED,Smiht WJ,Chmabers HG etal.Complications of lilac crest bone graft harvesting..Clin Ortho P1996;329:300-9.2
219 Ripamonti U,Duneas N.Tissue engineering of bone by osteoinductive biomaterials.MRS Bull 1996;21:36-9.
220 Racquet Zapanta LeGeros.Properties of Osteoconductive Biomaterials:Calcium Phosphates.Clin Orthop Relat Res.2002 Feb;(395):81-98.
221 Walsh WR,Chapman-Sh eath PJ,Cain S,et al.A resorbable porous ceramiccomposite bone graft substitute in a rabbit metaphyseal defect model.J Orthop Res,2003,21:655-661.
222 Caba as MV,Roddguez-Lorenzo LM,Vallet-Regi M.Setting behavior and invitro bioactivity of hydroxypatite/calcium sulfate cements.Chem Mater2002;14:3550-3555.
223 Wang JS,Nilsson M,Wielanek,et al.Factors controlling the injection andsetting of calcium sulphate with hydroxyapatite cement.In:Hawaii A,von RecumAF,Lucas LC,editors.Sixth World Biomaterials Congress Transactions,Society forBiomaterials;2000.p.805.
224 张梅霞:靳安民:闵少雄:丁金勇,仿生型生物玻璃/胶原蛋白/磷脂酰丝氨酸/透明质酸复合支架修复兔桡骨缺损,2006,29,382:42-50.
225 张梅霞:靳安民:杨春蓉:姚瑶:李妙.The compatibility of Osteoblast on the biomimetic composite scaffold BG-COL-HYA-PS.中国临床解剖学杂志,2006,4,33-36
226 李向军:陈晓峰:王迎军:赵娜如:杨春蓉.一种新型仿生骨组织工程支架的制备与表征,2007,9:56-58.
227 Thomsom RC,Yasko MJ,Powers JM et al.Hydroxyapatite Biomaterials,1998,19:fiber reinforcedpoly(a-hydmxyester) foams for bone regeneration.1935-1943
228 Petra Eiselt,Julia Yeh,Rachel K,et al.Porous carriers for biomedical applications based on alginate hydragels.Biomaterials,2000,21:1921-1927
229 Zhang R,Ma PX.Poly(a-hydroxyl acids)/hydmxyapatite porous composites for bone tissue engineering.J Biomed Mater Res,1999,44:446-455
230 Jeffrey D,Hartgerink,Ella Beniash,et al.Self-assembly and mineralization of peptide-amphihile nanofihers.Science,2001,294:1684-1687
231 Karen J.Lengmeermg.Burg,ScottBiomaterialsPorter,James F.kellam.Biomaterial developments for bone tissue2000,21:23-49
232 Huipin Yuan,Kenji Kurashina,Joost D.de Bruijn,et al.A preliminarystudy on osteoinduction of two kinds of calcium phosphate ceramics.Biomaterials.1999 Oct;20(19):1799-806.
233 Ishaug-Riley SL,Crane GM,Gurlek A,Miller MJ,YaskoYaszemski MJ,Mikos ACz Ectopic bone formation by marrow stromalsosteoblast transplantation using poly (L-lactic-co-glycolic poly (L-lactic-co-glycolic acid) foams implanted into the rat mesentery. JBiomed Mater Res 1997; 36:1-8.
234 G.W.R. Walsh a, PJ.Chapman-Sheath, S.Cain, et al.A resorbable porousmetap seal defectceramic composite bone graft substitute in a rabbitmodel.J Orthop Res, 2003 Ju1; 21(4):655-61.
235 Christine Loty, Jean-Michel Sautier, Habib Boulekbache.et al. In vitrobone formation on a bone-like apatite layer prepared by a biomimeticprocess on a bioactive glass-prepared by a biomimetic process on abioactive glass-ceramic. J Biomed Mater Res, 49, 423-434, 2000.
236 J. X. LU, B. FLAUTRE, K. ANSELME.et al. Role of interconnections inporous bioceramics on bone recolonization in vitro and in vivo. J MaterSci Mater Med. 1999 Feb; 10(2):111-20.
237 Felicity R. Rose, Lesley A. Cyster, David M. Grant,et al. In vitroassessment of cell penetration into porous droxyapatite scaffolds with a central aligned channel. Biomaterials. 2004 Nov; 25(24):5507-14.
238 Stubbs D, Deakin M, Chapman-Sheath P, et al.In vivo evaluation ofresorbable bone graft substitutes in a rabbit tibial defect model. Biomaterials, 2004, 25: 5037-5044.
2 Tracy W.The Use of an Injectable Bone Graft Substitute in Tibial Metaphysical Fractures Orthopedics,2004,1:S103-107.
3 Kelly CM,Wilkins RM.Treatment of benign bone lesion with an injectablecalcium sulphate-based bone graft substitute.Orthopedics,2004,27(1):131-135.
4 胡蕴玉.把握契机加快我国组织工程学的应用研究.中华骨科杂志,2000,20:517.
5 Joseph M L LTnT'e,Mathias PGB.Biosynthetic bone crafting.Clin Orthop,1999,367S:107-5117.
6 L,clwrcl.Bone morphogenetic protest-2.Clip Orthop,1996,324:39
7 Loin iMU V icki R.Bone morphogenetic protein bone morpho-genetic protein gene fimilv in bone formation end repair.Clin Ortbop,1999,346,26-37
8 Urist MR.Bone formation by auto induetion.Seienee,1965;150:893-899.
9 Urist MR,StratesBS.Bone morphogenetie Protein.JDentRes,1971:50(6):1392-1406.
10 Urist MR et al.A bovine low molecular weight bone morphogenetie Protein(BMP) fraction Clin Orthrop,1982:162:219-227.
11 Riley EA,LaneJM,Urist MR et aI.Bone morphogenetie Protein -2:Biology and application Clinic Orthrop,1996:324:39-6.
12 Iwasaki S,Hattori A,Sato M,et al.Characterization of the bone morphogenetic Protein-2 as a neurotrophic factor.Induction of neuronal differenation of PCI2 cells in the absence ofmitogen-activated Protein kinase activation.J Biol Chem,1996;271(29):17360-17365.
13 Mishina Y,Suzuki A,Gilbert DJ,et al.Genomic organization and chromososmal location ofthe mouse type I BMP-2 receptor.Biochem Biophys Res Commun,1995:206(1):310-317.
14 吴祖尧.诱导成骨与骨形态发生蛋白.中华骨科杂志,1988:(3):23卜234。
15 Nilsson OS,Urist MR,Dawson EG,et al.Bone repair induced by bone mophogenetic Protein in ulnar defects.J Bone Joint Surg(Br),1986:68:635-642.
16 R Osen V,Cox K,Hattersley G.Bone morphogenetic Protein.Princioles of bone biology.New York,Academic Press,1996:661-671.
17 Yatita H,oritno H,Shirai Y,et al.Expression of bone morphogenetie Proteins and rat distal-less homolog genes following gratfe moral fracture.J Bone Miner,2000;18(2):63-70.
18 Bostrom MP,Lane JM,Berberian WS,et al.Immunoloea lization and expression of bone Morphogenetic proteins-2 and 4 infracture healing.J Orthop Res,1995:13(3):357-367.
19 JI X, Chen D, Xu C, et al. Patterns of gene expression as sociated with BMP-2 induced osteo blast and adipocyte differentiation of mesenehymal Progenitor cell 3T3F442A.J Bone MinerMetab, 2000;18(3): 132-139
20 Okubo Y, Bessho K, Fujimura K, et al. osteoinduetion by reeombinant human bone morphogenetic Protein-2 at intrmuseular, intermuseular, subcutaneous and intrafat tysites, Int J Oral Maxillofac Su, 2000;29(1):62-66.
21 Haaijman A.Kerien M,Lanske B,et al. Inhibition of terminal chondroeyte differentiation by bone morphogenetic Protein-7 in vitro depends on the Periartcle region but is indendent Of parathyroid hormone-related Peptide. Bone.1999;25(4):397-04.
22 I.EIgayar, A.E. A lieu, A.R. Boccaccini. Structural analysis of bioacaive glasses. Journal of NonK-Crystalline Solids, 2005, (351):173-183.
23 Na Li, Qing Jic, Sumin Zhu. A new route to prepare macroporous bioactive sol-gel glasses with high meachanical strength [J]. Materials Letters, 2004, (5):2747-2750
24 Mlichela Bosetti, Mario Canvas. The effect of bioactive glasses on bone marrow stromal cell differentiation.Biomaterials, 2005, (26):3873-3879.
25 Richard M. Day, Aldo R. Boccaccini. Assessment of polyglycolic acid mesh and bioactiveglass for soft-tissue engineering scaffolds.Biomaterials. 2004, (25):5857-5866.
26 G. Jiang, M.E. Evans. Preparation of poly(e-caprolactone)/continuous bioglass fibre composite using monomer transfer moulding for bone implant.2004,(8):18.
27 C. Char, I. Thompson. Evaluation of Bioglass/dextran composite as a bone graft substitute. [J].lnt. J. Oral Maxillofac. Surg, 2002,(31):7377
28 Huc A.Collagen biomaterials characteristics and applications [J].J American Leather Chemists Association,1985,80(7):195}212.
29 Santin M, Motta A,Cannas M.Changes in serum conditioning profiles of glutaraldehyde-crosslinked collagen sponges after their treat-ment with calcification inhibition[J].J Biomed Res, 1998, 40(3): 434441
30 Laurent TC, Biochemistry of hyaluronan. Acta Otolaryngol(Strockh), 1987,442(1):724
31 Hunter G K, Hauschka P V, Poole A R et al. Nucleation and inhibition of hydroxyapatite formation by mineralized tissue proteins. J. of Biochem., 1996,317:59-64
32 Hulbert SF, Hench LL, Forbes D, Bowman LS.History of bioceramics. In: Ceramics in Surgery, Ed.P.Vincenzini, 1983, Elsevier Scientific Company, Amsterdam, and Netherlands.3-25.
33 Bieber EJ, Wood MB.Bone reconstruction.Clin Plast Surg.1986; 13:645-55.
34 Bos KE.Bone scintigraphy of experimental composite bone grafts revascularized by microvascular anastomoses.Plast Reconstr Surg.1979; 64:353-60.
35 Doi K, Tominaga S, Shibata T.Bone grafts with microvascular anastomoses ofvascular pedicles: an experimental study in dogs.J Bone Joint Surg Am. 1977; 59:809-15.
36 Enneking WF,Burchardt H,Puhl JJ,Piotrowski G.Physical and biologicalaspects of repair in dog cortical-bone transplants. J Bone Joint Surg Am.1975;57:237-52.
37 Lane JM, Tomin E, Bostrom MPG.Biosynthetic bone grafting.Clin Orthop.1999; 367S:107-17.
38 Mellonig JT, Prewett AB, Moyer MP.HIV inactivation in a bone allograft.J Periodontol.1992; 63:979-83.
39 Mizutani A,Fujita T,Watanabe S,Sakakida K,Okada Y.Experiments onantigenicity in allotransplanted cancellous bone.Int Orthop.1990;14:243-48.
40 Buck BE,Malinin TI,Brown MD.Bone transplantation and humanimmunodeficiency virus.An estimate of risk of acquired immuno deficiencysyndrome(AIDS).Clin Orthop.1989;240:129-36.
41 Bucholz RW, Carlton A, Holmes R.lnterporous hydroxyapatite as a bone graft substitute in tibial plateau fractures.Clin.Orthop.1989; 240:53-62.
42 Hench LL, Polak JM.Third-generation biomedical materials. Science. 2002; 295:1014-16.
43 Jacobs JJ,Skipor AK,Patterson LM,Hallab NJ,Paprosky WG,Black J,GalanteJO.Metal release in patients who have had a primary total hip arthroplasty:Aprospective, controlled,longitudinal study.J Bone Joint Surg Series A.1998;80:1447-58.
44 Okazaki Y,Gotoh E,Manabe T,Kobayashi K.Comparison of metalconcentrations in rat tibia tissues with various metallic implants.Biomaterials.2004;25:5913-20.
45Heinmann RB.Application of plasma sprayed ceramic coatings.Key Eng Mater.1996; 122-124:399-442.
46 Hamaouche M,Meunier A,Greenspan DC,Blanchat C,Zhong JP,La Torre GP,Sedel L.Bioactive of sol-gel bioactive glass coated alumina implants.J BiomedMater Res.2000;52:422-29.
47 Hench LL,Splinter RJ,Allen WC,Greenlee TK.Bonding mechanism at theinterface of ceramic prosthetic materials.J Biomed Mater Res Symp.1971:2:117-41.
48 钟吉平,Hench LL．生物玻璃的研究与进展．无机材料学报．1995;10：129-38.
49 Wang M.Dveloping bioactive composite materials for tissue replacement. Biomaterials.2003; 24:2133-51.
50 Kokubo T, Kim HM, Kawashita M.Novel bioactive materials with different mechanical properties.Biomaterials.2003; 24:2161-75.
51 ItlA,Koort J,Ylnen O,Hupa M,Aro HT.Biological significance of surface microroughing in bone incorporation of porous bioactive glass implants.JBiomed Mater Res.2003;67A:496-503.
52 Ducheyne P,Radin S,King L.The effect of calcium phosphate ceramic composition and structure on in vitro behavior. I .Dissolution.J Biomed MaterRes. 1993:27:25-34.
53 Radin SR,Ducheyne P.Ducheyne P.Radin S,King L.The effect of calciumphosphate ceramic composition and structure On in vitro behavior.Ⅱ.Precipitation.J Biomed Mater Res.1993;27:35-45.
54 李玉宝,生物医用材料,化学工业出版社,2003.80-122.
55 Peltier LF.The use of plaster of Paris to fill defects in bone.Clin Orthop.1961;21:1-31.
56 Peltier LF.Treatment of unicameral bone cyst by curettage and packing withplaster of Paris pellets.J Bone Joint Surg.1978;70:820-22.
57 Oesini G,Ricci J,Scarano A,Pecora G,Petrone G,Lezzi G,Piattelli A.Bone-defect healing with calcium-sulphate particles and cement:Anexperimental study in rabbit.J Biomed Mater Res.2004;68B:199-208.
58 Lu J,Descaps M,Dejou J.Koubi G,Hardouin P,Lemaitre J,Prout JP.Thebiodegradatiob mechanism of calcium phosphate biomaterials in bone.J BiomedMater Res.2002;63B:408-12.
59 Behravesh E,Zygourakis K.Adhesion and migration of marrow-derivedosteoblasts on injectable in situ crosslinkable poly(propylene fumarate-co-ethyleneglycol)-based hydrogels with a covalently linked RGDS peptide.Journal ofBiomedical Materials Research PartA,2003,65A:260-270.
60 Xu YH,Shi XY,Hu WY,et al.Osteogenic activity in vivo of true bone ceramicwith osteoblast compound substances.Journal of the fourth military medicaluniversity,2002,23:223-226.Chinese.
61 张阳德,顾红,李晓莉等.骨组织工程中的支架材料.中国医学工程,2005,13:199-202.
62 Greenspan DC,Zhong JP,Wheeler D.Bioactivity and biodegradability:melt vs.sol-gel-derived bioglass in vitro and in vivo.Bioceramics.1998;11:345-48.
63 Jones JR,Sepulveda P,Hench LL.Dose-dependent behavior of bioactive glassdissolution.J Biomed Mater Res.2002;59B:720-26.
64 Hamadouche M,Meunier A,Greespan DC,Blanchat C,Zhong JP,Torre GPL.Long-term in vivo bioactivity and degradability of bulk sol-gel bioactive glasses.J Biomed Mater Res.2001;54:560-66.
65 Laqueeiere P,Jallot E,Kilian L,Benhayoune H,Balossier G.Effects of bioactiveglass particles and their ionic product on intracellular concentrations.J BiomedMater Res.2003;65A:441-46.
66 Gough JE,Jones JR,Hench LL.Nodule formation and mineralisation of humanprimary osteoblasts cultured on a porous bioactive glass scaffold.Biomaterials.2004;25:2039-46.
67 Silver lA,Erecinska M.Interactions of osteoblastic and other cells with bioactiveglasses and silica in vitro and in vivo.Mat-wiss u Werksofftech.2003;34:1069-75.
68 Bielby R,Christodoulou IS,Pryce RS,Radford WJP,Hench LL,Polak JM.Time-and concentration-dependent effect of dissolution products of 58S sol-gelbioactive glass on proliferation and differentiation of murine and humanosteoblasts.Tiss Engin.2004;10:1018-26.
69 李沁华.天然大分子及其生物材料在组织工程中的应用.现代康复.2001: 5:21-23.
70 郑磊,王前,裴国献.骨组织工程中细胞外基质材料的选择.中华外科杂志.2000;38:745-48.
71 刘彦春,王炜,曹谊林等.卵磷脂、多聚赖氨酸和PLA包埋PGA与软骨细胞体外培养的实验研究.实用美容整形外科杂志.1997;8:225-27.
72 Verrier S,Blaker JJ,Maquet V,Hench LL,Boccaccini AR.PDLLA/Bioglass?composites for soft-tissue and hard-tissue engineering:an in vitro cell biologyassement.Biomaterials.2004;25:3013-21.
73 Kellom?ki M,Niiranen H,Puumanen K,Ashammakhi N,Waris T,Trml P。Bioabsorbable scaffolds for guided bone regeneration and generation.Biomaterials.2000;21:2495-505.
74 Wang XJ,Li YB.Development of biomimetic nano-hydroxyl-apatite /poly(hexamethylene adipamide) composites.Biomaterials,2002,23:4787-4791.
75 Yan YG,Li YB.Synthesis and properties of a copolymer of poly(1,4-phenylene sulfide)-poly(2,4-phenylene sulfide acid) and its HA reinforcedcomposite.European Polymer Journal.2003.39:411-416.
76 沈序辉,宋晨路,等.有机-羟基磷灰石复合骨替代材料.材料科学与工程,1999,17(4):85-90.
77 Bai MH,Liu XY,GE BF et al.An implant of a composite of bovine bonemorphogenetic protein and Plaster of Paris for treatment of femoral shaft nonunion,Int Surg,1996,81:390-392.
78 Takaoka K,Nakahara H,Yoshikawa H,et al.Ectopic bone induction on and in porous Hydroxyapatite combined with collagen and bone morphogenetic protein.Clin Orthop,1988;234:250-254.
79 King GN,King N,Hughes FJ.Effect of two delivery systems for recombinant human bone Morphogenetic protein-2 on periodontal regeneration in vivo.J Periodontal Res,1998;33(4):226-236.
80 Omura S,Mizuki N,Kawabe R.et al.A carrier for clinical use of recombinant human BMP-2:dehydrothermally cross-linked composite of fibrillar and denatured ateloeollagensponge.Int J Oral Maxillofac Surg,1998;27(2):129-134.
81 Mattioli Belmonte M,Gigante A,Muzzarelli RA,et al.N,N-dicarboxymethyl chitosan as delivery agent for bone morphogenetic protein in the repair of articular cartilage.Med BiolEng Comput,1999;37(1):130-134.
82 Schwartz Z,Somers A,Mellonig Jof,et al.Addition of human recombinant boneMorphogenetic protein-2 to inactive commercial human demineralized freeze-dried boneAllograft makes an effective composite bone inductive implant material.J Periodoniol,1998;69(12):1337-1345.
83 Ike M,Urist MR.Recycled dentin root matrix for a carrier of recombinant human boneMorphogenetic protein.J Oral Implantol,1998;24(3):124-132.
84 Katoh T,Sato K,Kawamura M,et al.Osteogenesis in sintered bone combined with bovineBone morphogenetic protein.Clin Orthop, 1993;(287):266-275.
85 胡蕴玉,陆裕朴,刘玮,等.异种骨移植修复骨缺损的实验研究.中华骨科杂志,1990;10(1):33-37.
86 刘玮.陆裕朴,胡蕴玉,等.重组合异种骨的研制及其生物学活性分析.中华医学杂志,1991;71(7):38-42.
87 李亚非,胡蕴玉,宋海燕,等.重组合异种骨在小鼠体内诱导成骨活性的剂量依赖性研究.中华骨科杂志,1995;15(7):447-53.
88 Mattioli Belmonte M,Gigante A,Muzzarelli RA,et al.N,N-dicarboxymethyl chitosan as delivery agent for bone morphogenetic protein in the repair of articular cartilage.Med BiolEng Comput,1999;37(1):130-134.
89 Kubler NR,Moser M,Berr K,et al.Biological activity of E.coli expressed BMp-4.MundKiefer Gesichtschir,1998:S149-S152.
90 Kawakami T,Kawai T,Takei N,et al.Evaluation of heterotopic bone formation inducedby squalane and bone morphogenetic protein composite.Clin Orthop,1997;337:261-266.
91 Kuboki Y,Saito T,Murata M,et al.Two distinctive BMP-carriers induce zonal chondrogenesis and membranous ossification,respectively;geometrical factors of matricesFor cell-differentiation.Connect Tissue Res,1995;32:219-226.
92 Kawakami T,Uji H,Antoh M,Squalane as a possible carrier of bone morphogeneticprotein.Biomaterials,1993;14(8):575-577.
93 Hedner E,Linde A.Efficacy of bone morphogenetic protein(BMP) with osteopromotive.Membranes-an experimental study in rat mandibular defects.Eur J Oral Sci,1995;103(4):236-241.
94 Hayashi K,Inadome T,Tsumura H,et al.Bone-implant interface mechanics of in vivoBioinert ceramics.Biomed Mater Res,1993;14:1173-1179.
95,Christel PS.Biocompatibility of surgical-grade dense polycrystalline alumina.Clin orthop,1992;282:10-18.
96 Gross U,Sehmitz HJ,Strunz V.Surface activities of bioactive glass,aluminum oxide,andTitanium in a living environment.Ann NY Acad Sci,1988;523:211-226.
97 Barbon F,Locardi B,Verita M,et al.Biocompatibility and osteogenetic characteristics of newBiocompatible glass.Biomaterials,1991;12:565-568.
98 Santos EM,Radin S,Shenker BJ,et aI.Si-Ca-P xerogels and bone morphogenetic protein actSynergistically on rat stromal marrow cell differentiation in vitro.J Biomed Mater Res,1998;41:87-94.
99 Ijiri S,Nakamura T,Fujisawa Y,et al.Ectopic bone induction in porous apatite-wollastonite-Containing glass ceramic combined with bone morphogenetic protein.J Biomed Mater Res,1997;35(4):421-432.
100 Kawai T,Mieki A,Ohno Y,et al.Osteoinduective activity of composites of boneMorphogenetic protein and pure titanium.Clin OrthoP,1993;290:296-305.
101 Peppas HA, Lanser R. New challenges in biomaterial、Science, 1994;263:1715-1720.
102 Lam K, Esselburge H, SchakenraadJ, et al. Biodegradable of porous versus non-porouspoly (L-lactic acid) films. J Mater Sci: Mater Med, 1994;5:101-110.
103 Uganuma J, Alexander H. Biological response of intermedullary bone to poly-L-lactic acid.JAppl Biomat, 1993;4:13-16.
104 Agrawal C, Achanasion KA.Technique to control PH in vicinity of biodegrading PLA-PAGimplants. J Biomed Mater Res, 1997:38:105-114.
105 Strunz V,Bunte M,Stellmach R,Gross U,Kuhl K,Newesely H,Bromer H,Deutscher K.Glass ceramics as a bioactive implantation material.DtschZahnarztl Z.1976;31(1):69-70
106 Kokubo T,Ito S.Sakka S.Formation of a high-strength bioactive glass-ceramicin the system MgO-CaO-SiO2-P2O5.J Mater Sci. 1986;21:536-40.
107 W.Vogel and W.HIand.Development,structure,properties and application ofglass-ceramics for medicine.J Non-Crys Sol. 1990; 123:349-53.
108 Zhong JP, Greenspan DC.Processing and properties of sol-gel bioactive glasses.J Biomed Mater Res.2000; 53A:694-701.
109 Li Rclark AE, Hench LL.An investigation of bioactive glass powders by sol-gelprocessing.J Appl Biomater.1999; 2:231-39.
110 Sepulveda P, Jones JR, Hench LL.Characterization of melt-derived 45S5 andsol-gel derived 58S bioactive glasses.J Biomed Mater Res.2001; 58A.734-40.
111 Perez-Pariente J, Balas F, Vallet-RegiM.Surface and chemical study ofSiO2·P2O5·CaO (MgO) bioactive glasses.Chem Mater.2000; 12:750-55.
112 Balas F, Perez-Pariente J, Vallet-RegiM.Relationship between bioactivity andtextural parameters in glasses.Bioceramics.1998; 11:125-28.
113 Arcos D, Greenspan DC, Vallet-Regf.lnfluence of the stabilization temperatureon textural and structural features and ion release in SiO2-CaO-P2O5 sol-gelglasses.Chem Mater.2002; 14:1515-22.
114 Gatti AM,Hench LL,Gonella F,Caccavale F.Test of bioactivity in four differentglasses.Bioceramics.1997;10:287-90
115 Ramila M, Vallet-RegiM.Static and dynamic in vitro study of a sol-gel glassbioactivity.Biomaterials.2001; 22:2301-06.
116 Izquierdo-Barba I, Salinas AJ, Vallet-Regi.ln vitro calcium phosphate layerformation on sol-gel glasses of the CaO-SiO2 system.J Biomed Mater Res.1999; 47:243-50.
117 Miyaji F,Kim HM,Handa S,Kokubo T,Nakamura T.Bonelike apatite coatingon organic polymers:novel nucleation process using sodium silicate solution.Biomaterials.1999;20:913-19.
118 Zhu P, Masuda Y, Koumoto K.The effect of surface charge on hydroxyapatite nucleation.Biomaterials.2004; 25:3915-21.
119 Hench LL, Wilson J.Bioactive glasses: present and future. Bioceramics.1998; 11:31-36.
120 Greenspan DC, Zhong JP, Chen XF, LaTorre GP.The evaluation of degradablityof melt and sol-gel derived bioglass in-vitro.Bioceramics.1997;10:391-94.
121 Huang ZJ,Yang YP,Guo X,Li CJ,Yang LH.Biodegradation of crystalline glasscontaining calcium phosphate.Bioceramics.1996;9:147-50.
122 Webster TJ,Ergun C,Doremus RH,et al.Enhanced osteoclast-like cell functionon nanophase ceramics.Biomatedals,2001,22:1327-1333.
123 王身国,杨健,蔡晴,石桂欣,贝建中.组织工程用生物材料及细胞支架研究进展.中华整形外科杂志.2000;16:328-30.
124 Zhong JP,Greenspan DC.Processing and propertiew of sol-gel bioactive glasses.J Biomed Mater Res A.2000;53:694-701.
125 Hench LL,Splinter RJ,Allen WC,Greenlee TK.Bonding mechanism at theinterface of ceramic prosthetic materials.J Biomed Mater Res Symp.1971;2:117-41
126 Kojubo T,Shigematsu M,Nagashima Y.Bull Inst Chem Res.Kyoto Univ.1982;60:260-68.
127 Kokubo T,Ito S,Yamamuro T.Formation of a high-strength bioactive glass-ceramic in the system MgO-CaO-SiO2-P2O5.J Mater Sci.1986;21:536-40.
128 Bromer H,Pfeil E,Kas HH.German Patent 2323100,1973.
129 Vogel W.玻璃科学技术前沿.1984年北京国际玻璃讨论会议论文集.1984,44.
130 Li R,Clark AE,Hench LL.An investigation of bioactive glass powders by sol-gel processing.J Appl Biomater.1991;2:231-39.
131 扬志明.组织工程 北京:化学工业出版社,2002.1-3
132 Bauer TW,Muschler GF.Bone graft materials.An overview of the basic science.Ciin Orthop Relat Res 2000[(371):10-27
133 Thomas J.Webster,Celaletd in Ergun,Robert H.Doremus,et al.Specific proteins mediate enhanced osteoblast adhesion on nanophase ceramics.J Biomed Mater Res.2000 Sep.5;51(3):475-83.
134 Thomas J.Webster,Richard W.Siegel,Rena Bizios.Osteoblast adhesion on nanophase ceramics.Biomaterials.1999 Ju1;20(13):1221-7.
135 王身国,贝建中.组织工程细胞支架及其相关技术的研究[J].中国创伤骨科杂志,2000,2(4):277-9
136 Houseman BT,Mrksich M.The microenvironment of immobilized Arg-Gly-Asppeptides is an important determinant of cell adhesion.Biomaterials 2001[22(9):943-55
137 付静.陈晓峰.张梅梅,等.医用生物活性玻璃的红外光谱分析及其生物活性探讨[J].生物医学工程杂志,1999,16(增刊):22-4
138 Termine JD,Belcourt AB,Conn KM,et al.Mineral and collagen-bindingproteins of fetal calf bone.J Biol Chem 1981[256(20):10403-8
139 Damien CJ,Ricci JL,Christel P,et al.Formation of a calcium phosphate-richlayer on absorbable calcium carbonate bone graft substitutes.Calcif Tissue Int1994[55(2):151-8
140 Saito N,Takaoka K.New synthetic biodegradable polymers as BMP carriers forbone tissue engineering.Biomaterials 2003,24:2287-93.
141 S.D.Putney,P.A.Burke,Improving protein therapeutics with sustained-releaseformulations.Nat.Biotechnol.1998,16:153 - 157.
142 Miyamoto S,Takaoka K,Okada T,Yoshikawa H,Hashimoto J,Suzuki S,Ono K.Evaluation of polylactic acid homopolymers as carriers for bone morphogeneticprotein.Clin Orthop 1992;278:274-85.
143 C.A.Kirker-Head,Potential applications and delivery strategies for bone morphogenetic proteins,Adv.Drug Deliv.2000 43(12):65-92.
144 Y.Tabata,Tissue regeneration based on growth factor release,Tissue Eng.2003,9(Suppl.l) S5-S 15.
145 Douglas S.Musgrave,Patrick Bosch,Joon Y.Lee.Ex Vivo Gene Therapy to Produce Bone Using Different CELL Types.Clin Orthop,2000,378:290-305.
146 R.Z.LeGeros,Properties of osteoconductive biomaterials:calcium phosphates,Clin.2002,(10):81-98.
147 L.Meinel,V.Kareourgiou,R.Fajardo,B.Snyder,V.Shinde-Patil,L.Zichner,D.Kaplan,R.Langer,G.Vunjak-Novakovic,Bone tissue engineering using humanmesenchymal stem cells:effects of scaffold material and medium flow,Ann.Biomed.Eng.2004,32:112-122.
148 Petite H,Viateau V,Bensaid W,Meunier A,Pollak C,Bourguignon M,Oudina K,Sedel L,Guillemin G.Tissueengineered bone regeneration.Nat Biotechnol2000;18:959-63.
149 T.W.Bauer,G.F.Muschler,Bone graft materials.An overview of the basic science.Clin.2000(10):10-27.
150 Filho OP,LaTorre GP,Hench LL.Effect of crystallization on apatite-layerformation of bioactive glass 45S5.J Biomed Mater Res.1996;30:509-14.
151 Rajendran V,Nishaa Begum A,Azooz MA,Batal FH.Microstructure aldependence on relevant physical-mechanical properties on SiO2-Na2O-CaO-P2O5 biological glasses.Biomaterials.2002;23:4263-75.
152 Lee YK,Kim KN,Choi SY,Kim CS.Effect of iron state on crystallization anddissolution in Fe2O3-CaO-SiO2 glasses.J Mater Sci:Mater Meal.2000;11:511-15.
153 Vallet-RegiM,Izquierdo-Barba I,Salinas AJ.Influence of P2O5 on crystallinityof apatite formed in vitro on surface of bioactive glasses.J Biomed Mater Res.1999;46:560-65.
154 中华人民共和国国家标准.多孔陶瓷性能测试方法.GB/T 1996.
155 Wake MC,Patrick CW,Mikos AG.Pore morphology affects on the fibrovasculartissue growth in porous polymer subst rates.Cell Transplant,1994,3:339-343.
156 Ishaug SL,Crane GM,Misser MJ.Bone formation by thrcc dimentional stromalosteoblast culture in biodegradable polymer scaffolds.J Biomed Mater Res,1997,36:17-28.
157 Cook AD,Hrkach JS,Gao NN,et al.Characterization and development ofRGD-peptide-modified poly(lactic acid-co-lysine)as an interactive,resorbablebiomatedals.J B iomed Mater Res,1997,35:513-523.
158 Zheng J,Northrup SR,Homsby PJ.Modification of materials formed formpoly (L-lactic-co-glycolic acid) to enable covalent binding of biopolymers:application to high-density three-dimensional cell culture in foams with attachedcollagen.In Vitro Cell Der Biol Anim,1998,34:679-684.
159 R.A.A.Muzzarelli,C.Zucchii,P.Llari,et al.Osteoconductive properties ofmethylpyrrolidinone chitosan in an animal model.Biomaterials.1993April 14(12):925-929.
160 K.A.HING,S.M.BEST,K.E.TANNER,et al.Quantification of boneingrowth within bone-derived porous hydroxyapatite implants of varyingdensity.J Mater Sci Mater Med.1999 Oct-Nov;10(10/11):663-70.
161 Flautre B,Descamps M,Delecourt C,et al.Porous HA ceramic for bonereplacement:role of the pores and interconnections -- experimental studyin the rabbit.Mater Sci Mater Med.2001 Aug;12(8):679-82.
162 Wei J,Li YB.Tissue engineering scaffold material of nanoapatite rystals and polyamide composite.Eur Polymer J,2004,40:509 -- 515.
163 Biomaterial aspects of Interpore-200 poroushydroxyapatite.Dent Clin North Am.1986 Jan;30(1):49-67.
164 柴本浦,汤学明,李慧.骼部骨折患者中股骨肋颈松质的破骨细胞性骨吸收.中华骨科杂志,1995,15(5):291-296.
165 Walsh W R,Labrador D P,Kim H K.Ultrasonic properties of cortical bone following fluorideion treatment.Am.Biomed.Eng.,1994,22:404-414.
166 Walsh W R,Ohno M,Guzelsu N.Bone composite behavior:effects of mineral organic bonding.J.Mater.Sci.Mater.Med.,1994,5:72-79.
167 薛庆善.体外培养的原理与技术.(第一版).北京.科学出版社.2001:p53.
168 Lin HR,Yeh YJ.Porous alginate/hydroxyapatite composite scaffolds for bonetissue engineering:preparation,characterization,and in vitro studies.J BiomedMater Res.2004;71B:52-65.
169 Kokubo T,Kushitani H,Sakka S,Kitsugi T,Yamamuro T.Solutions able toreproduce in vivo surfaces-tructure changes in bioactive glass-ceramic A-W.JBiomed Mater Res 1990;24:721-34.
170 Greenspan DC,Zhong JP,LaTorre GP.Effect of surface area to volume ratio onin vitro surface reactions of bioactive glass particulates.Bioceramics.1994;7:55-60.
171 涂杰等,生物玻璃矿化性能及其离子溶出对成骨细胞功能的影响。无机材料学报 2007,2。3-7。
172 Wang JS,Goodman S,Aspenberg P.Bone formation in the presence ofphagocytosable hydroxyapatite particles.Clin Orthop,1994,304:272-279.
173 Li JG.Characterization of calcium phosphates precipitated from simulated bodyfluid of different buffering capacities.Biomatedals,1997,18:743-747.
174 Tertinnikov ON.In vitro hydroxyapatite deposition onto a film surface-graftedwith organophosphate polymer.J Biomed Mater Res,1994,28:1365-1373.
175 Kokubo T.Apatite formation on organic polymers by a biomimetic process.EurJ Solid State Inorg Chem,1995,32:819-827.
176 Hats K,Kokubo T.Growth bone like apatite Layer on a substrate by abiomimetic process.J Am Ceram Soc,1995,78:1049-530.
177 Hench LL,Splinter RJ,Allen WC,Greenlee TK.Bonding mechanism at theinterface of ceramic prosthetic materials.J Biomed Mater Res Symp.1971;2:117-41
178 Hench LL.Bioceramics(Andersson,Happonen and Yli-Urpo Oxford:Butterworth-Heinemann).1990;7:241.
179 Kokubo T,Kushitani H,Sakka S,Kitsugi T,Yamamuro T.Solutions able toreproduce in vivo surfaces-tructure changes in bioactive glass-ceramic A-W.JBiomed Mater Res 1990;24:721-34.
180 Rizkalla AS,Jones QW,Routledge T,Hall GC,Langman M.Chemical reactivityof experimental bioactive glasses.Bioceramics.1998;11:133-40.
181 Ylnen H,Karlsson KH,Aro HT.Effect of immersion in SBF on porousbioactive bodies made by sintering bioactive glass microapheres.J Non-CrysSolids.2000;47:107-15.
182 Perez-Pariente J,Balas F,Roman J,Salinas AJ,Vallet-RegiM.Influence ofcomposition and surface characteristics on the in vitro bioactivity ofSiO2-CaO-P2O5-MgO sol-gel glasses.J Biomed Mater Res.1999;47:170-75.
183 李玉宝.生物医用材料.化学工业出版社.2003.5.p80-122.
184 Jones JR,Sepulveda P,Hench LL.Dose-dependent behavior of bioactive glassdissolution.J Biomed Mater Res.2002;59B:720-26.
185 Hamadouche M,Meunier A,Greenspan DC,Blanchat C,Zhong JP,Torre GPL.Long-term in vivo bioactivity and degradability of bulk sol-gel bioactive glasses.J Biomed Mater Res.2001;54:560-66.
186 Hench LL.Bioceramics:from concept to clinic.J Am Ceramics Soc,1991,74:1487.
187 Hench LL,Wilson H.An Introduction to Bioceramics,world Scientific,London,1993.
188 Kokubo T.Recent progress in.glass-based materials for biomedicalapplications.J Ceram Soc,Japan,1991,99:965-973.
189 Kokubo T.Bioactive glass ceramics:properties and application.Biomaterials,1991,12:155-163.
190 Khor KA,Li H,Cheang P,et al.In vitro behavior of HVOF sprayed calciumphosphate splats and coatings.Biomaterials,2003,24:723-735.
191 Gu YW,Khor KA,Cheang P.In vitro studies of plasma-sprayed hydroxyapatite/Ti-6Al-4V composite coatings in simulated body fluid(SBF).Biomaterials,2003,24:1603-1611.
192 彭雪林,李玉宝,王学江,等.医用纳米羟基磷灰石/聚酰胺66复合材料体外浸泡行为研究.功能材料,2004,35:253-256.
193 滕勇,胡蕴玉,王臻等。成人骨髓基质干细胞体外定向诱导分化为软骨细胞的实验研究。中国实验外科杂志,2005,22:17-19。
194 邓小明,朱科明主编:常用实验动物麻醉,上海:第二军医大学出版社,2001.
195 Kasten Griensven M,et al.Comparison of human bone marrow stromal cell seeded on calcium-deficient hydroxyap-antite,beta-tricalcium phosphate and demineralized bone matrix.Biomaterials,2003,24:2593-2603.
196 ISO 10993(ISO/TC 194):Biological evaluation of medical devices.
197 张真,卢晓风等.生物材料有效性和安全性评价的现状与趋势,生物医学工程杂 志,2002,19(1):117-121.
198 郝和平,奚廷斐,卜长生主编:医疗器械监督管理和评价,北京:中国医药科技出版社,2001.
199 杨晓芳,奚廷斐.生物材料生物相容性评价研究进展.生物医学工程杂志,2001,18(1):123-128.
200 Johson HJ.Biocompatibility test procedures for materials evalation invitro:comparative test system sensitivity.J Biomed Mater Res,1983,17:571-575.
201 张彩霞,闻学雷等.生物材料体内外试验相关性研究-细胞与软组织毒性.中国生物医学工程学报,2002,21(4):122-127.
202 郝和平主编:生物医学材料生物学评价标准实施指南,北京,中国标准出版社,2000.
203 BS 5736(United Kingdom):Evaluation of medical devices for biological harzards,1989
204 ASTM F748-95,Annual Book of ASTM Standards,1998,13(1)193-197
205 Sabita S.Screening of in vitro cytotoxicity by the adhecive test.Biomaterials,1990,11(3):133-136.
206 R.Yang,Y.J.Wang,X.F.Chen,N.R.Zhao.Biomimetic fabrication of BCP/COL/HCA scaffolds for bone tissue engineering.Materials Letters,2005,59:3635-3640.
207 张晓凯,陈晓峰.BG PHBV复合多孔组织工程支架材料的动物植入实验观察.电子显微学报,2004,6:169-172.
208 任耀彬,郑裕东.用于骨组织工程的羟基丁酸-戊酸共聚物生物活性玻璃复合多孔支架材料.高分子材料科学与工程,2003,20:193-199.
209 Yingjun Wang,Chunrong Yang,Xiaofeng Chen,Naru Zhao.Development and Characterization of NovelBiomimetic Composite Scaffolds Based on Bioglass-Collagen-Hyaluronic Acid-Phosphatidylserine for Tissue Engineering Applications.Macromolecular Material and Engineering,2005,10:1-8.
210 Cole BJ,Bostrom MP,Pritchard TL.et al.Use of bone morphogenetic protein 2 on ectopic porous coated implants in the rat.Clin Orthop Relat Res.1997:219-228.
211 Whang k.tsai DC,Nam EK.et al.Ectopic bone formation via rhBMP-2delivery from porous bioabsorbable polymer scaffolds.J Biomed Mater Res.1998,42:491-499.
212 Tsurga E,Takita H,Itoh H.et al.Pore size of porous hydroxyapatite as the cell-substratum controls BMP-induced osteogenesis.J Biochem 1997,121:317-324.
213 Ekelund A,Brosjo O,Nilsson OS.Experimental induction of heterotopic bone.Clin Orthop Relat Res,1991:102-112.
214 Hollinger JO,Schmitt JM,Buck DC.et al.Recombinant human bone morphogenetic protein-2 and collagen for bone regeneration.J Biomed Mater Res.1998,43:356-364.
215 K.A.HNIG,5.M.BEST,K.E.TANNER,etal.Quantification of bone ingrowth within bone-derived Porous hydroxyapatitc implants of varying density.J MaterSci Mater Med.1999Oet-Nov:10(10/11):663-70.
216 Kim HW,Kim HE,Salih V.Stimulation of osteoblast responses to biomimetic nanocomposites of gelatin-hydroxyapatite for tissue engineering scaffolds.Biomaterials 2005[26(25):5221-30
217 Liao SS,Cui FZ,Zhang W,et al.Hierarchically biomimetic bone scaffoldmaterials:nano-HA/collagen/PLA composite.Biomed Mater Res B ApplBiomater 2004[69(2):158-65Bauer TW,Muschler GF.Bone
218 Arrington ED,Smiht WJ,Chmabers HG etal.Complications of lilac crest bone graft harvesting..Clin Ortho P1996;329:300-9.2
219 Ripamonti U,Duneas N.Tissue engineering of bone by osteoinductive biomaterials.MRS Bull 1996;21:36-9.
220 Racquet Zapanta LeGeros.Properties of Osteoconductive Biomaterials:Calcium Phosphates.Clin Orthop Relat Res.2002 Feb;(395):81-98.
221 Walsh WR,Chapman-Sh eath PJ,Cain S,et al.A resorbable porous ceramiccomposite bone graft substitute in a rabbit metaphyseal defect model.J Orthop Res,2003,21:655-661.
222 Caba as MV,Roddguez-Lorenzo LM,Vallet-Regi M.Setting behavior and invitro bioactivity of hydroxypatite/calcium sulfate cements.Chem Mater2002;14:3550-3555.
223 Wang JS,Nilsson M,Wielanek,et al.Factors controlling the injection andsetting of calcium sulphate with hydroxyapatite cement.In:Hawaii A,von RecumAF,Lucas LC,editors.Sixth World Biomaterials Congress Transactions,Society forBiomaterials;2000.p.805.
224 张梅霞:靳安民:闵少雄:丁金勇,仿生型生物玻璃/胶原蛋白/磷脂酰丝氨酸/透明质酸复合支架修复兔桡骨缺损,2006,29,382:42-50.
225 张梅霞:靳安民:杨春蓉:姚瑶:李妙.The compatibility of Osteoblast on the biomimetic composite scaffold BG-COL-HYA-PS.中国临床解剖学杂志,2006,4,33-36
226 李向军:陈晓峰:王迎军:赵娜如:杨春蓉.一种新型仿生骨组织工程支架的制备与表征,2007,9:56-58.
227 Thomsom RC,Yasko MJ,Powers JM et al.Hydroxyapatite Biomaterials,1998,19:fiber reinforcedpoly(a-hydmxyester) foams for bone regeneration.1935-1943
228 Petra Eiselt,Julia Yeh,Rachel K,et al.Porous carriers for biomedical applications based on alginate hydragels.Biomaterials,2000,21:1921-1927
229 Zhang R,Ma PX.Poly(a-hydroxyl acids)/hydmxyapatite porous composites for bone tissue engineering.J Biomed Mater Res,1999,44:446-455
230 Jeffrey D,Hartgerink,Ella Beniash,et al.Self-assembly and mineralization of peptide-amphihile nanofihers.Science,2001,294:1684-1687
231 Karen J.Lengmeermg.Burg,ScottBiomaterialsPorter,James F.kellam.Biomaterial developments for bone tissue2000,21:23-49
232 Huipin Yuan,Kenji Kurashina,Joost D.de Bruijn,et al.A preliminarystudy on osteoinduction of two kinds of calcium phosphate ceramics.Biomaterials.1999 Oct;20(19):1799-806.
233 Ishaug-Riley SL,Crane GM,Gurlek A,Miller MJ,YaskoYaszemski MJ,Mikos ACz Ectopic bone formation by marrow stromalsosteoblast transplantation using poly (L-lactic-co-glycolic poly (L-lactic-co-glycolic acid) foams implanted into the rat mesentery. JBiomed Mater Res 1997; 36:1-8.
234 G.W.R. Walsh a, PJ.Chapman-Sheath, S.Cain, et al.A resorbable porousmetap seal defectceramic composite bone graft substitute in a rabbitmodel.J Orthop Res, 2003 Ju1; 21(4):655-61.
235 Christine Loty, Jean-Michel Sautier, Habib Boulekbache.et al. In vitrobone formation on a bone-like apatite layer prepared by a biomimeticprocess on a bioactive glass-prepared by a biomimetic process on abioactive glass-ceramic. J Biomed Mater Res, 49, 423-434, 2000.
236 J. X. LU, B. FLAUTRE, K. ANSELME.et al. Role of interconnections inporous bioceramics on bone recolonization in vitro and in vivo. J MaterSci Mater Med. 1999 Feb; 10(2):111-20.
237 Felicity R. Rose, Lesley A. Cyster, David M. Grant,et al. In vitroassessment of cell penetration into porous droxyapatite scaffolds with a central aligned channel. Biomaterials. 2004 Nov; 25(24):5507-14.
238 Stubbs D, Deakin M, Chapman-Sheath P, et al.In vivo evaluation ofresorbable bone graft substitutes in a rabbit tibial defect model. Biomaterials, 2004, 25: 5037-5044.