鸵鸟骨转化多相钙磷陶瓷制备及用于骨组织工程支架材料基础研究
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摘要
由肿瘤切除、创伤和感染造成的颌面骨缺损需要大量的骨移植物修复，自体和同种异体骨应用最多，但都有一定的局限性。开发的人工替代品有生物陶瓷、聚合物、合金以及复合材料等，其中钙磷陶瓷类的HA和β-TCP因具有良好的生物相容性和骨传导性能而得到广泛的研究。煅烧牛骨又称为陶瓷化骨(TBC)，是一种具有天然松质骨小梁结构的多孔生物材料，由无机骨矿物质组成。由于经过高温煅烧，材料无免疫原性，无毒性。拥有天然骨传导性，TBC与骨诱导因子如BMPs，骨髓和培养的成骨细胞复合后显示了良好的成骨性能。
鸵鸟松质骨(OCB)是一种新型异种生物材料，文献中很少提及。实验中对OCB进行化学处理后高温煅烧，将其转化为钙磷陶瓷(COB)。进一步用焦磷酸钠液浸泡后再次煅烧至1100℃，将COB中的HA成分转化为HA／β-TCP／NaCaPO_4多相钙磷陶瓷。课题研究了鸵鸟骨转化多相钙磷陶瓷的成分、特性、降解性能和生物相容性，并探索其用于骨组织工程支架材料的可行性。
1．鸵鸟及牛松质骨形态比较及成分测定、抗折强度分析
目的：制备鸵鸟及牛松质骨并比较其结构、成分和抗折强度。方法：新鲜鸵鸟及牛骨经过化学处理后制备出松质骨材料。观察材料表面结构，分析其水分、有机质、及无机物含量，测定其抗折强度。结果：鸵鸟松质骨表
第四军医大学博士学位论文
面及孔隙结构与牛松质骨相比有不同特点，与牛松质骨孔隙相比，鸵鸟松
质骨孔径大小更不均匀。鸵鸟及牛松质骨水分、有机质及无机物含量分别
为(6 .85士0.10)%、(28.75士0.83)%、(64.40士0.78)%和(6.36士0.16)%、
(2979土0.28)%、(63.85士0.35)%。两者的抗折强度分别为(14.18士2.50)
MPa和(22.93士3.93)MPa。结论:鸵鸟及牛松质骨在水分、有机质及无
机物含量方面接近。鸵鸟松质骨材料具有与牛松质骨不同的孔隙特点，有
望成为另一类有价值的异种骨替代材料。
2.陶瓷化鸵鸟松质骨支架制备及成分、性能分析
目的:制备陶瓷化鸵鸟松质骨支架并分析其成分及性能。方法:鸵鸟松质
骨化学处理后高温锻烧，将其转化为钙磷陶瓷。通过大体及扫描电镜观察
材料表面结构，测定材料孔隙率、矿物组成、元素比及抗折强度。结果:
陶瓷化鸵鸟松质骨是一种多孔钙磷陶瓷材料，主要成分为轻基磷灰石，钙
磷元素比为1.613。平均孔隙率为(70.27土6.23)%，多数材料孔隙大小不
均匀。平均抗折强度为(l .92士0.63)MPa。结论:陶瓷化鸵鸟松质骨是一
种孔隙结构特点与其他异种陶瓷骨不同的钙磷陶瓷材料，其孔隙特点可能
对成骨有利。
3.将陶瓷化鸵鸟松质骨转化为多相钙磷陶瓷
目的:将锻烧鸵鸟松质骨转化为多相钙磷陶瓷并对其性能、成分进行分析。
方法:陶瓷化鸵鸟松质骨用不同浓度焦磷酸钠浸泡后高温处理，将陶瓷化
鸵鸟松质骨的主要成分经基磷灰石(HA)转化为多相钙磷陶瓷。通过大
体及扫描电镜观察材料表面结构，测定材料孔隙率、抗折强度、矿物组成
及元素比。结果:部分可降解性陶瓷化鸵鸟松质骨支架是一种多孔钙磷陶
瓷材料，主要由HA、p一磷酸三钙(p一TCP)、和磷酸钙钠(NaCaP04)组
成。随着焦磷酸钠浓度的增加，HA含量减少，p一TcP和NaCaPO;含量增
多。材料平均抗折强度为(l .95士0.46) MPa。材料钙磷元素比值为1.511。
平均孔隙率为(60.71士6.9)%，孔隙大小不均匀。结论:通过在高温下与
焦磷酸钠作用，陶瓷化鸵鸟松质骨能够被转化为p一TCP旧户了NaCaP04多
相钙磷陶瓷，该材料具有独特的天然多孔结构，有可能成为一种新型植骨
第四军医大学博士学位论文
材料。
4.鸵鸟骨转化多相钙磷陶瓷支架细胞相容性研究
目的:评价由鸵鸟松质骨制备的多相钙磷陶瓷支架的细胞相容性。方法:
通过理、化方法将锻烧鸵鸟松质骨改性为H刀p一TCP加aCaPO;多相钙磷陶
瓷，然后分离兔骨髓基质细胞，体外扩增、诱导后接种于鸵鸟钙磷陶瓷支
架。骨髓基质细胞与支架复合培养8天，通过相差显微镜、扫描电镜观察
细胞在材料上的勃附、伸展及生长情况。通过细胞计数观察细胞增殖情况。
结果:骨髓基质细胞在多相钙磷陶瓷支架表面及孔隙内贴附、伸展、增殖
良好。结论:鸵鸟骨转化多相钙磷陶瓷支架具有良好的细胞相容性。
5.鸵鸟骨转化多相钙磷陶瓷生物相容性研究
目的:评价新型材料鸵鸟骨转化多相钙磷陶瓷支架的生物相容性。方法:
通过理、化方法将锻烧鸵鸟松质骨改性为H刀p一TCPfNacaPO;多相钙磷陶
瓷，然后进行溶血试验、凝血试验、热源试验、急性毒性试验及肌肉植入
试验。结果:材料无溶血现象，不影响凝血功能。动物实验发现材料不引
起阳性热源反应及急性毒性。肌肉植入试验显示纤维组织能够长入材料内
部，材料对肌肉无刺激。部分标本出现轻微的炎性反应，与材料部分降解
有关。结论:多相钙磷陶瓷支架具有良好的生物相容性。
6.鸵鸟骨转化多相钙磷陶瓷支架肌内降解性能研究
目的:观察两种不同比例H刀p一TCP加aCaPO4的多相钙磷陶瓷降解情况。
方法:通过理、化方法将锻烧鸵鸟松质骨转化为H刀p一TcP/N acaPo;多相
钙磷陶瓷。通过不同剂量焦磷酸钠处理得到不同比例HA/p一TcP/
NaCaP0
Large amounts of bone graft are frequently used to reconstruct the maxillofacial bone defects resulting from tumor resection, trauma, infection. Autograft and allograft bone are often used, but each has its limitations. To avoid the potential risk, artificial substitutes including bioceramics, polymers, alloys, and composite biomaterials have been studied. Among them calcium phosphate ceramics, e.g. hydroxyapatite(HA) and beta-tricalcium phosphate(P-TCP) have been extensively studied because their good biocompatible and osteoconductive properties. Sintered bovine bone, or true bone ceramic(TBC) is a porous biomaterial with a natural trabecular structure like that of cancellous bone and is composed of inorganic bone material. Because it is formed by sintering at a high temperature, TBC is not immunogenic, and no cytotoxicity is observed. Augmentation of the natural osteoconductivity of TBC with osteoinductive agents such as bone morphogenetic proteins (BMPs), bone marrow, and cultured osteoblasts has yielded
promising osteogenic properties.
Ostrich cancellous bone(OCB) is a kind of new xenogenic biomaterial which is rarely mentioned by other literatures. In our experiments, the OCB
was given a chemical management, then it was calcined to a high temperature and to be transformed to calcium phosphate ceramics(COB). Then the COB blocks were soaked in different concentration of sodium pyrophosphate (Na4P2O7-H2O, NP) solution and heated to 1100C to transform its constitution from HA into HA/p-TCP/NaCaP04 multiphasic calcium phosphate ceramics. In this study, we investigated the components, characterization, degradable ability, Biocompatibility of the multiphasic calcium phosphate ceramic and explored its application as the scaffold in bone tissue engineering.
1. Compare of heterogenous ostrich and bovine cancellous bone: configuration, components and bending strength
Objective: To prepare the ostrich and bovine cancellous bone(OCB and BCB) and compare their configuration, components and bending strength . Methods: preparing the ostrich and bovine cancellous bone by chemical management. Then observing the surface configuration and analyzing the component proportion of water, organic and mineral material of the cancellous bone. Determining the bending strength of the material. Results: The OCB had different surface configuration and porosity structure with that of BCB. The pore size of OCB was even more uneven than that of BCB. The component proportion of water, organic and mineral material of the OCB and BCB was separately(6.85+0.10)%, (28.75+0.83)%. (64.40+0.78)% and(6.36+0.16) %, (29.79+0.28) %, (63.85+0.35) %. The average bending strength of OCB and BCB was separately ( 14.18+2.50) Mpa (22.93+3.93) Mpa. Conclusion: Both OCB and BCB had similar component proportion of water, organic , mineral material. The OCB material has different porosity characteristics compared with BCB and it might become another valuable heterogenous bone graft material.
2. Preparation of ceramic-like ostrich cancellous bone scaffold and
analysis of its components and characterization
Objective: To prepare the COB scaffold and study its components and characterization. Methods. After the chemical management the OCB was heated to a high temperature and to be transformed to calcium phosphate ceramics. Then observing the surface configuration of the material by SEM and analyzing the following properties of the material: porosity, mineral composition, element ratio and bending strength. Results: The COB was a kind of porous calcium phosphate ceramic composed of hydroxyapatite(HA) and the Ca/P element ratio of COB was 1.613. the average porosity was (70.27+6.23 ) % and the pore size of most material was uneven. The average bending strength of COB was (1 92+0.63 ) MPa. Conclusion: The COB was a king of calcium phosphate ceramic with different porosity characteristics compared with other xenografts, for example, the bovine cancellous bone ceramic. The porosity characteristics of COB maybe make it more benefit to osteogenesis
鸵鸟松质骨(OCB)是一种新型异种生物材料，文献中很少提及。实验中对OCB进行化学处理后高温煅烧，将其转化为钙磷陶瓷(COB)。进一步用焦磷酸钠液浸泡后再次煅烧至1100℃，将COB中的HA成分转化为HA／β-TCP／NaCaPO_4多相钙磷陶瓷。课题研究了鸵鸟骨转化多相钙磷陶瓷的成分、特性、降解性能和生物相容性，并探索其用于骨组织工程支架材料的可行性。
1．鸵鸟及牛松质骨形态比较及成分测定、抗折强度分析
目的：制备鸵鸟及牛松质骨并比较其结构、成分和抗折强度。方法：新鲜鸵鸟及牛骨经过化学处理后制备出松质骨材料。观察材料表面结构，分析其水分、有机质、及无机物含量，测定其抗折强度。结果：鸵鸟松质骨表
第四军医大学博士学位论文
面及孔隙结构与牛松质骨相比有不同特点，与牛松质骨孔隙相比，鸵鸟松
质骨孔径大小更不均匀。鸵鸟及牛松质骨水分、有机质及无机物含量分别
为(6 .85士0.10)%、(28.75士0.83)%、(64.40士0.78)%和(6.36士0.16)%、
(2979土0.28)%、(63.85士0.35)%。两者的抗折强度分别为(14.18士2.50)
MPa和(22.93士3.93)MPa。结论:鸵鸟及牛松质骨在水分、有机质及无
机物含量方面接近。鸵鸟松质骨材料具有与牛松质骨不同的孔隙特点，有
望成为另一类有价值的异种骨替代材料。
2.陶瓷化鸵鸟松质骨支架制备及成分、性能分析
目的:制备陶瓷化鸵鸟松质骨支架并分析其成分及性能。方法:鸵鸟松质
骨化学处理后高温锻烧，将其转化为钙磷陶瓷。通过大体及扫描电镜观察
材料表面结构，测定材料孔隙率、矿物组成、元素比及抗折强度。结果:
陶瓷化鸵鸟松质骨是一种多孔钙磷陶瓷材料，主要成分为轻基磷灰石，钙
磷元素比为1.613。平均孔隙率为(70.27土6.23)%，多数材料孔隙大小不
均匀。平均抗折强度为(l .92士0.63)MPa。结论:陶瓷化鸵鸟松质骨是一
种孔隙结构特点与其他异种陶瓷骨不同的钙磷陶瓷材料，其孔隙特点可能
对成骨有利。
3.将陶瓷化鸵鸟松质骨转化为多相钙磷陶瓷
目的:将锻烧鸵鸟松质骨转化为多相钙磷陶瓷并对其性能、成分进行分析。
方法:陶瓷化鸵鸟松质骨用不同浓度焦磷酸钠浸泡后高温处理，将陶瓷化
鸵鸟松质骨的主要成分经基磷灰石(HA)转化为多相钙磷陶瓷。通过大
体及扫描电镜观察材料表面结构，测定材料孔隙率、抗折强度、矿物组成
及元素比。结果:部分可降解性陶瓷化鸵鸟松质骨支架是一种多孔钙磷陶
瓷材料，主要由HA、p一磷酸三钙(p一TCP)、和磷酸钙钠(NaCaP04)组
成。随着焦磷酸钠浓度的增加，HA含量减少，p一TcP和NaCaPO;含量增
多。材料平均抗折强度为(l .95士0.46) MPa。材料钙磷元素比值为1.511。
平均孔隙率为(60.71士6.9)%，孔隙大小不均匀。结论:通过在高温下与
焦磷酸钠作用，陶瓷化鸵鸟松质骨能够被转化为p一TCP旧户了NaCaP04多
相钙磷陶瓷，该材料具有独特的天然多孔结构，有可能成为一种新型植骨
第四军医大学博士学位论文
材料。
4.鸵鸟骨转化多相钙磷陶瓷支架细胞相容性研究
目的:评价由鸵鸟松质骨制备的多相钙磷陶瓷支架的细胞相容性。方法:
通过理、化方法将锻烧鸵鸟松质骨改性为H刀p一TCP加aCaPO;多相钙磷陶
瓷，然后分离兔骨髓基质细胞，体外扩增、诱导后接种于鸵鸟钙磷陶瓷支
架。骨髓基质细胞与支架复合培养8天，通过相差显微镜、扫描电镜观察
细胞在材料上的勃附、伸展及生长情况。通过细胞计数观察细胞增殖情况。
结果:骨髓基质细胞在多相钙磷陶瓷支架表面及孔隙内贴附、伸展、增殖
良好。结论:鸵鸟骨转化多相钙磷陶瓷支架具有良好的细胞相容性。
5.鸵鸟骨转化多相钙磷陶瓷生物相容性研究
目的:评价新型材料鸵鸟骨转化多相钙磷陶瓷支架的生物相容性。方法:
通过理、化方法将锻烧鸵鸟松质骨改性为H刀p一TCPfNacaPO;多相钙磷陶
瓷，然后进行溶血试验、凝血试验、热源试验、急性毒性试验及肌肉植入
试验。结果:材料无溶血现象，不影响凝血功能。动物实验发现材料不引
起阳性热源反应及急性毒性。肌肉植入试验显示纤维组织能够长入材料内
部，材料对肌肉无刺激。部分标本出现轻微的炎性反应，与材料部分降解
有关。结论:多相钙磷陶瓷支架具有良好的生物相容性。
6.鸵鸟骨转化多相钙磷陶瓷支架肌内降解性能研究
目的:观察两种不同比例H刀p一TCP加aCaPO4的多相钙磷陶瓷降解情况。
方法:通过理、化方法将锻烧鸵鸟松质骨转化为H刀p一TcP/N acaPo;多相
钙磷陶瓷。通过不同剂量焦磷酸钠处理得到不同比例HA/p一TcP/
NaCaP0
Large amounts of bone graft are frequently used to reconstruct the maxillofacial bone defects resulting from tumor resection, trauma, infection. Autograft and allograft bone are often used, but each has its limitations. To avoid the potential risk, artificial substitutes including bioceramics, polymers, alloys, and composite biomaterials have been studied. Among them calcium phosphate ceramics, e.g. hydroxyapatite(HA) and beta-tricalcium phosphate(P-TCP) have been extensively studied because their good biocompatible and osteoconductive properties. Sintered bovine bone, or true bone ceramic(TBC) is a porous biomaterial with a natural trabecular structure like that of cancellous bone and is composed of inorganic bone material. Because it is formed by sintering at a high temperature, TBC is not immunogenic, and no cytotoxicity is observed. Augmentation of the natural osteoconductivity of TBC with osteoinductive agents such as bone morphogenetic proteins (BMPs), bone marrow, and cultured osteoblasts has yielded
promising osteogenic properties.
Ostrich cancellous bone(OCB) is a kind of new xenogenic biomaterial which is rarely mentioned by other literatures. In our experiments, the OCB
was given a chemical management, then it was calcined to a high temperature and to be transformed to calcium phosphate ceramics(COB). Then the COB blocks were soaked in different concentration of sodium pyrophosphate (Na4P2O7-H2O, NP) solution and heated to 1100C to transform its constitution from HA into HA/p-TCP/NaCaP04 multiphasic calcium phosphate ceramics. In this study, we investigated the components, characterization, degradable ability, Biocompatibility of the multiphasic calcium phosphate ceramic and explored its application as the scaffold in bone tissue engineering.
1. Compare of heterogenous ostrich and bovine cancellous bone: configuration, components and bending strength
Objective: To prepare the ostrich and bovine cancellous bone(OCB and BCB) and compare their configuration, components and bending strength . Methods: preparing the ostrich and bovine cancellous bone by chemical management. Then observing the surface configuration and analyzing the component proportion of water, organic and mineral material of the cancellous bone. Determining the bending strength of the material. Results: The OCB had different surface configuration and porosity structure with that of BCB. The pore size of OCB was even more uneven than that of BCB. The component proportion of water, organic and mineral material of the OCB and BCB was separately(6.85+0.10)%, (28.75+0.83)%. (64.40+0.78)% and(6.36+0.16) %, (29.79+0.28) %, (63.85+0.35) %. The average bending strength of OCB and BCB was separately ( 14.18+2.50) Mpa (22.93+3.93) Mpa. Conclusion: Both OCB and BCB had similar component proportion of water, organic , mineral material. The OCB material has different porosity characteristics compared with BCB and it might become another valuable heterogenous bone graft material.
2. Preparation of ceramic-like ostrich cancellous bone scaffold and
analysis of its components and characterization
Objective: To prepare the COB scaffold and study its components and characterization. Methods. After the chemical management the OCB was heated to a high temperature and to be transformed to calcium phosphate ceramics. Then observing the surface configuration of the material by SEM and analyzing the following properties of the material: porosity, mineral composition, element ratio and bending strength. Results: The COB was a kind of porous calcium phosphate ceramic composed of hydroxyapatite(HA) and the Ca/P element ratio of COB was 1.613. the average porosity was (70.27+6.23 ) % and the pore size of most material was uneven. The average bending strength of COB was (1 92+0.63 ) MPa. Conclusion: The COB was a king of calcium phosphate ceramic with different porosity characteristics compared with other xenografts, for example, the bovine cancellous bone ceramic. The porosity characteristics of COB maybe make it more benefit to osteogenesis
引文
1．杨志明．组织工程基础与临床．成都：四川科学技术出版社，2000，14-15
2．方丽茹，翁文剑，沈鸽，韩高荣，Santos JD．骨组织工程支架及生物材料研究．生物医学工程学杂志，2003，20(1)：148-152
3．裴国献．骨组织工程研究现状与趋势．解放军医学杂志，2002，27(6)：472-474
4. Yamasaki H. Herterotopic bone formation around porous HA ceramics in the subcutis of dogs. Jpn J Oral Biol; 1990, 32: 190-192.
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7. Okumura M, Ohgushi H, Dohi Y, Katuda T, Tamai S, Koerten HK, Tabata S. Osteoblastic phenotype expression on the surface of HA ceramics. J Biomed Mater Res, 1997; 37(1): 122-129.
8. Cong Z, Jianxin W, Huaizhi F, Bing L, Xingdong Z. Repairing segmental bone defects with living porous ceramic cylinders: an experimental study in dog femora. J Biomed Mater Res, 2001; 55(1):28-32
9. Yoshikawa T, Ohgushi H. Autogenous cultured bone graft-bone reconstruction using tissue engineering approach. Ann Chir Gynaecol, 1999; 88 (3): 186-192
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3．裴国献．骨组织工程研究现状与趋势．解放军医学杂志，2002，27(6)：472-474
4. Yamasaki H. Herterotopic bone formation around porous HA ceramics in the subcutis of dogs. Jpn J Oral Biol; 1990, 32: 190-192.
5. Yuan H, Li Y, Yang Z, Feng J, Zhang X. An investigation on the osteoinduction of synthetic porous phase-pure HA ceramics. Biomed Eng Appl Basis Com, 1997; 9: 274-278.
6. Yuan H, Kurashina K, Bruijin JD, Li YB, de Groot K, Zhang X. A preliminary study on osteoinduction of two kinds of calcium phosphate ceramics. Biomaterials, 1999;20: 1799-1806
7. Okumura M, Ohgushi H, Dohi Y, Katuda T, Tamai S, Koerten HK, Tabata S. Osteoblastic phenotype expression on the surface of HA ceramics. J Biomed Mater Res, 1997; 37(1): 122-129.
8. Cong Z, Jianxin W, Huaizhi F, Bing L, Xingdong Z. Repairing segmental bone defects with living porous ceramic cylinders: an experimental study in dog femora. J Biomed Mater Res, 2001; 55(1):28-32
9. Yoshikawa T, Ohgushi H. Autogenous cultured bone graft-bone reconstruction using tissue engineering approach. Ann Chir Gynaecol, 1999; 88 (3): 186-192
10. den Boer FC, Wippermann BW, Blokhuis TJ, Parka P, Bakker FC, Haarman HJ. Healing of segmental bone defects with granular porous hydroxyapatite augmented with recombinant human osteogenic protein-1 or autologous bone marrow. J Orthopae Res, 2003; 21: 521-528
11. Muraglia A, Martin I, Cancedda R, Quarto R. A nude mouse model for human bone formation in unloaded conditions. Bone, 1998; 22(5 Suppl): 131S-134S
12. Kaitoa T , Myouia A, Takaokab K, Saito N, Nishikawa M, Tamai N, Ohgushi H, Yoshikawa H. Potentiation of the activity of bone morphogenetic protein-2 in bone regeneration by a PLA-PEG/ hydroxyapatite composite. Biomaterials, 2004; In Press.
13. Ge Z, Baguenard S, Yong L, Wee A, Khor E. Hydroxyapatite-chitin materials as potential tissue engineered bone substitutes. Biomaterials, 2004; 25: 1049-1058
14. Zhao F, Yin Y, Lu WW, Leong JC, Zhang W, Zhang J, Zhang M, Yao K. Preparation and histological evaluation of biomimetric three-dimensional hydroxyapatite/chitosan-gelatin network composite scaffolds. Biomaterials, 2002;23: 3227-3234
15. Chen G, Ushida T, Tateishi T. Development of biodegradable porous scaffolds for tissue engineering. Material-s Science and Engineering, 2001; 17: 63-69
16. Webster TJ, Ergun C, Doremus RH, Siegel RW, Bizios R. Specific proteins mediate enhanced osteoblast adhesion on nanophase ceramics. J Biomed Mater Res, 2000; 51(3): 475-83
17. Webster TJ, Siegel RW, Bizios R. Osteoblast adhesion on nanophase cerarnies. Biomaterials, 1999; 20: 1221-1227.
18. Borum-Nicholas L, Wilson Jr OC. Surface modification of hydroxylapatite. Part Ⅰ. Dodecyl alcohol. Biomaterials, 2003; 24: 3671-3679
19. Wei G, Ma PX. Structure and properties of nano-hydroxyapatite/polymer composite scaffolds for bone tissue engineering. Biomaterials, 2004; In Press.
20. Ehara A, Ogata K, Imazato S, Ebisu S, Nakano T, Umakoshi Y. Effects of a-TCP and TetCP on MC3T3-E1 proliferation, differentiation and
mineralization. Biomaterials, 2003; 24: 831-836
21. Sous M, Bareille R, Rouais E, Clement D, Amedee J, Dupuy B, Baquey Ch.Cellular biocompatibility and resistance to compression of macroporous β-tricalcium phosphate ceramics, biomaterials, 1998; 19 (23): 2147-2153
22. Fleming JE Jr, Cornell CN, Muschler GF. Bone cells and matrices in orthopedic tissue engineering. Orthop Clin North Am, 2000; 31(3): 357-374
23. Kurashina K, Kurita H, Wu Q, Ohtsuka A, Kobayashi H. Ectopic osteogenesis with biphasic ceramics of hydroxyapatite and tricalcium phosphate in rabbits. Biomaterials, 2002;23(2): 407-412
24. Dong J, Uemura T, Shirasaki Y, Tateish T. Promotion of bone formation using highly pure porous b-TCP combined with bone marrow-derived osteoprogenitor cells. Biomaterials, 2002; 23: 4493-4502
25. Yamada Y, Boo JS, Ozawa R, Nagasaka T, Okazaki Y, Hata Ki, Minoru Ueda M. Bone regeneration following injection of mesenchymal stem cells and fibrin glue with a biodegradable scaffold. J of Cranio-Maxillofac Surg, 2003; 31(1): 27-33
26. Arnold U, Lindenhayn K, Perka C. In vitro-cultivation of human periosteum derived cells in bioresorbable polymer-TCP-composites. Biomaterials, 2002; 23: 2303-2310
27. Sherwood JK, Riley SL, Palazzolo R, Brown SC, Monkhouse C, Coates M, Griffith LG, Landeen LK. A three-dimensional osteochondral composite scaffold for articular cartilage repair. Biomaterials, 2002; 23: 4739-4751
28. Aoki S, Yamaguchi S, Nakahira A, Suganuma K. A new approach to an artificial joint based on bio-cartilage/porous β-tricalcium phosphate system. Journal of the European Ceramic Society, 2003; 23: 2939-2946
29. Handschel J, Wiesmann HP, Stratmann U, Kleinheinz J, Meyer U, Joos U.
TCP is hardly resorbed and not osteoconductive in a non-loading calvarial model. Biomaterials, 2002; 23: 1689-169
30. Price N, Bendall SP, Frondoza C, Jinnah RH, Hungerford DS. Human osteoblast-like cells (MG63) proliferate on a bioactive glass surface. J Biomed Mater Res, 1997; 37(3): 394-400
31. Jones JR, Hench LL. Biomedical materials for new millennium: perspective on the future. Mater Sci Tech, 2001;17: 891-900
32. Maquet V, Boccaccini AR, Pravata L, Notingher I, Jerome R. Porous poly(a-hydroxyacid)/Bioglasss composite scaffolds for bone tissue engineering. Ⅰ: preparation and in vitro characterization. Biomaterials, 2004; 25: 4185-4194
33. Boccaccini AR, Maquet V. Bioresorbable and bioactive polymer/Bioglassl composites with tailored pore structure for tissue engineering applications. Composites Science and Technology. 2003; 63: 2417-2429
34. Asselin A, Hattar S, Oboeuf M, Greenspan D, Berdal A, Sautier JM. The modulation of tissue-specific gene expression in rat nasal chondrocyte cultures by bioactive glasses. Biomaterials, 2004; in press.
35. Ueno Y, Sasaki S, Shima Y, Ueyoshi A, Harada M, Terao K, Akiyama T. Studies of sintered bone as a bone substitute. Orthop Ceramic Implants, 1983; 3: 11-16.
36. Katoh T, Sato K, Kawamura M, Iwata H, Miura T. Osteogenesis in sintered bone combined with bovine bone morphogenetic protein. Clin Orthop, 1993; (287): 266-75
37. Werber KD, Brauer RB, Weiss W, Becker K.. Osseous integration of bovine hydroxyapatite ceramic in metaphyseat bone defects of the distal radius. J Hand Surg [Am], 2000; 25(5): 833-841
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