羟基磷灰石球粒堆积三维多孔支架及其体内异位成骨
|
摘要
骨组织工程支架作为组织工程学的一个分支得到了广泛的研究和发展,它为解决和改善治疗人们生活中的骨缺损、骨修复提供了新的思路,带来了新的希望。在骨组织工程支架的研究中,支架材料的选择是关键因素之一;大量研究表明可作为骨组织工程支架的材料种类很多,它们都必须具备的共同特点是:良好的生物相容性(无毒、不致畸、无炎症反应等),良好的生物降解性(降解可控),适宜的力学性能(满足实验所需),良好的材料表面微环境(微孔和粗糙程度等)。而支架的形貌和结构又直接影响着它的功能,随着研究的不断深入,对支架的要求也越来越具体:良好的三维贯通性,高的孔隙率,合适的孔径大小,均匀的孔隙分布,高的比表面积和结构可控、便于重复等等。为了满足这些要求,各种各样的支架制备方法被应用于实际,但是到目前为止,还没能找到一种简单易行、经济实惠的制备方法。以此为出发点,本论文进行了下面的探索性实验。
实验中选取以羟基磷灰石(HA)为原料:它属于生物陶瓷,其化学成份和晶体结构与脊椎动物的牙齿、骨组织中的无机成分相似,具有优良的生物亲和性,与骨组织极易结合,生物相容性好,更重要的是对人体组织无任何的毒副作用。实验中采用球粒堆积的方式制备了新型的多孔陶瓷支架,为考察该支架体系的生物活性,以动物狗为对象进行了体内非骨部位的诱导成骨性能研究,并取得了满意的实验结果,其主要结论如下:
1.采用溶胶-凝胶法和W/O乳化成球技术制备了多孔的HA球粒,并对其形貌结构进行了表征。结果显示:该方法制备的多孔HA球粒粒径分布均匀,球粒的粒径可通过搅拌的速率来调节且与搅拌的速率成反比,球形度优良,具有很好的力学性能和高的比表面积,单颗纯HA球粒的孔隙率分布在15%～20%之间。通过添加不同制孔剂的方法可以改变球粒内部的孔隙大小和孔隙形貌,并可以提高单颗球粒的孔隙率,平均值最高可达到30%。
2.采用有机泡沫模板法制备了多孔HA网管和盖子,通过球粒堆积的方式制备了新型的三维多孔圆柱状支架,赋予了其规整的外形,优良的三维贯通性和高孔隙率(平均分在布48%～66.9%左右,最高可达到70%)。该支架主要优点在于:支架结构、孔隙结构可控,孔隙大小分布广泛,微孔和宏孔相结合,孔隙形貌特别且可调。
3.在动物狗体内四个不同的非骨部位对支架的异位诱导成骨能力进行了研究,具体部位为腹腔内大网膜包裹(AC)、壁层腹膜内(P)、股部肌肉(M)、股骨旁骨膜覆盖(FP)。体内实验结果显示:在未载入任何生长因子或药物的前提下,六个月时,本支架体系表现出良好的异位骨诱导性:在部位P和M的支架,微球间骨基质生长良好,血管生长丰富,有大量成熟的骨细胞镶嵌在骨陷窝上;而在FP部位的支架是生长情况最好的,可以明显的见到骨组织生长优异且有片层状的新骨长成。这说明该支架孔隙结构合理,孔隙大小适宜,利于细胞的粘附生长和新生血管的长入,为组织液和氧份等提供了便捷的通道,有利于新陈代谢。在相同时间下,种植在AC部位的支架内血管生长数少,管径小,也未见到明显的骨基质生长。不同非骨部位的结果反应出支架的异位诱导能力跟种植的部位密切相关,且支架在植入前期的内部血管化程度是影响支架异位诱导能力的一个至关重要的因素。综合分析,在本实验中,支架在同物种不同非骨部位诱导成骨能力的强弱顺序排列如下:FP＞P=M＞AC。
The scaffold of bone tissue engineering as a branch of tissue engineering was got a broad study and development, it could be offer some new ideas and bring some hope for solving and improving the therapy of bone repair and replacement in people's daily life. In the study of this field, kinds of material is the key factor. A lot of study indicate that many kinds of materials can be used in bone tissue engineering, but they must have the co-characteristics: be good at biocompatibility (innocuity, no-teratogenesis, no-inflammation response etc), biodegradation (the velocity of degradation can be controlled), micro-environment of material's surface (include microporous and roughness) and mechanical property (to gratify the need of experiment). On a certain extent, function of the scaffold is influenced by its shape and structure, therefore, more and more idiographic requirements can be proposaled in the interest of improving capability of it. For instance: three-dimensional interconnection, high porosity and specific surface area, pore size and distribution, can be controlled and repeated easily. In order to satisfy this requirements many methods of fabrication scaffold were used in practice, but, up to now, people are much to seek a sort of preparation method which is simpleness and economy. At beginning of this, we put up a exploring experiment in this paper.
Hydroxyapatite (HA) belongs to bioceramic is performed in this study because its chemical composition and crystal structure is extraordinary similar with inorganic in dens and osseous tissue in vertebrate, which with excellent biocompatibility and combine with osseous tissue easily. A novel porous bioceramic scaffold is prepared by accumulating HA spherules and in order to study ectopia osteoinduction of the scaffolds in vivo which were implanted in four different non-osseous sites in dogs. At last, we get a useful and satisfying results, the main conclusions are drawn as follows:
1. Fabrication porous HA spherule by the method of sol-gel and water/oil emulsification technology. Results of characterization reveal that: porous HA spherules with a high specific surface area, a appropriate mechanical property and excellent sophericity, pores size is inverese ratio to stirring speed and porosity of HA spherule in the scope of 15% to 20%, micropores size and shape can be changed by pore-maker, under this conditions, porosity of HA spherules can be arrived at 30% in max.
2. Method of polymer sponge template is used to preparation porous HA tube and discs, and a novel three-dimensional porous bioceramic scaffold called the HA spherule scaffold with regular shape, excellent interconnection and high porosity (average is in the scope of 48% to 66.9%, the max. can be up to 70%) manufactured by accumulating HA spherules. The great advantages of this scaffold are the controlled interconnection of pores, the adjustable microstructure of HA spherules and the easy reconstruction of porous structure.
3. To study a ability of osteoinduction of the scaffolds which were implanted in four different non-osseous sites in dogs: in abdominal cavity (AC), peritoneum pocket (P), muscle (M) and beside the femur (FP). Samples are collected after six months and the results indicate that: the HA spherule scaffold can induce angiogenesis and bone formation without use of cytokines for vasculogenesis or bone-induction. There were not only a mass of blood vessels appeared and a lot of mature osteocytes inlayed on the bone lacuna but also the bone stroma grew well and a plenty of collagen fibres filled in it appeared around the spherules while speciments implanteded in P and M, and when the speciments in FP the growth conditions is the best that the osseous tissues developed quite perfect and the newly-formed bone even had a lamellar structure with many mature osteocytes. So, these proved that this scaffold have a reasonable pore structure, pore size and porosity, which in favor of attachment, differentiation and proliferation of cells, provide a convenient channels to transport tissue fluid and nutrient, speed up metabolism. In contrast, there were a small quantity of blood vessels and almost no newly formed bone in the specimens implanted in abdominal cavity while a few of collagen fibres around HA spherules. Different results reveal that ectopia osteoinduction is directly attached to the site of non-osseous and the degree of vascularization in prophase is a vital importance to osteoinduction. In this study, the sequence of osteoinduction ability at the four different non-osseous as follows: FP > P = M > AC.
实验中选取以羟基磷灰石(HA)为原料:它属于生物陶瓷,其化学成份和晶体结构与脊椎动物的牙齿、骨组织中的无机成分相似,具有优良的生物亲和性,与骨组织极易结合,生物相容性好,更重要的是对人体组织无任何的毒副作用。实验中采用球粒堆积的方式制备了新型的多孔陶瓷支架,为考察该支架体系的生物活性,以动物狗为对象进行了体内非骨部位的诱导成骨性能研究,并取得了满意的实验结果,其主要结论如下:
1.采用溶胶-凝胶法和W/O乳化成球技术制备了多孔的HA球粒,并对其形貌结构进行了表征。结果显示:该方法制备的多孔HA球粒粒径分布均匀,球粒的粒径可通过搅拌的速率来调节且与搅拌的速率成反比,球形度优良,具有很好的力学性能和高的比表面积,单颗纯HA球粒的孔隙率分布在15%～20%之间。通过添加不同制孔剂的方法可以改变球粒内部的孔隙大小和孔隙形貌,并可以提高单颗球粒的孔隙率,平均值最高可达到30%。
2.采用有机泡沫模板法制备了多孔HA网管和盖子,通过球粒堆积的方式制备了新型的三维多孔圆柱状支架,赋予了其规整的外形,优良的三维贯通性和高孔隙率(平均分在布48%～66.9%左右,最高可达到70%)。该支架主要优点在于:支架结构、孔隙结构可控,孔隙大小分布广泛,微孔和宏孔相结合,孔隙形貌特别且可调。
3.在动物狗体内四个不同的非骨部位对支架的异位诱导成骨能力进行了研究,具体部位为腹腔内大网膜包裹(AC)、壁层腹膜内(P)、股部肌肉(M)、股骨旁骨膜覆盖(FP)。体内实验结果显示:在未载入任何生长因子或药物的前提下,六个月时,本支架体系表现出良好的异位骨诱导性:在部位P和M的支架,微球间骨基质生长良好,血管生长丰富,有大量成熟的骨细胞镶嵌在骨陷窝上;而在FP部位的支架是生长情况最好的,可以明显的见到骨组织生长优异且有片层状的新骨长成。这说明该支架孔隙结构合理,孔隙大小适宜,利于细胞的粘附生长和新生血管的长入,为组织液和氧份等提供了便捷的通道,有利于新陈代谢。在相同时间下,种植在AC部位的支架内血管生长数少,管径小,也未见到明显的骨基质生长。不同非骨部位的结果反应出支架的异位诱导能力跟种植的部位密切相关,且支架在植入前期的内部血管化程度是影响支架异位诱导能力的一个至关重要的因素。综合分析,在本实验中,支架在同物种不同非骨部位诱导成骨能力的强弱顺序排列如下:FP＞P=M＞AC。
The scaffold of bone tissue engineering as a branch of tissue engineering was got a broad study and development, it could be offer some new ideas and bring some hope for solving and improving the therapy of bone repair and replacement in people's daily life. In the study of this field, kinds of material is the key factor. A lot of study indicate that many kinds of materials can be used in bone tissue engineering, but they must have the co-characteristics: be good at biocompatibility (innocuity, no-teratogenesis, no-inflammation response etc), biodegradation (the velocity of degradation can be controlled), micro-environment of material's surface (include microporous and roughness) and mechanical property (to gratify the need of experiment). On a certain extent, function of the scaffold is influenced by its shape and structure, therefore, more and more idiographic requirements can be proposaled in the interest of improving capability of it. For instance: three-dimensional interconnection, high porosity and specific surface area, pore size and distribution, can be controlled and repeated easily. In order to satisfy this requirements many methods of fabrication scaffold were used in practice, but, up to now, people are much to seek a sort of preparation method which is simpleness and economy. At beginning of this, we put up a exploring experiment in this paper.
Hydroxyapatite (HA) belongs to bioceramic is performed in this study because its chemical composition and crystal structure is extraordinary similar with inorganic in dens and osseous tissue in vertebrate, which with excellent biocompatibility and combine with osseous tissue easily. A novel porous bioceramic scaffold is prepared by accumulating HA spherules and in order to study ectopia osteoinduction of the scaffolds in vivo which were implanted in four different non-osseous sites in dogs. At last, we get a useful and satisfying results, the main conclusions are drawn as follows:
1. Fabrication porous HA spherule by the method of sol-gel and water/oil emulsification technology. Results of characterization reveal that: porous HA spherules with a high specific surface area, a appropriate mechanical property and excellent sophericity, pores size is inverese ratio to stirring speed and porosity of HA spherule in the scope of 15% to 20%, micropores size and shape can be changed by pore-maker, under this conditions, porosity of HA spherules can be arrived at 30% in max.
2. Method of polymer sponge template is used to preparation porous HA tube and discs, and a novel three-dimensional porous bioceramic scaffold called the HA spherule scaffold with regular shape, excellent interconnection and high porosity (average is in the scope of 48% to 66.9%, the max. can be up to 70%) manufactured by accumulating HA spherules. The great advantages of this scaffold are the controlled interconnection of pores, the adjustable microstructure of HA spherules and the easy reconstruction of porous structure.
3. To study a ability of osteoinduction of the scaffolds which were implanted in four different non-osseous sites in dogs: in abdominal cavity (AC), peritoneum pocket (P), muscle (M) and beside the femur (FP). Samples are collected after six months and the results indicate that: the HA spherule scaffold can induce angiogenesis and bone formation without use of cytokines for vasculogenesis or bone-induction. There were not only a mass of blood vessels appeared and a lot of mature osteocytes inlayed on the bone lacuna but also the bone stroma grew well and a plenty of collagen fibres filled in it appeared around the spherules while speciments implanteded in P and M, and when the speciments in FP the growth conditions is the best that the osseous tissues developed quite perfect and the newly-formed bone even had a lamellar structure with many mature osteocytes. So, these proved that this scaffold have a reasonable pore structure, pore size and porosity, which in favor of attachment, differentiation and proliferation of cells, provide a convenient channels to transport tissue fluid and nutrient, speed up metabolism. In contrast, there were a small quantity of blood vessels and almost no newly formed bone in the specimens implanted in abdominal cavity while a few of collagen fibres around HA spherules. Different results reveal that ectopia osteoinduction is directly attached to the site of non-osseous and the degree of vascularization in prophase is a vital importance to osteoinduction. In this study, the sequence of osteoinduction ability at the four different non-osseous as follows: FP > P = M > AC.
引文
1.R M Nerem.Tissue engineering in the USA.Med Biol Eng Comput,1992;30(4):8-12.
2.Y L Cao,C A Vacanti,J Upton,et al.Transplantation of chondrucytes utilizing polymer-cell constructs to produce new cartilage in the shape of a human ear.Plast Reconstr Surg,1997;100(2):297-302
3.C Maniatopoulos,J Sodek,A H Melcher.Bone formation in vitro by stromal cells obtained from bone marrow of yong adule rats.Cell Tissue Res,1988;254(3):317-320
4.G M Crane,S L Lshaug,A G Mikos,et al.Bone Tissue Engineening.Nature Medicine,1995;1(12):1322
5.D J Mooney,B S Kim.Development of biocompatible synthetic extracellular matrices for tissue engineering.Trends Biotechnol,1998;16(5):224-230
6.L Cui,W Liu,et al.Research and development of tissue engineering.Academic Journal of Shanghai Second Medical University,2004;24(4):229-231
7.王身国,涂赤枫,李光明,等.细胞支架及其构建技术的研究.第三届全国组织工程学术会议暨第一届中国国际组织工程会议论文汇编,成都.2002;453-455
8.W H Dietmar.Scaffolds in tissue engineering bone and cartilage.Biomaterials,2000;21(24):2529-2543
9.B S Kim,D J Mooney.Development of biocompatible synthetic extracellular matrices for tissue engineering.Trends in Biotechnology,1998;16(5):224-230
10.C M Agrwal,R B Ray.Biodegradable polymer scaffolds for musculoskeletal tissue engineering.J Biomed Mater Res,2001;55(2):141-150
11.高建平,马朋高,姚康德,等.组织工程与生物可降解高分子骨架.高分子通报,2000;4:89-95
12.罗丙红,卢泽俭.组织工程用高度多孔生物可降解支架的制备.国外医学生物医学工程分册,2001;24(4):154-158
13.Y H Tsuang,F H Lin,J S Sun,et at.In vitro cell behavior of osteoblasts on pyrost bone substitute.Anat Rec,1997;247(2):164-169
14.S Hofman,M Sidqui,D Abensur,et al.Effects of Laddec on the formation of calcrfied bone matrix in rat calvariae cells culture.Biomaterials,1999;20(13):1155-1166
15.Y J Seol,J Y Lee,Y J Park,et al.Chitosan sponges as tissue engineering scaffolds for bone formation.Biotechnol Lett,2004;26(13):1037-1041
16.E Arnaud,C De Pollak,A Meunier,et al.Osteogenesis with coral is increased by BMP and BMC in a rat cranioplasty.1 999;20(20):1909-1918
17.J E Wergedal,K H Lau,D J Baylink.Fluoride and bovine bone extract influence cell proliferation and phosphatase activities in human bone cell culture.Clin Orthop,1988;(233):274-282
18.H Xing,X M Chen,H Q Zhang.Scaffold materials for bone tissue engineering.Foshan Ceramics,2004;14(12):33-35
19.C A Vacanti,W Kim,J Upton,et al.Tissue-engineered growth of bone and cartilage.Transplant Proc,1993;25(2):1019-1021
20.M Borden,M Attawia,Y Khan,et al.Tissue-engineered bone formation in vivo using a novel sintered polymeric microsphere matrix.J Bone Joint Surg Br,2004;86(8):1200-1208
21.C D Sims,P E Butler,Y L Cao,et al.Tissue engineered neocartilage using plasma derived polymer substrates and chondrocytes.Plast Reconstr Surg,1998;101(6):1580-1585
22.J E Devin,M A Attawia,C T Laurencin.Three-dimensional degradable porous polymer ceramic matrices for use in bone repair.J Biomater Sci Polymer,1996;7(8):661-669
23.H H Lu,S F El-Amin,K D Scott,et al.Three-dimensional,bioactive,biodegradable,polymer-bioactive glass composite scaffolds with improved.mechanical properties support collagen synthesis and mineralization of human osteoblast-like cells in vitro.J Biomed Mater Res A,2003;64(3):465-474
24.F Y Hsu,S C Chueh,and Y J Wang.Microspheres of hydroxyapatite /reconstituted collagen as supports for osteoblast cell growth.Biomaterials,1999;20:1931-1936
25.D Bakos,M Soldan,et al.Hydroxyapatite-collagen-hyaluronic acid composite.Biomaterials,1999;20(2):191-195
26.L B Wu,J D Ding.Advances in fabrication methodology and technology of three-dimensional porous scaffolds for tissue engineering.Journal of Functional Polymers,2003;16(1):91-96
27.AG Mikos,Y Bao,L G Cima,et al.Preparation of poly(glycolic acid)bonded fiber structures for cell attachment and transplantation.J Biomed Mater Res.2004;27(2):183-189
28.D J Mooney,K Mcnamara,D Hem,et al.Stabilized polyglycolic acid fiber-based tubes for tissue engineering.Biomaterials.1996:17:115-124
29.翁雨来,商庆新,曹谊林.至命科学的新增长点——组织工程.牙体牙髓牙周病学杂志,2000;10(5):249-254
30.A G Mikos,A J Thorsen,et al.Preparation and characterization of poly(L-lacticacid)foam.Polymer,1994;35(5):1068-1077
31.V P Shastri,I Martin,et al.Macroporous polymer foams by hydrocarbon templating.Proceedings of the National Academy of Science,USA,2000;97(5):1970-1975
32.M H Sheridan,L D Shea,D J Mooney,et al.Bioabsorbable polymer scaffolds for tissue engineering capable of sustained growth factor delivery.J Controlled Release,2000;64(1-3):91-102
33.Y S Nam,J J Yoon,et al.A novel fabrication method of macroporous biodegradable polymer scaffolds using gas foaming salt as a porogen additive.Biomed Mater Res(Appl Biomat).2000;53(1):1-7
34.K Whang,T K Goldstick,K E Healy.A biodegradable polymer scaffold for delivery of osteotropic factors.Biomaterials,2000;21(24):2545-2551
35.Y S Nam,T G Park.Porous biodegradable polymeric scaffolds prepared by thermally induced phase separation.J Biomed Mater Res,1999;47(1):8-17
36.P X Ma,R Y Zhang.Synthetic nano-scale fibrous extracellular matrix.J Biomed Mater Res.1999;46(1):60-72
37.M Borden,M Attawia,et al.Tissue engineered microsphere-based matrices for bone repair:design and evaluation.Biomatedals,2002;23(2):551-559
38.R Zhang,P X Ma.Synthetic nano-fibdllar extracellular matrix with predesigned macroporous architectures.J Biomed Mater Res,2000;52(2):430-438
39.丁焕文,唐春雷,赵中岳,等.个体化组织工程支架CAD设计与RP制作方法的研究.生物骨科材料与临床研究,2005;2(1):1-4
40.王臻,滕勇,李涤尘,等.基于快速成型技术的个体化人工股骨髁关节面的设计与应用.中华外科杂志,2004;42(12):746-749
41.T Cao,K H Ho,S H Teoh.Scaffold design and in vitro study of osteochondral coculture in a three-dimensional porous polycaprolactone scaffold fabricated by fused deposition modeling.Tissue Engineering,2003;9:103-112
42.沈兴全,王爱玲.快速成型技术在生物医学工程的应用.第三届全国快速成型与快速制造学术会议论文集,昆明:原子能出版社,2004
43.S Hermann,R Wolfgang,I Stephan,et al.Three-dimensional printing of porous ceramic scaffolds for bone tissue engineering.Journal of Biomedical Materials Research(Part B),2005;74B(2):782-788
44.M R Urist.Bone:formation by autoinduction.Science,1965;150(3698):893-899
45.J Chalmer et al.Obsevations on the induction of bone in soft tissue.JBJS,1975;57-B(1):36-45
46.J F Piecuch.Extraskeletal implantation of a porous hydroxyapatite ceramic.J Dent Res,1982;61(12):1458-1460
47.D D Deligianni,N D Katsala,et al.Effect of surface roughness of hydroxyapatite on human bone marrow cell adhesion,proliferation,differentiation and detachment strength.Biomaterials,2001;22(1):87-96
48.D Kubies,F Ryapeek,et al.Microdomain structure in polylactide block poly(ethylene oxide) copolymer films.Biomaterials,2000;21:529-536
49.S M Cannizzaro,R F Padera,R Langer,et al.A novel biotinylaied degradable polymer for cell-interactive applications.Biotechnol &Bioengng.1998;58(5):529-535
50.K Wang,C H Thomas,K E Healy.A novel method to fabricate bioabsorbable scaffolds.Polymer,1995;36(4):837-842
51.陈光,周平等.天然生物材料壳聚糖支架上人胚肺成纤维细胞的生长.化学学报,2004;62(10):992-997
52.谢德明.BMP/PLA复合骨细胞培养支架材料.暨南大学学报,2000;21(1):92-94
53.杨耀武,毛天球,等.鸵鸟羟基磷灰石陶瓷支架负载骨髓基质细胞异位 成骨性能.第四军医大学学报,2004;25(5):421-423
54.王洪涛,陈璧,等.人胎儿毛乳头细胞在聚羟基乙酸真皮支架上的生长特性观察.西北国防医学杂志,2006;27(4):244-246
55.柴枫,王忠义等.RP构建不同孔隙率骨支架材料对成骨细胞增殖的影响.口腔颌面修复学杂志,2003;4(3):137-139
56.K Webb,V Hlady,P A Tresco.Relationships among cell attachment,spreading,cytoskeletal organization,and migration rate for anchorage-dependent cells on model surfaces.Journal of Biomedical Materials Research,2000;49(3):362-368
57.J J Klawitter.A basic investigation of bone growth into a porous ceramic material.Doctoral Thesis,Clemson University,Clemson,SC,1970
58.S F Hulbert,J J Klawitter,et al.A histological study of ceramic-bone compalibility.IADR Progr & Abst,1970;49(75)
59.M R Urist,et al.The bone induction principle.Clin OrthoP Rel Res,1967;53:243-283
60.D M Roy and S K Linnehan.Hydroxyapatite formed from coral skeletal carbonate by hydrothermal exchange.Nature,1974;247:220-222
61.E W White,et al.Replamineform porous biomaterials for hard tissue implant applications.J Biomed Mater Res,1995;9(4):23-27
62.R T Chiroff,et al.Tissue ingrowth of replamineform implants.J Biomed Mater Res,1995;9(4):29-459
63.R E Holmes,et al.Bone regeneration within a coralline hydroxyapatite implant.Plast Reconster Surg,1979;63(5):626-633
64.R Finn,et al.Interpositional grafting with autogenous bone and coralline hydroxyapatite.J Maxillofac Surg,1980;8(3):217-227
65.J F Piecuch,et al.Subperiosteal ridge augmentation with porous hydroxyapatite ceramic implant.IADR Pro r & Abst,1981;601(1167)
66.M Jarcho,et al.Calcium phosphate ceramics as hard tissue prosthetics.Clin Orthop Rel Res.1981;157:259-278
67.J O Hollinger,J Brekke,E Gruskin,et al.Role of bone substitutes.Clin Orthop Rel Res,1996;324:55-65
68.H Yamasaki,H Sakai.Osteogenic response to porous hydroxyapatite ceramics under the skin of dogs.Biomaterials,1992;13(55):308-312
69.Z J Yang,H P Yuan,W D Tong,et al.Osteogenesis in extraskeletally implanted porous phosphate ceramics:variability among different kinds of animals.Biomaterlals,1996;17(22):2131-2137
70.U Ripamonti,et al.Osteoinduction in porous hydroxyapatite implanted in heterotopic sites of different animal models.Biomaterials,1996;17(1):31-35
71.E Sachlos,J T Czernuszka.Making tissue engineering scaffolds work:review on the application of solid freeform fabrication technology to the production of tissue engineering scaffolds.European Cells and Materials,2003;5:29-40
72.M R Urist,et al.A bovine low molecular weight BMP fraction.Clin Orthop.1982;162:219-232
73.M R Urist,et al.Purification of bovine bone morphogenetic by hydroxyapatite chromatography.Proc Natl Acad Sci,1984;81(2):371-375
74.A Santosh,K C Remant,N Dharmaraj,et al.Synthesis and characterization of hydroxyapatite using carbon nanotubes as a nano-matrix.Scripta Materialia,2006;54:131-135
75.李世普.生物医用材料导论.武汉工业大学出版社,2000;7-5629-1645-4:53-196
76.S P Li,S C Zhang,F Cheng.Studies on effects of apatite ultrafinepowder on cancer cells.J of Wuhan University of Techology,1996;18(1):5-8
77.R Rmaachnadra Rao,et al.Solid tate Synthesis and thermal stability of HAP and HAP- β -TCP composite ceramic Powders.Jomual of Material Science:Materials In Medicine,1997;8(8):511-518
78.熊兆贤.无机材料研究方法.厦门大学出版社,2001;7-5615-1727-0
79.D M Roy.Hydroxyapatite formed from coral skeletal carbonate by Hydrothermal exchange.Nature,1974;247(438):220-222
80.王友法,闰玉华,梁飞等.水热条件下针状羟基磷灰石单晶体的均相合成.硅酸盐通报,2001;2:30-34
81.C M Lopatin,V Pizziconi,et al.Hydroxyapatite powders and thin films prepared by a sol-gel technique.Thin Solid Films,1998;326(1-2):227-232
82.邬鸿彦,朱明刚,孔令宜等.纳米级羟基磷灰石生物陶瓷粉末的制备新方法.河北师范大学学报,1997;21(3):266-269
83.P Layrolle,A Lebugle.Characterization and reactivity of nanosized calcium phosphates prepared in anhydrous ethanol.Chem.Mater.,1994;6(11):1996-2004
84.C A Vacant,L J Bonassar.An overview of tissue engineered bone.Clin Orthop,1999;367(427):375-381.
85.C S Wu.Preparation of macro-porous scaffold in bone tissue engineering.Chin J Clinical Rehabilitation(in Chinese),2004;8(5):114-117
86.J L Burgk,S Porter,J F Kellam.Biomaterial developments for bone tissue engineering.Biomaterials,2000;21(23):2347-2359
87.H P Yuan,et al.A preliminary study on osteoinduction of two kinds of calcium phosphate ceramics.Biomaterials,1999;20(19):1799-1806
88.J N Dent.On the interaction of thyroxine and of oxytocin with prolactin on the growth of the tail fin in the red-spotted newt,1982;105:993-998
89.Y Takafumi,O Hajime.Human marrow cell-derived cultured bone in porous ceramics.Bio-Med Mater Eng,1998;8(3):311-320
90.B S Chang,C K Lee,K S Hong.Osteoconduction at porous hydroxyapatite with various pore configurations.Biomaterials,2000;21(12):1291-1298
91.G A Silval,O P Coutinho,P Ducheyne and R L Reis.Materials in particulate form for tissue engineering-applications in Bone.J Tissue Eng Regen Med,2007:1(2):97-109
92.W Paul,C P Sharma.Antibiotic loaded hydroxyapatite osteoconductive implant material- in vitro release studies.Materials Science Letters,1995;14(24):1792-1794
93.D F Luo,K Zhao,et al.Fabrication of interconnected spherical porous hydroxyapatite scaffold.J Chinese Ceramic Society,2007;35(3):368-372
94.C Ma,Z Wang,J X Lu,et al.Quantification of vascularization within spherical porous β -TCP scaffold in vivo.Orthopedic Journal of China,2008;16(10):774-777
95.H D Kim,R F Valentini.Retention and activity of BMP-2 in hyaluronic acid-based scaffolds in vitro.Journal of Biomedical Materials Research,2002;59(3):573-584
96.Y Hu,D W Grainger,S R Winn,et al.Fabrication of poly(alpha-hydroxy acid) foam scaffolds using multiple solvent systems.Journal of Biomedical Matedals Research,2002;59(3):563-572
97.R Nazarov,H J Jin,D L Kaplan.Porous 3-D scaffolds from regeneratedsilk fibroin.Biomacromolecules,2004;5(3):718-726
98.刘培生,马晓明.多孔材料检测方法.冶金工业出版社,2006
99.J Dong,H Kojima,T Uemura,et al.In vivo evaluation of a novel porous hydroxyapatite to sustain osteogenesis of.transplantedbone marrow-derived osteoblastic cells.Journal of Biomedical Materials Research,2001;57(2):208-216
100.European Pharmacopoeia 6th ed,Council of Europe,Strasbourg,2006
101.H R Ramay,M Zhang.Preparation of porous hydroxyapatite scaffolds by combination of the gel-casting and polymer sponge methods.Biomaterials,2003;24(19):3293-3202
102.叶大年,韩成,曾荣树.等大球的任意堆积.科学通报,1986;31(12):920-924
103.叶大年,张金民.非等大球的任意堆积.地质科学,1990;2:127-136
104.B John,J K Arun,N Ange,et al.Trapping heavy metals by using calcium hydroxyapatite and dielectrophoresis.Journal of Hazardous Materials,2007;139(3):461-466
105.L Bertinetti,A Tampied,E Landi,et al.Surface modification of hydroxyapatite.Part Ⅱ.Silica.Biomaterials,2003;24(21):3681-3688
106.Q Liu,et al.Surface modification of nano-apaptite by grafting organic polymer.Biomaterials,1998;19(11-12):1067-1072
107.应伟,孙桂君.以羟基磷灰石为吸附剂进行细菌浓缩实验研究.中国卫生检验杂志,1999:9(1):43—44
108.E A Arias.An overview of current delivery systems in cancer gene therapy.J Cont Rel,2004;94(1):1-14
109.C Deng,J Weng,B Feng,et al.Review of surface adsorption property of hydroxyapatite.Materials Review,2007;21(9):84-87
110.G Yin,J Zhan,et al.Characterization of the adsorption of bovine serum album in on hydroxyapatite.Chemical Journal of Chinese Universities,2001;22(5):771-775
111.J Zhang,D P Wang,et al.New research development of absorption property and preparation technology of hydroxyapatite.Materials Review,2008;22(11):54-58
112.X D Zhang,W Q Cheng,J Weng,et al.Initiation of the osteoinduction in calcium phosphate ceramics without any bone growth factor.Trans 19th Annual Meeting of the Society for Biomaterials, 28 April-2 May, 1993; Birmingham AL, USA, 299
113.Z J Yang, H P Yuan, W D Tong, et al. Osteogenesis in extraskeletally implanted porous phosphate ceramics: variability among different kinds of animals. Biomaterlals, 1996; 17(22): 2131-2137
114.U Ripamonti, et al. Osteoinduction in porous hydroxyapatite implanted in heterotopic sites of different animal models. Biomaterials, 1996; 17(1): 31-35
115.H P Yuan, K Kurashina, J D Bruijn, et al. A preliminary study on osteoinduction of two kinds of calcium phosphate ceramics. Biomaterials, 1999; 20(19): 1799-1806
116.K Kurashina, H Kurita, Q Wu, et al. Ectopic osteogenesis with biphasic and tricalcium phosphate in rabbits. Biomaterials, 2002; 23(2): 407-412
117.K Vassilis , K David . Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials, 2005; 26(27): 5474-5491
118.P Kasten, B Ingo, et al. Porosity and pore size of β-tricalcium phosphate scaffold can influence protein production and osteogenic differentiation of human mesenchymal stem cells: An in vitro and in vivo study. Acta Biomaterials, 2008; 4(6): 1904-1915
119.M Gelinsky, A Bernhardt, et al. Porous three-dimensional scaffolds made of mineralised collagen : Preparation and properties of a biomimetic nanocomposite material for tissue engineering of bone . Chemical Engineering Journal, 2008; 137(1): 84-96
2.Y L Cao,C A Vacanti,J Upton,et al.Transplantation of chondrucytes utilizing polymer-cell constructs to produce new cartilage in the shape of a human ear.Plast Reconstr Surg,1997;100(2):297-302
3.C Maniatopoulos,J Sodek,A H Melcher.Bone formation in vitro by stromal cells obtained from bone marrow of yong adule rats.Cell Tissue Res,1988;254(3):317-320
4.G M Crane,S L Lshaug,A G Mikos,et al.Bone Tissue Engineening.Nature Medicine,1995;1(12):1322
5.D J Mooney,B S Kim.Development of biocompatible synthetic extracellular matrices for tissue engineering.Trends Biotechnol,1998;16(5):224-230
6.L Cui,W Liu,et al.Research and development of tissue engineering.Academic Journal of Shanghai Second Medical University,2004;24(4):229-231
7.王身国,涂赤枫,李光明,等.细胞支架及其构建技术的研究.第三届全国组织工程学术会议暨第一届中国国际组织工程会议论文汇编,成都.2002;453-455
8.W H Dietmar.Scaffolds in tissue engineering bone and cartilage.Biomaterials,2000;21(24):2529-2543
9.B S Kim,D J Mooney.Development of biocompatible synthetic extracellular matrices for tissue engineering.Trends in Biotechnology,1998;16(5):224-230
10.C M Agrwal,R B Ray.Biodegradable polymer scaffolds for musculoskeletal tissue engineering.J Biomed Mater Res,2001;55(2):141-150
11.高建平,马朋高,姚康德,等.组织工程与生物可降解高分子骨架.高分子通报,2000;4:89-95
12.罗丙红,卢泽俭.组织工程用高度多孔生物可降解支架的制备.国外医学生物医学工程分册,2001;24(4):154-158
13.Y H Tsuang,F H Lin,J S Sun,et at.In vitro cell behavior of osteoblasts on pyrost bone substitute.Anat Rec,1997;247(2):164-169
14.S Hofman,M Sidqui,D Abensur,et al.Effects of Laddec on the formation of calcrfied bone matrix in rat calvariae cells culture.Biomaterials,1999;20(13):1155-1166
15.Y J Seol,J Y Lee,Y J Park,et al.Chitosan sponges as tissue engineering scaffolds for bone formation.Biotechnol Lett,2004;26(13):1037-1041
16.E Arnaud,C De Pollak,A Meunier,et al.Osteogenesis with coral is increased by BMP and BMC in a rat cranioplasty.1 999;20(20):1909-1918
17.J E Wergedal,K H Lau,D J Baylink.Fluoride and bovine bone extract influence cell proliferation and phosphatase activities in human bone cell culture.Clin Orthop,1988;(233):274-282
18.H Xing,X M Chen,H Q Zhang.Scaffold materials for bone tissue engineering.Foshan Ceramics,2004;14(12):33-35
19.C A Vacanti,W Kim,J Upton,et al.Tissue-engineered growth of bone and cartilage.Transplant Proc,1993;25(2):1019-1021
20.M Borden,M Attawia,Y Khan,et al.Tissue-engineered bone formation in vivo using a novel sintered polymeric microsphere matrix.J Bone Joint Surg Br,2004;86(8):1200-1208
21.C D Sims,P E Butler,Y L Cao,et al.Tissue engineered neocartilage using plasma derived polymer substrates and chondrocytes.Plast Reconstr Surg,1998;101(6):1580-1585
22.J E Devin,M A Attawia,C T Laurencin.Three-dimensional degradable porous polymer ceramic matrices for use in bone repair.J Biomater Sci Polymer,1996;7(8):661-669
23.H H Lu,S F El-Amin,K D Scott,et al.Three-dimensional,bioactive,biodegradable,polymer-bioactive glass composite scaffolds with improved.mechanical properties support collagen synthesis and mineralization of human osteoblast-like cells in vitro.J Biomed Mater Res A,2003;64(3):465-474
24.F Y Hsu,S C Chueh,and Y J Wang.Microspheres of hydroxyapatite /reconstituted collagen as supports for osteoblast cell growth.Biomaterials,1999;20:1931-1936
25.D Bakos,M Soldan,et al.Hydroxyapatite-collagen-hyaluronic acid composite.Biomaterials,1999;20(2):191-195
26.L B Wu,J D Ding.Advances in fabrication methodology and technology of three-dimensional porous scaffolds for tissue engineering.Journal of Functional Polymers,2003;16(1):91-96
27.AG Mikos,Y Bao,L G Cima,et al.Preparation of poly(glycolic acid)bonded fiber structures for cell attachment and transplantation.J Biomed Mater Res.2004;27(2):183-189
28.D J Mooney,K Mcnamara,D Hem,et al.Stabilized polyglycolic acid fiber-based tubes for tissue engineering.Biomaterials.1996:17:115-124
29.翁雨来,商庆新,曹谊林.至命科学的新增长点——组织工程.牙体牙髓牙周病学杂志,2000;10(5):249-254
30.A G Mikos,A J Thorsen,et al.Preparation and characterization of poly(L-lacticacid)foam.Polymer,1994;35(5):1068-1077
31.V P Shastri,I Martin,et al.Macroporous polymer foams by hydrocarbon templating.Proceedings of the National Academy of Science,USA,2000;97(5):1970-1975
32.M H Sheridan,L D Shea,D J Mooney,et al.Bioabsorbable polymer scaffolds for tissue engineering capable of sustained growth factor delivery.J Controlled Release,2000;64(1-3):91-102
33.Y S Nam,J J Yoon,et al.A novel fabrication method of macroporous biodegradable polymer scaffolds using gas foaming salt as a porogen additive.Biomed Mater Res(Appl Biomat).2000;53(1):1-7
34.K Whang,T K Goldstick,K E Healy.A biodegradable polymer scaffold for delivery of osteotropic factors.Biomaterials,2000;21(24):2545-2551
35.Y S Nam,T G Park.Porous biodegradable polymeric scaffolds prepared by thermally induced phase separation.J Biomed Mater Res,1999;47(1):8-17
36.P X Ma,R Y Zhang.Synthetic nano-scale fibrous extracellular matrix.J Biomed Mater Res.1999;46(1):60-72
37.M Borden,M Attawia,et al.Tissue engineered microsphere-based matrices for bone repair:design and evaluation.Biomatedals,2002;23(2):551-559
38.R Zhang,P X Ma.Synthetic nano-fibdllar extracellular matrix with predesigned macroporous architectures.J Biomed Mater Res,2000;52(2):430-438
39.丁焕文,唐春雷,赵中岳,等.个体化组织工程支架CAD设计与RP制作方法的研究.生物骨科材料与临床研究,2005;2(1):1-4
40.王臻,滕勇,李涤尘,等.基于快速成型技术的个体化人工股骨髁关节面的设计与应用.中华外科杂志,2004;42(12):746-749
41.T Cao,K H Ho,S H Teoh.Scaffold design and in vitro study of osteochondral coculture in a three-dimensional porous polycaprolactone scaffold fabricated by fused deposition modeling.Tissue Engineering,2003;9:103-112
42.沈兴全,王爱玲.快速成型技术在生物医学工程的应用.第三届全国快速成型与快速制造学术会议论文集,昆明:原子能出版社,2004
43.S Hermann,R Wolfgang,I Stephan,et al.Three-dimensional printing of porous ceramic scaffolds for bone tissue engineering.Journal of Biomedical Materials Research(Part B),2005;74B(2):782-788
44.M R Urist.Bone:formation by autoinduction.Science,1965;150(3698):893-899
45.J Chalmer et al.Obsevations on the induction of bone in soft tissue.JBJS,1975;57-B(1):36-45
46.J F Piecuch.Extraskeletal implantation of a porous hydroxyapatite ceramic.J Dent Res,1982;61(12):1458-1460
47.D D Deligianni,N D Katsala,et al.Effect of surface roughness of hydroxyapatite on human bone marrow cell adhesion,proliferation,differentiation and detachment strength.Biomaterials,2001;22(1):87-96
48.D Kubies,F Ryapeek,et al.Microdomain structure in polylactide block poly(ethylene oxide) copolymer films.Biomaterials,2000;21:529-536
49.S M Cannizzaro,R F Padera,R Langer,et al.A novel biotinylaied degradable polymer for cell-interactive applications.Biotechnol &Bioengng.1998;58(5):529-535
50.K Wang,C H Thomas,K E Healy.A novel method to fabricate bioabsorbable scaffolds.Polymer,1995;36(4):837-842
51.陈光,周平等.天然生物材料壳聚糖支架上人胚肺成纤维细胞的生长.化学学报,2004;62(10):992-997
52.谢德明.BMP/PLA复合骨细胞培养支架材料.暨南大学学报,2000;21(1):92-94
53.杨耀武,毛天球,等.鸵鸟羟基磷灰石陶瓷支架负载骨髓基质细胞异位 成骨性能.第四军医大学学报,2004;25(5):421-423
54.王洪涛,陈璧,等.人胎儿毛乳头细胞在聚羟基乙酸真皮支架上的生长特性观察.西北国防医学杂志,2006;27(4):244-246
55.柴枫,王忠义等.RP构建不同孔隙率骨支架材料对成骨细胞增殖的影响.口腔颌面修复学杂志,2003;4(3):137-139
56.K Webb,V Hlady,P A Tresco.Relationships among cell attachment,spreading,cytoskeletal organization,and migration rate for anchorage-dependent cells on model surfaces.Journal of Biomedical Materials Research,2000;49(3):362-368
57.J J Klawitter.A basic investigation of bone growth into a porous ceramic material.Doctoral Thesis,Clemson University,Clemson,SC,1970
58.S F Hulbert,J J Klawitter,et al.A histological study of ceramic-bone compalibility.IADR Progr & Abst,1970;49(75)
59.M R Urist,et al.The bone induction principle.Clin OrthoP Rel Res,1967;53:243-283
60.D M Roy and S K Linnehan.Hydroxyapatite formed from coral skeletal carbonate by hydrothermal exchange.Nature,1974;247:220-222
61.E W White,et al.Replamineform porous biomaterials for hard tissue implant applications.J Biomed Mater Res,1995;9(4):23-27
62.R T Chiroff,et al.Tissue ingrowth of replamineform implants.J Biomed Mater Res,1995;9(4):29-459
63.R E Holmes,et al.Bone regeneration within a coralline hydroxyapatite implant.Plast Reconster Surg,1979;63(5):626-633
64.R Finn,et al.Interpositional grafting with autogenous bone and coralline hydroxyapatite.J Maxillofac Surg,1980;8(3):217-227
65.J F Piecuch,et al.Subperiosteal ridge augmentation with porous hydroxyapatite ceramic implant.IADR Pro r & Abst,1981;601(1167)
66.M Jarcho,et al.Calcium phosphate ceramics as hard tissue prosthetics.Clin Orthop Rel Res.1981;157:259-278
67.J O Hollinger,J Brekke,E Gruskin,et al.Role of bone substitutes.Clin Orthop Rel Res,1996;324:55-65
68.H Yamasaki,H Sakai.Osteogenic response to porous hydroxyapatite ceramics under the skin of dogs.Biomaterials,1992;13(55):308-312
69.Z J Yang,H P Yuan,W D Tong,et al.Osteogenesis in extraskeletally implanted porous phosphate ceramics:variability among different kinds of animals.Biomaterlals,1996;17(22):2131-2137
70.U Ripamonti,et al.Osteoinduction in porous hydroxyapatite implanted in heterotopic sites of different animal models.Biomaterials,1996;17(1):31-35
71.E Sachlos,J T Czernuszka.Making tissue engineering scaffolds work:review on the application of solid freeform fabrication technology to the production of tissue engineering scaffolds.European Cells and Materials,2003;5:29-40
72.M R Urist,et al.A bovine low molecular weight BMP fraction.Clin Orthop.1982;162:219-232
73.M R Urist,et al.Purification of bovine bone morphogenetic by hydroxyapatite chromatography.Proc Natl Acad Sci,1984;81(2):371-375
74.A Santosh,K C Remant,N Dharmaraj,et al.Synthesis and characterization of hydroxyapatite using carbon nanotubes as a nano-matrix.Scripta Materialia,2006;54:131-135
75.李世普.生物医用材料导论.武汉工业大学出版社,2000;7-5629-1645-4:53-196
76.S P Li,S C Zhang,F Cheng.Studies on effects of apatite ultrafinepowder on cancer cells.J of Wuhan University of Techology,1996;18(1):5-8
77.R Rmaachnadra Rao,et al.Solid tate Synthesis and thermal stability of HAP and HAP- β -TCP composite ceramic Powders.Jomual of Material Science:Materials In Medicine,1997;8(8):511-518
78.熊兆贤.无机材料研究方法.厦门大学出版社,2001;7-5615-1727-0
79.D M Roy.Hydroxyapatite formed from coral skeletal carbonate by Hydrothermal exchange.Nature,1974;247(438):220-222
80.王友法,闰玉华,梁飞等.水热条件下针状羟基磷灰石单晶体的均相合成.硅酸盐通报,2001;2:30-34
81.C M Lopatin,V Pizziconi,et al.Hydroxyapatite powders and thin films prepared by a sol-gel technique.Thin Solid Films,1998;326(1-2):227-232
82.邬鸿彦,朱明刚,孔令宜等.纳米级羟基磷灰石生物陶瓷粉末的制备新方法.河北师范大学学报,1997;21(3):266-269
83.P Layrolle,A Lebugle.Characterization and reactivity of nanosized calcium phosphates prepared in anhydrous ethanol.Chem.Mater.,1994;6(11):1996-2004
84.C A Vacant,L J Bonassar.An overview of tissue engineered bone.Clin Orthop,1999;367(427):375-381.
85.C S Wu.Preparation of macro-porous scaffold in bone tissue engineering.Chin J Clinical Rehabilitation(in Chinese),2004;8(5):114-117
86.J L Burgk,S Porter,J F Kellam.Biomaterial developments for bone tissue engineering.Biomaterials,2000;21(23):2347-2359
87.H P Yuan,et al.A preliminary study on osteoinduction of two kinds of calcium phosphate ceramics.Biomaterials,1999;20(19):1799-1806
88.J N Dent.On the interaction of thyroxine and of oxytocin with prolactin on the growth of the tail fin in the red-spotted newt,1982;105:993-998
89.Y Takafumi,O Hajime.Human marrow cell-derived cultured bone in porous ceramics.Bio-Med Mater Eng,1998;8(3):311-320
90.B S Chang,C K Lee,K S Hong.Osteoconduction at porous hydroxyapatite with various pore configurations.Biomaterials,2000;21(12):1291-1298
91.G A Silval,O P Coutinho,P Ducheyne and R L Reis.Materials in particulate form for tissue engineering-applications in Bone.J Tissue Eng Regen Med,2007:1(2):97-109
92.W Paul,C P Sharma.Antibiotic loaded hydroxyapatite osteoconductive implant material- in vitro release studies.Materials Science Letters,1995;14(24):1792-1794
93.D F Luo,K Zhao,et al.Fabrication of interconnected spherical porous hydroxyapatite scaffold.J Chinese Ceramic Society,2007;35(3):368-372
94.C Ma,Z Wang,J X Lu,et al.Quantification of vascularization within spherical porous β -TCP scaffold in vivo.Orthopedic Journal of China,2008;16(10):774-777
95.H D Kim,R F Valentini.Retention and activity of BMP-2 in hyaluronic acid-based scaffolds in vitro.Journal of Biomedical Materials Research,2002;59(3):573-584
96.Y Hu,D W Grainger,S R Winn,et al.Fabrication of poly(alpha-hydroxy acid) foam scaffolds using multiple solvent systems.Journal of Biomedical Matedals Research,2002;59(3):563-572
97.R Nazarov,H J Jin,D L Kaplan.Porous 3-D scaffolds from regeneratedsilk fibroin.Biomacromolecules,2004;5(3):718-726
98.刘培生,马晓明.多孔材料检测方法.冶金工业出版社,2006
99.J Dong,H Kojima,T Uemura,et al.In vivo evaluation of a novel porous hydroxyapatite to sustain osteogenesis of.transplantedbone marrow-derived osteoblastic cells.Journal of Biomedical Materials Research,2001;57(2):208-216
100.European Pharmacopoeia 6th ed,Council of Europe,Strasbourg,2006
101.H R Ramay,M Zhang.Preparation of porous hydroxyapatite scaffolds by combination of the gel-casting and polymer sponge methods.Biomaterials,2003;24(19):3293-3202
102.叶大年,韩成,曾荣树.等大球的任意堆积.科学通报,1986;31(12):920-924
103.叶大年,张金民.非等大球的任意堆积.地质科学,1990;2:127-136
104.B John,J K Arun,N Ange,et al.Trapping heavy metals by using calcium hydroxyapatite and dielectrophoresis.Journal of Hazardous Materials,2007;139(3):461-466
105.L Bertinetti,A Tampied,E Landi,et al.Surface modification of hydroxyapatite.Part Ⅱ.Silica.Biomaterials,2003;24(21):3681-3688
106.Q Liu,et al.Surface modification of nano-apaptite by grafting organic polymer.Biomaterials,1998;19(11-12):1067-1072
107.应伟,孙桂君.以羟基磷灰石为吸附剂进行细菌浓缩实验研究.中国卫生检验杂志,1999:9(1):43—44
108.E A Arias.An overview of current delivery systems in cancer gene therapy.J Cont Rel,2004;94(1):1-14
109.C Deng,J Weng,B Feng,et al.Review of surface adsorption property of hydroxyapatite.Materials Review,2007;21(9):84-87
110.G Yin,J Zhan,et al.Characterization of the adsorption of bovine serum album in on hydroxyapatite.Chemical Journal of Chinese Universities,2001;22(5):771-775
111.J Zhang,D P Wang,et al.New research development of absorption property and preparation technology of hydroxyapatite.Materials Review,2008;22(11):54-58
112.X D Zhang,W Q Cheng,J Weng,et al.Initiation of the osteoinduction in calcium phosphate ceramics without any bone growth factor.Trans 19th Annual Meeting of the Society for Biomaterials, 28 April-2 May, 1993; Birmingham AL, USA, 299
113.Z J Yang, H P Yuan, W D Tong, et al. Osteogenesis in extraskeletally implanted porous phosphate ceramics: variability among different kinds of animals. Biomaterlals, 1996; 17(22): 2131-2137
114.U Ripamonti, et al. Osteoinduction in porous hydroxyapatite implanted in heterotopic sites of different animal models. Biomaterials, 1996; 17(1): 31-35
115.H P Yuan, K Kurashina, J D Bruijn, et al. A preliminary study on osteoinduction of two kinds of calcium phosphate ceramics. Biomaterials, 1999; 20(19): 1799-1806
116.K Kurashina, H Kurita, Q Wu, et al. Ectopic osteogenesis with biphasic and tricalcium phosphate in rabbits. Biomaterials, 2002; 23(2): 407-412
117.K Vassilis , K David . Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials, 2005; 26(27): 5474-5491
118.P Kasten, B Ingo, et al. Porosity and pore size of β-tricalcium phosphate scaffold can influence protein production and osteogenic differentiation of human mesenchymal stem cells: An in vitro and in vivo study. Acta Biomaterials, 2008; 4(6): 1904-1915
119.M Gelinsky, A Bernhardt, et al. Porous three-dimensional scaffolds made of mineralised collagen : Preparation and properties of a biomimetic nanocomposite material for tissue engineering of bone . Chemical Engineering Journal, 2008; 137(1): 84-96