可原位固化磷酸钙生物活性材料的研究
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摘要
在骨缺损修复材料的应用上，已从惰性材料发展到生物活性材料；在操作技术上，则从创伤性手术向微创技术发展。然而现在口腔临床上使用的骨修复材料多为颗粒型，虽然具有一定的疗效，但其可塑性、机械性能、操作性能差，并且由于材料缺乏骨诱导活性常常需要配合生物膜使用，治疗周期长。为了减轻患者痛苦、缩短治疗周期、降低医疗资源消耗以及减少术后并发症。因此在骨缺损修复治疗领域，寻求可在原位固化，具有良好操作性能的磷酸钙骨水泥材料成为当前的研究热点。
目前已有磷酸钙骨水泥产品开始应用于临床，但是现有的材料抗弯强度低，脆性大，在生理环境中的疲劳与破坏强度不高，尤其是在湿环境下断裂韧性很低，属于一种典型的脆性材料，因此，在没有增韧的条件下，它只能用于不承受负荷或仅承受纯压力负荷的情况。然而在口腔中，颌骨和牙体、种植体周围的牙槽骨由于咀嚼功能等原因处于周期性的拉力和压力环境，而且磷酸钙骨水泥的生成产物主要为羟基磷灰石，其通过骨传导的方式促进骨的形成，骨的生成速度慢，使磷酸钙骨水泥的应用受到很大的限制。因此有必要从磷酸钙骨水泥的生物力学性能和骨诱导性两个方面进行改性和不断的完善。
本研究首先通过湿法反应制备α-TCP磷酸钙骨水泥，在磷酸钙骨水泥中添加天然材料蚕丝丝素增强磷酸钙材料的机械性能，弥补磷酸钙材料脆性大、抗弯强度低的缺点；然后在磷酸钙骨水泥调和液中添加地塞米松、β-甘油磷酸钠、L-抗坏血酸做为骨诱导剂增强材料的骨诱导活性，获得改良的磷酸钙材料，并进行了细胞、分子生物学检测，为动物试验、临床应用打下基础。
本研究结果及提示：
1．通过湿法反应法，以碳酸钙和磷酸为原料，可以获得高纯、微细的α—TCP粉末。以磷酸氢钙、碳酸钙为辅料的α—TCP体系骨水泥，采用0.25MNaH_2PO_4／Na_2HPO_4为骨水泥调和液，其初凝时间在7min左右，终凝时间在17min左右，pH值接近中性，抗压强度为7.4628MPa，抗弯强度为5.1629MPa，基本满足临床要求。骨水泥粉体颗粒水化后，在SBF中转化为细小的磷灰石晶体。
2．在胰酶浓度为0.25％，温度37℃，脱胶时间12h情况下，可以良好的除去蚕丝丝胶，并且保持蚕丝优良的机械性能。对蚕丝丝素纤维进行编织，以3mm的长度加入磷酸钙骨水泥，不影响磷酸钙骨水泥的凝固性能，抗压强度增加到12.541MPa，抗弯强度增加到8.8822MPa。
3．在骨水泥调和液中加入骨诱导配方不影响骨水泥的性能，不同复合方式的骨水泥(骨水泥组；骨水泥复合丝素组；骨水泥复合骨诱导配方组；骨水泥复合丝素、骨诱导配方组)与骨髓基质干细胞共培养，在细胞增殖活性和空白对照组没有统计学差异，细胞粘附形态上与对照组相似。
4．不同复合方式的骨水泥与细胞共培养后，RT—PCR检测均表达成骨相关基因ALP、COL—Ⅰ和OCN，空白对照组表达ALP、COL—Ⅰ，不表达OCN；ELISA检测添加了骨诱导配方的骨水泥在细胞与材料共培养早期表达成骨特异性蛋白OCN，未添加组在2周后表达OCN蛋白，空白组不表达OCN蛋白，添加骨诱导配方的磷酸钙骨水泥与未添加骨诱导配方的磷酸钙骨水泥在骨特异性蛋白的表达上有显著性差异。
综上所述，本研究通过湿法反应法制备了高纯，微细的α-TCP粉末，以磷酸氢钙、碳酸钙为辅料获得了基本满足临床要求的磷酸钙骨水泥材料；在磷酸钙骨水泥中添加天然材料蚕丝丝素增强磷酸钙材料的抗弯、抗压性能；在磷酸钙骨水泥调和液中添加地塞米松、β-甘油磷酸钠、L-抗坏血酸做为骨诱导剂增强材料的骨诱导性能，最终获得具有骨诱导性和一定韧性的磷酸钙骨水泥材料。
Nowadays, with the development of biomaterial science, the bone defects repair materials developed from the traditional mechanical fixation to biomaterial implantation and the technique of surgery developed from traumatic to minimal invasive technology. However, most of the biomaterials used in oral clinical is particle and not good in shaping, biomechanics, handling and lack of osteoinductivity which always have to be used with biomembrane. In order to relieve the pain of patients and reduce the syndromes, seeking for a more ideal material such as calcium phosphate cement which could owns the properties of self-setting in situ, easy handling and bone inductivity became the most attractive point.
Some of the calcium phosphate cement (CPC) has been used in clinic; however, the relatively low strength and susceptibility to brittle catastrophic fracture of the cement have severely limited its use to only non load bearingm applications. CPC sets to form hydroxyapatite which lack of osteoinductive ability, So we have to improve the the biomechanic and osteoinductive ability of the CPC.
The aim of the study is to synthesize the CPC with improved mechanics and osteoinductivity. First theα-TCP particle and the CPC based onα-TCP was synthesized. Then the degummed silk is used to improve the strength and fracture resistance of materials. Ascorbic acid,β-glycerophosphate and dexamethasone are added in CPC liquid to improve the osteoinductivity of the materials. The results of the study show that:
1.α-TCP was synthesized by the reaction between phosphoric acid and CaCO_3 slurry. The assist agents of CPC are CaCO_3 and DCPD. The miture powders were mixed with 0.25M 0.25MNaH_2PO_4/Na_2HPO_4. The initial setting time is about 7 min, the final setting time is about 17min. The compressive strength reached 7.46MPa and the bending strength reached 5.16MPa.
2. Trypsin was picked out as degumming reagent for the ability of preserving the mechanic integrity of silk. The examination of degummed silk suggested that the sericin can be totally removed under our degumming protocols.The simple twisting method was adopted by us for the sake of adding the degummed silk in 3mm length. The CPC added with degummed silk can reach 12.54MPa of compressive strength and 8.882MPa of bending strength. The setting time is almost the same between the CPC group and the CPC added with degummed silk and osteoinductive agents.
3. In vitro experiments were designed and carried out to evaluate the biological reaction of the CPC. The BMSCs cells were cultured on CPCsurfaces in vitro. Cell attachment, spreading, cell proliferation and differentiation were evaluated and there is no statistic difference between CPC and control group.
4. The mRNA level of osteoblast-related genes ALP, Col-I and OCNwere examined using RT-PCR; The mRNA of ALP, Col-I and OCNwere expressed in all CPC groups and wasn't expressed in control group. The protein level of OCN was examined using ELISA, there is statistic difference between CPC and CPC+osteoinductive group. With the limitation of these findings,α-TCP with the assist agents of CaCO_3 and DCPD can almost meet the clinic demands. The compressive and bending stress were improved with the adding degummed silk fiber to CPC and the osteogenic ability of the CPC were improved by adding the osteoinductive agents to CPC.
目前已有磷酸钙骨水泥产品开始应用于临床，但是现有的材料抗弯强度低，脆性大，在生理环境中的疲劳与破坏强度不高，尤其是在湿环境下断裂韧性很低，属于一种典型的脆性材料，因此，在没有增韧的条件下，它只能用于不承受负荷或仅承受纯压力负荷的情况。然而在口腔中，颌骨和牙体、种植体周围的牙槽骨由于咀嚼功能等原因处于周期性的拉力和压力环境，而且磷酸钙骨水泥的生成产物主要为羟基磷灰石，其通过骨传导的方式促进骨的形成，骨的生成速度慢，使磷酸钙骨水泥的应用受到很大的限制。因此有必要从磷酸钙骨水泥的生物力学性能和骨诱导性两个方面进行改性和不断的完善。
本研究首先通过湿法反应制备α-TCP磷酸钙骨水泥，在磷酸钙骨水泥中添加天然材料蚕丝丝素增强磷酸钙材料的机械性能，弥补磷酸钙材料脆性大、抗弯强度低的缺点；然后在磷酸钙骨水泥调和液中添加地塞米松、β-甘油磷酸钠、L-抗坏血酸做为骨诱导剂增强材料的骨诱导活性，获得改良的磷酸钙材料，并进行了细胞、分子生物学检测，为动物试验、临床应用打下基础。
本研究结果及提示：
1．通过湿法反应法，以碳酸钙和磷酸为原料，可以获得高纯、微细的α—TCP粉末。以磷酸氢钙、碳酸钙为辅料的α—TCP体系骨水泥，采用0.25MNaH_2PO_4／Na_2HPO_4为骨水泥调和液，其初凝时间在7min左右，终凝时间在17min左右，pH值接近中性，抗压强度为7.4628MPa，抗弯强度为5.1629MPa，基本满足临床要求。骨水泥粉体颗粒水化后，在SBF中转化为细小的磷灰石晶体。
2．在胰酶浓度为0.25％，温度37℃，脱胶时间12h情况下，可以良好的除去蚕丝丝胶，并且保持蚕丝优良的机械性能。对蚕丝丝素纤维进行编织，以3mm的长度加入磷酸钙骨水泥，不影响磷酸钙骨水泥的凝固性能，抗压强度增加到12.541MPa，抗弯强度增加到8.8822MPa。
3．在骨水泥调和液中加入骨诱导配方不影响骨水泥的性能，不同复合方式的骨水泥(骨水泥组；骨水泥复合丝素组；骨水泥复合骨诱导配方组；骨水泥复合丝素、骨诱导配方组)与骨髓基质干细胞共培养，在细胞增殖活性和空白对照组没有统计学差异，细胞粘附形态上与对照组相似。
4．不同复合方式的骨水泥与细胞共培养后，RT—PCR检测均表达成骨相关基因ALP、COL—Ⅰ和OCN，空白对照组表达ALP、COL—Ⅰ，不表达OCN；ELISA检测添加了骨诱导配方的骨水泥在细胞与材料共培养早期表达成骨特异性蛋白OCN，未添加组在2周后表达OCN蛋白，空白组不表达OCN蛋白，添加骨诱导配方的磷酸钙骨水泥与未添加骨诱导配方的磷酸钙骨水泥在骨特异性蛋白的表达上有显著性差异。
综上所述，本研究通过湿法反应法制备了高纯，微细的α-TCP粉末，以磷酸氢钙、碳酸钙为辅料获得了基本满足临床要求的磷酸钙骨水泥材料；在磷酸钙骨水泥中添加天然材料蚕丝丝素增强磷酸钙材料的抗弯、抗压性能；在磷酸钙骨水泥调和液中添加地塞米松、β-甘油磷酸钠、L-抗坏血酸做为骨诱导剂增强材料的骨诱导性能，最终获得具有骨诱导性和一定韧性的磷酸钙骨水泥材料。
Nowadays, with the development of biomaterial science, the bone defects repair materials developed from the traditional mechanical fixation to biomaterial implantation and the technique of surgery developed from traumatic to minimal invasive technology. However, most of the biomaterials used in oral clinical is particle and not good in shaping, biomechanics, handling and lack of osteoinductivity which always have to be used with biomembrane. In order to relieve the pain of patients and reduce the syndromes, seeking for a more ideal material such as calcium phosphate cement which could owns the properties of self-setting in situ, easy handling and bone inductivity became the most attractive point.
Some of the calcium phosphate cement (CPC) has been used in clinic; however, the relatively low strength and susceptibility to brittle catastrophic fracture of the cement have severely limited its use to only non load bearingm applications. CPC sets to form hydroxyapatite which lack of osteoinductive ability, So we have to improve the the biomechanic and osteoinductive ability of the CPC.
The aim of the study is to synthesize the CPC with improved mechanics and osteoinductivity. First theα-TCP particle and the CPC based onα-TCP was synthesized. Then the degummed silk is used to improve the strength and fracture resistance of materials. Ascorbic acid,β-glycerophosphate and dexamethasone are added in CPC liquid to improve the osteoinductivity of the materials. The results of the study show that:
1.α-TCP was synthesized by the reaction between phosphoric acid and CaCO_3 slurry. The assist agents of CPC are CaCO_3 and DCPD. The miture powders were mixed with 0.25M 0.25MNaH_2PO_4/Na_2HPO_4. The initial setting time is about 7 min, the final setting time is about 17min. The compressive strength reached 7.46MPa and the bending strength reached 5.16MPa.
2. Trypsin was picked out as degumming reagent for the ability of preserving the mechanic integrity of silk. The examination of degummed silk suggested that the sericin can be totally removed under our degumming protocols.The simple twisting method was adopted by us for the sake of adding the degummed silk in 3mm length. The CPC added with degummed silk can reach 12.54MPa of compressive strength and 8.882MPa of bending strength. The setting time is almost the same between the CPC group and the CPC added with degummed silk and osteoinductive agents.
3. In vitro experiments were designed and carried out to evaluate the biological reaction of the CPC. The BMSCs cells were cultured on CPCsurfaces in vitro. Cell attachment, spreading, cell proliferation and differentiation were evaluated and there is no statistic difference between CPC and control group.
4. The mRNA level of osteoblast-related genes ALP, Col-I and OCNwere examined using RT-PCR; The mRNA of ALP, Col-I and OCNwere expressed in all CPC groups and wasn't expressed in control group. The protein level of OCN was examined using ELISA, there is statistic difference between CPC and CPC+osteoinductive group. With the limitation of these findings,α-TCP with the assist agents of CaCO_3 and DCPD can almost meet the clinic demands. The compressive and bending stress were improved with the adding degummed silk fiber to CPC and the osteogenic ability of the CPC were improved by adding the osteoinductive agents to CPC.
引文
[1] Sd G, L C, M D, et al. Posterolateral lumbar spine fusion with INFUSE bone graft[J]. Spine Journal: Official Journal of the North American Spine Society, 2007,7(1):44～49.
[2] Jr D, Sd G, Kj B, et al. Clinical outcomes and fusion success at 2 years of single-level instrumented posterolateral fusions with recombinant human bone morphogenetic protein-2/compression resistant matrix versus iliac crest bone graft[J]. Spine, 2006,31 (22):2534～2540.
[3] Ci E, A A, Es R, et al. Therapeutic management for immediate implant placement in sites with periapical deficiencies where coronal bone is present: technique and case report[J]. International Journal of Oral & Maxillofacial Implants, 2006,21 (3):476～480.
[4] L S, F G, Gb F, et al. Langerhans' cell histioeytosis: a case report of an eosinophilic granuloma of the mandible treated with bone graft surgery and endosseous titanium implants[J]. 2006, 2006,21(1):124～130.
[5] 郭颖，李玉宝．骨修复材料的研究进展[J]．世界科技研究与发展，2001，23(1)：33～37．
[6] M N, L W, Js W, et al. Factors influencing the compressive strength of an injectable calcium sulfate-hydroxyapatite cement[J]. JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, 2003,14(5):399～404.
[7] Hhk X, Le C, Cg S, et al. Premixed calcium phosphate cements: Synthesis, physical properties, and cell cytotoxicity[J]. DENTAL MATERIALS, 2007,23(4):433～441.
[8] F B, L G, V J, et al. Short-fibre reinforcement of calcium phosphate bone cement[J]. PROCEEDINGS OF THE INSTITUTION OF MECHANICAL ENGINEERS PART H-JOURNAL OF ENGINEERING IN MEDICINE, 2007,221 (H2):203～211.
[9] Xp W, Jd Y, Yj W, et al. Reinforcement of calcium phosphate cement by bio-mineralized carbon nanotube[J]. JOURNAL OF THE AMERICAN CERAMIC SOCIETY, 2007,90(3):962～964.
[10] J C. Anchorage of the femoral head prosthesis to the shaft of the femur[J]. Journal of Bone & Joint Surgery - British Volume, 1960,42-B:28～30.
[11] J C. Surgery of the hip-joint: present and future developments[J]. British Medical Journal, 1960,1 (5176):821～826.
[12] Em O, Jg W, van de Mt H, et al. Histological evaluation of the bone response to calcium phosphate cement implanted in cortical bone[J]. Biomaterials, 2003,24(6):989～1000.
[13] H M, T T, R T, et al. Mechanical properties of the femur filled with calcium phosphate cement under torsional loading: a model in rabbits[J]. 2002, 2002,7(5):562～569.
[14] Th L, Gt B, Sm R, et al. Biomechanical evaluation of an injectable calcium phosphate cement for vertebroplasty[J]. Spine, 2002,27(12): 1297～1302.
[15] Lcc W E B. A new calcium phosphate, water-settlng cemen[J]. American Ceramic Society, 1986:352～379.
[16] 俞耀庭，张兴栋．生物医用材料[M]．天津大学出版社，2001．
[17] 刘昌胜，沈卫，顾燕芳，et al．非陶瓷羟基磷灰石人工骨的研究[J]．化工进展，1996(1)：10～14．
[18] We B, M F. Kinetics of hydroxyapatite formation at low temperature[J]. J Am Ceram Soc, 1991,74(5):934～940.
[19] Br C, Ic I, Mt F, et al. Skeletal repair by in situ formation of the mineral phase of bone[J]. Science, 1995,267(5205): 1796～1799.
[20] Cd F, Pd C, S T, et al. BoneSource hydroxyapatite cement: a novel biomaterial for craniofacial skeletal tissue engineering and reconstruction[J]. Journal of Biomedical Materials Research, 1998,43(4):428～432.
[21] A T, S L, K M, et al. Comparative fixation of tibial plateau fractures using alpha-BSM, a calcium phosphate cement, versus cancellous bone graft[J]. Journal of Orthopaedic Trauma, 2005,19(10):698～702.
[22] k H H, Jbq X, Takagi S, et al. Synergistic reinforcement of in situ hardening calcium phosphate composite scaffole for bone tissue engineering[J]. Biomaterials, 2004,25(6): 1029～1037.
[23] L S, Hh X, S T, et al. Fast setting calcium phosphate cement-chitosan composite: mechanical properties and dissolution rates[J]. Journal of Biomaterials Applications, 2007,21(3):299～315.
[24] Hh X, Jr S C. Fast setting calcium phosphate-chitosan scaffold: mechanical properties and biocompatibility[J]. Biomaterials, 2005,26(12): 1337～1348.
[25] 沈卫，刘昌胜，顾燕芳，et al．磷酸钙骨水泥的水化反应机理研究[J]．无机材料学报，1996，11(4)：685～690．
[26] Ap O, Fa N, Jl L, et al. Synthesis and characterization of single-phase silicon-substituted alpha-triealcium phosphate[J]. Biomaterials, 2006,27(15):2916～2925.
[27] Kh P, R K, Cp O, et al. Conductometric study of precursor compound formation during wet-chemical synthesis of nanocrystalline hydroxyapatite[J]. Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces & Biophysical., 2006,110(48):24457～24462.
[28] Ac T, F K, M T, et al. An investigation of the chemical synthesis and high-temperature sintering behaviour of calcium hydroxyapatite (HA) and tricalcium phosphate (TCP) bioceramics[J]. JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, 1997,8(2):91～96.
[29] 胡常伟．大学化学[M]．北京市：化学工业出版社，2004：63～517．
[30] 张雁冰，何萍芬，李青，et al．化学[M]．郑州市：郑州大学出版社，2003：34～76．
[31] 陈晓旭，高立达，毛伯镛，et al．磷酸钙骨水泥临床应用类型选择及微结构观察[J]． 生物医学工程学杂志，2001，18(4)：568～572．
[32] 戴红莲，闫玉华，李世普，et al．α-磷酸三钙-磷酸四钙生物骨水泥的研究[J]．材料科学与工程，2002，20(3)：331～335．
[33] Mp G, E F, Mg B, et al. Compliance of an apatitic calcium phosphate cement with the short-term clinical requirements in bone surgery, orthopaedics and dentistry[J]. Clinical Materials, 1994,17(2):99～104.
[34] 高岐．分析化学[M]．北京市：高等教育出版社，2006：237～249．
[35] On T, K K, Y I. In vitro hydroxyapatite deposition onto a film surface-grated with organophosphate polymer[J]. Journal of Biomedical Materials Research, 1994,28(11):1365～1373.
[36] 吴文进，杨为中，周大利，et al．碳纤维增强α-磷酸三钙骨水泥的研究[J]．生物医学工程学杂志，2006，23(3)：569～572．
[37] D S, M H, Y A, et al. Ollier's disease treated with grafting using alpha-triealeium phosphate cement. A case report[J]. Upsala Journal of Medical Sciences, 2006,111 (2):249～256.
[38] M B, Ak M, CI C, et al. Combining particle size distribution and isothermal calorimetry data to determine the reaction kinetics of alpha-triealeium phosphate-water mixtures[J]. Acta Biomaterialia, 2006,2(3):343～348.
[39] Ap O, Fa N, Ji L, et al. Evaluation of a double-setting alpha-tricalcium phosphate cement in eviscerated rabbit eyes[J]. Ophthalmic Plastic & Reconstructive Surgery, 2006,22(2):126～130.
[40] Ef B, F G, Lc C. A water setting tetraealeium phosphate-dicalcium phosphate dihydrate cement[J]. Journal of Biomedical Materials Research. Part A, 2004,71(2):275～282.
[41] D G, K X, X Z, et al. Development of a strontium-containing hydroxyapatite bone cement[J]. Biomaterials, 2005,26(19):4073～4083.
[42] G D, X K, S H, et al. Physicochemieal properties of TTCP/DCPA system cement formed in physiological saline solution and its cytotoxieity[J]. Journal of Biomedical Materials Research. Part A, 2006,77(2):313～323.
[43] Hh X, S T, L S, et al. Development of a nonrigid, durable calcium phosphate cement for use in periodontal bone repair[J]. Journal of the American Dental Association, 2006,137(8):1311～1318.
[44] 郑治，向其军，刘咏，et al．医用磷酸钙骨水泥的制备及性能的实验研究[J]．生物医学工程学杂志，2006，23(5)：1048～1051．
[45] 向其军，刘咏，郑治，et al．磷酸钙骨水泥生物材料用磷酸四钙的制备[J]．粉末冶金材料科学与工程，2005，10(4)：211～215．
[46] 郭大刚，徐可为，憨勇．固相反应合成磷酸四钙的物相演变[J]．无机材料学报，2005，20(2)：317～322．
[47] Y F, Ed E, S T, et al. Setting reactions and compressive strengths of calcium phosphate cements[J]. Journal of Dental Research, 1990,69(12):1852～1856.
[48] 戴红莲，闫玉华，王友法，et al．磷酸四钙粉末的制备研究[J]．硅酸盐通报，2002(4)：56～59．
[49] 郑昌琼，冉均国．新型无机材料[M]．北京市：科学出版社，2003：73～103．
[50] Laurencin C T. Bone Resorption Mediators Elicited by Degradation Products of Orthopedic Polymer[J]. Society for Biomateriais, 1998(22-26):309.
[51] 俞超，薛文东，张双燕，et al．股骨头负重区松质骨的压缩力学特性[J]．上海生物医学工程，2004，25(1)：22～23．
[52] 赵宝林，程杰平，马洪顺，et al．股骨头松质骨力学性质实验研究[J]．医用生物力学，2003，18(4)：234～238．
[53] 李英普，陈雷．大骨节病对股骨头松质骨力学性质影响实验研究[J]．中国地方病防治杂志，2004，19(2)：81～82．
[54] 李世普．生物医用材料导论[M]．武汉：武汉工业大学出版社，2000：8．
[55] K K，A O,A K,et al.Histological and microradiographic evaluation of hydrated and hardened alpha-tricalcium phosphate/calcium phosphate dibasic mixtures[J].Biomaterials,1994,15(6):429～432.
[56] K K,H K,A K,et al.In vivo study of a calcium phosphate cement consisting of alpha-tricalcium phosphate/diealcium phosphate dibasic/tetracalcium phosphate monoxide[J].Biomaterials,1997,18(2):147～151.
[57] K K,H K,M H,et al.In vivo study ofcalcium phosphate cements:implantation of an aJpha-tricalcitma phosphateldicalcium phosphate dibasic/tetracalcium phosphate monoxide cement paste[J].Biomaterials,1997,18(7):539～543．
[58] K K,H K,A K,et al.Experimental cranioplasty and skeletal augmentation using an alpha-tricalcium phosphate/dicalcium phosphate dibasic/tetracalcium phosphate monoxide cement: a preliminary short-term experiment in rabbits[J]. Biomaterials,1998,19(7-9):701～706．
[59] Mp G,E F,de Ea M,et al.Setting reaction and hardening of an apatitic calcium phosphate cement[J].Journal ofDental Research,1997,76(4):905～912.
[60] 戴红莲，陈芳，闫玉华．a-TCP骨水泥水化产物及其影响因素[J]．武汉理工大学学报，1996，18(1)：43～6。
[61] Y L, X Z, de K G. Hydrolysis and phase transition of aipha-trlcalcium phosphate[J]. Biomaterials, 1997,18(10):737～741.
[62] C D, Pw B. alpha-Triealcium phosphate hydrolysis to hydroxyapatite at and near physiological temperature[J]. JOURNAL OF MATER/ALS SCIENCE-MATERIALS IN MEDICINE, 2000,11(6):365～371.
[63] H M, T K. The hydration of α-tricalcium phosphate.[J]. Journal of the ceramic society of Japan, 2000,108(8):75～80.
[64] Ro O, Fc D, Ja P, et al. Growth and differentiation of human bone marrow osteoprogenitors on novel calcium phosphate cements[J]. Biomatefials, 1998,19(20): 1845～1854.
[65] I K, Mg B, Fe D, et al. Effect of calcium carbonate on the compliance of an apatitic calcium phosphate bone cement[J]. Biomaterials, 1997,18(23):1535～1539.
[66] As G, Ve F, Ab M. Structural and mechanical characteristics of silk fibroin and ehitosan blend scaffolds for tissue regeneration[J]. Journal of Biomedical Materials Research, 2005,74(3):465～473.
[67] J C, Gh A, V K, et al. Human bone marrow stromal cell and ligament fibroblast responses on RGD-modified silk fibers[J]. Journal of Biomedical Materials Research. Part A, 2003,67(2):559～570.
[68] Gh A, Rl H, Hh L, et al. Silk matrix for tissue engineered anterior cruciate ligaments[J]. Biomaterials, 2002,23(20):4131～4141.
[69] B P, Gh A, J C, et al. Macrophage responses to silk[J]. Biomaterials, 2003,24(18):3079～3085.
[70] S S, Mb M, G G, et al. Functionalized silk-based biomaterials for bone formation[J]. Journal of Biomedical Materials Research, 2001,54(1):139～148.
[71] N M, S A, M H, et al. Attachment and growth of fibroblast cells on silk fibroin[J]. Biochemical & Biophysical Research Communications, 1995,208(2):511～516.
[72] K I, M K, S N, et al. Use of Bombyx mori silk fibroin as a substratum for cultivation of animal cells[J]. Journal of Biochemical & Biophysical Methods, 1998,37(3):159～164.
[73] Cai X, Lin Y, Ou G, et al. Ectopic osteogenesis and chondrogenesis of bone marrow stromal stem cells in alginate system[J]. Cell Biology International, 2007(in press).
[74] van der E W, Am V, Pj T B, et al. The in vitro behavior of as-prepared and pre-immersed RF-sputtered calcium phosphate thin films in a rat bone marrow cell model[J]. Biomatedals, 2006,27(8):1333～1340.
[75] T S. Bone morphogenetic proteins: from basic studies to clinical approaches[J]. Bone, 1998,22(6):591～603.
[76] 江莹，陈槐卿，周闻达，et al．蚕丝丝素纤维的制备及其与骨髓间充质干细胞相容性的研究[J]．生物医学工程学杂志，2006，23(3)：583～588．
[77] J V, D K. Biopolymer-based biomaterials as scaffolds for tissue engineering[J]. Advances in Bioehemlcal Englneering-Biotechnoiogy, 2006,102:187～238.
[78] L P, Ak S, S S, et al. Different substitute biomaterials as potential scaffolds in tissue engineering[J]. International Journal of Oral & Maxillofacial Implants, 2006,21 (2):225～231.
[79] Dw H. Scaffolds in tissue engineering bone and cartilage[J]. Biomaterials, 2000,21 (24):2529～2543.
[80] Dl K, Sm M. Protein based materials[M]. Boston:Birkhauser, 1998:103～131.
[81] Xy L, Xd L, Hs F, et al. In situ synthesis of bone-like apatite/collagen nano-composite at low temperature[J]. MATERIALS LETTERS, 2004,58(27-28):3569～3572.
[82] Yq Z. Applications of natural silk protein seriein in biomaterials[J]. BIOTECHNOLOGY ADVANCES, 2002,20(2):91～100.
[83] Gh A, F D, C J, et al. Silk-based biomaterials[J]. Biomaterials, 2003,24(3):401～416.
[84] 吕靖．蚕丝和蜘蛛丝的结构与生物纺丝过程[J]．现代纺织技术，2004,12(1)：40～42．
[85] Rl M, A L, A Z. Commonly used suture materials in skin surgery[J]. American Family Physician, 1991,44(4):2123～2128.
[86] Hk S, Kr K. Adverse reactions to virgin silk sutures in cataract surgery[J]. Ophthalmology, 1984,91 (5):479～483.
[87] S K, H O, M K, et al. Fibroin allergy. IgE mediated hypersensitivity to silk suture materials[J]. Journal of the Nippon Medical School, 1999,66(1):41～44.
[88] S W, Dl K. Molecular biology of spider silk[J]. Journal of Bioteclmology, 2000,74(2):85～93.
[89] 小松计一．各种脱胶方法的比较[J]．国外丝绸，1992，11(2)：2～7．
[90] 蒋少军，吴红玲．蚕丝的酶处理[J]．四川丝绸，2002(4)：23～25．
[91] 胜野盛夫．蚕丝场实验报告[J]．日本蚕丝学杂志，1985，8(5)：40～43．
[92] Nh L, Yy C, T C, et al. Aeryiie resin reinforced with chopped high performance polyethylene fiber—properties and denture construction[J]. Dental Materials, 1993,9(2):128～135.
[93] Aj G, Cj B, I H, et al. Screening of matrices and fibers for reinforced thermoplastics intended for dental applications[J]. Journal of Biomedical Materials Research, 1994,28(2):167～173.
[94] B P, 4th R H, P S, et al. Fracture toughness of Kevlar 29/poly(methyl methacrylate) composite materials for surgical implantations[J]. Annals of Biomedical Engineering, 1986,14(3):277～294.
[95] Ld T, P D, Jm C. The effects of centrifugation and titanium fiber reinforcement on fatigue failure mechanisms in poly(methyl methaerylate) bone cement[J]. Journal of Biomedical Materials Research, 1995,29(3):299～307.
[96] von As G, Jr K, Jm A. The effects of centrifugation and titanium fiber reinforcement on fatigue failure mechanisms in poly(methyl methacrylate) bone cement[J]. Journal of Biomedical Materials Research, 1999,29(3):299-307.
[97] Hh X, Jb Q. Calcium phosphate cement containing resorbable fibers for short-term reinforcement and macroporosity[J]. Biomaterials, 2002,23(1):193～202.
[98] Aj C, Ja I, Re T, et al. Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone[J]. Proceedings of the National Academy of Sciences of the United States of America, 1990,87(24):9843～9847.
[99] Af S, Gd P, Ch E. Gene therapy in the musculoskeletal system[J]. Current Opinion in Orthopaedics, 2004,15(5):318～324.
[100] Td A, P V, Df K. Bone morphogenetie protein gene therapy[J]. Spine, 2002,27(16S):87～93.
[101] X J, D C, C X, et al. Patterns of gene expression associated with BMP-2-induced osteoblast and adipocyte differentiation of mesenchymal progenitor cell 3T3-F442A[J]. Journal of Bone & Mineral Metabolism, 2000,18(3):132～139.
[102] Ah R. Initiation and promotion of endochondral bone formation by bone morphogenetic proteins: Potential implications for avian tibial dyschondroplasia[J]. POULTRY SCIENCE, 2000,79(7):978～981.
[103] S W, Gr J, C J. High concentrations of dexamethasone suppress the proliferation but not the differentiation or further maturation of human osteoblast precursors in vitro:relevance to glucocorticoid-induced osteoporosis[J]. Rheumatology, 2001,40(1):74～83.
[104] Dj M, Md R Jf B. Matrix deposition by a calcifying human osteogenic sarcoma cell line (SAOS-2)[J]. Bone, 1995,16(4):415～426.
[105] E O, A Y, S H, et al. Characterization of osteoblastic differentiation of stromal cell line ST2 that is induced by ascorbic acid[J]. American Journal of Physiology, 1999,277(1 Pt1):132～138.
[106] Cm V. Adult stem cells: assessing the case for pludpotency[J]. Trends in Cell Biology, 2002,12(11):502～508.
[107] Ll W. Translating stem and progenitor cells biology to the clinic: barrier and opportunities[J]. Science, 2000,287(5457):1442～1446.
[108] Y J, Bn J, RI R, et al. Pluripotency of mesenchymal stem cells derived from adult marrow[J]. Nature, 2002,418(6893):41～49.
[109] M R, A D, B J, et al. Origin of endothelial progenitors in human postnatal bone marrow[J]. Journal of Clinical Investigation, 2002,109(3):337～346.
[110] Gc K, Dj P, Dg P. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains[J]. Proceedings of the National Academy of Sciences of the United States of America, 1999,96(19):10771-10716.
[111] Re S, M R,L K, et al. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells[J]. Journal of Clinical Investigation, 2002,109(10): 1291～1302.
[112] Jr M, V V, DI K. Role of adult mesenchymal stem cells in bone tissue engineering applications: current status and future prospects[J]. Tissue Engineeing, 2005,11 (5-6):787～802.
[113] 傅远飞，陈德敏，张建中．MTT比色法评价掺锶羟磷灰石固溶体细胞毒性[J]．生物医学工程学杂志，2001，18(3)：389～390．
[114] Bg M, Fr S, Lp W, et al. Long-term culture of cells from bone affected by Paget's disease[J]. Calcified Tissue International, 1979,29(2):79～87.
[115] Mf P, Am M, Sc B, et al. Multilineage potential of adult human mesenchymal stem cells[J]. Science, 1999,284(5411):143～147.
[116] Aj F, Rk C, Uv G. Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers[J]. Cell & Tissue Kinetics, 1987,20(3):263～272.
[117] Sp B, N J, Ns R, et al. Mesenchymal stem cells in osteobiology and applied bone regeneration[J]. Clinical Orthopaedics & Related Research, 1998(355 supple):247～256.
[118] Gc K, Dj P, Dg P. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains[J]. Proceedings of the National Academy of Sciences of the United States of America, 1999,96(19):10711-10716.
[119] Dj P. Marrow stromal cells as stem cells for nonhematopoietic tissues[J]. Science, 1997,276(5309):71-74.
[120] 段小军，杨柳，周强．人间充质干细胞成骨诱导培养后的细胞成分研究[J]．中国临床康复，2002，6(22)：3337～3338．
[121] Rs T. Biology of developmental and regenerative skeletogenesis[J]. Clinical Orthopaedics & Related Research, 2004(427 supple):105～117.
[122] Eh J, Kj B, Aw F. Mesenchymal stem cells: paradoxes of passaging[J]. Experimental Hematology, 2004,32(5):414～425.
[123] 曹聪，董英海，董宇启，et al．人血源性间充质干细胞培养与体外成骨研究[J]．中国修复重建外科杂志，2005，19(8)：642～647．
[124] Mf H. In vitro study of biodegradation of a Co-Cr alloy using a human cell culture model[J]. Journal of Biomatefials Science, Polymer Edition, 1995,6(9):809～814.
[125] 郝和平．医疗器械生物学评价标准实施指南[M]．北京：中国标准出版社，2000：100～109．
[126] T M. Rapid eolorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays[J]. Journal of Immunological Methods, 1983,65(1-2):55～63.
[127] H L, As A, D S, et al. Response of rat osteoblast-like cells to microstructured model surfaces in vitro[J]. Biomaterials, 2003,24(4):649～654.
[128] 黄永光，陈治清．硬组织替代材料对成骨细胞骨钙蛋白和ALP水平的影响[J]．华西口腔医学杂志，2000，18(3)：192-194．
[129] Ag D, Ma L, At T C, et al. In vitro studies of calcium phosphate glass ceramics with different solubility with the use of human bone marrow cells[J]. Journal of Biomedical Materials Research. Part A, 2005,74(3):347～355.
[130] J T, Ra G, M M, et al. Improved cell adhesion and proliferation on synthetic phosphonic acid-containing hydrogels[J]. Biomaterials, 2005,26(17):3663～3671.
[131] Fc F, Gc M. Osteoblasts attachment and adhesion: how bone cells fit fibronectin-coated surfaces[J]. Materials Science and Engineering, 2004,24(C):637～641.
[132] Al O, Cm A, RI R. Cell adhesion and proliferation on biomimetic calcium-phosphate coatings produced by a sodium silicate gel methodology[J]. Journal of Materials Science:Materials in Medicine, 2002,13(12):1181～1188.
[133] C E, F Y, Mc A, et al. Plasma-and chemical-induced graft polymerization on the surface of starch-based biomaterials aimed at improving cell adhesion and proliferation[J]. Journal of Materials Science:Materials in Medicine, 2003,14(2): 187～194.
[134] K W, V H, Pa T. Relative importance of surface wettability and charged functional groups on NIH 3T3 fihrohlast attachment, spreading, and cytoskeletal organization[J]. Journal of Biomedical Materials Research, 1998,41(3):422～430.
[135] Yw W, Q W, Gq C. Attachment, proliferation and differentiation of osteoblasts on random biopolyester poly (3-hydmxybutyrate-co-3-hydroxyhexanoate) scaffolds[J]. Biomaterials, 2004,25(4):669～675.
[136] Le C, Hh X, Jr S C, et al. Premixed rapid-setting calcium phosphate composites for bone repair[J]. Biomaterials, 2005,26(24):5002～5014.
[137] Am P. The cellular basis of bone remodeling:the quantum concept reexamined in light of recent advances in the cell biology of bone[J]. Calcified Tissue International, 1984,36(S1):37～45.
[138] O S, S K, T K, et al. Bone formation enhanced by implanted octacalcium phosphate involving conversion into Ca-deficient hydroxyapatite[J]. Biomaterials, 2006,27(13):2671～2681.
[139] Pm S, Y L, Pr C, et ai. Bone marrow cell gene expression and tissue construct assembly using octacaicium phosphate microscaffolds[J]. Biomaterials, 2006,27(14):2874～2881.
[140] Tl A, T T, J M, et al. A comparative study of biphasic calcium phosphate ceramics for human mesenchymal stem-cell-induced bone formation[J]. Biomaterials, 2005,26(17):3631-3638.
[141] Ek P, Ye L, Jy C, et al. Cellular biocompatibility and stimuiatory effects of calcium metaphosphate on osteoblastic differentiation of human bone marrow-derived stromal cells[J]. Biomaterials, 2004,25(17):3403～3411.
[142] Mc S, Xf W, Sc L, et al. Electrostatic spray deposition (ESD) of calcium phosphate coatings, an in vitro study with osteoblast-like cells[J]. Biomaterials, 2004,25(11):2019～2027.
[143] T K, N T. Regulatory mechanisms of osteoblast and osteoclast differentiation[J]. Oral Diseases, 2002,8(3):147～159.
[144] K N, X Z, G K, et ai. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation[J]. Cell, 2002,108(1):17～29.
[145] A J, Gl B, Bo J, et ai. runt homology domain transcription factors (Runx, Cbfa, and AML) mediate repression of the bone siaioprotein promoter: evidence for promoter context-dependent activity of Cbfa proteins[J]. Molecular & Cellular Biology, 2001,21(8):2891～2905.
[146] Dm T, Sa C, Dm P, et al. The retinoblastoma protein acts as a transcriptional coactivator required for osteogenic differentiation[J]. Molecular Cell, 2001,8(2):303～316.
[147] 杨志明．组织工程[M]．北京市：化学工业出版社，2002：161～162．
[148] de Da U, K M, A E, et ai. Comparison of multi-lineage cells from human adipose tissue and bone marrow[J]. Cells Tissues Organs, 2003,174(3):101～109.
[149] P K, R L, van M G, et al. Comparison of human bone marrow stromal cells seeded on calcium-deficient hydroxyapafite, beta-tricalcium phosphate and demineralized bone matrix[J]. Biomaterials, 2003,24(15):2593～2603.
[150] J D, T U, Y S, et al. Promotion of bone formation using highly pure porous beta-TCP combined with bone marrow-derived osteoprogenitor cells[J]. Biomaterials, 2002,23(23):4493～4502.
[151] Sj P, L L, Dj K, et al. Marrow stromal osteoblast function on a poly(propylene fumarate)/beta-tricalcium phosphate biodegradable orthopaedic composite[J]. Biomaterials, 2000,21(12):1207～1213.
[1] Vassilios I, Sikavitsas JST, Antonios G Mikos. Biomaterials and bone mechanotransduction[J]. Biomaterials, 2001, 22:2581-2593
[2] 葛建华，王迎军，郑裕东．可降解及可吸收骨科材料研究进展[J]．化工新型材料，2003，31(2)：34-39
[3] 刘昌胜，沈卫，顾燕芳，等．非陶瓷羟基磷灰石人工骨的研究[J]．化工进展，1996，1：10-14
[4] 郭颖，李玉宝．骨修复材料的研究进展[J]．世界科技研究与发展，2001；23：33-37
[5] M.Nilsson LW, J.-S.Wang, K.E.Tanner, et al. Factors influencing the compressive strength of an injectable calcium sulfate-hydroxyapatite cement[J]. Journal of Materials Science:Materials in Medicine, 2003, 14:399-404
[6] 阮建明，邹俭鹏，黄伯云编著．生物材料学[M]．北京：科学出版社，2004
[7] 俞耀庭等主编．生物医用材料[M]．天津：天津大学出版社，2001
[8] 吴常生，尹玉姬，杨悦，等。骨组织工程中大孔支架材料制备的研究[J]．中国临床康复，2004，8(5)：929-931
[9] Hulbert SF, Morfison S J, Klawitter JJ.Tissue reaction to three ceramics of porous an non-porous structures[J] J Biomed Mater Res, 1972, 6(5):374-378
[10] Chamley J. [J]. Bone Joint Surg, 1960, 42 B:28-30.
[11] Weam FM, Masahiko Kobayashi. Biological and mechanical properties of PMMA-based bioactive bone cements[J]. Biomaterials, 2000, 21:2137-2146.
[12] Rejda BV, Rieger MR. Porous Acrylic Cement[J]. J Biomed Mater Res, 1977, 11:373,
[13] WE. Brown LCC. A new calcium phosphate, water-setting cement[J]. American Ceramic Society, 1986: 352-379.
[14] 俞耀庭，张兴栋．生物医用材料[M]．天津：天津大学出版社，2001
[15] Doi Y, Takezawa Y, Shibata, et al, Self-setting apatite cement, In physicochemical properties[J]. J japan Soe Dent Matals Devices, 1987, 6:53
[16] Fukase Y, Eanes ED, Chow LC. Setting reaction and compressive strengths of calcium phosphate cements[J]. J Dent Res, 1990, 69(12):1852
[17] Brown WE, Fulmer M. Kinetics of hydroxyapatite formation at low temperature[J]. J Am Ceram Soc, 1991, 74(5):934-940
[18] 戴红莲，陈芳，闫玉华，等．武汉工业大学学报，1996，18(1)：431
[19] GinebraM P, et al. J Dent Res, 1997, 76(4):905
[20] Monoa H, Goto M, Kohmura T. Gypsum & Lime, 1984, 188:11-16
[21] Li Yubao, Zhang Xingdong, K.de Groot. Biomaterials, 1997, 737-741
[22] C.Durucan. α-tricalcium phosphate hydrolysis to hydroxyapatite at and near physiological temperature[J]. Journal of materials science: materials in medicine, 2000, 11:365
[23] Monma H, Kanazawa T. The hydration of α-tricalcium phosphate[J]. Journal of the ceramic society of Japan, 2000, 108(8):75-80
[24] Y. Fukase EDE ST, L.C, Chow, W.E. Brown. Setting reaction and compressive strength of calcium phosphate[J]. J Dent Res, 1990, 69:1852-1856
[25] Lacout JL, Mejdoubi E, et al. Journal of Mater Sci:Mater in Med, 1996, 7:375
[26] Changsheng Liu YH, Jianguo Chen. The physicochemical properties of the solidification of calcium phosphate cement[J]. Journal of Biomedical Materials Research, 2004, 69B:73-78
[27] Fukase Y, Eanes D, Takagi S, et al. JDent Res, 1990, 69:1852
[28] Tenhuisen KS, et al. J Mater Sci:Mater In Med, 1996, 7:309-316
[29] LeGeros RZ1. Properties of osteoconductive biomaterials: calcium phosphates[J]. Clin Orthop, 2002, (395):812-815
[30] Ignjatovic N, Tomic S, DakicM, et al. Synthesis and properties of hydroxyapatite polyLactide composite biomaterials[J]. Biomaterials, 1999, 20 (2):809-816
[31] M iyamo to Y, lsh ikaw a K, Fukao H, et al. In vivo setting behaviour of fast-setting calcium phosphate cement[J]. Biomaterials, 1995, 16 (11):855-860
[32] Khairoun I, Boltong MG, Driessens F, et al. Effect of calcium on the compliance of an apatitic calcium phosphate bone cement [J], Biomaterials, 1997, (18): 1535-1539
[33] 王文波，陈中伟，陈统一，等．自固化磷酸钙人工骨的生物学安全性实验研究[J]．中国生物医学工程学报，2001，20(3)：193-199
[34] Costantino PD, Friedman CD, Jones K, et al. Hydroxyapatite cement Ⅰ:Basic chemistry and reconstruction of the eat frontal sinus[J]. Arch O to laryngol Head Neck Surg, 1991, 117:385
[35] Huiping Yuan YL. Tissue responses of calcium phospliate cement:a study in dogs[J]. Biomatedals, 2000, 21:1283-1290
[36] Kuboki Y, Takita H, Kobayashi D, et al. BMP2 induced osteogenesis on the surface hydroxyapalite with geometrically feasible and nonfeasible structures: topology of osteogenesis[J]. J Biomed Mater Res, 1998, 39:1902-1991
[37] Hulbert SF, Mordson SJ, Klawitter JJ. Tissue reaction to three ceramics of porous an non-porous structures[J]. J Biomed Mater Res, 1972, 6(5):374-379
[38] Lu JX, Flautre B, Anselme K, et al. Role of interconnections in porous bioceramics on bone recolonization in vitro and in vivo[J]. J Mater Sci:Mater med, 1999, 10:111-118
[39] Simon CG Jr, Khatri CA, Wight SA, et ai. Preliminary report on the biocompatibility of a moldable, resorbable, composite bone gratt consisting of calcium phosphate cement and poly(lactide-co-glyeolide) mierospheres[J]. J Ortho Res, 2002, 20:473-482
[40] Yoshikawa T SY, Ohgushi H, Tamai S, et al. Self setting hydroxyapatite cement as a carrier for bone-forming cells[J]. Bio-Medical Materials And Engineering, 1996, 6:345-351
[41] Hoekin HK, Xu JBQ, Shozo Takagi, et al. Synergistic reinforcement of in situ hardening calcium phosphate composite scaffole for bone tissue engineering[J]. Biomaterials, 2004, 25:1029-1037
[42] Xu HH EF, Giuseppetti AA. Reinforcement of a self-setting calcium phosphate cement with different fibers[J]. J Biomed Mater Res, 2000, 52:107-114
[43] Xu HH QJ, Takagi S, et al, Strong and macroporous calcium phosphate cement: effects of porosity and fiber reinforcement on mechanical properties[J]. J Biomed Mater Res, 2001, 57:457-466
[44] del Real RP, Wolke J GC, Vallet-Regi M, et al. A new method to produce macropores in calcium phosphate cements[J]. Biomaterials, 2002, 23:3673-3680
[45] del Real RP, Ooms E, Wolke JGC, et al, In vivo bone response to porous calcium phosphate cement[J]. J biomed Mater Res, 2003, 65A:30-36
[46] J.E.Barralet LG, T.Gaunt, A.J.Wfight, et al. Preparation of macroporous calcium phosphate cement tissue engineering scaffold[J]. Biomaterials, 2002, 23:3063-3072
[47] Constantz BR, Ison IC, Fulmer MT, et al, Science, 1995, 267(5205): 1796-1799
[48] Lew androw ski KU, Gresser JD,W ise DL, et al, Osteoconduct ivity of an injectable and bioresorable poly (p ropylene glyeo 12co2funrnarie acid) bone cement[J]. B iomaterials, 2000, 21(3):293-298.
[49] Hardouin P, Lemaitre J. New Injectable composites for bone replace2mentd[J]. Semin Musculoskelet Radiol, 1997, 1(2):319-324
[50] Takagi Shozo, Hirayama Satoshi, Sugawara Akiyoshi, Premixed calcium-phosphate cement pastes[J]. Journal of Biomedical Materials Research (Applied Biomaterials), 2003, 67:689-696
[51] Daculsi G, Rohanizadeh R, Weiss P, et al. Crystal polymer interaction with new injectable bone substitute; SEM and Hr TEM study[J]. J Biomed Mater Res, 2000, 50(1):1-7
[52] L. Leroux ZH, M, Freche, JL, Lacout, Effect of varous adjuvants (lactic acid, glycerol and chitosan) on the injectability of a calcium phosphate cement[J]. Bone, 1999, 25:31S-34S
[53] S.Takagi SH, A. Sugawara, L.C. Chow. Premixed calcium phosphate cement paste[J]. Six World Biomaterials Congress (USA), 2000, 1:19
[54] 李又欣，冯新德．高分子通报，1991(1)：19-26
[55] Otsuka M, Nakahigashi Y, Matsuda Y, et al. Effect of geometrical cement size on in vitro and in vivo indomethacin release from self-setting apatite cement[J]. Journal of Controlled Release, 1998, 52:281-289
[56] Otsuka M, Nakahigashi Y, Matsuda Y, et al. A novel skeletal drug delivery system using self-setting calcium phosphate cement 7:Effect of biologic factors on indomethacin release from the cement loaded on bovine bone[J]. J Pharmterials, 1995, 16(7):5227-5232
[57] Hamanishi C, Kitamoto K, Tanaka S, et al. J Biomed Mater Res, 1996, 33: 139-143
[58] Otsuka M, M atsuda Y, Suwa Y, et al. A novel skeletal drug delivery system using self-setting calcium phosphate cement: Physicochemical properties and drug release rate oftbe cement-containing indomethacin[J]. J Pharm Sci, 1994, 83(5):611
[59] Otsuka M, Matsuda Y, Suwa Y, et al. A novel skeletaldrug-delicery system using self-setting calcium phosphate cement: 3. Physicochemical properties and drug-releaserate of bovine insulin and bovine albumin[J]. J Pharm Sci, 1994, 83(2):255
[60] Otsuka M, Matsuda Y, Suwa Y, et al. A novel skeletal drug-delivery system using self2setting calcium phosphate cement: 4. Effects of the mixing solution volume on drug-release rate of heterogeneous aspirin21oad cement[J]. J Pharm Sci, 1994, 83(2):259
[61] Yu D, Wong J, M atsude Y, et al. Self-setting hydroxyapatitite cement: a novel skeletal drug-delivery system forantibiotics[J]. J Phrma Sci, 1992, 81(6):529
[62] 王传军，陈统一，张键，等．自固化磷酸钙人工骨(CPC)载药妥布霉素体外抗菌活性评价[J]．中国临床医学，11(5)：794-797
[63] Celeste A J, Iannazzi JA, Taylor RC, et al. Identification of transforming growth factor-beta family members present in bone-inductive protein purified from bovine bone[J]. Proc Natl Acad Sci USA, 1990, 87(24):9843-9847
[64] Sakou T. Bone morphogenetic proteins: from basic studies to clinical approaches[J]. Bone, 1998, 22(6):591-603
[65] Reddi AH, Cunningham NS. Initiation and promotion of bone differentiation by bone morphogenetic proteins[J]. J Bone Miner Res, 1993, 8:S499-502
[66] Ji X, Chen D, Xu C, et al. Patterns of gene expression associated with BMP-2-induced osteoblast and adipocyte differentiation of mesenchymal progenitor cell 3T3-F442A[J]. J Bone Miner Metab, 2000, 18:132-139
[67] Li G, Allen W, McHenry S, et al. Microvascular endothelial cells are chemotactic to rhBMP-2[J]. Trans Orthop Res Soc, 2001, 12(3):583-588
[68] Padley RA, Cobb CM, Killoy W J, et al. In vitro chemtactic response of osteoblast-like osteosaecoma cells to a partially purified protein extract of demineralized bone matrix[J]. J Periodont, 1991, 62:15-20
[69] Wozney JM. The bone morphogenetic protein family and ostcogenesis[J]. Mol Reprod Dev, 1992, 32:160-167
[70] Urit MD, Nilsson O, Rasmussen J, et al. Bone regeneration under the influence of a bone morphogenetic protein(BMP) beta tricalcium phosphate(α-TCP) composite in skull trephine defects in dogs[J]. Clin Orthop, 1987, 214:295-304
[71] Ohum K, Hamanishi C, Tanaka S, et al. Healing of segmantal bone defect in rats induced by a beta-TCP-MCPM cement combinated with rhBMP-2[J]. Biomed Mater Res, 1999, 44(2):168-175
[72] O hura K,Mamamishi C, Tnaka S, et al. The healing of segmental bone defects, induced by bioresorbable calcium phorphate cement combined with recombinated human bone morphogenetic protein-2[J]. Bioceramics, 1996, 9:247-250
[73] 孙明林，胡蕴玉，张瑞萍．磷酸钙骨水泥／骨形态发生蛋白复合人工骨修复骨缺损的实验研究[J]．现代康复，2001，5(5)：32-33
[74] Ouicheux J, Gauthier O, L aguado E, et al. Growth hormone-loaded macroporous calcium phosphate ceramic: in vitro biopharmaceutical characterizat ion and preliminary in vivo study[J]. Biomed Mater Res, 1998, 40(4):560-566
[75] Guicheux J, Kimakhe S, Heymann D, et al. Growth hormonest imulates the degradation of calcium phosphate biomaterial by human monocytes nacrophages in vitro[J]. BiomedM ater Res, 1998, 40(1):79-85
[76] Costantino PD, Friedman CD.Synthetic bone graft substitutes. O to laryngol Clin North Am, 1994, 27:1037
[77] Friedman CD, Costantino PD, Takagi S, et al. J Biomed Mater Res, 1998, 43(4):428-432
[78] Knaack D, Goad ME, Aiolova M, et al. J Biomed Mater Res, 1998, 43(4):399-409
[79] Hollinger JO, Brekke J, Gruskin E. Role of bone substitutes[J]. Clin Orthop, 1996, 324:55
[80] Lacout JL, Mejdoub E, Hamad M, Crystallization mechanisms of calcium phosphate cement for biological uses[J]. J Mater Sci, 1996, 7:371
[81] 杨志平，李建民，李昕等．磷酸钙骨水泥修复良性骨肿瘤骨缺损[J]．山东大学学报(医学版)，2003，41(4)：415-417
[82] Okada E, Maruyama Y, Hayashi A. Nasal augmentation using calcium phosphate cement[J]. Craniofac surg, 2004, 15(1): 102-105
[83] Kamerer DB, Hirsh BE, Syoderman CH, et al. Hydroxyapatite cement:A new method for achieving watertight closure in transtemp oral surgery[J]. Am J O to l, 1994, 15:47
[84] 翁雨来．磷酸三钙一次根管治疗的初步报告[J]．中华口腔医学杂志，1991，26：2
[85] Yoshikawa M, lnamoto T, Hakata T, et al. Apical canal sealing ability ofcalcium phosphate based cements[J]. J Osaka Dent Univ, 1996, 30(122): 12
[86] Sugawara A, Chow L C, Takagi S, et al. In vitro evaluation of the sealing ability of a calcium phosphate cement when used as a root canal sealer filler[J]. J ended, 1990, 16(4):162
[87] Tchaou WS, Turng BF, Minah GE, et al. Inhibition of pure culture of oral bacteria by root canal filling material[J]. Pediatr Dent, 1996, 18(7):444
[88] Goodell GG, Mork TO, Hurter JW, et al. Linear dye penetration of a calcium phosphate cement apical barrier[j]. J Ended, 1997, 23(3):174
[89] Miyamoto Y, Ishikaway K, Takechi M, et al. Basic properties of calcium phosphate cement containing atelocllagen in this liquid or powder phases[J]. Biomatedals, 1998, 19(729):707-715
[90] Hong CY, Lin SK, Kok SH, et al. Histologic reaction to a newly developed calaium phosphate cement implant in the periapcal and periodontal tissues[J]. J Formos Med Assoc, 1990, 89(4):297
[91] Hong YC, Wang T, Hong CY, et al. The pedapical tissue reaction to a calcium phosphate cement in the teeth of monkeys[J]. J Biomod mater Res, 1991, 25(4):485
[92] 宁江海，刘洪臣，毛克亚等．生物活性多肽修饰的碳磷酸钙骨水泥修复牙周骨缺损的实验研究[J]．华西口腔医学杂志，2003，38(6)：464-466
[93] 李善昌，苗波，魏良富．磷酸钙骨水泥与骨形成蛋白修复即刻种植牙骨缺损的实验研究[J]．口腔医学研究，2003，19(4)：255-257
[94] 黄辉，王建华．磷酸钙骨水泥修复髓室底穿孔渗露的实验研究[J]．临床口腔医学杂志，2002，18(1)：20-21
[95] 束红雷，蔡传敏，吴东．磷酸钙骨水泥复合盖髓剂用于活髓保存的临床研究[J]．口腔综合杂志，2001，17(1)：54-56
[96] Lim TH, Brebach GT, Rermer SM, et al. Biomechanical evaluation of an injectable calcium phosphate cement for vertebroplasty[J]. Spline, 2002, 27:1297-1302
[97] Verlaan JJ, van Helden WH, Oner FC, et al.Balloon vertebroplasty with calcium phosphate cement augmentation for direct restoration of traumatic thoracolumbar vertebral fractures[J]. Spline, 2002, 27:543-548
[98] 曾忠友，金才益，陆金荣等．椎弓根螺钉系统加自固化磷酸钙人工骨灌注治疗腰胸椎骨骨折[J]．中华创伤杂志，2001，17：284-286
[99] Yetkinler DN, Ladd AL, Poser RD, et al.Biomechanieal evaluation of fixation of intra-artieular fractures of the distal part of the radius in cadavera:Kirschaner wires coMPared with calcium phosphate bone cemnet[J].J Bone JointSurg(Am), 1999, 81: 391-399
[100] Hidaka N, Yamano Y, Kadoya Y, et al.Calcium phosphate bone cement for treatment of distal radius fractures:A preliminary report[J]. J Orthop Sci, 2002, 7:182-187
[101] Yetkinler DN, Mc Clellan RT, Reindel ES, et al.Biomechanical coMPared of conventional open reduction and internal fixation versus calcium phosphate cement coMPared of central depressed tibial plateau fracture[J]. J Orthop Trauma, 2001, 15:197-206
[102] Schildhaucr TA, Bauer TW, Josten C, et al.Open reduction and augmentation of internal fixation with an injectable skeletal cement for the treatment of complex calcaneal fractures[J]. J Orthop Trauma, 2000, 14:309-317
[103] Csizy M, BucKley RE, Fennell C, Benign calcaneal bone cyst and pathologic fracture-surgical treatment with injectable calcium phosphate bone cement(Norian):A case report[J]. Food Article Int, 2001, 22:507-510
[104] Eriksson F, Mattsson P, Larsson S. The effect of augmentation with resorbable or conventional bone cement on the holding strength for femoral neck fracture devices[J]. J Orthop Trauma, 2002, 16:302-310
[105] Yetkinler DN, Goodman SB, Reindel ES, et al. Mechanical evaluation of carbonated apaitecement in the fixation of unstable intertrochanteric fractures[J]. Acta Orthop scand, 2002, 73:157-164
[106] Elder S, Frankenburg E, Goulet J, et al.Biomechanical evaluation of calcium phosphate cement-augmented fixation of unstable intertrochanteric fractures[J]. J Or thop Trauma, 2000. 14:386-393
[2] Jr D, Sd G, Kj B, et al. Clinical outcomes and fusion success at 2 years of single-level instrumented posterolateral fusions with recombinant human bone morphogenetic protein-2/compression resistant matrix versus iliac crest bone graft[J]. Spine, 2006,31 (22):2534～2540.
[3] Ci E, A A, Es R, et al. Therapeutic management for immediate implant placement in sites with periapical deficiencies where coronal bone is present: technique and case report[J]. International Journal of Oral & Maxillofacial Implants, 2006,21 (3):476～480.
[4] L S, F G, Gb F, et al. Langerhans' cell histioeytosis: a case report of an eosinophilic granuloma of the mandible treated with bone graft surgery and endosseous titanium implants[J]. 2006, 2006,21(1):124～130.
[5] 郭颖，李玉宝．骨修复材料的研究进展[J]．世界科技研究与发展，2001，23(1)：33～37．
[6] M N, L W, Js W, et al. Factors influencing the compressive strength of an injectable calcium sulfate-hydroxyapatite cement[J]. JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, 2003,14(5):399～404.
[7] Hhk X, Le C, Cg S, et al. Premixed calcium phosphate cements: Synthesis, physical properties, and cell cytotoxicity[J]. DENTAL MATERIALS, 2007,23(4):433～441.
[8] F B, L G, V J, et al. Short-fibre reinforcement of calcium phosphate bone cement[J]. PROCEEDINGS OF THE INSTITUTION OF MECHANICAL ENGINEERS PART H-JOURNAL OF ENGINEERING IN MEDICINE, 2007,221 (H2):203～211.
[9] Xp W, Jd Y, Yj W, et al. Reinforcement of calcium phosphate cement by bio-mineralized carbon nanotube[J]. JOURNAL OF THE AMERICAN CERAMIC SOCIETY, 2007,90(3):962～964.
[10] J C. Anchorage of the femoral head prosthesis to the shaft of the femur[J]. Journal of Bone & Joint Surgery - British Volume, 1960,42-B:28～30.
[11] J C. Surgery of the hip-joint: present and future developments[J]. British Medical Journal, 1960,1 (5176):821～826.
[12] Em O, Jg W, van de Mt H, et al. Histological evaluation of the bone response to calcium phosphate cement implanted in cortical bone[J]. Biomaterials, 2003,24(6):989～1000.
[13] H M, T T, R T, et al. Mechanical properties of the femur filled with calcium phosphate cement under torsional loading: a model in rabbits[J]. 2002, 2002,7(5):562～569.
[14] Th L, Gt B, Sm R, et al. Biomechanical evaluation of an injectable calcium phosphate cement for vertebroplasty[J]. Spine, 2002,27(12): 1297～1302.
[15] Lcc W E B. A new calcium phosphate, water-settlng cemen[J]. American Ceramic Society, 1986:352～379.
[16] 俞耀庭，张兴栋．生物医用材料[M]．天津大学出版社，2001．
[17] 刘昌胜，沈卫，顾燕芳，et al．非陶瓷羟基磷灰石人工骨的研究[J]．化工进展，1996(1)：10～14．
[18] We B, M F. Kinetics of hydroxyapatite formation at low temperature[J]. J Am Ceram Soc, 1991,74(5):934～940.
[19] Br C, Ic I, Mt F, et al. Skeletal repair by in situ formation of the mineral phase of bone[J]. Science, 1995,267(5205): 1796～1799.
[20] Cd F, Pd C, S T, et al. BoneSource hydroxyapatite cement: a novel biomaterial for craniofacial skeletal tissue engineering and reconstruction[J]. Journal of Biomedical Materials Research, 1998,43(4):428～432.
[21] A T, S L, K M, et al. Comparative fixation of tibial plateau fractures using alpha-BSM, a calcium phosphate cement, versus cancellous bone graft[J]. Journal of Orthopaedic Trauma, 2005,19(10):698～702.
[22] k H H, Jbq X, Takagi S, et al. Synergistic reinforcement of in situ hardening calcium phosphate composite scaffole for bone tissue engineering[J]. Biomaterials, 2004,25(6): 1029～1037.
[23] L S, Hh X, S T, et al. Fast setting calcium phosphate cement-chitosan composite: mechanical properties and dissolution rates[J]. Journal of Biomaterials Applications, 2007,21(3):299～315.
[24] Hh X, Jr S C. Fast setting calcium phosphate-chitosan scaffold: mechanical properties and biocompatibility[J]. Biomaterials, 2005,26(12): 1337～1348.
[25] 沈卫，刘昌胜，顾燕芳，et al．磷酸钙骨水泥的水化反应机理研究[J]．无机材料学报，1996，11(4)：685～690．
[26] Ap O, Fa N, Jl L, et al. Synthesis and characterization of single-phase silicon-substituted alpha-triealcium phosphate[J]. Biomaterials, 2006,27(15):2916～2925.
[27] Kh P, R K, Cp O, et al. Conductometric study of precursor compound formation during wet-chemical synthesis of nanocrystalline hydroxyapatite[J]. Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces & Biophysical., 2006,110(48):24457～24462.
[28] Ac T, F K, M T, et al. An investigation of the chemical synthesis and high-temperature sintering behaviour of calcium hydroxyapatite (HA) and tricalcium phosphate (TCP) bioceramics[J]. JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, 1997,8(2):91～96.
[29] 胡常伟．大学化学[M]．北京市：化学工业出版社，2004：63～517．
[30] 张雁冰，何萍芬，李青，et al．化学[M]．郑州市：郑州大学出版社，2003：34～76．
[31] 陈晓旭，高立达，毛伯镛，et al．磷酸钙骨水泥临床应用类型选择及微结构观察[J]． 生物医学工程学杂志，2001，18(4)：568～572．
[32] 戴红莲，闫玉华，李世普，et al．α-磷酸三钙-磷酸四钙生物骨水泥的研究[J]．材料科学与工程，2002，20(3)：331～335．
[33] Mp G, E F, Mg B, et al. Compliance of an apatitic calcium phosphate cement with the short-term clinical requirements in bone surgery, orthopaedics and dentistry[J]. Clinical Materials, 1994,17(2):99～104.
[34] 高岐．分析化学[M]．北京市：高等教育出版社，2006：237～249．
[35] On T, K K, Y I. In vitro hydroxyapatite deposition onto a film surface-grated with organophosphate polymer[J]. Journal of Biomedical Materials Research, 1994,28(11):1365～1373.
[36] 吴文进，杨为中，周大利，et al．碳纤维增强α-磷酸三钙骨水泥的研究[J]．生物医学工程学杂志，2006，23(3)：569～572．
[37] D S, M H, Y A, et al. Ollier's disease treated with grafting using alpha-triealeium phosphate cement. A case report[J]. Upsala Journal of Medical Sciences, 2006,111 (2):249～256.
[38] M B, Ak M, CI C, et al. Combining particle size distribution and isothermal calorimetry data to determine the reaction kinetics of alpha-triealeium phosphate-water mixtures[J]. Acta Biomaterialia, 2006,2(3):343～348.
[39] Ap O, Fa N, Ji L, et al. Evaluation of a double-setting alpha-tricalcium phosphate cement in eviscerated rabbit eyes[J]. Ophthalmic Plastic & Reconstructive Surgery, 2006,22(2):126～130.
[40] Ef B, F G, Lc C. A water setting tetraealeium phosphate-dicalcium phosphate dihydrate cement[J]. Journal of Biomedical Materials Research. Part A, 2004,71(2):275～282.
[41] D G, K X, X Z, et al. Development of a strontium-containing hydroxyapatite bone cement[J]. Biomaterials, 2005,26(19):4073～4083.
[42] G D, X K, S H, et al. Physicochemieal properties of TTCP/DCPA system cement formed in physiological saline solution and its cytotoxieity[J]. Journal of Biomedical Materials Research. Part A, 2006,77(2):313～323.
[43] Hh X, S T, L S, et al. Development of a nonrigid, durable calcium phosphate cement for use in periodontal bone repair[J]. Journal of the American Dental Association, 2006,137(8):1311～1318.
[44] 郑治，向其军，刘咏，et al．医用磷酸钙骨水泥的制备及性能的实验研究[J]．生物医学工程学杂志，2006，23(5)：1048～1051．
[45] 向其军，刘咏，郑治，et al．磷酸钙骨水泥生物材料用磷酸四钙的制备[J]．粉末冶金材料科学与工程，2005，10(4)：211～215．
[46] 郭大刚，徐可为，憨勇．固相反应合成磷酸四钙的物相演变[J]．无机材料学报，2005，20(2)：317～322．
[47] Y F, Ed E, S T, et al. Setting reactions and compressive strengths of calcium phosphate cements[J]. Journal of Dental Research, 1990,69(12):1852～1856.
[48] 戴红莲，闫玉华，王友法，et al．磷酸四钙粉末的制备研究[J]．硅酸盐通报，2002(4)：56～59．
[49] 郑昌琼，冉均国．新型无机材料[M]．北京市：科学出版社，2003：73～103．
[50] Laurencin C T. Bone Resorption Mediators Elicited by Degradation Products of Orthopedic Polymer[J]. Society for Biomateriais, 1998(22-26):309.
[51] 俞超，薛文东，张双燕，et al．股骨头负重区松质骨的压缩力学特性[J]．上海生物医学工程，2004，25(1)：22～23．
[52] 赵宝林，程杰平，马洪顺，et al．股骨头松质骨力学性质实验研究[J]．医用生物力学，2003，18(4)：234～238．
[53] 李英普，陈雷．大骨节病对股骨头松质骨力学性质影响实验研究[J]．中国地方病防治杂志，2004，19(2)：81～82．
[54] 李世普．生物医用材料导论[M]．武汉：武汉工业大学出版社，2000：8．
[55] K K，A O,A K,et al.Histological and microradiographic evaluation of hydrated and hardened alpha-tricalcium phosphate/calcium phosphate dibasic mixtures[J].Biomaterials,1994,15(6):429～432.
[56] K K,H K,A K,et al.In vivo study of a calcium phosphate cement consisting of alpha-tricalcium phosphate/diealcium phosphate dibasic/tetracalcium phosphate monoxide[J].Biomaterials,1997,18(2):147～151.
[57] K K,H K,M H,et al.In vivo study ofcalcium phosphate cements:implantation of an aJpha-tricalcitma phosphateldicalcium phosphate dibasic/tetracalcium phosphate monoxide cement paste[J].Biomaterials,1997,18(7):539～543．
[58] K K,H K,A K,et al.Experimental cranioplasty and skeletal augmentation using an alpha-tricalcium phosphate/dicalcium phosphate dibasic/tetracalcium phosphate monoxide cement: a preliminary short-term experiment in rabbits[J]. Biomaterials,1998,19(7-9):701～706．
[59] Mp G,E F,de Ea M,et al.Setting reaction and hardening of an apatitic calcium phosphate cement[J].Journal ofDental Research,1997,76(4):905～912.
[60] 戴红莲，陈芳，闫玉华．a-TCP骨水泥水化产物及其影响因素[J]．武汉理工大学学报，1996，18(1)：43～6。
[61] Y L, X Z, de K G. Hydrolysis and phase transition of aipha-trlcalcium phosphate[J]. Biomaterials, 1997,18(10):737～741.
[62] C D, Pw B. alpha-Triealcium phosphate hydrolysis to hydroxyapatite at and near physiological temperature[J]. JOURNAL OF MATER/ALS SCIENCE-MATERIALS IN MEDICINE, 2000,11(6):365～371.
[63] H M, T K. The hydration of α-tricalcium phosphate.[J]. Journal of the ceramic society of Japan, 2000,108(8):75～80.
[64] Ro O, Fc D, Ja P, et al. Growth and differentiation of human bone marrow osteoprogenitors on novel calcium phosphate cements[J]. Biomatefials, 1998,19(20): 1845～1854.
[65] I K, Mg B, Fe D, et al. Effect of calcium carbonate on the compliance of an apatitic calcium phosphate bone cement[J]. Biomaterials, 1997,18(23):1535～1539.
[66] As G, Ve F, Ab M. Structural and mechanical characteristics of silk fibroin and ehitosan blend scaffolds for tissue regeneration[J]. Journal of Biomedical Materials Research, 2005,74(3):465～473.
[67] J C, Gh A, V K, et al. Human bone marrow stromal cell and ligament fibroblast responses on RGD-modified silk fibers[J]. Journal of Biomedical Materials Research. Part A, 2003,67(2):559～570.
[68] Gh A, Rl H, Hh L, et al. Silk matrix for tissue engineered anterior cruciate ligaments[J]. Biomaterials, 2002,23(20):4131～4141.
[69] B P, Gh A, J C, et al. Macrophage responses to silk[J]. Biomaterials, 2003,24(18):3079～3085.
[70] S S, Mb M, G G, et al. Functionalized silk-based biomaterials for bone formation[J]. Journal of Biomedical Materials Research, 2001,54(1):139～148.
[71] N M, S A, M H, et al. Attachment and growth of fibroblast cells on silk fibroin[J]. Biochemical & Biophysical Research Communications, 1995,208(2):511～516.
[72] K I, M K, S N, et al. Use of Bombyx mori silk fibroin as a substratum for cultivation of animal cells[J]. Journal of Biochemical & Biophysical Methods, 1998,37(3):159～164.
[73] Cai X, Lin Y, Ou G, et al. Ectopic osteogenesis and chondrogenesis of bone marrow stromal stem cells in alginate system[J]. Cell Biology International, 2007(in press).
[74] van der E W, Am V, Pj T B, et al. The in vitro behavior of as-prepared and pre-immersed RF-sputtered calcium phosphate thin films in a rat bone marrow cell model[J]. Biomatedals, 2006,27(8):1333～1340.
[75] T S. Bone morphogenetic proteins: from basic studies to clinical approaches[J]. Bone, 1998,22(6):591～603.
[76] 江莹，陈槐卿，周闻达，et al．蚕丝丝素纤维的制备及其与骨髓间充质干细胞相容性的研究[J]．生物医学工程学杂志，2006，23(3)：583～588．
[77] J V, D K. Biopolymer-based biomaterials as scaffolds for tissue engineering[J]. Advances in Bioehemlcal Englneering-Biotechnoiogy, 2006,102:187～238.
[78] L P, Ak S, S S, et al. Different substitute biomaterials as potential scaffolds in tissue engineering[J]. International Journal of Oral & Maxillofacial Implants, 2006,21 (2):225～231.
[79] Dw H. Scaffolds in tissue engineering bone and cartilage[J]. Biomaterials, 2000,21 (24):2529～2543.
[80] Dl K, Sm M. Protein based materials[M]. Boston:Birkhauser, 1998:103～131.
[81] Xy L, Xd L, Hs F, et al. In situ synthesis of bone-like apatite/collagen nano-composite at low temperature[J]. MATERIALS LETTERS, 2004,58(27-28):3569～3572.
[82] Yq Z. Applications of natural silk protein seriein in biomaterials[J]. BIOTECHNOLOGY ADVANCES, 2002,20(2):91～100.
[83] Gh A, F D, C J, et al. Silk-based biomaterials[J]. Biomaterials, 2003,24(3):401～416.
[84] 吕靖．蚕丝和蜘蛛丝的结构与生物纺丝过程[J]．现代纺织技术，2004,12(1)：40～42．
[85] Rl M, A L, A Z. Commonly used suture materials in skin surgery[J]. American Family Physician, 1991,44(4):2123～2128.
[86] Hk S, Kr K. Adverse reactions to virgin silk sutures in cataract surgery[J]. Ophthalmology, 1984,91 (5):479～483.
[87] S K, H O, M K, et al. Fibroin allergy. IgE mediated hypersensitivity to silk suture materials[J]. Journal of the Nippon Medical School, 1999,66(1):41～44.
[88] S W, Dl K. Molecular biology of spider silk[J]. Journal of Bioteclmology, 2000,74(2):85～93.
[89] 小松计一．各种脱胶方法的比较[J]．国外丝绸，1992，11(2)：2～7．
[90] 蒋少军，吴红玲．蚕丝的酶处理[J]．四川丝绸，2002(4)：23～25．
[91] 胜野盛夫．蚕丝场实验报告[J]．日本蚕丝学杂志，1985，8(5)：40～43．
[92] Nh L, Yy C, T C, et al. Aeryiie resin reinforced with chopped high performance polyethylene fiber—properties and denture construction[J]. Dental Materials, 1993,9(2):128～135.
[93] Aj G, Cj B, I H, et al. Screening of matrices and fibers for reinforced thermoplastics intended for dental applications[J]. Journal of Biomedical Materials Research, 1994,28(2):167～173.
[94] B P, 4th R H, P S, et al. Fracture toughness of Kevlar 29/poly(methyl methacrylate) composite materials for surgical implantations[J]. Annals of Biomedical Engineering, 1986,14(3):277～294.
[95] Ld T, P D, Jm C. The effects of centrifugation and titanium fiber reinforcement on fatigue failure mechanisms in poly(methyl methaerylate) bone cement[J]. Journal of Biomedical Materials Research, 1995,29(3):299～307.
[96] von As G, Jr K, Jm A. The effects of centrifugation and titanium fiber reinforcement on fatigue failure mechanisms in poly(methyl methacrylate) bone cement[J]. Journal of Biomedical Materials Research, 1999,29(3):299-307.
[97] Hh X, Jb Q. Calcium phosphate cement containing resorbable fibers for short-term reinforcement and macroporosity[J]. Biomaterials, 2002,23(1):193～202.
[98] Aj C, Ja I, Re T, et al. Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone[J]. Proceedings of the National Academy of Sciences of the United States of America, 1990,87(24):9843～9847.
[99] Af S, Gd P, Ch E. Gene therapy in the musculoskeletal system[J]. Current Opinion in Orthopaedics, 2004,15(5):318～324.
[100] Td A, P V, Df K. Bone morphogenetie protein gene therapy[J]. Spine, 2002,27(16S):87～93.
[101] X J, D C, C X, et al. Patterns of gene expression associated with BMP-2-induced osteoblast and adipocyte differentiation of mesenchymal progenitor cell 3T3-F442A[J]. Journal of Bone & Mineral Metabolism, 2000,18(3):132～139.
[102] Ah R. Initiation and promotion of endochondral bone formation by bone morphogenetic proteins: Potential implications for avian tibial dyschondroplasia[J]. POULTRY SCIENCE, 2000,79(7):978～981.
[103] S W, Gr J, C J. High concentrations of dexamethasone suppress the proliferation but not the differentiation or further maturation of human osteoblast precursors in vitro:relevance to glucocorticoid-induced osteoporosis[J]. Rheumatology, 2001,40(1):74～83.
[104] Dj M, Md R Jf B. Matrix deposition by a calcifying human osteogenic sarcoma cell line (SAOS-2)[J]. Bone, 1995,16(4):415～426.
[105] E O, A Y, S H, et al. Characterization of osteoblastic differentiation of stromal cell line ST2 that is induced by ascorbic acid[J]. American Journal of Physiology, 1999,277(1 Pt1):132～138.
[106] Cm V. Adult stem cells: assessing the case for pludpotency[J]. Trends in Cell Biology, 2002,12(11):502～508.
[107] Ll W. Translating stem and progenitor cells biology to the clinic: barrier and opportunities[J]. Science, 2000,287(5457):1442～1446.
[108] Y J, Bn J, RI R, et al. Pluripotency of mesenchymal stem cells derived from adult marrow[J]. Nature, 2002,418(6893):41～49.
[109] M R, A D, B J, et al. Origin of endothelial progenitors in human postnatal bone marrow[J]. Journal of Clinical Investigation, 2002,109(3):337～346.
[110] Gc K, Dj P, Dg P. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains[J]. Proceedings of the National Academy of Sciences of the United States of America, 1999,96(19):10771-10716.
[111] Re S, M R,L K, et al. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells[J]. Journal of Clinical Investigation, 2002,109(10): 1291～1302.
[112] Jr M, V V, DI K. Role of adult mesenchymal stem cells in bone tissue engineering applications: current status and future prospects[J]. Tissue Engineeing, 2005,11 (5-6):787～802.
[113] 傅远飞，陈德敏，张建中．MTT比色法评价掺锶羟磷灰石固溶体细胞毒性[J]．生物医学工程学杂志，2001，18(3)：389～390．
[114] Bg M, Fr S, Lp W, et al. Long-term culture of cells from bone affected by Paget's disease[J]. Calcified Tissue International, 1979,29(2):79～87.
[115] Mf P, Am M, Sc B, et al. Multilineage potential of adult human mesenchymal stem cells[J]. Science, 1999,284(5411):143～147.
[116] Aj F, Rk C, Uv G. Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers[J]. Cell & Tissue Kinetics, 1987,20(3):263～272.
[117] Sp B, N J, Ns R, et al. Mesenchymal stem cells in osteobiology and applied bone regeneration[J]. Clinical Orthopaedics & Related Research, 1998(355 supple):247～256.
[118] Gc K, Dj P, Dg P. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains[J]. Proceedings of the National Academy of Sciences of the United States of America, 1999,96(19):10711-10716.
[119] Dj P. Marrow stromal cells as stem cells for nonhematopoietic tissues[J]. Science, 1997,276(5309):71-74.
[120] 段小军，杨柳，周强．人间充质干细胞成骨诱导培养后的细胞成分研究[J]．中国临床康复，2002，6(22)：3337～3338．
[121] Rs T. Biology of developmental and regenerative skeletogenesis[J]. Clinical Orthopaedics & Related Research, 2004(427 supple):105～117.
[122] Eh J, Kj B, Aw F. Mesenchymal stem cells: paradoxes of passaging[J]. Experimental Hematology, 2004,32(5):414～425.
[123] 曹聪，董英海，董宇启，et al．人血源性间充质干细胞培养与体外成骨研究[J]．中国修复重建外科杂志，2005，19(8)：642～647．
[124] Mf H. In vitro study of biodegradation of a Co-Cr alloy using a human cell culture model[J]. Journal of Biomatefials Science, Polymer Edition, 1995,6(9):809～814.
[125] 郝和平．医疗器械生物学评价标准实施指南[M]．北京：中国标准出版社，2000：100～109．
[126] T M. Rapid eolorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays[J]. Journal of Immunological Methods, 1983,65(1-2):55～63.
[127] H L, As A, D S, et al. Response of rat osteoblast-like cells to microstructured model surfaces in vitro[J]. Biomaterials, 2003,24(4):649～654.
[128] 黄永光，陈治清．硬组织替代材料对成骨细胞骨钙蛋白和ALP水平的影响[J]．华西口腔医学杂志，2000，18(3)：192-194．
[129] Ag D, Ma L, At T C, et al. In vitro studies of calcium phosphate glass ceramics with different solubility with the use of human bone marrow cells[J]. Journal of Biomedical Materials Research. Part A, 2005,74(3):347～355.
[130] J T, Ra G, M M, et al. Improved cell adhesion and proliferation on synthetic phosphonic acid-containing hydrogels[J]. Biomaterials, 2005,26(17):3663～3671.
[131] Fc F, Gc M. Osteoblasts attachment and adhesion: how bone cells fit fibronectin-coated surfaces[J]. Materials Science and Engineering, 2004,24(C):637～641.
[132] Al O, Cm A, RI R. Cell adhesion and proliferation on biomimetic calcium-phosphate coatings produced by a sodium silicate gel methodology[J]. Journal of Materials Science:Materials in Medicine, 2002,13(12):1181～1188.
[133] C E, F Y, Mc A, et al. Plasma-and chemical-induced graft polymerization on the surface of starch-based biomaterials aimed at improving cell adhesion and proliferation[J]. Journal of Materials Science:Materials in Medicine, 2003,14(2): 187～194.
[134] K W, V H, Pa T. Relative importance of surface wettability and charged functional groups on NIH 3T3 fihrohlast attachment, spreading, and cytoskeletal organization[J]. Journal of Biomedical Materials Research, 1998,41(3):422～430.
[135] Yw W, Q W, Gq C. Attachment, proliferation and differentiation of osteoblasts on random biopolyester poly (3-hydmxybutyrate-co-3-hydroxyhexanoate) scaffolds[J]. Biomaterials, 2004,25(4):669～675.
[136] Le C, Hh X, Jr S C, et al. Premixed rapid-setting calcium phosphate composites for bone repair[J]. Biomaterials, 2005,26(24):5002～5014.
[137] Am P. The cellular basis of bone remodeling:the quantum concept reexamined in light of recent advances in the cell biology of bone[J]. Calcified Tissue International, 1984,36(S1):37～45.
[138] O S, S K, T K, et al. Bone formation enhanced by implanted octacalcium phosphate involving conversion into Ca-deficient hydroxyapatite[J]. Biomaterials, 2006,27(13):2671～2681.
[139] Pm S, Y L, Pr C, et ai. Bone marrow cell gene expression and tissue construct assembly using octacaicium phosphate microscaffolds[J]. Biomaterials, 2006,27(14):2874～2881.
[140] Tl A, T T, J M, et al. A comparative study of biphasic calcium phosphate ceramics for human mesenchymal stem-cell-induced bone formation[J]. Biomaterials, 2005,26(17):3631-3638.
[141] Ek P, Ye L, Jy C, et al. Cellular biocompatibility and stimuiatory effects of calcium metaphosphate on osteoblastic differentiation of human bone marrow-derived stromal cells[J]. Biomaterials, 2004,25(17):3403～3411.
[142] Mc S, Xf W, Sc L, et al. Electrostatic spray deposition (ESD) of calcium phosphate coatings, an in vitro study with osteoblast-like cells[J]. Biomaterials, 2004,25(11):2019～2027.
[143] T K, N T. Regulatory mechanisms of osteoblast and osteoclast differentiation[J]. Oral Diseases, 2002,8(3):147～159.
[144] K N, X Z, G K, et ai. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation[J]. Cell, 2002,108(1):17～29.
[145] A J, Gl B, Bo J, et ai. runt homology domain transcription factors (Runx, Cbfa, and AML) mediate repression of the bone siaioprotein promoter: evidence for promoter context-dependent activity of Cbfa proteins[J]. Molecular & Cellular Biology, 2001,21(8):2891～2905.
[146] Dm T, Sa C, Dm P, et al. The retinoblastoma protein acts as a transcriptional coactivator required for osteogenic differentiation[J]. Molecular Cell, 2001,8(2):303～316.
[147] 杨志明．组织工程[M]．北京市：化学工业出版社，2002：161～162．
[148] de Da U, K M, A E, et ai. Comparison of multi-lineage cells from human adipose tissue and bone marrow[J]. Cells Tissues Organs, 2003,174(3):101～109.
[149] P K, R L, van M G, et al. Comparison of human bone marrow stromal cells seeded on calcium-deficient hydroxyapafite, beta-tricalcium phosphate and demineralized bone matrix[J]. Biomaterials, 2003,24(15):2593～2603.
[150] J D, T U, Y S, et al. Promotion of bone formation using highly pure porous beta-TCP combined with bone marrow-derived osteoprogenitor cells[J]. Biomaterials, 2002,23(23):4493～4502.
[151] Sj P, L L, Dj K, et al. Marrow stromal osteoblast function on a poly(propylene fumarate)/beta-tricalcium phosphate biodegradable orthopaedic composite[J]. Biomaterials, 2000,21(12):1207～1213.
[1] Vassilios I, Sikavitsas JST, Antonios G Mikos. Biomaterials and bone mechanotransduction[J]. Biomaterials, 2001, 22:2581-2593
[2] 葛建华，王迎军，郑裕东．可降解及可吸收骨科材料研究进展[J]．化工新型材料，2003，31(2)：34-39
[3] 刘昌胜，沈卫，顾燕芳，等．非陶瓷羟基磷灰石人工骨的研究[J]．化工进展，1996，1：10-14
[4] 郭颖，李玉宝．骨修复材料的研究进展[J]．世界科技研究与发展，2001；23：33-37
[5] M.Nilsson LW, J.-S.Wang, K.E.Tanner, et al. Factors influencing the compressive strength of an injectable calcium sulfate-hydroxyapatite cement[J]. Journal of Materials Science:Materials in Medicine, 2003, 14:399-404
[6] 阮建明，邹俭鹏，黄伯云编著．生物材料学[M]．北京：科学出版社，2004
[7] 俞耀庭等主编．生物医用材料[M]．天津：天津大学出版社，2001
[8] 吴常生，尹玉姬，杨悦，等。骨组织工程中大孔支架材料制备的研究[J]．中国临床康复，2004，8(5)：929-931
[9] Hulbert SF, Morfison S J, Klawitter JJ.Tissue reaction to three ceramics of porous an non-porous structures[J] J Biomed Mater Res, 1972, 6(5):374-378
[10] Chamley J. [J]. Bone Joint Surg, 1960, 42 B:28-30.
[11] Weam FM, Masahiko Kobayashi. Biological and mechanical properties of PMMA-based bioactive bone cements[J]. Biomaterials, 2000, 21:2137-2146.
[12] Rejda BV, Rieger MR. Porous Acrylic Cement[J]. J Biomed Mater Res, 1977, 11:373,
[13] WE. Brown LCC. A new calcium phosphate, water-setting cement[J]. American Ceramic Society, 1986: 352-379.
[14] 俞耀庭，张兴栋．生物医用材料[M]．天津：天津大学出版社，2001
[15] Doi Y, Takezawa Y, Shibata, et al, Self-setting apatite cement, In physicochemical properties[J]. J japan Soe Dent Matals Devices, 1987, 6:53
[16] Fukase Y, Eanes ED, Chow LC. Setting reaction and compressive strengths of calcium phosphate cements[J]. J Dent Res, 1990, 69(12):1852
[17] Brown WE, Fulmer M. Kinetics of hydroxyapatite formation at low temperature[J]. J Am Ceram Soc, 1991, 74(5):934-940
[18] 戴红莲，陈芳，闫玉华，等．武汉工业大学学报，1996，18(1)：431
[19] GinebraM P, et al. J Dent Res, 1997, 76(4):905
[20] Monoa H, Goto M, Kohmura T. Gypsum & Lime, 1984, 188:11-16
[21] Li Yubao, Zhang Xingdong, K.de Groot. Biomaterials, 1997, 737-741
[22] C.Durucan. α-tricalcium phosphate hydrolysis to hydroxyapatite at and near physiological temperature[J]. Journal of materials science: materials in medicine, 2000, 11:365
[23] Monma H, Kanazawa T. The hydration of α-tricalcium phosphate[J]. Journal of the ceramic society of Japan, 2000, 108(8):75-80
[24] Y. Fukase EDE ST, L.C, Chow, W.E. Brown. Setting reaction and compressive strength of calcium phosphate[J]. J Dent Res, 1990, 69:1852-1856
[25] Lacout JL, Mejdoubi E, et al. Journal of Mater Sci:Mater in Med, 1996, 7:375
[26] Changsheng Liu YH, Jianguo Chen. The physicochemical properties of the solidification of calcium phosphate cement[J]. Journal of Biomedical Materials Research, 2004, 69B:73-78
[27] Fukase Y, Eanes D, Takagi S, et al. JDent Res, 1990, 69:1852
[28] Tenhuisen KS, et al. J Mater Sci:Mater In Med, 1996, 7:309-316
[29] LeGeros RZ1. Properties of osteoconductive biomaterials: calcium phosphates[J]. Clin Orthop, 2002, (395):812-815
[30] Ignjatovic N, Tomic S, DakicM, et al. Synthesis and properties of hydroxyapatite polyLactide composite biomaterials[J]. Biomaterials, 1999, 20 (2):809-816
[31] M iyamo to Y, lsh ikaw a K, Fukao H, et al. In vivo setting behaviour of fast-setting calcium phosphate cement[J]. Biomaterials, 1995, 16 (11):855-860
[32] Khairoun I, Boltong MG, Driessens F, et al. Effect of calcium on the compliance of an apatitic calcium phosphate bone cement [J], Biomaterials, 1997, (18): 1535-1539
[33] 王文波，陈中伟，陈统一，等．自固化磷酸钙人工骨的生物学安全性实验研究[J]．中国生物医学工程学报，2001，20(3)：193-199
[34] Costantino PD, Friedman CD, Jones K, et al. Hydroxyapatite cement Ⅰ:Basic chemistry and reconstruction of the eat frontal sinus[J]. Arch O to laryngol Head Neck Surg, 1991, 117:385
[35] Huiping Yuan YL. Tissue responses of calcium phospliate cement:a study in dogs[J]. Biomatedals, 2000, 21:1283-1290
[36] Kuboki Y, Takita H, Kobayashi D, et al. BMP2 induced osteogenesis on the surface hydroxyapalite with geometrically feasible and nonfeasible structures: topology of osteogenesis[J]. J Biomed Mater Res, 1998, 39:1902-1991
[37] Hulbert SF, Mordson SJ, Klawitter JJ. Tissue reaction to three ceramics of porous an non-porous structures[J]. J Biomed Mater Res, 1972, 6(5):374-379
[38] Lu JX, Flautre B, Anselme K, et al. Role of interconnections in porous bioceramics on bone recolonization in vitro and in vivo[J]. J Mater Sci:Mater med, 1999, 10:111-118
[39] Simon CG Jr, Khatri CA, Wight SA, et ai. Preliminary report on the biocompatibility of a moldable, resorbable, composite bone gratt consisting of calcium phosphate cement and poly(lactide-co-glyeolide) mierospheres[J]. J Ortho Res, 2002, 20:473-482
[40] Yoshikawa T SY, Ohgushi H, Tamai S, et al. Self setting hydroxyapatite cement as a carrier for bone-forming cells[J]. Bio-Medical Materials And Engineering, 1996, 6:345-351
[41] Hoekin HK, Xu JBQ, Shozo Takagi, et al. Synergistic reinforcement of in situ hardening calcium phosphate composite scaffole for bone tissue engineering[J]. Biomaterials, 2004, 25:1029-1037
[42] Xu HH EF, Giuseppetti AA. Reinforcement of a self-setting calcium phosphate cement with different fibers[J]. J Biomed Mater Res, 2000, 52:107-114
[43] Xu HH QJ, Takagi S, et al, Strong and macroporous calcium phosphate cement: effects of porosity and fiber reinforcement on mechanical properties[J]. J Biomed Mater Res, 2001, 57:457-466
[44] del Real RP, Wolke J GC, Vallet-Regi M, et al. A new method to produce macropores in calcium phosphate cements[J]. Biomaterials, 2002, 23:3673-3680
[45] del Real RP, Ooms E, Wolke JGC, et al, In vivo bone response to porous calcium phosphate cement[J]. J biomed Mater Res, 2003, 65A:30-36
[46] J.E.Barralet LG, T.Gaunt, A.J.Wfight, et al. Preparation of macroporous calcium phosphate cement tissue engineering scaffold[J]. Biomaterials, 2002, 23:3063-3072
[47] Constantz BR, Ison IC, Fulmer MT, et al, Science, 1995, 267(5205): 1796-1799
[48] Lew androw ski KU, Gresser JD,W ise DL, et al, Osteoconduct ivity of an injectable and bioresorable poly (p ropylene glyeo 12co2funrnarie acid) bone cement[J]. B iomaterials, 2000, 21(3):293-298.
[49] Hardouin P, Lemaitre J. New Injectable composites for bone replace2mentd[J]. Semin Musculoskelet Radiol, 1997, 1(2):319-324
[50] Takagi Shozo, Hirayama Satoshi, Sugawara Akiyoshi, Premixed calcium-phosphate cement pastes[J]. Journal of Biomedical Materials Research (Applied Biomaterials), 2003, 67:689-696
[51] Daculsi G, Rohanizadeh R, Weiss P, et al. Crystal polymer interaction with new injectable bone substitute; SEM and Hr TEM study[J]. J Biomed Mater Res, 2000, 50(1):1-7
[52] L. Leroux ZH, M, Freche, JL, Lacout, Effect of varous adjuvants (lactic acid, glycerol and chitosan) on the injectability of a calcium phosphate cement[J]. Bone, 1999, 25:31S-34S
[53] S.Takagi SH, A. Sugawara, L.C. Chow. Premixed calcium phosphate cement paste[J]. Six World Biomaterials Congress (USA), 2000, 1:19
[54] 李又欣，冯新德．高分子通报，1991(1)：19-26
[55] Otsuka M, Nakahigashi Y, Matsuda Y, et al. Effect of geometrical cement size on in vitro and in vivo indomethacin release from self-setting apatite cement[J]. Journal of Controlled Release, 1998, 52:281-289
[56] Otsuka M, Nakahigashi Y, Matsuda Y, et al. A novel skeletal drug delivery system using self-setting calcium phosphate cement 7:Effect of biologic factors on indomethacin release from the cement loaded on bovine bone[J]. J Pharmterials, 1995, 16(7):5227-5232
[57] Hamanishi C, Kitamoto K, Tanaka S, et al. J Biomed Mater Res, 1996, 33: 139-143
[58] Otsuka M, M atsuda Y, Suwa Y, et al. A novel skeletal drug delivery system using self-setting calcium phosphate cement: Physicochemical properties and drug release rate oftbe cement-containing indomethacin[J]. J Pharm Sci, 1994, 83(5):611
[59] Otsuka M, Matsuda Y, Suwa Y, et al. A novel skeletaldrug-delicery system using self-setting calcium phosphate cement: 3. Physicochemical properties and drug-releaserate of bovine insulin and bovine albumin[J]. J Pharm Sci, 1994, 83(2):255
[60] Otsuka M, Matsuda Y, Suwa Y, et al. A novel skeletal drug-delivery system using self2setting calcium phosphate cement: 4. Effects of the mixing solution volume on drug-release rate of heterogeneous aspirin21oad cement[J]. J Pharm Sci, 1994, 83(2):259
[61] Yu D, Wong J, M atsude Y, et al. Self-setting hydroxyapatitite cement: a novel skeletal drug-delivery system forantibiotics[J]. J Phrma Sci, 1992, 81(6):529
[62] 王传军，陈统一，张键，等．自固化磷酸钙人工骨(CPC)载药妥布霉素体外抗菌活性评价[J]．中国临床医学，11(5)：794-797
[63] Celeste A J, Iannazzi JA, Taylor RC, et al. Identification of transforming growth factor-beta family members present in bone-inductive protein purified from bovine bone[J]. Proc Natl Acad Sci USA, 1990, 87(24):9843-9847
[64] Sakou T. Bone morphogenetic proteins: from basic studies to clinical approaches[J]. Bone, 1998, 22(6):591-603
[65] Reddi AH, Cunningham NS. Initiation and promotion of bone differentiation by bone morphogenetic proteins[J]. J Bone Miner Res, 1993, 8:S499-502
[66] Ji X, Chen D, Xu C, et al. Patterns of gene expression associated with BMP-2-induced osteoblast and adipocyte differentiation of mesenchymal progenitor cell 3T3-F442A[J]. J Bone Miner Metab, 2000, 18:132-139
[67] Li G, Allen W, McHenry S, et al. Microvascular endothelial cells are chemotactic to rhBMP-2[J]. Trans Orthop Res Soc, 2001, 12(3):583-588
[68] Padley RA, Cobb CM, Killoy W J, et al. In vitro chemtactic response of osteoblast-like osteosaecoma cells to a partially purified protein extract of demineralized bone matrix[J]. J Periodont, 1991, 62:15-20
[69] Wozney JM. The bone morphogenetic protein family and ostcogenesis[J]. Mol Reprod Dev, 1992, 32:160-167
[70] Urit MD, Nilsson O, Rasmussen J, et al. Bone regeneration under the influence of a bone morphogenetic protein(BMP) beta tricalcium phosphate(α-TCP) composite in skull trephine defects in dogs[J]. Clin Orthop, 1987, 214:295-304
[71] Ohum K, Hamanishi C, Tanaka S, et al. Healing of segmantal bone defect in rats induced by a beta-TCP-MCPM cement combinated with rhBMP-2[J]. Biomed Mater Res, 1999, 44(2):168-175
[72] O hura K,Mamamishi C, Tnaka S, et al. The healing of segmental bone defects, induced by bioresorbable calcium phorphate cement combined with recombinated human bone morphogenetic protein-2[J]. Bioceramics, 1996, 9:247-250
[73] 孙明林，胡蕴玉，张瑞萍．磷酸钙骨水泥／骨形态发生蛋白复合人工骨修复骨缺损的实验研究[J]．现代康复，2001，5(5)：32-33
[74] Ouicheux J, Gauthier O, L aguado E, et al. Growth hormone-loaded macroporous calcium phosphate ceramic: in vitro biopharmaceutical characterizat ion and preliminary in vivo study[J]. Biomed Mater Res, 1998, 40(4):560-566
[75] Guicheux J, Kimakhe S, Heymann D, et al. Growth hormonest imulates the degradation of calcium phosphate biomaterial by human monocytes nacrophages in vitro[J]. BiomedM ater Res, 1998, 40(1):79-85
[76] Costantino PD, Friedman CD.Synthetic bone graft substitutes. O to laryngol Clin North Am, 1994, 27:1037
[77] Friedman CD, Costantino PD, Takagi S, et al. J Biomed Mater Res, 1998, 43(4):428-432
[78] Knaack D, Goad ME, Aiolova M, et al. J Biomed Mater Res, 1998, 43(4):399-409
[79] Hollinger JO, Brekke J, Gruskin E. Role of bone substitutes[J]. Clin Orthop, 1996, 324:55
[80] Lacout JL, Mejdoub E, Hamad M, Crystallization mechanisms of calcium phosphate cement for biological uses[J]. J Mater Sci, 1996, 7:371
[81] 杨志平，李建民，李昕等．磷酸钙骨水泥修复良性骨肿瘤骨缺损[J]．山东大学学报(医学版)，2003，41(4)：415-417
[82] Okada E, Maruyama Y, Hayashi A. Nasal augmentation using calcium phosphate cement[J]. Craniofac surg, 2004, 15(1): 102-105
[83] Kamerer DB, Hirsh BE, Syoderman CH, et al. Hydroxyapatite cement:A new method for achieving watertight closure in transtemp oral surgery[J]. Am J O to l, 1994, 15:47
[84] 翁雨来．磷酸三钙一次根管治疗的初步报告[J]．中华口腔医学杂志，1991，26：2
[85] Yoshikawa M, lnamoto T, Hakata T, et al. Apical canal sealing ability ofcalcium phosphate based cements[J]. J Osaka Dent Univ, 1996, 30(122): 12
[86] Sugawara A, Chow L C, Takagi S, et al. In vitro evaluation of the sealing ability of a calcium phosphate cement when used as a root canal sealer filler[J]. J ended, 1990, 16(4):162
[87] Tchaou WS, Turng BF, Minah GE, et al. Inhibition of pure culture of oral bacteria by root canal filling material[J]. Pediatr Dent, 1996, 18(7):444
[88] Goodell GG, Mork TO, Hurter JW, et al. Linear dye penetration of a calcium phosphate cement apical barrier[j]. J Ended, 1997, 23(3):174
[89] Miyamoto Y, Ishikaway K, Takechi M, et al. Basic properties of calcium phosphate cement containing atelocllagen in this liquid or powder phases[J]. Biomatedals, 1998, 19(729):707-715
[90] Hong CY, Lin SK, Kok SH, et al. Histologic reaction to a newly developed calaium phosphate cement implant in the periapcal and periodontal tissues[J]. J Formos Med Assoc, 1990, 89(4):297
[91] Hong YC, Wang T, Hong CY, et al. The pedapical tissue reaction to a calcium phosphate cement in the teeth of monkeys[J]. J Biomod mater Res, 1991, 25(4):485
[92] 宁江海，刘洪臣，毛克亚等．生物活性多肽修饰的碳磷酸钙骨水泥修复牙周骨缺损的实验研究[J]．华西口腔医学杂志，2003，38(6)：464-466
[93] 李善昌，苗波，魏良富．磷酸钙骨水泥与骨形成蛋白修复即刻种植牙骨缺损的实验研究[J]．口腔医学研究，2003，19(4)：255-257
[94] 黄辉，王建华．磷酸钙骨水泥修复髓室底穿孔渗露的实验研究[J]．临床口腔医学杂志，2002，18(1)：20-21
[95] 束红雷，蔡传敏，吴东．磷酸钙骨水泥复合盖髓剂用于活髓保存的临床研究[J]．口腔综合杂志，2001，17(1)：54-56
[96] Lim TH, Brebach GT, Rermer SM, et al. Biomechanical evaluation of an injectable calcium phosphate cement for vertebroplasty[J]. Spline, 2002, 27:1297-1302
[97] Verlaan JJ, van Helden WH, Oner FC, et al.Balloon vertebroplasty with calcium phosphate cement augmentation for direct restoration of traumatic thoracolumbar vertebral fractures[J]. Spline, 2002, 27:543-548
[98] 曾忠友，金才益，陆金荣等．椎弓根螺钉系统加自固化磷酸钙人工骨灌注治疗腰胸椎骨骨折[J]．中华创伤杂志，2001，17：284-286
[99] Yetkinler DN, Ladd AL, Poser RD, et al.Biomechanieal evaluation of fixation of intra-artieular fractures of the distal part of the radius in cadavera:Kirschaner wires coMPared with calcium phosphate bone cemnet[J].J Bone JointSurg(Am), 1999, 81: 391-399
[100] Hidaka N, Yamano Y, Kadoya Y, et al.Calcium phosphate bone cement for treatment of distal radius fractures:A preliminary report[J]. J Orthop Sci, 2002, 7:182-187
[101] Yetkinler DN, Mc Clellan RT, Reindel ES, et al.Biomechanical coMPared of conventional open reduction and internal fixation versus calcium phosphate cement coMPared of central depressed tibial plateau fracture[J]. J Orthop Trauma, 2001, 15:197-206
[102] Schildhaucr TA, Bauer TW, Josten C, et al.Open reduction and augmentation of internal fixation with an injectable skeletal cement for the treatment of complex calcaneal fractures[J]. J Orthop Trauma, 2000, 14:309-317
[103] Csizy M, BucKley RE, Fennell C, Benign calcaneal bone cyst and pathologic fracture-surgical treatment with injectable calcium phosphate bone cement(Norian):A case report[J]. Food Article Int, 2001, 22:507-510
[104] Eriksson F, Mattsson P, Larsson S. The effect of augmentation with resorbable or conventional bone cement on the holding strength for femoral neck fracture devices[J]. J Orthop Trauma, 2002, 16:302-310
[105] Yetkinler DN, Goodman SB, Reindel ES, et al. Mechanical evaluation of carbonated apaitecement in the fixation of unstable intertrochanteric fractures[J]. Acta Orthop scand, 2002, 73:157-164
[106] Elder S, Frankenburg E, Goulet J, et al.Biomechanical evaluation of calcium phosphate cement-augmented fixation of unstable intertrochanteric fractures[J]. J Or thop Trauma, 2000. 14:386-393