可注射性碳酸化羟基磷灰石骨水泥的相关研究
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摘要
目的
在碳酸化羟基磷灰石(Carbonated hydroxyapatite，CHA)水泥原位固化基础上进行改性研究，通过改变其流变学特性，达到具有良好注射性能的可注射性碳酸化羟基磷灰石(Injectable carbonated hydroxyapatite，ICHA)水泥，为骨科的微创治疗提供新方法：(1)制备ICHA水泥，完成理化性质的检测；(2)进行ICHA水泥的生物相容性评价：(3)探讨ICHA水泥在桡骨远端骨折应用的生物力学固定强度；(4)研究ICHA水泥在实验性大动物胫骨平台压缩性骨折中应用的力学稳定性、降解性能及成骨性能。
方法
1．ICHA水泥理化性质检测：制备ICHA水泥，在体外测定ICHA水泥的固化时间、固化强度、注射性能、抗稀散性、稠度、固化温度、成孔率等理化性质，通过扫描电镜、XRD和FTIR检测ICHA水泥的固化产物。
2．生物相容性评价：通过采用ICHA水泥浸提液和水泥试件与骨髓基质细胞共培养，MTT法测定细胞相对增殖率，进行细胞毒性反应分级，光镜和扫描电镜观察细胞生长形态和生长活性；水泥试件植入兔肌肉内，观察炎症反应和纤维包膜形成情况；进行ICHA水泥溶血和热原的检测等多种方法对ICHA的生物相容性进行评价。
3．ICHA水泥在人桡骨远端骨折应用的生物力学研究：采用人桡骨标本制备桡骨远端骨折模型，分别用克氏针、ICHA水泥、ICHA水泥联合克氏针进行固定，进行扭转实验和压缩实验。检测扭转刚度、最大扭矩、最大扭转角度、压缩刚度、压缩位移2mm时压缩强度和最大压缩强度，记录压缩实验
中国人民解放军军医进修学院博士论文
中文摘要
时挠骨远端骨折块的旋转角度。
4.ICHA水泥在羊胫骨平台压缩性骨折中的应用:制备羊双侧后肢外侧
胫骨平台压缩性骨折模型，压缩骨折复位后的骨缺损分别用ICHA水泥和自体
骨填充。术后3个月和6个月时取材，拍X光片，检测胫骨平台骨折块抗压
刚度，制备不脱钙切片，观察ICHA水泥和自体骨的吸收与成骨情况，进行骨
计量学静态参数与动态参数的检测。
结果
1.理化性质检测:ICHA水泥可原位固化，固化过程中不产热，初凝时
间和终凝时间与CHA水泥无明显差别，分别为gmin和15min，固化强度ld
时为ZOMPa，7d时可达高峰，平均为35MPa，成孔率较CHA水泥略有增加。
ICHA水泥的注射性能优异，可很轻松地由注射器中完全推出，注射能力系数
可达95%以上，而CHA水泥仅为70%，同时ICHA水泥具有非常好的抗稀散
能力，早期注入到蒸馏水中固化过程不受影响。固化过程中ICHA水泥在各个
时间点的稠度均较CHA水泥低，有显著性差异(P<0.001)，稠度一时间曲线变
化呈对数规律，早期稠度很低，随后迅速升高，至后期下降平缓。注射ICHA
水泥所需推力与注射器的直径、注射管道的长度成正比，注射器直径越大、
注射管道越长，注射所需推力越大。扫描电镜、X线衍射和傅立叶变换红外
分析显示ICHA水泥的固化产物仍为CHA，晶类细小，与天然骨类似。
2.生物相容性评价:ICHA水泥浸提液和试件与骨髓基质细胞共培养，
细胞生长形态良好，数量逐渐增加，细胞毒性反应为0一I级，基本无毒性。
浸提液的溶血率<0.05%，注入兔耳缘静脉后未引起发热反应。ICHA水泥试件
植入兔肌肉中观察24周，早期有淋巴细胞浸润，包膜形成，晚期淋巴减少或
消失，包膜稳定，无增厚趋势，未见有白细胞浸润。
中国人民解放军军医进修学院博士论文
中文摘要
3 .ICHA水泥在人挠骨远端骨折应用的生物力学研究:在扭转100范围以
内，ICHA水泥固定组、ICHA水泥克氏针联合固定组的扭转刚度、最大扭矩
均较克氏针固定组大(P<0.01)，而最大扭转角度则较小(P<0 .05)，为4一5o，
克氏针固定组为9.5“。压缩刚度、远端骨块在冠状面和矢状面的旋转角度三组
无明显差别(P>0.05)。压缩位移Zmm时的压缩强度和最大压缩强度ICHA水
泥固定组、ICHA水泥克氏针联合固定组均较克氏针组大，差异具有显著性
(P<0 .01)。
4.ICHA水泥在羊外侧胫骨平台压缩性骨折中的应用:大体观察发现3
个月和6个月两个时间点的自体骨组关节面出现塌陷的程度和数量均较骨水
泥组严重。X光片示自体骨组3个月时已基本愈合，6个月时完全愈合，骨水
泥组3个月时水泥被吸收分割成几块，边缘模糊，6个月时大部分吸收殆尽。
胫骨平台骨折块压缩刚度两组在两个时间点无明显差异。组织学观察与骨计
量参数表明，ICHA水泥组有大量的成骨细胞和破骨细胞，较自体骨组明显增
多，骨水泥大部被吸收，3个月时为43.8%，6个月时仅剩29.9%。ICHA水泥
表面有新生骨小梁生成，两者之间结合紧密，骨水泥吸收边缘未见任何纤维
组织，也未见任何炎症细胞，骨水泥吸收速度与新骨生成速度基本持平。
结论
1.制备了可注射性碳酸化轻基磷灰石(ICHA)骨水泥，该材料注射性能
良好，可作为骨组织替代材料进行骨缺损的微创治疗。
2.ICHA水泥化学成分与天然骨无机相类似，具有与松质骨相当的抗压
强度，适宜的固化时间(可调)，良好的抗稀散性，符合临床应用要求。
.ICHA水泥具有良好的生物相容性。
.ICHA水泥用于挠骨远端骨折和胫骨平台压缩性骨性具有相当好的固
中国人民解放军军医进修学院博
Purpose
By adding additives in carbonated hydroxyapatite (CHA) cement to increase its rheology to prepare injectable carbonated hydroxyapatite (ICHA) cement. (1) Test the physicochemistry characteristics of ICHA cement. (2) Evaluate the biocompatibility of ICHA cement. (3) Biomechanical appreciation of ICHA cement used in distal radius fracture. (4) Study the mechanical stability, degradation and bone formation ability of ICHA cement used in goat lateral tibial plateau compression fracture.
Materials and Methods
Physicochemical examination of ICHA cement: Physicochemical characteristics of setting time, compression strength, injectability, anti-washout, consistency, setting temperature and porosity were evaluated in vitro. Product of ICHA cement were tested by scanning electron microscope (SEM), X-ray diffraction and Fouriery transform infrared analysis.
Biocompatibility evaluation of ICHA cement: Marrow stroma cells were cultured with ICHA cement extracting solution or cement specimen. Cell relative growth rate was measured by MTT methods. Cement specimen were implanted in rabbit muscle to evaluate inflammation reaction. Hemolytic test and pyrogen test were performed.
Biomechanical evaluation of ICHA cement in distal radius fracture: human distal radius fracture models were made and fixed with Kirschner wire, ICHA
cement or ICHA cement combined with Kirschner wire. Torsion and compression test were performed. Torsion rigidity, maximum torque, maximum torsion angle, compression rigidity, compression strength of 2mm displacement, maximum compression strength and rotational angle of distal fragment was recorded.
Application of ICHA cement in goat lateral tibial plateau compression fracture: Bilateral tibial plateau compression fractures were made in ten goats. The fractures were reduced and fixed with ICHA cement or autograft. Specimens of tibial plateau were retrieved 3 months and 6 months after operation. X-ray and tibia plateau compression rigidity were tested. Degradation of ICHA cement and new bone formation were evaluated in nondecalcified section.
Results
Physicochemical property examination of ICHA cement: ICHA cement set in situ without heat emission under room temperature. Its initial setting time is 9 min and final setting time is 15 min, which is the same with CHA cement. The compression strength is about 20 MPa on 1 day and reach maximum of 35 MPa on 7 days. Porosity increase a little compared with CHA cement. Compared with CHA cement, ICHA cement has excellent injectability. The injectability coefficient is more than 95% for ICHA, and only 70% for CHA. At the same time, ICHA cement is a kind of anti-washout cement. It can not be washed out if the paste is immersed in distilled waster immediately after mixing. ICHA cement has lower consistency compare with CHA cement during setting process (P<0.01). The push force when injecting ICHA cement from syringe is proportion to syringe diameter and catheter length. The product of ICHA is still CHA as show by SEM, XRD and FITR.
Biocompatibility evaluation of ICHA cement: Marrow stroma cells grow well with toxicity rank zero to I when cocultured with ICHA cement extracting solution or cement specimen. The hemolysis rate is no more than 0.05% and no pyrogenetic reaction after injecting extracting solution into vein of rabbit. ICHA cement specimens were implanted in rabbit muscle for 24 weeks. Lymphocytes infiltrating and fibular capsule formation can be seen in the early stage and lymphocytes decrease or disappeared and capsule became stability in the late stage.
Biomechanical evaluation of ICHA cement in distal radius fracture: At the range of no more than 10 degree, the torsion rigidity and maximum torque is higher in ICHA group and ICHA combined with Kirschner wire group (P<0.01) than Kirschner wire group. The maximum torsion angle is lower in ICHA group and ICHA combined with Kirschner wire group with 4~5 degree than Kirschner wire group with 9.5 degree (P<0.05). Compression rigidity, distal fragment rotation angle in coronal or sagittal plate has no
在碳酸化羟基磷灰石(Carbonated hydroxyapatite，CHA)水泥原位固化基础上进行改性研究，通过改变其流变学特性，达到具有良好注射性能的可注射性碳酸化羟基磷灰石(Injectable carbonated hydroxyapatite，ICHA)水泥，为骨科的微创治疗提供新方法：(1)制备ICHA水泥，完成理化性质的检测；(2)进行ICHA水泥的生物相容性评价：(3)探讨ICHA水泥在桡骨远端骨折应用的生物力学固定强度；(4)研究ICHA水泥在实验性大动物胫骨平台压缩性骨折中应用的力学稳定性、降解性能及成骨性能。
方法
1．ICHA水泥理化性质检测：制备ICHA水泥，在体外测定ICHA水泥的固化时间、固化强度、注射性能、抗稀散性、稠度、固化温度、成孔率等理化性质，通过扫描电镜、XRD和FTIR检测ICHA水泥的固化产物。
2．生物相容性评价：通过采用ICHA水泥浸提液和水泥试件与骨髓基质细胞共培养，MTT法测定细胞相对增殖率，进行细胞毒性反应分级，光镜和扫描电镜观察细胞生长形态和生长活性；水泥试件植入兔肌肉内，观察炎症反应和纤维包膜形成情况；进行ICHA水泥溶血和热原的检测等多种方法对ICHA的生物相容性进行评价。
3．ICHA水泥在人桡骨远端骨折应用的生物力学研究：采用人桡骨标本制备桡骨远端骨折模型，分别用克氏针、ICHA水泥、ICHA水泥联合克氏针进行固定，进行扭转实验和压缩实验。检测扭转刚度、最大扭矩、最大扭转角度、压缩刚度、压缩位移2mm时压缩强度和最大压缩强度，记录压缩实验
中国人民解放军军医进修学院博士论文
中文摘要
时挠骨远端骨折块的旋转角度。
4.ICHA水泥在羊胫骨平台压缩性骨折中的应用:制备羊双侧后肢外侧
胫骨平台压缩性骨折模型，压缩骨折复位后的骨缺损分别用ICHA水泥和自体
骨填充。术后3个月和6个月时取材，拍X光片，检测胫骨平台骨折块抗压
刚度，制备不脱钙切片，观察ICHA水泥和自体骨的吸收与成骨情况，进行骨
计量学静态参数与动态参数的检测。
结果
1.理化性质检测:ICHA水泥可原位固化，固化过程中不产热，初凝时
间和终凝时间与CHA水泥无明显差别，分别为gmin和15min，固化强度ld
时为ZOMPa，7d时可达高峰，平均为35MPa，成孔率较CHA水泥略有增加。
ICHA水泥的注射性能优异，可很轻松地由注射器中完全推出，注射能力系数
可达95%以上，而CHA水泥仅为70%，同时ICHA水泥具有非常好的抗稀散
能力，早期注入到蒸馏水中固化过程不受影响。固化过程中ICHA水泥在各个
时间点的稠度均较CHA水泥低，有显著性差异(P<0.001)，稠度一时间曲线变
化呈对数规律，早期稠度很低，随后迅速升高，至后期下降平缓。注射ICHA
水泥所需推力与注射器的直径、注射管道的长度成正比，注射器直径越大、
注射管道越长，注射所需推力越大。扫描电镜、X线衍射和傅立叶变换红外
分析显示ICHA水泥的固化产物仍为CHA，晶类细小，与天然骨类似。
2.生物相容性评价:ICHA水泥浸提液和试件与骨髓基质细胞共培养，
细胞生长形态良好，数量逐渐增加，细胞毒性反应为0一I级，基本无毒性。
浸提液的溶血率<0.05%，注入兔耳缘静脉后未引起发热反应。ICHA水泥试件
植入兔肌肉中观察24周，早期有淋巴细胞浸润，包膜形成，晚期淋巴减少或
消失，包膜稳定，无增厚趋势，未见有白细胞浸润。
中国人民解放军军医进修学院博士论文
中文摘要
3 .ICHA水泥在人挠骨远端骨折应用的生物力学研究:在扭转100范围以
内，ICHA水泥固定组、ICHA水泥克氏针联合固定组的扭转刚度、最大扭矩
均较克氏针固定组大(P<0.01)，而最大扭转角度则较小(P<0 .05)，为4一5o，
克氏针固定组为9.5“。压缩刚度、远端骨块在冠状面和矢状面的旋转角度三组
无明显差别(P>0.05)。压缩位移Zmm时的压缩强度和最大压缩强度ICHA水
泥固定组、ICHA水泥克氏针联合固定组均较克氏针组大，差异具有显著性
(P<0 .01)。
4.ICHA水泥在羊外侧胫骨平台压缩性骨折中的应用:大体观察发现3
个月和6个月两个时间点的自体骨组关节面出现塌陷的程度和数量均较骨水
泥组严重。X光片示自体骨组3个月时已基本愈合，6个月时完全愈合，骨水
泥组3个月时水泥被吸收分割成几块，边缘模糊，6个月时大部分吸收殆尽。
胫骨平台骨折块压缩刚度两组在两个时间点无明显差异。组织学观察与骨计
量参数表明，ICHA水泥组有大量的成骨细胞和破骨细胞，较自体骨组明显增
多，骨水泥大部被吸收，3个月时为43.8%，6个月时仅剩29.9%。ICHA水泥
表面有新生骨小梁生成，两者之间结合紧密，骨水泥吸收边缘未见任何纤维
组织，也未见任何炎症细胞，骨水泥吸收速度与新骨生成速度基本持平。
结论
1.制备了可注射性碳酸化轻基磷灰石(ICHA)骨水泥，该材料注射性能
良好，可作为骨组织替代材料进行骨缺损的微创治疗。
2.ICHA水泥化学成分与天然骨无机相类似，具有与松质骨相当的抗压
强度，适宜的固化时间(可调)，良好的抗稀散性，符合临床应用要求。
.ICHA水泥具有良好的生物相容性。
.ICHA水泥用于挠骨远端骨折和胫骨平台压缩性骨性具有相当好的固
中国人民解放军军医进修学院博
Purpose
By adding additives in carbonated hydroxyapatite (CHA) cement to increase its rheology to prepare injectable carbonated hydroxyapatite (ICHA) cement. (1) Test the physicochemistry characteristics of ICHA cement. (2) Evaluate the biocompatibility of ICHA cement. (3) Biomechanical appreciation of ICHA cement used in distal radius fracture. (4) Study the mechanical stability, degradation and bone formation ability of ICHA cement used in goat lateral tibial plateau compression fracture.
Materials and Methods
Physicochemical examination of ICHA cement: Physicochemical characteristics of setting time, compression strength, injectability, anti-washout, consistency, setting temperature and porosity were evaluated in vitro. Product of ICHA cement were tested by scanning electron microscope (SEM), X-ray diffraction and Fouriery transform infrared analysis.
Biocompatibility evaluation of ICHA cement: Marrow stroma cells were cultured with ICHA cement extracting solution or cement specimen. Cell relative growth rate was measured by MTT methods. Cement specimen were implanted in rabbit muscle to evaluate inflammation reaction. Hemolytic test and pyrogen test were performed.
Biomechanical evaluation of ICHA cement in distal radius fracture: human distal radius fracture models were made and fixed with Kirschner wire, ICHA
cement or ICHA cement combined with Kirschner wire. Torsion and compression test were performed. Torsion rigidity, maximum torque, maximum torsion angle, compression rigidity, compression strength of 2mm displacement, maximum compression strength and rotational angle of distal fragment was recorded.
Application of ICHA cement in goat lateral tibial plateau compression fracture: Bilateral tibial plateau compression fractures were made in ten goats. The fractures were reduced and fixed with ICHA cement or autograft. Specimens of tibial plateau were retrieved 3 months and 6 months after operation. X-ray and tibia plateau compression rigidity were tested. Degradation of ICHA cement and new bone formation were evaluated in nondecalcified section.
Results
Physicochemical property examination of ICHA cement: ICHA cement set in situ without heat emission under room temperature. Its initial setting time is 9 min and final setting time is 15 min, which is the same with CHA cement. The compression strength is about 20 MPa on 1 day and reach maximum of 35 MPa on 7 days. Porosity increase a little compared with CHA cement. Compared with CHA cement, ICHA cement has excellent injectability. The injectability coefficient is more than 95% for ICHA, and only 70% for CHA. At the same time, ICHA cement is a kind of anti-washout cement. It can not be washed out if the paste is immersed in distilled waster immediately after mixing. ICHA cement has lower consistency compare with CHA cement during setting process (P<0.01). The push force when injecting ICHA cement from syringe is proportion to syringe diameter and catheter length. The product of ICHA is still CHA as show by SEM, XRD and FITR.
Biocompatibility evaluation of ICHA cement: Marrow stroma cells grow well with toxicity rank zero to I when cocultured with ICHA cement extracting solution or cement specimen. The hemolysis rate is no more than 0.05% and no pyrogenetic reaction after injecting extracting solution into vein of rabbit. ICHA cement specimens were implanted in rabbit muscle for 24 weeks. Lymphocytes infiltrating and fibular capsule formation can be seen in the early stage and lymphocytes decrease or disappeared and capsule became stability in the late stage.
Biomechanical evaluation of ICHA cement in distal radius fracture: At the range of no more than 10 degree, the torsion rigidity and maximum torque is higher in ICHA group and ICHA combined with Kirschner wire group (P<0.01) than Kirschner wire group. The maximum torsion angle is lower in ICHA group and ICHA combined with Kirschner wire group with 4~5 degree than Kirschner wire group with 9.5 degree (P<0.05). Compression rigidity, distal fragment rotation angle in coronal or sagittal plate has no
引文
1. Ambrosio AM, Sahota JS, Khan Yet al. A novel amorphous calcium phosphate polymer ceramic for bone repair: Ⅰ. Synthesis and characterization. J Biomed Mater Res. 2001, 58(3): 295-301.
2．高芳坤，于普林，郑宏等．北京城乡几种常见老年病流行病学调查．中华流行病学杂志，1998，19(3)：159-161．
3．李宁华，区品中，朱汉民，等．中国中老年人群骨折患病率调查[J]．中国临床康复．2003，7(8)：1284-5．
4．王静思 栾荣生 李幼平等．成都城乡几种常见老年病流行病学调查．中国慢性病预防与控制．1999，7(6)：267-269．
5．朱汉民，王赞舜，杨俭英等．老年人骨折的流行病学及其对生命质量的影响．中华老年医学杂志，1993，12(3)：168-172．
6. Larsson S, Bauer TW. Use of injectable calcium phosphate cement for fracture fixation: a review. Clin Orthop. 2002, 395: 23-32.
7. Constantz BR, Ison IC, Fulmer MT, Poser RD, Smith ST, Van Wagoner M, Ross J, Goldstein SA, Jupiter JB, Rosenthal DI. Skeletal repair by in situ formation of the mineral phase of bone. Science, 1995, 267: 1796-1799.
8. Khairoun I, Boltong MG, Driessens FCM, Planell JA. Some factors controlling the injectability of calcium phosphate bone cements. J Mater Sci Mater Med. 1998, 9: 425-428.
9. Ginebra MP, Rilliard A, Fernandez E, Elvira C, Roman JS, Planell JA. Mechanical and rheological improvement of a calcium phosphate cement by the addition of a polymeric drug. J Biomed Mater Res 2001, 57(1): 113-8.
10. El Briak H, Durand D, Nurit J, Munier S, Pauvert B, Boudeville P. Study of a hydraulic dicalcium phosphate dihydrate/calcium oxide-based cement for dental applications. J Biomed Mater Res 2002;63(4):447-53.
11. Becker TA, Kipke DR. Flow properties of liquid calcium alginate polymer injected through medical microcatheters for endovascular embolization. J Biomed Mater Res 2002; 61(4): 533-540.
12. Khairoun I, Magne D, Gauthier O, Bouler JM, Aguado E, Daculsi G, Weiss P.
In vitro characterization and in vivo properties of a carbonated apatite bone cement. J Biomed Mater Res 2002; 60(4):633-42.
13. Leroux L, Hatim Z, Freche M, Lacout JL. Effects of various adjuvants(lactic acid, glycerol, and chitosan)on the injectability of a calcium phosphate cement. Bone 1999; 25(2 Suppl): 31S-34S.
14. Sarda S, Fernandez E, Nilsson M, Balcells M, Planell JA. Kinetic study of citric acid influence on calcium phosphate bone cements as water-reducing agent. J Biomed Mater Res 2002; 61(4): 653-9.
15. Khairoun I, Boltong MG; Driessens FC, Planell JA Effect of calcium carbonate on the compliance of an apatitic calcium phosphate bone cement. Biomaterials. 1997, 18(23): 1535-9.
16. Khairoun I, Boltong MG, Driessens FC, Planell JA. Effect of calcium carbonate on clinical compliance of apatitic calcium phosphate bone cement. J Biomed Mater Res. 1997 38(4):356-60.
17. Van Landuyt P, Peter B, Beluze L, Lemaitre J. Reinforcement of osteosynthesis screws with brushite cement. Bone 1999; 25(2 Suppl):95S-98S.
18. Cherng A, Takagi S, Chow C. Effects of hydroxypropyl methylcellulose and other gelling agents on the handling properties of calcium phosphate cement. J Biomed Mater Res 1997; 35(2):273-77.
19. Takechi M, Miyamoto Y, Ishikawa K, Nagayama M, Kon M, Asaoka K, Suzuki K. Effects of added antibiotics on the basic properties of anti-washout-type fast-setting calcium phosphate cement. J Biomed Mater Res. 1998, 39(2): 308-16.
20. Ishikawa K, Miyamoto Y, Kon M, Nagayama M, Asaoke K. Non-decay type fast-setting calcium phosphate cement: composite with sodium alginate. Biomaterials. 1995, 16(7): 527-532.
21. Lee RW, Volz RG, Sheridan D. The role of fixation and bone quality on the mechanical stability of tibial knee components. Clin Orthop Rel Res. 1991, 273: 177-83.
22. Fernandez E, Gil F, Ginerbra MP et al. Calcium phosphate bone cements for clinical applications: Part Ⅱ: precipitation formation during setting reactions. J Mater Sci Mater Med. 1999, 10: 177-183.
23. Miyamoto Y, Ishikawa K, Takechi M, Yuasa M, Kon M, Nagayama M, Asaoka K. Non-decay type fast-setting calcium phosphate cement: setting behaviour in calf serum and its tissue response. Biomaterials. 1996, 17(14): 1429-1435.
24. Khairoun I, Driessens FC, Boltong MG, Planell JA, Wenz R. Addition of cohesion promotors to calcium phosphate cements. Biomaterials. 1999, 20(4): 393-8.
25. Driessens FCM, Boltong MG, Bermudez O, Planell JA. Formulation and setting times of some calcium orthophosphate cements: a plot study.J. Mater. Sci. Mater. Med. 1993, 4:503-508.
26. Liu C, Wang W, Shen W, Chen Tongyi, Hu L, Chert Z. Evaluation of the biocompatibility of a noceramic hydroxyapatite. J Endodontics. 1997, 23(8): 490-493.
27. Li Y W, Leong JC, Lu WW, Luk KD, Cheung KM, Chiu KY, Chow SP. A novel injectable bioactive bone cement for spinal surgery: a developmental and preclinical study. J Biomed Mater Res. 2000, 52(1): 164-70.
28. Keating JF, Hajducka CL, Harper J. Minimal intemal fixation and calcium-phosphate cement in the treatment of fractures of the tibial plateau. A pilot study. J Bone Joint Surg Br. 2003, 85(1):68-73.
29. Kopylov P, Runnqvist K, Jonsson K, Aspenberg P. Norian SRS versus external fixation in redisplaced distal radial fractures. A randomized study in 40 patients. Acta Orthop Scand 1999 Feb;70(1): 1-5.
30. Higgins TF, Dodds SD, Wolfe SW. A biomechanical analysis of fixation of intra-articular distal radial fractures with calcium-phosphate bone cement. J Bone Joint Surg Am. 2002 Sep;84-A(9): 1579-86.
31. Yetkinler DN, Ladd AL, Poser RD, Constantz BR, Carter AD, California C. Biomechanical evaluation of fixation of intra-articular fractures of the distal part of the radius in cadavera: Kirschner wires compared with calcium-phosphate bone cement. J Bone Joint Surg Am. 1999, 81(3):391-9.
32. Wolfe SW, Lorenze MD, Austin G, Swigart CR, Panjabi MM. Load-displacement behavior in a distal radial fracture model. J Bone Joint Surg Am. 1999, 81(1): 53-59.
33. Wolfe SW, Swigart CR, Grauer J, Slade Ⅲ JF, Panjabi MM. Augmented external fixation of distal radius fractures: a biomechanical analysis. J Hand
Surg. 1998, 23A: 127-134.
34. Wolfe SW, Austin G, Lorenze M, Swighart CR, Panjabi MM. A biomechanical comparison of different wrist external fixators with and without K-wire augmentation. J Hand Surg Am. 1999, 24: 516-524.
35. Naidu SH, Capo JT, Moulton M, Ciccone Ⅱ W, Radin A, Hershey. Percutaneous pinning of distal radius fractures: a biomechanical study. J Hand Surg. 1997, 22A: 252-257.
36. Saeki Y, Hashizume H, Nagoshi M, Tanaka H, Inoue H. Mechanical strength of intramedullary pinning and transfragmental kirschner wire fixation for colles' fractures. J Hand Surg Br. 2001, 26B: 550-555.
37. Kopylov P, Jonsson K, Thorngren KG, Aspenberg P. Injectable calcium phosphate in the treatment of distal radial fractures. J Hand Surg. 1996, 21B(6): 768-71.
38. Goulet JA, Senunas LE, Desilva GL, Greenfield ML. Autogenous iliac crest bone graft, complications and functional assessment. Clin Orthop. 1997, 339: 76-81
39. Mjberg B, Pettersson H, Rosenqvist R et al. Bone cement, thermal injury and the radiolucent zone. Acta Orthopaedica Scandinavica. 1984, 55: 597-600.
40. Jeyam M, Andrew JG, Muir LTSW, Mcgovern A. Controlled trial of distal radial fractures treated with a resorbable bone mineral substitute. J Hand Surg. 2002, 27B(2): 146-49.
41. Sanchez-Sotelo J, Munuera L, Madero R. Treatment of fractures of the distal radius with a remodellable bone cement: a prospective, randomised study using Norian SRS. J Bone Joint Surg Br, 2000; 82-B(6): 856-63.
42. Zimmermann R, Gabl M, Lutz M, Angermann P, Gschwentner M, Pechlaner S. Injectable calcium phosphate bone cement Norian SRS for the treatment of intra-articular compression fractures of the distal radius in osteoporotic women. Arch Orthop Trauma Surg, 2003; 123(1):22-7.
43. Schatzker J, McBroom R, Bruce D. The tibial plateau fracture. The Toronto experience 1968-1975. Clin Orthop. 1979, 138: 94-104.
44. Yetkinler DN, McClellan RT, Reindel ES, Carter D, Poser RD. Biomechanical comparison of conventional open reduction and internal
fixation versus calcium phosphate cement fixation of a central depressed tibial plateau fracture. J Orthop Trauma. 2001, 15(3): 197-206.
45. Keating J, Hajducka C. The use of Norian SRS and minimal internal fixation in the management of tibial plateau fractures. Trans Orthop Trauma Assoc. 1999, 15: 411.
46. Horstmann WG, Verheyen CC, Leemans R. An injectable calcium phosphate cement as a bone-graft substitute in the treatment of displaced lateral tibial plateau fractures. Injury. 2003, 34(2): 141-4.
47. Lobenhoffer P, Gerich T, Witte F, Tscheme H. Use of an injectable calcium phosphate bone cement in the treatment of tibial plateau fractures: a prospective study of twenty-six cases with twenty-month mean follow-up. J Orthop Trauma. 2002, 16(3): 143-9.
48. Frankenburg EP, Goldstein SA, Bauer TW, Harris SA, Poser RD. Biomechanical and histological evaluation of a calcium phosphate cement. J Bone Joint Surg Am. 1998, 80(8): 1112-24.
49. Ooms EM, Wolke JG, van der Waerden JP, Jansen JA. Trabecular bone response to injectable calcium phosphate(Ca-P)cement. J Biomed Mater Res. 2002, 61(1): 9-18.
50. Welch RD, Zhang H, Bronson DG.. Experimental tibial plateau fractures augmented with calcium phosphate cement or autologous bone graft. J Bone Joint Surg Am. 2003, 85-A(2): 222-31.
51. Parfitt AM. Osteonal and hemi-osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem. 1994, 55(3): 273-86.
52. Brown WE, Chow LC. A new calcium phosphate setting cement. J Dent Res. 1983, 62: 672.
53. Bermudez O, Boltong MG Driessens FCM, Planell JA. Compressive strength and diametral tensile strength of some calcium-orthophosphate cements: a pilot study. J. Mater. Sci. Mater. Med. 1993, 4: 389-393.
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6. Larsson S, Bauer TW. Use of injectable calcium phosphate cement for fracture fixation: a review. Clin Orthop. 2002, 395: 23-32.
7. Constantz BR, Ison IC, Fulmer MT, Poser RD, Smith ST, Van Wagoner M, Ross J, Goldstein SA, Jupiter JB, Rosenthal DI. Skeletal repair by in situ formation of the mineral phase of bone. Science, 1995, 267: 1796-1799.
8. Khairoun I, Boltong MG, Driessens FCM, Planell JA. Some factors controlling the injectability of calcium phosphate bone cements. J Mater Sci Mater Med. 1998, 9: 425-428.
9. Ginebra MP, Rilliard A, Fernandez E, Elvira C, Roman JS, Planell JA. Mechanical and rheological improvement of a calcium phosphate cement by the addition of a polymeric drug. J Biomed Mater Res 2001, 57(1): 113-8.
10. El Briak H, Durand D, Nurit J, Munier S, Pauvert B, Boudeville P. Study of a hydraulic dicalcium phosphate dihydrate/calcium oxide-based cement for dental applications. J Biomed Mater Res 2002;63(4):447-53.
11. Becker TA, Kipke DR. Flow properties of liquid calcium alginate polymer injected through medical microcatheters for endovascular embolization. J Biomed Mater Res 2002; 61(4): 533-540.
12. Khairoun I, Magne D, Gauthier O, Bouler JM, Aguado E, Daculsi G, Weiss P.
In vitro characterization and in vivo properties of a carbonated apatite bone cement. J Biomed Mater Res 2002; 60(4):633-42.
13. Leroux L, Hatim Z, Freche M, Lacout JL. Effects of various adjuvants(lactic acid, glycerol, and chitosan)on the injectability of a calcium phosphate cement. Bone 1999; 25(2 Suppl): 31S-34S.
14. Sarda S, Fernandez E, Nilsson M, Balcells M, Planell JA. Kinetic study of citric acid influence on calcium phosphate bone cements as water-reducing agent. J Biomed Mater Res 2002; 61(4): 653-9.
15. Khairoun I, Boltong MG; Driessens FC, Planell JA Effect of calcium carbonate on the compliance of an apatitic calcium phosphate bone cement. Biomaterials. 1997, 18(23): 1535-9.
16. Khairoun I, Boltong MG, Driessens FC, Planell JA. Effect of calcium carbonate on clinical compliance of apatitic calcium phosphate bone cement. J Biomed Mater Res. 1997 38(4):356-60.
17. Van Landuyt P, Peter B, Beluze L, Lemaitre J. Reinforcement of osteosynthesis screws with brushite cement. Bone 1999; 25(2 Suppl):95S-98S.
18. Cherng A, Takagi S, Chow C. Effects of hydroxypropyl methylcellulose and other gelling agents on the handling properties of calcium phosphate cement. J Biomed Mater Res 1997; 35(2):273-77.
19. Takechi M, Miyamoto Y, Ishikawa K, Nagayama M, Kon M, Asaoka K, Suzuki K. Effects of added antibiotics on the basic properties of anti-washout-type fast-setting calcium phosphate cement. J Biomed Mater Res. 1998, 39(2): 308-16.
20. Ishikawa K, Miyamoto Y, Kon M, Nagayama M, Asaoke K. Non-decay type fast-setting calcium phosphate cement: composite with sodium alginate. Biomaterials. 1995, 16(7): 527-532.
21. Lee RW, Volz RG, Sheridan D. The role of fixation and bone quality on the mechanical stability of tibial knee components. Clin Orthop Rel Res. 1991, 273: 177-83.
22. Fernandez E, Gil F, Ginerbra MP et al. Calcium phosphate bone cements for clinical applications: Part Ⅱ: precipitation formation during setting reactions. J Mater Sci Mater Med. 1999, 10: 177-183.
23. Miyamoto Y, Ishikawa K, Takechi M, Yuasa M, Kon M, Nagayama M, Asaoka K. Non-decay type fast-setting calcium phosphate cement: setting behaviour in calf serum and its tissue response. Biomaterials. 1996, 17(14): 1429-1435.
24. Khairoun I, Driessens FC, Boltong MG, Planell JA, Wenz R. Addition of cohesion promotors to calcium phosphate cements. Biomaterials. 1999, 20(4): 393-8.
25. Driessens FCM, Boltong MG, Bermudez O, Planell JA. Formulation and setting times of some calcium orthophosphate cements: a plot study.J. Mater. Sci. Mater. Med. 1993, 4:503-508.
26. Liu C, Wang W, Shen W, Chen Tongyi, Hu L, Chert Z. Evaluation of the biocompatibility of a noceramic hydroxyapatite. J Endodontics. 1997, 23(8): 490-493.
27. Li Y W, Leong JC, Lu WW, Luk KD, Cheung KM, Chiu KY, Chow SP. A novel injectable bioactive bone cement for spinal surgery: a developmental and preclinical study. J Biomed Mater Res. 2000, 52(1): 164-70.
28. Keating JF, Hajducka CL, Harper J. Minimal intemal fixation and calcium-phosphate cement in the treatment of fractures of the tibial plateau. A pilot study. J Bone Joint Surg Br. 2003, 85(1):68-73.
29. Kopylov P, Runnqvist K, Jonsson K, Aspenberg P. Norian SRS versus external fixation in redisplaced distal radial fractures. A randomized study in 40 patients. Acta Orthop Scand 1999 Feb;70(1): 1-5.
30. Higgins TF, Dodds SD, Wolfe SW. A biomechanical analysis of fixation of intra-articular distal radial fractures with calcium-phosphate bone cement. J Bone Joint Surg Am. 2002 Sep;84-A(9): 1579-86.
31. Yetkinler DN, Ladd AL, Poser RD, Constantz BR, Carter AD, California C. Biomechanical evaluation of fixation of intra-articular fractures of the distal part of the radius in cadavera: Kirschner wires compared with calcium-phosphate bone cement. J Bone Joint Surg Am. 1999, 81(3):391-9.
32. Wolfe SW, Lorenze MD, Austin G, Swigart CR, Panjabi MM. Load-displacement behavior in a distal radial fracture model. J Bone Joint Surg Am. 1999, 81(1): 53-59.
33. Wolfe SW, Swigart CR, Grauer J, Slade Ⅲ JF, Panjabi MM. Augmented external fixation of distal radius fractures: a biomechanical analysis. J Hand
Surg. 1998, 23A: 127-134.
34. Wolfe SW, Austin G, Lorenze M, Swighart CR, Panjabi MM. A biomechanical comparison of different wrist external fixators with and without K-wire augmentation. J Hand Surg Am. 1999, 24: 516-524.
35. Naidu SH, Capo JT, Moulton M, Ciccone Ⅱ W, Radin A, Hershey. Percutaneous pinning of distal radius fractures: a biomechanical study. J Hand Surg. 1997, 22A: 252-257.
36. Saeki Y, Hashizume H, Nagoshi M, Tanaka H, Inoue H. Mechanical strength of intramedullary pinning and transfragmental kirschner wire fixation for colles' fractures. J Hand Surg Br. 2001, 26B: 550-555.
37. Kopylov P, Jonsson K, Thorngren KG, Aspenberg P. Injectable calcium phosphate in the treatment of distal radial fractures. J Hand Surg. 1996, 21B(6): 768-71.
38. Goulet JA, Senunas LE, Desilva GL, Greenfield ML. Autogenous iliac crest bone graft, complications and functional assessment. Clin Orthop. 1997, 339: 76-81
39. Mjberg B, Pettersson H, Rosenqvist R et al. Bone cement, thermal injury and the radiolucent zone. Acta Orthopaedica Scandinavica. 1984, 55: 597-600.
40. Jeyam M, Andrew JG, Muir LTSW, Mcgovern A. Controlled trial of distal radial fractures treated with a resorbable bone mineral substitute. J Hand Surg. 2002, 27B(2): 146-49.
41. Sanchez-Sotelo J, Munuera L, Madero R. Treatment of fractures of the distal radius with a remodellable bone cement: a prospective, randomised study using Norian SRS. J Bone Joint Surg Br, 2000; 82-B(6): 856-63.
42. Zimmermann R, Gabl M, Lutz M, Angermann P, Gschwentner M, Pechlaner S. Injectable calcium phosphate bone cement Norian SRS for the treatment of intra-articular compression fractures of the distal radius in osteoporotic women. Arch Orthop Trauma Surg, 2003; 123(1):22-7.
43. Schatzker J, McBroom R, Bruce D. The tibial plateau fracture. The Toronto experience 1968-1975. Clin Orthop. 1979, 138: 94-104.
44. Yetkinler DN, McClellan RT, Reindel ES, Carter D, Poser RD. Biomechanical comparison of conventional open reduction and internal
fixation versus calcium phosphate cement fixation of a central depressed tibial plateau fracture. J Orthop Trauma. 2001, 15(3): 197-206.
45. Keating J, Hajducka C. The use of Norian SRS and minimal internal fixation in the management of tibial plateau fractures. Trans Orthop Trauma Assoc. 1999, 15: 411.
46. Horstmann WG, Verheyen CC, Leemans R. An injectable calcium phosphate cement as a bone-graft substitute in the treatment of displaced lateral tibial plateau fractures. Injury. 2003, 34(2): 141-4.
47. Lobenhoffer P, Gerich T, Witte F, Tscheme H. Use of an injectable calcium phosphate bone cement in the treatment of tibial plateau fractures: a prospective study of twenty-six cases with twenty-month mean follow-up. J Orthop Trauma. 2002, 16(3): 143-9.
48. Frankenburg EP, Goldstein SA, Bauer TW, Harris SA, Poser RD. Biomechanical and histological evaluation of a calcium phosphate cement. J Bone Joint Surg Am. 1998, 80(8): 1112-24.
49. Ooms EM, Wolke JG, van der Waerden JP, Jansen JA. Trabecular bone response to injectable calcium phosphate(Ca-P)cement. J Biomed Mater Res. 2002, 61(1): 9-18.
50. Welch RD, Zhang H, Bronson DG.. Experimental tibial plateau fractures augmented with calcium phosphate cement or autologous bone graft. J Bone Joint Surg Am. 2003, 85-A(2): 222-31.
51. Parfitt AM. Osteonal and hemi-osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem. 1994, 55(3): 273-86.
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