氧化锆/氧化钛改性可注射磷酸钙骨水泥的研究
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摘要
磷酸钙骨水泥(Calcium Phosphate Cement,CPC)是由一种或几种磷酸钙盐粉末组成的混合物,与调和液发生水化凝固反应,在生理条件下具有自固化能力及降解活性、成骨活性的骨修复材料。随着临床技术的发展,对手术创口的要求越来越小,对于一些骨水泥用量少而且需要定位的“小”外科手术(如牙根管充填),若采用导管插入注射CPC来完成,手术将更方便。因此近年来,可注射CPC成为骨水泥领域内研究的重点。多数学者认为可注射性骨水泥是一种具备良好的流动性能且同时保持了普通CPC优良特性的骨水泥,可通过注射的方式,直接填入骨缺损部位,从而与骨缺损部位的宿主骨充分接触。但同时由于它与普通CPC相比具有较低的固液比,使得可注射CPC的抗压力学强度较低,不能满足大多数条件下人体骨的力学强度要求。因此,提高可注射CPC的可注射性能和抗压力学强度成为关注的重点。
经相关文献报道,ZrO_2和TiO_2常被用来做增强材料以提高材料的强度同时具有良好的生物相容性,且柠檬酸(Citric Acid,CA)也多被作为液相成分用于CPC的制备。因此本论文采取通过在柠檬酸体系CPC中添加不同含量的TiO_2或ZrO_2,以增强可注射磷酸钙骨水泥的抗压力学强度和可注射性能,并研究了这两种可注射骨水泥的生物相容性。
本论文根据文献选取CPC的固相:固相成分为α-TCP(α-磷酸三钙)98 wt%、HA(羟基磷灰石)2 wt%。α-TCP和HA均为本实验自制合成,烧结并经球磨后待用。液相成分选取不同浓度的CA(0.1 mol/l、0.2 mol/l、0.3 mol/l、0.5mol/l)。以不同的固液比(2 g/ml、2.5 g/ml、3 g/ml、3.5 g/ml)制备CPC,进行优化CPC的制备工艺。采用Instron 5670万能力学试验机测试CPC的抗压强度,采用维卡仪对骨水泥的初/终凝时间进行测定,根据文献提供的方法测试CPC的可注射性能(挤压注射法),优化液相成分柠檬酸的浓度和CPC的固液比。再在以此CA浓度和固液比条件下制备的CPC中,分别加入不同比例的ZrO_2和TiO_2(5%、10%、15%、20%wt),制得ZCPC和TCPC。分别测试各组试样的抗压强度,初、终凝时间和可注射性;对ZCPC和TCPC的相成分采用X'Pert Pro MPD型X射线衍射仪进行研究。用QUANTA200型扫描电镜观察骨水泥的形貌特征。用Nicolet SXFYIRI 70/Magna 550型红外监测仪对骨水泥进行红外检测。采用XSAM-800型X射线光电子能谱仪对ZCPC和TCPC中的锆元素和钛元素进行XPS高分辨检测。为了考查添加ZrO_2和TiO_2后CPC的生物相容性,进行了SBF模拟体液培养和体外细胞培养实验,用光镜观察细胞形态,并通过四甲基偶氮唑盐微量酶反应比色法(MTT法)检测成骨细胞的增殖作用。
试验结果表明,通过优化试验表明,当CA的浓度为0.5 mol/l,固液比为3g/ml时的CPC同时具备最大的力学强度(14 MPa)和可注射性能(60%)。通过在该CA浓度和固液比条件下制备的CPC中分别加入不同比例的ZrO_2和TiO_2,制备了ZCPC和TCPC。ZCPC的初/终凝时间为分别为5-10 min和10-20 min。TCPC的初/终凝时间为分别为10-15 min和20-30 min。当ZrO_2和TiO_2的含量为15 wt%时,ZCPC和TCPC的抗压力学强度达到最高值,分别为23 MPa和38 MPa,可注射性能分别为80%和93%。通过XRD、SEM、红外分析和XPS的分析,认为ZCPC和TCPC在固化过程中,ZCPC和TCPC中的主要成分为HA,均产生了Ca(HPO_4)_2·H_2O(DCPD)和柠檬酸钙,并且在ZCPC中产生了Zr(HPO_4)_2·H_2O。对SBF模拟体液浸泡后的骨水泥材料进行XRD、红外、XPS检测,表明ZCPC和TCPC中的主要成分仍为HA,并在骨水泥的表面吸附了少量的沉积盐,但并没有影响骨水泥的固化过程。体外细胞实验表明,成骨细胞增殖良好,通过MTT检测,表明ZCPC和TCPC均比CPC具有更好的生物活性,且ZCPC比TCPC拥有更好的生物相容性。
Calcium phosphate cements(CPCs)possess the excellent biocompatibility and osteoconductivity due to their similar component as those of the natural bone and have been used as bone replacement in clinic successfully.A major disadvantage of current CPC is that they exist in hardened forms,requiring the surgeon to fit the surgical site around the implant or to carve the graft to the desired shape.This can lead to increases in bone loss,trauma to the surrounding tissue,and prolong surgical time.The injectability of CPC is important in clinical applications that involve defects with limited accessibility or narrow cavities, when there is a need for precise placement of the paste to conform to a defect area.However,the drawbacks of injectable CPC,including the lack of low strength,have limited its clinical use.According to some studies,ZrO_2 and TiO_2 often were used to improve strength of materials and both of them have good biocompatibility.Citric Acid as the liquid component was used to prepare injectable CPC.In this study,ZrO_2 or TiO_2 were added into citirc acid CPC to improve CPC properties which including strength and injectability.
In this study,the powder component of CPC contain 98 wt%α-TCP and HA 2 wt%and the liquid component were different concentrations citric acid(0.1 mol/1、0.2 mol/1、0.3 mol/1、0.5 mol/1)with different ratios of powder to liquid(2 g/ml、2.5 g/ml、3 g/ml、3.5 g/ml).The compress strength of CPC were tested by mechanical instrument(instron 5670).The extrusion method was used to test the injectability of CPC.The optimization concentration of citric acid and the ratio of powder to liquid were obtained.Then,different mass fracions ZrO_2 and TiO_2(5%、10%、15%、20%,wt)were added into the CPC,respectively,which named as ZCPC and TCPC.The CPC was used as the control.The Vicat was used to test the initial time and final time of as-received CPCs.The compressive strength and injectability were test as the previous description.X-ray diffraction(XRD)was employed to analyse the phase of as-prepared CPC.Scanning Electron Microscope(SEM)and Energy dispersive spertrum(EDS)were used to observe the morphology and indicate the element components of CPC.(Fourier transform infrared spectroscopy,FTIR)was worked to analyse the components of ZCPC and TCPC.X-ray Photoelectron Spectroscopy(XPS)were made to test element of Zr and Ti in the ZCPC and TCPC,respectively.The cell culture and immersed in simulation body solution(SBF)in vitro experiment were carried out to evaluate the biocompatibility and biodegradability of as-received CPCs.
The present results show that the maximum compressive strength of CPC is 14 MPa and the injectability is 60%while citirc acid concentration was 0.5 mol/l and the powder to liquid ratio was 3 g/ml.The initial and final time of ZCPC and TCPC were 5-10 min、10-20 min and 10-15 min、20-30 min,respectivety.When the mass fraction of ZrO_2 and TiO_2 were 15 wt%,the maximum compressive strength are 23 MPa and 38 MPa for ZCPC and TCPC,respectivety,amd the injectability are 80%and 93%.XRD、SEM、FTIR and XPS analyse indicate that HA was the main product in the ZCPC and TCPC.Ca(HPO_4)_2·H_2O(DCPD)and calcium citric acid occured during CPC self-setting process.Zr(HPO_4)_2·H_2O also could be found in ZCPC.HA was the main product in the ZCPC and TCPC after immersion in SBF.Cell toxicity experiment illuminate that both of ZCPC and TCPC have good biocompatibility than normal CPC.Furthermore,ZCPC have better biocompatibility than TCPC.
经相关文献报道,ZrO_2和TiO_2常被用来做增强材料以提高材料的强度同时具有良好的生物相容性,且柠檬酸(Citric Acid,CA)也多被作为液相成分用于CPC的制备。因此本论文采取通过在柠檬酸体系CPC中添加不同含量的TiO_2或ZrO_2,以增强可注射磷酸钙骨水泥的抗压力学强度和可注射性能,并研究了这两种可注射骨水泥的生物相容性。
本论文根据文献选取CPC的固相:固相成分为α-TCP(α-磷酸三钙)98 wt%、HA(羟基磷灰石)2 wt%。α-TCP和HA均为本实验自制合成,烧结并经球磨后待用。液相成分选取不同浓度的CA(0.1 mol/l、0.2 mol/l、0.3 mol/l、0.5mol/l)。以不同的固液比(2 g/ml、2.5 g/ml、3 g/ml、3.5 g/ml)制备CPC,进行优化CPC的制备工艺。采用Instron 5670万能力学试验机测试CPC的抗压强度,采用维卡仪对骨水泥的初/终凝时间进行测定,根据文献提供的方法测试CPC的可注射性能(挤压注射法),优化液相成分柠檬酸的浓度和CPC的固液比。再在以此CA浓度和固液比条件下制备的CPC中,分别加入不同比例的ZrO_2和TiO_2(5%、10%、15%、20%wt),制得ZCPC和TCPC。分别测试各组试样的抗压强度,初、终凝时间和可注射性;对ZCPC和TCPC的相成分采用X'Pert Pro MPD型X射线衍射仪进行研究。用QUANTA200型扫描电镜观察骨水泥的形貌特征。用Nicolet SXFYIRI 70/Magna 550型红外监测仪对骨水泥进行红外检测。采用XSAM-800型X射线光电子能谱仪对ZCPC和TCPC中的锆元素和钛元素进行XPS高分辨检测。为了考查添加ZrO_2和TiO_2后CPC的生物相容性,进行了SBF模拟体液培养和体外细胞培养实验,用光镜观察细胞形态,并通过四甲基偶氮唑盐微量酶反应比色法(MTT法)检测成骨细胞的增殖作用。
试验结果表明,通过优化试验表明,当CA的浓度为0.5 mol/l,固液比为3g/ml时的CPC同时具备最大的力学强度(14 MPa)和可注射性能(60%)。通过在该CA浓度和固液比条件下制备的CPC中分别加入不同比例的ZrO_2和TiO_2,制备了ZCPC和TCPC。ZCPC的初/终凝时间为分别为5-10 min和10-20 min。TCPC的初/终凝时间为分别为10-15 min和20-30 min。当ZrO_2和TiO_2的含量为15 wt%时,ZCPC和TCPC的抗压力学强度达到最高值,分别为23 MPa和38 MPa,可注射性能分别为80%和93%。通过XRD、SEM、红外分析和XPS的分析,认为ZCPC和TCPC在固化过程中,ZCPC和TCPC中的主要成分为HA,均产生了Ca(HPO_4)_2·H_2O(DCPD)和柠檬酸钙,并且在ZCPC中产生了Zr(HPO_4)_2·H_2O。对SBF模拟体液浸泡后的骨水泥材料进行XRD、红外、XPS检测,表明ZCPC和TCPC中的主要成分仍为HA,并在骨水泥的表面吸附了少量的沉积盐,但并没有影响骨水泥的固化过程。体外细胞实验表明,成骨细胞增殖良好,通过MTT检测,表明ZCPC和TCPC均比CPC具有更好的生物活性,且ZCPC比TCPC拥有更好的生物相容性。
Calcium phosphate cements(CPCs)possess the excellent biocompatibility and osteoconductivity due to their similar component as those of the natural bone and have been used as bone replacement in clinic successfully.A major disadvantage of current CPC is that they exist in hardened forms,requiring the surgeon to fit the surgical site around the implant or to carve the graft to the desired shape.This can lead to increases in bone loss,trauma to the surrounding tissue,and prolong surgical time.The injectability of CPC is important in clinical applications that involve defects with limited accessibility or narrow cavities, when there is a need for precise placement of the paste to conform to a defect area.However,the drawbacks of injectable CPC,including the lack of low strength,have limited its clinical use.According to some studies,ZrO_2 and TiO_2 often were used to improve strength of materials and both of them have good biocompatibility.Citric Acid as the liquid component was used to prepare injectable CPC.In this study,ZrO_2 or TiO_2 were added into citirc acid CPC to improve CPC properties which including strength and injectability.
In this study,the powder component of CPC contain 98 wt%α-TCP and HA 2 wt%and the liquid component were different concentrations citric acid(0.1 mol/1、0.2 mol/1、0.3 mol/1、0.5 mol/1)with different ratios of powder to liquid(2 g/ml、2.5 g/ml、3 g/ml、3.5 g/ml).The compress strength of CPC were tested by mechanical instrument(instron 5670).The extrusion method was used to test the injectability of CPC.The optimization concentration of citric acid and the ratio of powder to liquid were obtained.Then,different mass fracions ZrO_2 and TiO_2(5%、10%、15%、20%,wt)were added into the CPC,respectively,which named as ZCPC and TCPC.The CPC was used as the control.The Vicat was used to test the initial time and final time of as-received CPCs.The compressive strength and injectability were test as the previous description.X-ray diffraction(XRD)was employed to analyse the phase of as-prepared CPC.Scanning Electron Microscope(SEM)and Energy dispersive spertrum(EDS)were used to observe the morphology and indicate the element components of CPC.(Fourier transform infrared spectroscopy,FTIR)was worked to analyse the components of ZCPC and TCPC.X-ray Photoelectron Spectroscopy(XPS)were made to test element of Zr and Ti in the ZCPC and TCPC,respectively.The cell culture and immersed in simulation body solution(SBF)in vitro experiment were carried out to evaluate the biocompatibility and biodegradability of as-received CPCs.
The present results show that the maximum compressive strength of CPC is 14 MPa and the injectability is 60%while citirc acid concentration was 0.5 mol/l and the powder to liquid ratio was 3 g/ml.The initial and final time of ZCPC and TCPC were 5-10 min、10-20 min and 10-15 min、20-30 min,respectivety.When the mass fraction of ZrO_2 and TiO_2 were 15 wt%,the maximum compressive strength are 23 MPa and 38 MPa for ZCPC and TCPC,respectivety,amd the injectability are 80%and 93%.XRD、SEM、FTIR and XPS analyse indicate that HA was the main product in the ZCPC and TCPC.Ca(HPO_4)_2·H_2O(DCPD)and calcium citric acid occured during CPC self-setting process.Zr(HPO_4)_2·H_2O also could be found in ZCPC.HA was the main product in the ZCPC and TCPC after immersion in SBF.Cell toxicity experiment illuminate that both of ZCPC and TCPC have good biocompatibility than normal CPC.Furthermore,ZCPC have better biocompatibility than TCPC.
引文
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