CPC水化过程液固态演化及其复合材料的研究
摘要
磷酸钙骨水泥(CPC)以其良好的生物相容性、骨诱导性及可降解性被广泛应用于牙科、整形外科及骨重建手术中的骨替代领域。但CPC有其固有的缺陷,如脆性大、力学强度较低、降解和骨替代速度较慢等,并且CPC植入体常会引起术后发炎感染,使其临床应用受到限制,因此制备强度较高并且可以在人体内缓慢释放药物的CPC复合材料具有重要的现实意义。此外,CPC水化过程中液固态演化方面的研究还不全面,不同程度的影响了CPC的改进设计。
本文基于上述问题,首先制备了α_H-TCP和TTCP/DCPA两种骨水泥粉体,利用XRD分析、SEM观察、DSC分析,尤其是首次采用了液态XRD分析等方法,对两种CPC由液态到固态演化过程中的物相、微观结构及热效应等的变化情况进行了动态的检测观察;然后将TTCP/DCPA骨水泥粉体与可降解高分子聚合物聚乳酸(PLA),以及抗生素头孢唑啉钠(Cefazolin)复合,制备出CPC/PLA/Cefazolin复合材料,使其同时获得良好的力学性能与抗菌功能,并对复合材料的抗压强度、微观结构、降解情况和药物缓释情况等进行了研究。
通过对两种CPC水化过程的比较分析得出,α_H-TCP和TTCP骨水泥粉体水化时的液固态演化过程呈现大致相同的规律,水化过程可分为早期、中期、后期三个阶段。物相上,反应物逐渐溶解并反应生成主晶相羟基磷灰石(HA);微观结构从少而分散的点状结构,到薄膜结构,再到突出的点状结构,进而演变为棒状或针状结构,同时还存在一种密集的不规则皱状结构;水化放热曲线同水泥的相似,水化反应可分为初始期、诱导期、加速反应期、减速反应期、稳定期五个阶段,每个阶段反应的控制机理不同;液态XRD检测出的信号变化与其液固态演化的规律基本一致,初始时液体中原子团簇排列的混乱度很大,主要以非晶状态存在,水化过程中,液态结构的变化较为稳定,液体中的团簇结构没有突变现象发生,而是作为晶胚直接形核,其形核方式为“稳定形核模式”,随着HA逐渐晶化,团簇的有序度也逐渐提高。
在复合材料制备过程中,采用将CPC粉体与PLA颗粒球磨混合,将Cefazolin粉末溶于去离子水中制成调和液,使药物在固液相混合时载入的方法,成功制备出CPC/PLA/Cefazolin复合材料。Cefazolin的载入使CPC基体的孔隙增多,强度降低,而复合进PLA后,可使基体结构更加密实,孔隙减少,强度大幅度提高,并且可以缓和Cefazolin对材料抗压强度的减弱作用。
通过对材料降解性能的研究,发现HA的降解不太显著,加入PLA后,由于PLA的降解速度较快,降解后形成较大的孔洞,可加快HA的降解,而且形成的多孔结构利于成骨细胞的粘附、迁移和增殖。
复合材料前期的体外缓释研究表明,该载药复合材料具有药物缓释的功能,初期缓释速度较快,5d左右后,基本趋于稳定;载药量对缓释作用有一定的影响,载药量越大,初期缓释速度越快,总释药量也越大;PLA的加入对药物的前期释放也有影响,载药量较高时可促进药物的释放,而载药量较低时会阻滞药物的释放。此外,PLA的降解对药物的长期释放有积极的作用,50d后缓释仍在进行。
Calcium Phosphate Cement (CPC) is widely used as bone substitutes in dentistry, orthopedics and reconstructive surgery, because of its biocompatibility, osteoconductivity and biodegradability. However, the high brittleness, low strength and slow biodegradation restrict its clinical application. And implant-caused infections are considered to be very serious too. As a result, it is very important to improve the mechanical strength of CPC as well as to make it antibacterial. In addition, there are few reports on the changes of CPC during hydration process from liquid to solid, which influence the improvement of CPC.
So in this experiment, two kinds of CPC powders, aH-TCP and TTCP/DCPA, were prepared first and studied the changes of them during hydration process from liquid to solid by X-ray diffraction (XRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and especially high temperature X-ray diffraction. Then, The composites CPC/PLA/Cefazolin were prepared to make CPC high strength and antibacterial at the same time. The strength, microstructure, the properties of degradation and releasing antibiotics and so on were studied whereafter.
The results of different tests showed consistency. The changes of aH-TCP and TTCP/DCPA bone cements were similar during hydration process, and the hydration process could be divided into three periods. The reactant dissolved gradually and the last product was the same HA; The microstructure was granular first, then was filmy, and granular protrudently, and claviform or acicle further, a close-grained corrugated structure was existent at the same time; The hydrate heat evolution curve of CPC was similar with cement. The reaction could be divided into five periods with different mechanisms. The results tested by high temperature X-ray diffraction was accordant with the changes of CPC during hydration process from liquid to solid. In earlier period, the cluster was noncrystal and very disordered. Liquid structure changed steadily without shape change of cluster. The crystal nucleus formed steadily, and the cluster was ordered gradually with the crystallization of HA.
The strength of CPC added Cefazolin could be decreased because of the increase of pores; however, adding PLA could cause the close-grained structure, so the strength of CPC increased. Moreover, macropore created by PLA hydrolysing could accelerate the degradation of CPC and the ingrowth of new bone tissue. The composites with Cefazolin could release antibiotics slowly. In the earlier period, the speed of release was faster. About 5 days later, Cefazolin was released steadily. The earlier released speed and the total amount of Cefazolin released increased with the increase of Cefazolin contents. The addition of PLA had influence on the release of Cefazolin and had contribution to the long-term release after 50 days.
本文基于上述问题,首先制备了α_H-TCP和TTCP/DCPA两种骨水泥粉体,利用XRD分析、SEM观察、DSC分析,尤其是首次采用了液态XRD分析等方法,对两种CPC由液态到固态演化过程中的物相、微观结构及热效应等的变化情况进行了动态的检测观察;然后将TTCP/DCPA骨水泥粉体与可降解高分子聚合物聚乳酸(PLA),以及抗生素头孢唑啉钠(Cefazolin)复合,制备出CPC/PLA/Cefazolin复合材料,使其同时获得良好的力学性能与抗菌功能,并对复合材料的抗压强度、微观结构、降解情况和药物缓释情况等进行了研究。
通过对两种CPC水化过程的比较分析得出,α_H-TCP和TTCP骨水泥粉体水化时的液固态演化过程呈现大致相同的规律,水化过程可分为早期、中期、后期三个阶段。物相上,反应物逐渐溶解并反应生成主晶相羟基磷灰石(HA);微观结构从少而分散的点状结构,到薄膜结构,再到突出的点状结构,进而演变为棒状或针状结构,同时还存在一种密集的不规则皱状结构;水化放热曲线同水泥的相似,水化反应可分为初始期、诱导期、加速反应期、减速反应期、稳定期五个阶段,每个阶段反应的控制机理不同;液态XRD检测出的信号变化与其液固态演化的规律基本一致,初始时液体中原子团簇排列的混乱度很大,主要以非晶状态存在,水化过程中,液态结构的变化较为稳定,液体中的团簇结构没有突变现象发生,而是作为晶胚直接形核,其形核方式为“稳定形核模式”,随着HA逐渐晶化,团簇的有序度也逐渐提高。
在复合材料制备过程中,采用将CPC粉体与PLA颗粒球磨混合,将Cefazolin粉末溶于去离子水中制成调和液,使药物在固液相混合时载入的方法,成功制备出CPC/PLA/Cefazolin复合材料。Cefazolin的载入使CPC基体的孔隙增多,强度降低,而复合进PLA后,可使基体结构更加密实,孔隙减少,强度大幅度提高,并且可以缓和Cefazolin对材料抗压强度的减弱作用。
通过对材料降解性能的研究,发现HA的降解不太显著,加入PLA后,由于PLA的降解速度较快,降解后形成较大的孔洞,可加快HA的降解,而且形成的多孔结构利于成骨细胞的粘附、迁移和增殖。
复合材料前期的体外缓释研究表明,该载药复合材料具有药物缓释的功能,初期缓释速度较快,5d左右后,基本趋于稳定;载药量对缓释作用有一定的影响,载药量越大,初期缓释速度越快,总释药量也越大;PLA的加入对药物的前期释放也有影响,载药量较高时可促进药物的释放,而载药量较低时会阻滞药物的释放。此外,PLA的降解对药物的长期释放有积极的作用,50d后缓释仍在进行。
Calcium Phosphate Cement (CPC) is widely used as bone substitutes in dentistry, orthopedics and reconstructive surgery, because of its biocompatibility, osteoconductivity and biodegradability. However, the high brittleness, low strength and slow biodegradation restrict its clinical application. And implant-caused infections are considered to be very serious too. As a result, it is very important to improve the mechanical strength of CPC as well as to make it antibacterial. In addition, there are few reports on the changes of CPC during hydration process from liquid to solid, which influence the improvement of CPC.
So in this experiment, two kinds of CPC powders, aH-TCP and TTCP/DCPA, were prepared first and studied the changes of them during hydration process from liquid to solid by X-ray diffraction (XRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and especially high temperature X-ray diffraction. Then, The composites CPC/PLA/Cefazolin were prepared to make CPC high strength and antibacterial at the same time. The strength, microstructure, the properties of degradation and releasing antibiotics and so on were studied whereafter.
The results of different tests showed consistency. The changes of aH-TCP and TTCP/DCPA bone cements were similar during hydration process, and the hydration process could be divided into three periods. The reactant dissolved gradually and the last product was the same HA; The microstructure was granular first, then was filmy, and granular protrudently, and claviform or acicle further, a close-grained corrugated structure was existent at the same time; The hydrate heat evolution curve of CPC was similar with cement. The reaction could be divided into five periods with different mechanisms. The results tested by high temperature X-ray diffraction was accordant with the changes of CPC during hydration process from liquid to solid. In earlier period, the cluster was noncrystal and very disordered. Liquid structure changed steadily without shape change of cluster. The crystal nucleus formed steadily, and the cluster was ordered gradually with the crystallization of HA.
The strength of CPC added Cefazolin could be decreased because of the increase of pores; however, adding PLA could cause the close-grained structure, so the strength of CPC increased. Moreover, macropore created by PLA hydrolysing could accelerate the degradation of CPC and the ingrowth of new bone tissue. The composites with Cefazolin could release antibiotics slowly. In the earlier period, the speed of release was faster. About 5 days later, Cefazolin was released steadily. The earlier released speed and the total amount of Cefazolin released increased with the increase of Cefazolin contents. The addition of PLA had influence on the release of Cefazolin and had contribution to the long-term release after 50 days.
引文
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