纳米羟基磷灰石与壳聚糖复合硬组织修复材料研究
摘要
单纯的有机或无机材料很难满足临床上对骨修复材料生物活性及生物力学性能的综合要求。理想的骨修复材料,应当具有良好的生物相容性和高的生物活性,其力学性能与天然骨相当或稍优于天然骨。因此,设计和制备更接近骨矿物组成的纳米羟基磷灰石及其复合材料成为当前骨组织修复材料研究的热点。
羟基磷灰石(HA)是骨组织的主要无机成分,生物相容性好,具有较高的生物活性,能够与骨组织形成化学键合,但其脆性和不易加工性也限制了其应用。聚合物材料具有较好的韧性,但缺乏生物活性。如果综合二者的性能,扬长避短,优势互补,可望得到一种理想的骨修复替代材料。
天然骨的主要矿物成分是弱结晶态含碳酸根的纳米磷灰石晶体,在体内参与骨的新陈代谢,具有很高的生物活性。因此,合成组成和形态类似于骨矿物质的纳米类骨磷灰石晶体是制备高性能复合骨修复材料的前提。
本文以Ca(OH)_2和H_3PO_4为原料,通过中和反应法合成羟基磷灰石前驱体,并于140℃、0.3MPa条件下进行水热处理,得到羟基磷灰石晶体。研究结果表明,该磷灰石晶体呈纳米短棒状形态,属弱结晶结构,并含有少量的CO_3~(2-),与天然骨磷灰石晶体的结构和组分相似。合成磷灰石晶体中的CO_3~(2-)是在合成及水热处理过程中引入的,其含量低于天然骨磷灰石。为使合成的磷灰石晶体结构和组分更接近于骨矿物质,本文通过在反应物中引入碳酸盐,用相同的方法合成了含CO_3~(2-)羟基磷灰石(CHA)晶体。研究结果表明,CHA中碳酸根的含量与天然骨磷灰石相当,晶粒尺寸显著减小,与骨磷灰石晶体尺寸极其接近。由于碳酸根进入CHA晶格内部,使CHA的晶体结构不完整,呈现与骨磷灰石
Single organic or inorganic materials is hard to meet the integrated requirements for the bioactivity and biomechanical properties of bone-repair materials in clinic. Ideal bone-repair materials should be of good biocompatibility and high bioactivity. Besides, their mechanical properties should be equivalent to or better than those of natural bone. Therefore, to design and prepare nano-hydroxyapatite with a composition closer to bone mineral and its composite become a hot topic at present for bone-repair materials research.Hydroxyapatite (HA) is the main inorganic composition of bone tissue and is of good biocompatibility and high bioactivity, which makes HA be able to chemically bond to bone tissue. However, the brittleness and hard machining limit its extensive clinical use. It is well known that polymers have better toughness, but it lacks bioactivity. So, if combine the properties of the two materials, i.e., to carry their good properties forward and get rid of their shortcomings, it will be hopeful to obtain a good bone substitute material.The main mineral of natural bone is carbonated nano-apatite crystals with poorly crystallinity. It participates in bone metabolism and possesses high bioactivity. So, it is the premise for the preparation of such a composite to prepare bone-like apatite crystals with similar composition and morphology to bone apatite.In the paper, HA precipitates were prepared using Ca(0H)2 and H3PO4 as reactants, then treated by a hydrothermal method at 140℃, 0.3 MPa for 2 hours, and
finally nano-HA crystals were obtained. Compared the HA crystals with the mineral phase of natural bone, it can be seen that the synthesized HA has similar composition and structure to bone apatite. The nano-rod HA crystals with a poorly crystallinity contain a little CO32", which was introduced during the process of preparation and hydrothermal treatment. In order to increase the content of CO32" in HA crystals, carbonate was purposely introduced into the reactants to prepare carbonated hydroxyapatite crystals (CHA) by the same method. The results show that CHA synthesized here contains CO32" equivalent to that in natural bone apatite approximately; the size of CHA crystals is smaller and was closer to that of bone apatite crystals. Ingoing of CO32' into the crystal lattice results in the structure deformity of CHA crystals, thus makes it show poorly crystallinity similar to bone apatite.Chitosan is a natural biodegradable polymer. Its degradation product is alkalescent and is not harm and toxic to human body or tissue. Compounding chitosan with n-HA could overcome the brittleness of HA ceramics, and that the degradation of chitosan also makes room for the ingrowth of cells and tissues and speeds the formation of new bone. Chitosan could precipitate from its solution at pH>6, and HA precipitation also appears under the pH condition. Therefore, co-precipitation method is employed in the paper to prepare nano-hydroxyapatite/chitosan (n-HA/CS) composite. Testing results show that HA in the composite is poorly crystalline carbonated nano-crystals and dispersed uniformly in the organic CS phase. The two phases in n-HA/CS composite have an excellent miscibility and no phase-separation occurs in the blend. Stronger interactions exists between the two phases of n-HA and CS, which endows the materials with excellent mechanical strength. When the weight content of chitosan is 30%, the compressive strength of the composite is best, about 120 MPa. In vitro test shows that the organic phase in the composite degrades gradually during the immersion, and, at the same time, bone-like apatite deposits onto the surface of the composite, indicating that the composite with a chitosan/n-HA weight ratio of 30/70 demonstrate good bioactivity.n-HA/CS porous scaffold is fabricated by porogen-leaching method in the paper.
Results show that macro-pores and micro-pores coexist in the scaffold, and abundant micro-pores also exist on the wall of macro-pores, and these pores are highly interconnected. When the porosity is 53.4%, the compressive strength of the scaffold can still reach 17 MPa, and can satisfy the demand of tissue engineering when as a cell scaffold. The porous scaffold takes on good degradability and water-adsorption, and the degradation speed and bioactivity can be controlled and improved by treatment of basic solution.In order to enhance the applicability of n-HA/CS composite in clinic, a new type of bone cement which can fast set in air, water, 0.9% NaCl solution or blood is prepared by introducing ZnO powder into n-HA/CS composite and choosing appropriate liquid. Study results indicate that, when the weight ratio of ZnO/composite is 1/8 and liquid/powder is 1.2 ml/g, the compressive strength and setting time of the cement are both appropriate value. The compressive strength of the cement in 0.9% NaCl solution increases with the immersing time, and reaches the maximum after 72 hrs, then declines due to the degradation of chitosan. The pH of the cement immersing in 0.9% NaCl solution for 20 days is close to the pH of human body fluid. In addition, the cement shows very small water contact angle, indicating that the cement has high wettability. The results of IR, XRD and XPS analyses demonstrate that Zn2+ in ZnO chelateds with the -NH2 group in the chains of chitosan and produces CS-Zn2+ chelate complex, thus accelerates the setting of the cement. SEM observation illuminates that large numbers of micro-pores exist in the setting cement, which was desirable for the ingrowth or creeping substitute of bone tissue. In vitro research on the bioactivity explains that the cement behaves good bioactivity when immersing into SBF.Antibacterial tests indicate that pure n-HA/CS composite hardly inhibits S.aureus and E.coli, but the antibacterial properties of the cement with ZnO is improved dramatically, and the antibacterial ability is strengthened with the increase of the content of ZnO in the cement.
羟基磷灰石(HA)是骨组织的主要无机成分,生物相容性好,具有较高的生物活性,能够与骨组织形成化学键合,但其脆性和不易加工性也限制了其应用。聚合物材料具有较好的韧性,但缺乏生物活性。如果综合二者的性能,扬长避短,优势互补,可望得到一种理想的骨修复替代材料。
天然骨的主要矿物成分是弱结晶态含碳酸根的纳米磷灰石晶体,在体内参与骨的新陈代谢,具有很高的生物活性。因此,合成组成和形态类似于骨矿物质的纳米类骨磷灰石晶体是制备高性能复合骨修复材料的前提。
本文以Ca(OH)_2和H_3PO_4为原料,通过中和反应法合成羟基磷灰石前驱体,并于140℃、0.3MPa条件下进行水热处理,得到羟基磷灰石晶体。研究结果表明,该磷灰石晶体呈纳米短棒状形态,属弱结晶结构,并含有少量的CO_3~(2-),与天然骨磷灰石晶体的结构和组分相似。合成磷灰石晶体中的CO_3~(2-)是在合成及水热处理过程中引入的,其含量低于天然骨磷灰石。为使合成的磷灰石晶体结构和组分更接近于骨矿物质,本文通过在反应物中引入碳酸盐,用相同的方法合成了含CO_3~(2-)羟基磷灰石(CHA)晶体。研究结果表明,CHA中碳酸根的含量与天然骨磷灰石相当,晶粒尺寸显著减小,与骨磷灰石晶体尺寸极其接近。由于碳酸根进入CHA晶格内部,使CHA的晶体结构不完整,呈现与骨磷灰石
Single organic or inorganic materials is hard to meet the integrated requirements for the bioactivity and biomechanical properties of bone-repair materials in clinic. Ideal bone-repair materials should be of good biocompatibility and high bioactivity. Besides, their mechanical properties should be equivalent to or better than those of natural bone. Therefore, to design and prepare nano-hydroxyapatite with a composition closer to bone mineral and its composite become a hot topic at present for bone-repair materials research.Hydroxyapatite (HA) is the main inorganic composition of bone tissue and is of good biocompatibility and high bioactivity, which makes HA be able to chemically bond to bone tissue. However, the brittleness and hard machining limit its extensive clinical use. It is well known that polymers have better toughness, but it lacks bioactivity. So, if combine the properties of the two materials, i.e., to carry their good properties forward and get rid of their shortcomings, it will be hopeful to obtain a good bone substitute material.The main mineral of natural bone is carbonated nano-apatite crystals with poorly crystallinity. It participates in bone metabolism and possesses high bioactivity. So, it is the premise for the preparation of such a composite to prepare bone-like apatite crystals with similar composition and morphology to bone apatite.In the paper, HA precipitates were prepared using Ca(0H)2 and H3PO4 as reactants, then treated by a hydrothermal method at 140℃, 0.3 MPa for 2 hours, and
finally nano-HA crystals were obtained. Compared the HA crystals with the mineral phase of natural bone, it can be seen that the synthesized HA has similar composition and structure to bone apatite. The nano-rod HA crystals with a poorly crystallinity contain a little CO32", which was introduced during the process of preparation and hydrothermal treatment. In order to increase the content of CO32" in HA crystals, carbonate was purposely introduced into the reactants to prepare carbonated hydroxyapatite crystals (CHA) by the same method. The results show that CHA synthesized here contains CO32" equivalent to that in natural bone apatite approximately; the size of CHA crystals is smaller and was closer to that of bone apatite crystals. Ingoing of CO32' into the crystal lattice results in the structure deformity of CHA crystals, thus makes it show poorly crystallinity similar to bone apatite.Chitosan is a natural biodegradable polymer. Its degradation product is alkalescent and is not harm and toxic to human body or tissue. Compounding chitosan with n-HA could overcome the brittleness of HA ceramics, and that the degradation of chitosan also makes room for the ingrowth of cells and tissues and speeds the formation of new bone. Chitosan could precipitate from its solution at pH>6, and HA precipitation also appears under the pH condition. Therefore, co-precipitation method is employed in the paper to prepare nano-hydroxyapatite/chitosan (n-HA/CS) composite. Testing results show that HA in the composite is poorly crystalline carbonated nano-crystals and dispersed uniformly in the organic CS phase. The two phases in n-HA/CS composite have an excellent miscibility and no phase-separation occurs in the blend. Stronger interactions exists between the two phases of n-HA and CS, which endows the materials with excellent mechanical strength. When the weight content of chitosan is 30%, the compressive strength of the composite is best, about 120 MPa. In vitro test shows that the organic phase in the composite degrades gradually during the immersion, and, at the same time, bone-like apatite deposits onto the surface of the composite, indicating that the composite with a chitosan/n-HA weight ratio of 30/70 demonstrate good bioactivity.n-HA/CS porous scaffold is fabricated by porogen-leaching method in the paper.
Results show that macro-pores and micro-pores coexist in the scaffold, and abundant micro-pores also exist on the wall of macro-pores, and these pores are highly interconnected. When the porosity is 53.4%, the compressive strength of the scaffold can still reach 17 MPa, and can satisfy the demand of tissue engineering when as a cell scaffold. The porous scaffold takes on good degradability and water-adsorption, and the degradation speed and bioactivity can be controlled and improved by treatment of basic solution.In order to enhance the applicability of n-HA/CS composite in clinic, a new type of bone cement which can fast set in air, water, 0.9% NaCl solution or blood is prepared by introducing ZnO powder into n-HA/CS composite and choosing appropriate liquid. Study results indicate that, when the weight ratio of ZnO/composite is 1/8 and liquid/powder is 1.2 ml/g, the compressive strength and setting time of the cement are both appropriate value. The compressive strength of the cement in 0.9% NaCl solution increases with the immersing time, and reaches the maximum after 72 hrs, then declines due to the degradation of chitosan. The pH of the cement immersing in 0.9% NaCl solution for 20 days is close to the pH of human body fluid. In addition, the cement shows very small water contact angle, indicating that the cement has high wettability. The results of IR, XRD and XPS analyses demonstrate that Zn2+ in ZnO chelateds with the -NH2 group in the chains of chitosan and produces CS-Zn2+ chelate complex, thus accelerates the setting of the cement. SEM observation illuminates that large numbers of micro-pores exist in the setting cement, which was desirable for the ingrowth or creeping substitute of bone tissue. In vitro research on the bioactivity explains that the cement behaves good bioactivity when immersing into SBF.Antibacterial tests indicate that pure n-HA/CS composite hardly inhibits S.aureus and E.coli, but the antibacterial properties of the cement with ZnO is improved dramatically, and the antibacterial ability is strengthened with the increase of the content of ZnO in the cement.
引文
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