羟基磷灰石/聚乙烯醇复合材料的制备与研究
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摘要
硬组织植入材料不仅要求具有良好的生物相容性、生物活性和足够的机械强度,而且要与人体硬组织的弹性模量匹配。单一材料己很难满足承载硬组织植入材料的要求,开发与硬组织弹性模量匹配的新型生物复合材料具有重要意义。羟基磷灰石(HAP)与聚合物复合材料作为骨替代材料具有很好的应用前景。
首先用仿生法制备了HAP/聚乙烯醇(PVA)复合膜材料。采用预先对PVA膜进行CaCl_2溶液和K_2HPO_4溶液的交互处理(Ca/P处理),然后在模拟体液(1.5SBF)中浸泡在短时间内(1～6天)就能在PVA表面沉积出大量HAP,3天在PVA膜表面沉积的HAP厚度可达0.5μm。而未经Ca/P处理的PVA膜即使经过长时间在1.5SBF中浸泡也没有HAP形成。在1.5SBF中添加了不同有机组分,如柠檬酸、胶原蛋白和三磷酸腺苷(ATP),发现胶原蛋白和柠檬酸都能促进HAP在PVA膜表面的生长,而ATP难以促使HAP的产生。对所形成的HAP经过XRD和红外分析,证实了它们的结构,基本为含有CO_3~(2-)的且CO_3~(2-)取代PO_4~(3-)的B型取代HAP。
将PVA纺成纤维。用交互浸渍法制备了HAP/PVA复合纤维。随交互浸渍周期的增多,沉积在PVA纤维表面的HAP数量增加。10周期的交互浸渍HAP已基本能将PVA纤维表面覆盖。在PVA纤维表面生成的HAP还有提高PVA纤维力学性能的作用,纤维的断裂强度、杨氏模量都随HAP的沉积量增多而提高,从而使HAP/PVA复合纤维的应用性能进一步改善。
通过溶液共混法制备了PVA与丝素蛋白(SF)的共混膜(PVA/SF),SF的加入不但能有效地改善膜的力学性能,即显著提高膜的模量和断裂强度,而且也能促进HAP在膜表面的生长。随共混膜中SF含量增多,在相同交互浸渍条件下所形成的HAP质量增加。
在PVA膜中混入聚丙烯酸(PAA)则对在交互浸渍过程中HAP在PVA/PAA共混膜上的沉积起到抑制作用,使生成的HAP数量显著减少。但同时也发现PAA存在时在共混膜上形成的HAP尺寸减小,酸性PAA的存在一方面使溶液的pH值降低,不利于HAP的形成;另一方面,PAA又能与溶液中的HPO_4~(2-)和PVA形成氢键,把HPO_4~(2-)引入聚合物基体上,再通过静电作用吸附溶液中的Ca~(2+),完成HAP成核过程。也就是说,PAA在聚合物相中是成核剂,在溶液相中是HAP的抑制剂。
采用共沉淀的方法在PVA/PAA膜上也能沉积和形成磷酸盐类物质。随沉淀速度的不同,以及是否在溶液中添加柠檬酸而得到具有不同形态和组成稍有不同的磷酸盐。分析推断,共沉淀过程形成的是HAP(Ca_(10)(PO_4)_6(OH)_2)、OCP(Ca_8(HPO_4)_2(PO_4)_4·5H_2O)、β-TCP(β-Ca_3(PO_4)_2)和DCPA(CaHPO_4)的混合物,后三者OCP、β-TCP和DCPA是HAP的前驱体,并且一定条件下很容易转化为HAP。
HAP的形成分为成核和生长两个阶段,成核的位垒相对较高。预先进行Ca/P处理增大了PVA膜表面与模拟体液浸润性,减小了接触角,使成核容易进行,由此加速了HAP的生长。
在模拟体液中加入的胶原蛋白和柠檬酸等有机组分首先能与PVA通过氢键结合,同时其上又含有容易与Ca~(2+)和PO_4~(3-)耦合的-COO~-,所以也是通过成核促进HAP的形成。
在共沉淀过程中,经历尿素分解、碱与酸反应以及盐沉析三个过程。尿素分解的快慢直接影响溶液的pH值,而柠檬酸的加入也会影响pH值,而在不同pH值时有不同磷酸钙析出,所以共沉淀形成的产物组成和形态都随条件而变化。
本文从聚合物基体、HAP生长方法、液相组成等多方面考察了HAP/聚合物复合材料制备过程。研究内容对理解HAP在聚合物表面形成以及其它聚合物体系与羟基磷灰石复合材料应有积极的借鉴意义和参考价值。
In recent years,the development of new bioactive and biocompatible materials has received great attention.It has been previously reported that bioactive materials have the ability to induce direct bonding to living bone,which is related to the formation of a carbonate hydroxyapatite layer on bioactive materials surfaces when in contact with body fluids or solutions mimicking properties of human plasma(simulated body fluid,SBF).Bioactive hydroxyapatite-polymer composites are a wide and very interesting alternative for bone tissue regeneration,as they combine the properties of polymer and hydroxm yapatite.In our study,Poly(vinyl alcohol)(PVA) was selected as polymeric substrate,biomimetic method,alternating soaking process,co-precipitation were adopted to prepare HAP/ PVA composites.Morphology,mechanical properties,bioactivity of the componete were investigated.
HAP/PVA composite was prepared by a biomimetic method.PVA films were pretreated with calcium chloride solution and dipotassium hydrogen phosphate solution(Ca/P treatment),and then were immersed in 1.5 SBF for different time intervals(1 to 6 days) to induce the growth of HAP onto the films.A great amount of HAP was found on the surface of PVA films after a short period of time.The thickness of HAP deposited on PVA films reached 0.5μm after 3 days immersion. The PVA film without the Ca/P treatment could not generate HAP at the same period immersion. We also study the effect of different organic components in 1.5SBF on the growth of HAP.Citric acid,collagen and ATP(adenosine triphosphate) were added into 1.5 SBF to prepare different incubation media.We found that collagen and citric acid can promote the growth of HAP on the surface of PVA films,while ATP was hard to promote the generating of HAP.The obtained HAP was confirmed by XRD and infrared analysis as B-HAP in which some positions of PO43" were replaced by CO_3~(2-).
PVA was wet-spun into fiber.HAP / PVA composite fibers were prepared by alternative soaking process.The amount of HAP which deposited on PVA fibers was increased along with interaction cycles.After 10 cycles of alternative soaking,the surfaces of PVA fibers were covered with HAP.The mechanical properties of PVA fibers were also improved owing to the existing of HAP.Breaking strength,Young's modulus of PVA fibers were enhanced by the coating of HAP on their surface.
Silk fibroin(SF) was blended with PVA to improve its mechanical properties and bioactivity. PVA/SF(silk fibroin) films were prepared by solution blending.The addition of SF was not only improved mechanical performance of the films,such as significantly enhanced the film's modulus and fracture strength,but also promoted HAP growth on the film surface,which was verified by alternate soaking process.With the same reaction cycles,the amount of deposited HAP was increased with the content of SF in the film.
PVA/PAA films of different PVA:PAA ratios were prepared,their HAP forming ability was investigated by alternate soaking process.Under the same circumstance,HAP growth was decreased with the content of PAA in PVA/PAA films.And it was found that the size of the HAP was reduced with the presence of PAA.It could be deduced from the results that on one hand the dissolution of acid PAA into solution lowered pH value which went against the formation of HAP; on the other hand,PAA formed hydrogen bonds with HPO_4~(2-) and PVA which could introduce HPO_4~(2-) into polymer matrix and then adsorpted Ca~(2+) existed in the solution through the electrostatic interaction for the completion of HAP nucleation process.In other words,PAA was nucleating agent in the polymer phase and HAP inhibitors in the solution phase.
Co-precipitation methods could be used to deposit phosphate-type materials on PVA/PAA films.Different rates of sedimentation and the addition of citric acid in the solution could induce the formation of varied shape and compositions of calcium salts.It could be concluded that HAP (Ca_(10)(PO_4)_6(OH)_2),OCP(Ca_8(HPO_4)_2(PO_4)_4·5H_2O octacalcium phosphate),β-TCP(β-Ca_3(PO_4)_2β-tri-Calcium phosphate) and DCPA(CaHPO_4 dicalcium phosphate anhydrate) mixture were formed during the co-precipitation process.OCP,P-TCP and DCPA were precursor of HAP and could be transformed to HAP easily under certain conditions.
It has been known that,the formation of HAP includes two steps:nucleation and increase. The barrier for nucleation was relatively high and hard to overcome in common circumstance.The infiltration between PVA film surface and simulated body fluid was increased and the contact angle between them was reduced by Pre-Ca/P processing.After that step,HAP nucleating became easily and the growth of HAP was accelerated.
Collagen,citric acid and other organic molecules in 1.5 SBF combined with PVA through hydrogen bonds firstly.-COO~- groups in these molecules could easily form some chelate with Ca~(2+) and PO_4~(3-) ions from 1.5SBF,thus promote the nucleation of HAP and also facilitate its growth in PVA substrates.
The co-precipitation process includes three steps:the hydrolization and decomposition of urea,the acid-base reaction and salt precipitation process.The decomposition of urea directly affected the speed of the pH variations,citric acid would also join in the effect of pH value,and different calcium phosphate precipitation occurred with different pH value.The composition and patterns of these precipitations were influenced by the conditions.
In this study,different factors of the preparation of HAP/polymer were studied in many aspects,such as polymeric substrates,approaches of depositing HAP and the composition of incubation media.The results would be useful in the research of HAP formation on the surface of polymer and help people to get a better understanding of preparation of HAP/polymer.And these also provide valuable information to the study and development of bone tissue engineering.
首先用仿生法制备了HAP/聚乙烯醇(PVA)复合膜材料。采用预先对PVA膜进行CaCl_2溶液和K_2HPO_4溶液的交互处理(Ca/P处理),然后在模拟体液(1.5SBF)中浸泡在短时间内(1～6天)就能在PVA表面沉积出大量HAP,3天在PVA膜表面沉积的HAP厚度可达0.5μm。而未经Ca/P处理的PVA膜即使经过长时间在1.5SBF中浸泡也没有HAP形成。在1.5SBF中添加了不同有机组分,如柠檬酸、胶原蛋白和三磷酸腺苷(ATP),发现胶原蛋白和柠檬酸都能促进HAP在PVA膜表面的生长,而ATP难以促使HAP的产生。对所形成的HAP经过XRD和红外分析,证实了它们的结构,基本为含有CO_3~(2-)的且CO_3~(2-)取代PO_4~(3-)的B型取代HAP。
将PVA纺成纤维。用交互浸渍法制备了HAP/PVA复合纤维。随交互浸渍周期的增多,沉积在PVA纤维表面的HAP数量增加。10周期的交互浸渍HAP已基本能将PVA纤维表面覆盖。在PVA纤维表面生成的HAP还有提高PVA纤维力学性能的作用,纤维的断裂强度、杨氏模量都随HAP的沉积量增多而提高,从而使HAP/PVA复合纤维的应用性能进一步改善。
通过溶液共混法制备了PVA与丝素蛋白(SF)的共混膜(PVA/SF),SF的加入不但能有效地改善膜的力学性能,即显著提高膜的模量和断裂强度,而且也能促进HAP在膜表面的生长。随共混膜中SF含量增多,在相同交互浸渍条件下所形成的HAP质量增加。
在PVA膜中混入聚丙烯酸(PAA)则对在交互浸渍过程中HAP在PVA/PAA共混膜上的沉积起到抑制作用,使生成的HAP数量显著减少。但同时也发现PAA存在时在共混膜上形成的HAP尺寸减小,酸性PAA的存在一方面使溶液的pH值降低,不利于HAP的形成;另一方面,PAA又能与溶液中的HPO_4~(2-)和PVA形成氢键,把HPO_4~(2-)引入聚合物基体上,再通过静电作用吸附溶液中的Ca~(2+),完成HAP成核过程。也就是说,PAA在聚合物相中是成核剂,在溶液相中是HAP的抑制剂。
采用共沉淀的方法在PVA/PAA膜上也能沉积和形成磷酸盐类物质。随沉淀速度的不同,以及是否在溶液中添加柠檬酸而得到具有不同形态和组成稍有不同的磷酸盐。分析推断,共沉淀过程形成的是HAP(Ca_(10)(PO_4)_6(OH)_2)、OCP(Ca_8(HPO_4)_2(PO_4)_4·5H_2O)、β-TCP(β-Ca_3(PO_4)_2)和DCPA(CaHPO_4)的混合物,后三者OCP、β-TCP和DCPA是HAP的前驱体,并且一定条件下很容易转化为HAP。
HAP的形成分为成核和生长两个阶段,成核的位垒相对较高。预先进行Ca/P处理增大了PVA膜表面与模拟体液浸润性,减小了接触角,使成核容易进行,由此加速了HAP的生长。
在模拟体液中加入的胶原蛋白和柠檬酸等有机组分首先能与PVA通过氢键结合,同时其上又含有容易与Ca~(2+)和PO_4~(3-)耦合的-COO~-,所以也是通过成核促进HAP的形成。
在共沉淀过程中,经历尿素分解、碱与酸反应以及盐沉析三个过程。尿素分解的快慢直接影响溶液的pH值,而柠檬酸的加入也会影响pH值,而在不同pH值时有不同磷酸钙析出,所以共沉淀形成的产物组成和形态都随条件而变化。
本文从聚合物基体、HAP生长方法、液相组成等多方面考察了HAP/聚合物复合材料制备过程。研究内容对理解HAP在聚合物表面形成以及其它聚合物体系与羟基磷灰石复合材料应有积极的借鉴意义和参考价值。
In recent years,the development of new bioactive and biocompatible materials has received great attention.It has been previously reported that bioactive materials have the ability to induce direct bonding to living bone,which is related to the formation of a carbonate hydroxyapatite layer on bioactive materials surfaces when in contact with body fluids or solutions mimicking properties of human plasma(simulated body fluid,SBF).Bioactive hydroxyapatite-polymer composites are a wide and very interesting alternative for bone tissue regeneration,as they combine the properties of polymer and hydroxm yapatite.In our study,Poly(vinyl alcohol)(PVA) was selected as polymeric substrate,biomimetic method,alternating soaking process,co-precipitation were adopted to prepare HAP/ PVA composites.Morphology,mechanical properties,bioactivity of the componete were investigated.
HAP/PVA composite was prepared by a biomimetic method.PVA films were pretreated with calcium chloride solution and dipotassium hydrogen phosphate solution(Ca/P treatment),and then were immersed in 1.5 SBF for different time intervals(1 to 6 days) to induce the growth of HAP onto the films.A great amount of HAP was found on the surface of PVA films after a short period of time.The thickness of HAP deposited on PVA films reached 0.5μm after 3 days immersion. The PVA film without the Ca/P treatment could not generate HAP at the same period immersion. We also study the effect of different organic components in 1.5SBF on the growth of HAP.Citric acid,collagen and ATP(adenosine triphosphate) were added into 1.5 SBF to prepare different incubation media.We found that collagen and citric acid can promote the growth of HAP on the surface of PVA films,while ATP was hard to promote the generating of HAP.The obtained HAP was confirmed by XRD and infrared analysis as B-HAP in which some positions of PO43" were replaced by CO_3~(2-).
PVA was wet-spun into fiber.HAP / PVA composite fibers were prepared by alternative soaking process.The amount of HAP which deposited on PVA fibers was increased along with interaction cycles.After 10 cycles of alternative soaking,the surfaces of PVA fibers were covered with HAP.The mechanical properties of PVA fibers were also improved owing to the existing of HAP.Breaking strength,Young's modulus of PVA fibers were enhanced by the coating of HAP on their surface.
Silk fibroin(SF) was blended with PVA to improve its mechanical properties and bioactivity. PVA/SF(silk fibroin) films were prepared by solution blending.The addition of SF was not only improved mechanical performance of the films,such as significantly enhanced the film's modulus and fracture strength,but also promoted HAP growth on the film surface,which was verified by alternate soaking process.With the same reaction cycles,the amount of deposited HAP was increased with the content of SF in the film.
PVA/PAA films of different PVA:PAA ratios were prepared,their HAP forming ability was investigated by alternate soaking process.Under the same circumstance,HAP growth was decreased with the content of PAA in PVA/PAA films.And it was found that the size of the HAP was reduced with the presence of PAA.It could be deduced from the results that on one hand the dissolution of acid PAA into solution lowered pH value which went against the formation of HAP; on the other hand,PAA formed hydrogen bonds with HPO_4~(2-) and PVA which could introduce HPO_4~(2-) into polymer matrix and then adsorpted Ca~(2+) existed in the solution through the electrostatic interaction for the completion of HAP nucleation process.In other words,PAA was nucleating agent in the polymer phase and HAP inhibitors in the solution phase.
Co-precipitation methods could be used to deposit phosphate-type materials on PVA/PAA films.Different rates of sedimentation and the addition of citric acid in the solution could induce the formation of varied shape and compositions of calcium salts.It could be concluded that HAP (Ca_(10)(PO_4)_6(OH)_2),OCP(Ca_8(HPO_4)_2(PO_4)_4·5H_2O octacalcium phosphate),β-TCP(β-Ca_3(PO_4)_2β-tri-Calcium phosphate) and DCPA(CaHPO_4 dicalcium phosphate anhydrate) mixture were formed during the co-precipitation process.OCP,P-TCP and DCPA were precursor of HAP and could be transformed to HAP easily under certain conditions.
It has been known that,the formation of HAP includes two steps:nucleation and increase. The barrier for nucleation was relatively high and hard to overcome in common circumstance.The infiltration between PVA film surface and simulated body fluid was increased and the contact angle between them was reduced by Pre-Ca/P processing.After that step,HAP nucleating became easily and the growth of HAP was accelerated.
Collagen,citric acid and other organic molecules in 1.5 SBF combined with PVA through hydrogen bonds firstly.-COO~- groups in these molecules could easily form some chelate with Ca~(2+) and PO_4~(3-) ions from 1.5SBF,thus promote the nucleation of HAP and also facilitate its growth in PVA substrates.
The co-precipitation process includes three steps:the hydrolization and decomposition of urea,the acid-base reaction and salt precipitation process.The decomposition of urea directly affected the speed of the pH variations,citric acid would also join in the effect of pH value,and different calcium phosphate precipitation occurred with different pH value.The composition and patterns of these precipitations were influenced by the conditions.
In this study,different factors of the preparation of HAP/polymer were studied in many aspects,such as polymeric substrates,approaches of depositing HAP and the composition of incubation media.The results would be useful in the research of HAP formation on the surface of polymer and help people to get a better understanding of preparation of HAP/polymer.And these also provide valuable information to the study and development of bone tissue engineering.
引文
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