PPF/CaSO_4/β-TCP复合材料的制备与降解研究
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摘要
本课题目的是研究一种新型的可生物降解骨移植材料,使材料实现原位成孔,并使材料整体的降解速度慢于材料的成孔速度。
首先采用三步法合成了聚富马酸丙二醇酯(poly(propylene fumarate),PPF),并对其进行了表征。制备了CaSO4和β-TCP粉体,探索了CaSO4/β-TCP陶瓷小球的制备和烧成工艺,制取了力学性能较好的CaSO4/β-TCP陶瓷小球。以PPF为基体,N-乙烯吡咯烷酮(N-VP)为交联剂,过氧化苯甲酰(BP)为引发剂,N,N-二甲基对甲苯胺(DMT)作为促进剂,CaSO4/β-TCP陶瓷小球为无机填料,37℃下交联固化,制备了PPF/CaSO4/β-TCP复合材料。
交联固化研究发现,不同组成的复合材料交联固化时的最高温度变化不大,从38~43℃,在人体组织的承受范围之内。聚合物分子量以及无机填料CaSO4/β-TCP的含量对交联固化温度的影响最为明显,且聚合物PPF分子量越大CaSO4/β-TCP含量越高,交联固化温度越高。材料的凝胶点在2~13min之间, PPF分子量对凝胶点的影响最大,增大PPF的分子量,会迅速达到凝胶点。增大引发剂的浓度也有同样的效果,但对凝胶点的影响要稍弱一些。降低N-VP/PPF比,增大BP/PPF比率,均会使材料的抗压强度和抗压模量增大。材料的抗压强度在3.94~61.87 MPa,抗压模量在94.24~1149.20 MPa。
采用PBS缓冲盐作为降解液,选用长12mm,直径6mm的圆柱状试样,在37℃下研究了PPF/CaSO4/β-TCP复合材料体外降解时的性能。体外降解研究表明复合材料中CaSO4的摩尔分数越大,降解失重越快。交联剂(N-VP)的含量越低,分子量越高,材料的降解速率就越小。N-VP/ PPF和CaSO4/β-TCP越高,材料的抗压强度和抗压模量越低。6周后材料的抗压强度为3.12±1.99MPa~20.56±2.87MPa,抗压模量为57.05±38.34MPa~712.03±284.85MPa。
选取性能较好的组成的材料植入日本大耳白兔胫骨,对材料的生物相容性进行了研究。研究发现,材料具有较好的原位成孔性能和良好的生物相容性,可作为小梁骨的替代材料,具有良好的应用前景。
The objective of the research presented here is to design a novel biodegradable material which can be used as bone substitute. This new material can form pores in situ, and may have a rate of degradation that acts slower than that of pores formation.
Poly(propylene fumarate)(PPF) were synthesized by a three-step method, and characterized with 1H-NMR, FITR, and GPC. We fabricated CaSO4 powder by sintering CaSO4·2H2O, and preparedβ-TCP with chemical coprecipitation method, then we investigated on the preparation of porous spherical CaSO4/β-TCP granules. PPF can be crosslinked with a vinyl pyrroliidinone at 37℃. N-vinyl pyrrolidinone (N-VP) was used as a crosslinking monomer, benzoyl peroxide (BP) as a radical polymerization initiator and N, N-dimethyl-p-toluidine (DMT) as an accelerator. PPF/CaSO4/β-TCP composites were formed through the incorporation of porous spherical CaSO4/β-TCP granules as an osteoconductive agent.
We examined the effects of PPF molecular weight, N-VP/PPF ratio, BP/PPF ratio, and CaSO4/β-TCP ratio on the crosslinking temperature, gel point, and the compressive strength and modulus. The maximum crosslinking temperature did not vary widely among formulations, with the absolute values falling between 38°and 43°C, which was acceptable for orthopedic application. The maximum crosslinking temperature was most affected by the PPF molecular weight and CaSO4/β-TCP content. The gel point was affected strongly by the PPF molecular weight, with a increase in PPF molecular weight more rapidly leading to a gel point. An increase in initiator concentration had the same effect to a lesser degree. The gel point time frame was varied from 2 to 13 min, allowing the composite to be tailored to specific applications. The compressive strength and compressive modulus values increased with decreasing N-VP/PPF and increasing BP/PPF ratio. For all formulations, the compressive strength values fell between 3.94 and 61.87 MPa, and the compressive modulus values fell between 94.24 and 1149.20 MPa.
Through the in vitro biodegradation of PPF/CaSO4/β-TCP composites in PBS, we investigated the properties PPF/CaSO4/β-TCP. The effects of varying PPF molecular, PPF to N-VP,and CaSO4 toβ-TCP of porous spherical CaSO4/β-TCP granules on the weight loss, water content, swelling degree and the composite compressive strength and modulus are examined by using cylindrical specimens with lengths of 12mm and diameters of 6mm.The composite degradated faster with a high CaSO4/β-TCP, a high N-VP/PPF or a low PPF molecular. The compressive strength and modulus decreased with decreasing the N-VP/PPF and increasing the CaSO4/β-TCP. For all formulations, the compressive strength values fell between 3.12±1.99MPa and 20.56±2.87MPa, and the compressive modulus values fell between 57.05±38.34MPa and 712.03±284.85MPa throughout 6 week’s in vitro degradation.
According to the in vitro biodegradation results, we selected three different formations, and implanted the samples into the tibias of fourteen healthy, Japan white rabbits. The in vivo degradation results demonstrate that PPF/CaSO4/β-TCP composites have a good ability of forming porous morphology in situ and biocompatibility, and can be used as a substitute of trabecular bone.
首先采用三步法合成了聚富马酸丙二醇酯(poly(propylene fumarate),PPF),并对其进行了表征。制备了CaSO4和β-TCP粉体,探索了CaSO4/β-TCP陶瓷小球的制备和烧成工艺,制取了力学性能较好的CaSO4/β-TCP陶瓷小球。以PPF为基体,N-乙烯吡咯烷酮(N-VP)为交联剂,过氧化苯甲酰(BP)为引发剂,N,N-二甲基对甲苯胺(DMT)作为促进剂,CaSO4/β-TCP陶瓷小球为无机填料,37℃下交联固化,制备了PPF/CaSO4/β-TCP复合材料。
交联固化研究发现,不同组成的复合材料交联固化时的最高温度变化不大,从38~43℃,在人体组织的承受范围之内。聚合物分子量以及无机填料CaSO4/β-TCP的含量对交联固化温度的影响最为明显,且聚合物PPF分子量越大CaSO4/β-TCP含量越高,交联固化温度越高。材料的凝胶点在2~13min之间, PPF分子量对凝胶点的影响最大,增大PPF的分子量,会迅速达到凝胶点。增大引发剂的浓度也有同样的效果,但对凝胶点的影响要稍弱一些。降低N-VP/PPF比,增大BP/PPF比率,均会使材料的抗压强度和抗压模量增大。材料的抗压强度在3.94~61.87 MPa,抗压模量在94.24~1149.20 MPa。
采用PBS缓冲盐作为降解液,选用长12mm,直径6mm的圆柱状试样,在37℃下研究了PPF/CaSO4/β-TCP复合材料体外降解时的性能。体外降解研究表明复合材料中CaSO4的摩尔分数越大,降解失重越快。交联剂(N-VP)的含量越低,分子量越高,材料的降解速率就越小。N-VP/ PPF和CaSO4/β-TCP越高,材料的抗压强度和抗压模量越低。6周后材料的抗压强度为3.12±1.99MPa~20.56±2.87MPa,抗压模量为57.05±38.34MPa~712.03±284.85MPa。
选取性能较好的组成的材料植入日本大耳白兔胫骨,对材料的生物相容性进行了研究。研究发现,材料具有较好的原位成孔性能和良好的生物相容性,可作为小梁骨的替代材料,具有良好的应用前景。
The objective of the research presented here is to design a novel biodegradable material which can be used as bone substitute. This new material can form pores in situ, and may have a rate of degradation that acts slower than that of pores formation.
Poly(propylene fumarate)(PPF) were synthesized by a three-step method, and characterized with 1H-NMR, FITR, and GPC. We fabricated CaSO4 powder by sintering CaSO4·2H2O, and preparedβ-TCP with chemical coprecipitation method, then we investigated on the preparation of porous spherical CaSO4/β-TCP granules. PPF can be crosslinked with a vinyl pyrroliidinone at 37℃. N-vinyl pyrrolidinone (N-VP) was used as a crosslinking monomer, benzoyl peroxide (BP) as a radical polymerization initiator and N, N-dimethyl-p-toluidine (DMT) as an accelerator. PPF/CaSO4/β-TCP composites were formed through the incorporation of porous spherical CaSO4/β-TCP granules as an osteoconductive agent.
We examined the effects of PPF molecular weight, N-VP/PPF ratio, BP/PPF ratio, and CaSO4/β-TCP ratio on the crosslinking temperature, gel point, and the compressive strength and modulus. The maximum crosslinking temperature did not vary widely among formulations, with the absolute values falling between 38°and 43°C, which was acceptable for orthopedic application. The maximum crosslinking temperature was most affected by the PPF molecular weight and CaSO4/β-TCP content. The gel point was affected strongly by the PPF molecular weight, with a increase in PPF molecular weight more rapidly leading to a gel point. An increase in initiator concentration had the same effect to a lesser degree. The gel point time frame was varied from 2 to 13 min, allowing the composite to be tailored to specific applications. The compressive strength and compressive modulus values increased with decreasing N-VP/PPF and increasing BP/PPF ratio. For all formulations, the compressive strength values fell between 3.94 and 61.87 MPa, and the compressive modulus values fell between 94.24 and 1149.20 MPa.
Through the in vitro biodegradation of PPF/CaSO4/β-TCP composites in PBS, we investigated the properties PPF/CaSO4/β-TCP. The effects of varying PPF molecular, PPF to N-VP,and CaSO4 toβ-TCP of porous spherical CaSO4/β-TCP granules on the weight loss, water content, swelling degree and the composite compressive strength and modulus are examined by using cylindrical specimens with lengths of 12mm and diameters of 6mm.The composite degradated faster with a high CaSO4/β-TCP, a high N-VP/PPF or a low PPF molecular. The compressive strength and modulus decreased with decreasing the N-VP/PPF and increasing the CaSO4/β-TCP. For all formulations, the compressive strength values fell between 3.12±1.99MPa and 20.56±2.87MPa, and the compressive modulus values fell between 57.05±38.34MPa and 712.03±284.85MPa throughout 6 week’s in vitro degradation.
According to the in vitro biodegradation results, we selected three different formations, and implanted the samples into the tibias of fourteen healthy, Japan white rabbits. The in vivo degradation results demonstrate that PPF/CaSO4/β-TCP composites have a good ability of forming porous morphology in situ and biocompatibility, and can be used as a substitute of trabecular bone.
引文
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