生物活性可降解颈椎椎间融合器的研究与制作
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摘要
目的
通过开环聚合和化学共沉淀法制备相对高分子量的PLLA和HAp晶体粉末，测试它们的基本理化性能；以氯仿为溶剂，将超细微HAp粉末按比例分散在PLLA的氯仿溶液中，用溶液—超声分散法合成不同组分(50/50、35/65、15/85、0/100)的HAp/PLLA复合材料，热压模铸并车削加工成一定规格的颈椎椎间融合cage样件，对其基本生物学性能和体内外降解特征进行研究，选择并制备出性能良好的生物活性可降解颈椎椎间融合器。
方法
一．原材料的制备和表征
(一)相对高分子量PLLA的制备
1．国产L—乳酸在催化剂氧化锌的作用下脱水、缩聚成相对低分子量的聚L—乳酸，减压并高温裂解得LLA。
2．用乙酸乙酯重结晶的丙交酯单体在引发剂作用下真空聚合生成PLLA粗品。
3．将聚合物粗品用氯仿溶解、甲醇中沉淀过滤，真空干燥后底精品PLLA。
(二)超微HAp粉末的制备
1．在pH为9、反应温度60℃、反应时间7小时条件下，使0.3％的H_3PO_4溶液和Ca(OH)_2悬浮液发生中和反应，负压抽滤并真空干燥得产物HAp。
2．生成物HAp在800℃下高温煅烧3h，研磨过175μm筛制得HAp超微粉。
(三)原材料的表征
1．粘度法测算PLLA分子的粘均分子量，并对其分子的旋光度、核磁
光谱和金属元素成份进行分析。
2.X一射线衍射(XRD)分析法测定HAp的晶相特征，比重瓶法测算
HAp的密度和比重。
二·HAp/PLLA cage的制作及性能测定
(一)HAp/PLLA复合材料的共混复合
以氯仿为溶剂，将超细微队p粉末按比例分散在PLLA的氯仿溶液中，
用溶液一超声分散法合成不同组分(50/50、35/65、一5/85、0/100)的
HAp/PLLA复合材料。
(二)HAp/PLLA eage的模铸加工
1.在模铸温度为170℃、压力10MPa、恒压巧分钟条件下，将粉碎
后的HAp/PLLA材料在干燥柱形模具中热压成圆柱形棒材。
2.将压成圆柱形棒材在普通车床上车削加工成螺柱状空心cage。
(三)HAp/PL以cage的性能测定
1.粘度法队p/PLLA复合材料热压前后粘均分子量测定。
2.HAp/PLLA cage初始力学强度分析，测定不同组分Cage样件的
初始生物力学强度和弹性模量。
3.用扫描电子显微镜对HAp/PLLA Cage表面进行分析观察。
4.不同组分的HAp/PLLA cage体内外降解性能测定，样件的力学性
能、失重率、和粘均分子量进行分析比较。
结果
一用国产L一乳酸缩聚产物LLA开环聚合后制得的PLLA粗品经甲
醇溶解沉淀得精PLLA的分子量为318.363KDa。合成相对高分子质量PL以
的最佳条件是单体LLA/引发剂异辛酸亚锡的摩尔比为8000/1，反应温度
130oC，反应时间48h。
二.用化学液相一沉淀法制得的HAp材料具有较理想的结晶度，队p
材料Ca/P(摩尔比)=1.67，密度为2.499/em。H3PO。和Ca(OH)2的最
佳反应浓度分别为0.3%和0.smol/l，反应温度60℃，反应液pH值9，
反应时间7小时。
三.用溶液一超声分散法合成密度均匀的队p/PLLA复合材料，热压
模铸法制备颈椎椎间融合cage的最佳压制温度为170℃、压力IOMPa、
压力保持时间巧分钟。
四.HAp/PLLAcage特征与成份比重有显著相关性:PLLA比重增大，
材料的粘均分子量、初始力学强度和弹性模量均相应增高，而降解速度
缓慢;HAp/PLLA cage降解速度与降解时间呈类反比曲线特征:前16周
降解较快，24周后速度减缓;
五.组分为35/65的HAp/PLLA cage体内降解速度快于体外降解，
在体内降解40周的整个过程中表现出足够的生物力学性能(。:a、
>94.7MPa)。
结论
一利用国产左旋乳酸可以制得高光学活性的PLLA。
二.利用化学液相共沉淀法和高温烧结可以制得高结晶度的HAp。
三.利用溶液超声分散法可以合成密度均匀的HAp/PLLA复合材料。
四.HAp/PLLA复合材料的热压模铸、车床车削可以加工成形螺纹柱
状、锥度为8“的空心颈椎椎间融合cage。
五.35/65组分的HAp/PLLA复合材料制备的颈椎椎间融合器(cage)，
具有优良的初始生物力学性能和体内外降解特征，结合临床要求，是其
中的最优选择。
Objective To fabricate the active biodegradable polymer cage of cervical intervertebral fusion, the poly-L-lactide with high molecular weight and the powders of hydroxyapatite will be firstly prepared by chemical codeposition and open-loop polymerization respectively. They will be commixed well-proportioned in the solution of chloroform in different ratio of weight, the composite will be hot-pressed and machined into cages which are in definite specs, the best one with well characteristics of physics and chemistry will be choosed.
Methods
1. The preparation and token of raw and processed materials.
CD The preparation of poly-L-lactic with high molecular weight: L-lactic monomers made in China were dehydrated and polymerized into poly-L-lactics which were purified by filtration and deposition.
(2) The preparation of powder of hydroxyapatite: The counteraction was taken between 0.3% H3PO4 and Ca (OH) 2 in solution, the productions were filtrated and sintered at 800 C,then they were comminuted into powder.
(3) The token of raw and processed materials: The viscosity-average molecular weight, the rotation of the plane of polarization of polarized light, the 'H-NMR spectrum and the contents of tantalum of PLLA were measured. The characteristics (density and crystallization) of hydroxyapatite were analyzed.
2. The fabrication and machining of HAp/PLLA cages.
?The compounding of HAp/PLLA: The powder of hydroxyapatite and poly-L-lactic was mixed symmetrically together in the solution of
chloroform in different ratio of weight (50/50, 35/65, 15/85 and 0/100) .
(D After the chloroform was vaporized completely, the dry composites were hot-pressed and founded in cylindrical mold, and then machined into cages which are hollow and whose surface is screw threaded.
(3) The measuring of the characteristics of HAp/PLLA cage: The surficial structural character of HAp/PLLA composites were observed by scanning electron microscope (SEM). The viscosity-average molecular weight of HAp/PLLA composites pre-hot pressing and pro-hot pressing and the prime biomechanics of HAp/PLLA cage including terminal compressive stress and the module of elasticity were measured. The degradation characteristics of HAp/PLLA cage in different ratio of weight were also analyzed in vitro and in vivo.
Result
1. The PLLA with higher viscosity-average molecular weight 318.363KDa was achieved by using monomer/initiator mole ratio of 8000 and polymerization at 130C for 48h.The purification of PLLA can be increased by dissolution-precipitation treatment of the as-products.
2. The HAp with higher purification and crystallization can be achieved by using the concentration of H3PO4and Ca (OH) 2 of 0.3% and 0.5mol/l respectively, and reaction at 60 癈 and pH value 9 for 7h.
3. The HAp/PLLA composites of different ratio of weight can be gained using solution-ultrasonic decentralization. The HAp/PLLA cage can be founded at 170癈 and under the pressure of lOMPa for 15min.
4. The study on HAp/PLLA cages on different ratio of weight indicated that the correlation is positive between the characteristics including viscosity-average molecular weight, prime biomechanical stress and module of elasticity and the content of PLLA in composites, but the velocity of degradation is reverse. The relation of velocity and times of degradation shows a similarity of inverse proportion curves, the change is larger pre 16 weeks, and smaller pro 24 weeks.
5. The experiments of degradation of HAp/PLLA cages with 35/65
weight ratio showed that the velocity of degradation in vivo is faster than in vitro, the biomechanics of that are all well.
Conclusion The PLLA with higher viscosity-average molecular weight can be synthesized using L-lactic monomers made in China by open-loop polymerization. The powder of HAp with high purification and crystallization can be gained by chemical codeposition and sintered. The HAp/PLLA composites have symmetrical density by solution-ultrasonic deconcentration, the HAp/PLLA cage
通过开环聚合和化学共沉淀法制备相对高分子量的PLLA和HAp晶体粉末，测试它们的基本理化性能；以氯仿为溶剂，将超细微HAp粉末按比例分散在PLLA的氯仿溶液中，用溶液—超声分散法合成不同组分(50/50、35/65、15/85、0/100)的HAp/PLLA复合材料，热压模铸并车削加工成一定规格的颈椎椎间融合cage样件，对其基本生物学性能和体内外降解特征进行研究，选择并制备出性能良好的生物活性可降解颈椎椎间融合器。
方法
一．原材料的制备和表征
(一)相对高分子量PLLA的制备
1．国产L—乳酸在催化剂氧化锌的作用下脱水、缩聚成相对低分子量的聚L—乳酸，减压并高温裂解得LLA。
2．用乙酸乙酯重结晶的丙交酯单体在引发剂作用下真空聚合生成PLLA粗品。
3．将聚合物粗品用氯仿溶解、甲醇中沉淀过滤，真空干燥后底精品PLLA。
(二)超微HAp粉末的制备
1．在pH为9、反应温度60℃、反应时间7小时条件下，使0.3％的H_3PO_4溶液和Ca(OH)_2悬浮液发生中和反应，负压抽滤并真空干燥得产物HAp。
2．生成物HAp在800℃下高温煅烧3h，研磨过175μm筛制得HAp超微粉。
(三)原材料的表征
1．粘度法测算PLLA分子的粘均分子量，并对其分子的旋光度、核磁
光谱和金属元素成份进行分析。
2.X一射线衍射(XRD)分析法测定HAp的晶相特征，比重瓶法测算
HAp的密度和比重。
二·HAp/PLLA cage的制作及性能测定
(一)HAp/PLLA复合材料的共混复合
以氯仿为溶剂，将超细微队p粉末按比例分散在PLLA的氯仿溶液中，
用溶液一超声分散法合成不同组分(50/50、35/65、一5/85、0/100)的
HAp/PLLA复合材料。
(二)HAp/PLLA eage的模铸加工
1.在模铸温度为170℃、压力10MPa、恒压巧分钟条件下，将粉碎
后的HAp/PLLA材料在干燥柱形模具中热压成圆柱形棒材。
2.将压成圆柱形棒材在普通车床上车削加工成螺柱状空心cage。
(三)HAp/PL以cage的性能测定
1.粘度法队p/PLLA复合材料热压前后粘均分子量测定。
2.HAp/PLLA cage初始力学强度分析，测定不同组分Cage样件的
初始生物力学强度和弹性模量。
3.用扫描电子显微镜对HAp/PLLA Cage表面进行分析观察。
4.不同组分的HAp/PLLA cage体内外降解性能测定，样件的力学性
能、失重率、和粘均分子量进行分析比较。
结果
一用国产L一乳酸缩聚产物LLA开环聚合后制得的PLLA粗品经甲
醇溶解沉淀得精PLLA的分子量为318.363KDa。合成相对高分子质量PL以
的最佳条件是单体LLA/引发剂异辛酸亚锡的摩尔比为8000/1，反应温度
130oC，反应时间48h。
二.用化学液相一沉淀法制得的HAp材料具有较理想的结晶度，队p
材料Ca/P(摩尔比)=1.67，密度为2.499/em。H3PO。和Ca(OH)2的最
佳反应浓度分别为0.3%和0.smol/l，反应温度60℃，反应液pH值9，
反应时间7小时。
三.用溶液一超声分散法合成密度均匀的队p/PLLA复合材料，热压
模铸法制备颈椎椎间融合cage的最佳压制温度为170℃、压力IOMPa、
压力保持时间巧分钟。
四.HAp/PLLAcage特征与成份比重有显著相关性:PLLA比重增大，
材料的粘均分子量、初始力学强度和弹性模量均相应增高，而降解速度
缓慢;HAp/PLLA cage降解速度与降解时间呈类反比曲线特征:前16周
降解较快，24周后速度减缓;
五.组分为35/65的HAp/PLLA cage体内降解速度快于体外降解，
在体内降解40周的整个过程中表现出足够的生物力学性能(。:a、
>94.7MPa)。
结论
一利用国产左旋乳酸可以制得高光学活性的PLLA。
二.利用化学液相共沉淀法和高温烧结可以制得高结晶度的HAp。
三.利用溶液超声分散法可以合成密度均匀的HAp/PLLA复合材料。
四.HAp/PLLA复合材料的热压模铸、车床车削可以加工成形螺纹柱
状、锥度为8“的空心颈椎椎间融合cage。
五.35/65组分的HAp/PLLA复合材料制备的颈椎椎间融合器(cage)，
具有优良的初始生物力学性能和体内外降解特征，结合临床要求，是其
中的最优选择。
Objective To fabricate the active biodegradable polymer cage of cervical intervertebral fusion, the poly-L-lactide with high molecular weight and the powders of hydroxyapatite will be firstly prepared by chemical codeposition and open-loop polymerization respectively. They will be commixed well-proportioned in the solution of chloroform in different ratio of weight, the composite will be hot-pressed and machined into cages which are in definite specs, the best one with well characteristics of physics and chemistry will be choosed.
Methods
1. The preparation and token of raw and processed materials.
CD The preparation of poly-L-lactic with high molecular weight: L-lactic monomers made in China were dehydrated and polymerized into poly-L-lactics which were purified by filtration and deposition.
(2) The preparation of powder of hydroxyapatite: The counteraction was taken between 0.3% H3PO4 and Ca (OH) 2 in solution, the productions were filtrated and sintered at 800 C,then they were comminuted into powder.
(3) The token of raw and processed materials: The viscosity-average molecular weight, the rotation of the plane of polarization of polarized light, the 'H-NMR spectrum and the contents of tantalum of PLLA were measured. The characteristics (density and crystallization) of hydroxyapatite were analyzed.
2. The fabrication and machining of HAp/PLLA cages.
?The compounding of HAp/PLLA: The powder of hydroxyapatite and poly-L-lactic was mixed symmetrically together in the solution of
chloroform in different ratio of weight (50/50, 35/65, 15/85 and 0/100) .
(D After the chloroform was vaporized completely, the dry composites were hot-pressed and founded in cylindrical mold, and then machined into cages which are hollow and whose surface is screw threaded.
(3) The measuring of the characteristics of HAp/PLLA cage: The surficial structural character of HAp/PLLA composites were observed by scanning electron microscope (SEM). The viscosity-average molecular weight of HAp/PLLA composites pre-hot pressing and pro-hot pressing and the prime biomechanics of HAp/PLLA cage including terminal compressive stress and the module of elasticity were measured. The degradation characteristics of HAp/PLLA cage in different ratio of weight were also analyzed in vitro and in vivo.
Result
1. The PLLA with higher viscosity-average molecular weight 318.363KDa was achieved by using monomer/initiator mole ratio of 8000 and polymerization at 130C for 48h.The purification of PLLA can be increased by dissolution-precipitation treatment of the as-products.
2. The HAp with higher purification and crystallization can be achieved by using the concentration of H3PO4and Ca (OH) 2 of 0.3% and 0.5mol/l respectively, and reaction at 60 癈 and pH value 9 for 7h.
3. The HAp/PLLA composites of different ratio of weight can be gained using solution-ultrasonic decentralization. The HAp/PLLA cage can be founded at 170癈 and under the pressure of lOMPa for 15min.
4. The study on HAp/PLLA cages on different ratio of weight indicated that the correlation is positive between the characteristics including viscosity-average molecular weight, prime biomechanical stress and module of elasticity and the content of PLLA in composites, but the velocity of degradation is reverse. The relation of velocity and times of degradation shows a similarity of inverse proportion curves, the change is larger pre 16 weeks, and smaller pro 24 weeks.
5. The experiments of degradation of HAp/PLLA cages with 35/65
weight ratio showed that the velocity of degradation in vivo is faster than in vitro, the biomechanics of that are all well.
Conclusion The PLLA with higher viscosity-average molecular weight can be synthesized using L-lactic monomers made in China by open-loop polymerization. The powder of HAp with high purification and crystallization can be gained by chemical codeposition and sintered. The HAp/PLLA composites have symmetrical density by solution-ultrasonic deconcentration, the HAp/PLLA cage
引文
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