新型改性的n-HA与PLGA复合材料的制备及性能研究

引用本文

蒋立新, 蒋柳云, 马驰, 韩崇涛, 徐莉娟, 熊成东. 新型改性的n-HA与PLGA复合材料的制备及性能研究. 无机材料学报, 2013, 28(7): 751-756
JIANG Li-Xin, JIANG Liu-Yun, MA Chi, HAN Chong-Tao, XU Li-Juan, XIONG Cheng-Dong. Preparation and Characterization of Nano-hydroxyapatite/PLGA Composites with Novel Surface-modified Nano-hydroxyapatite. Journal of Inorganic Materials, 2013, 28(7): 751-756 复制到剪切板

Permissions

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

新型改性的n-HA与PLGA复合材料的制备及性能研究

蒋立新^1,², 蒋柳云¹, 马驰^1,², 韩崇涛^1,², 徐莉娟^1,², 熊成东¹

1. 中国科学院成都有机化学研究所, 成都 610041

2. 中国科学院大学, 北京 100049

蒋柳云, 副研究员. E-mail:jlytxg@163.com

蒋立新(1987-), 男, 硕士研究生. E-mail:jlx198765@126.com

基金:中国科学院“西部之光”人才培养计划项目; 国家自然科学基金(31000440);

摘要

采用硅烷偶联剂(KH550)和L-丙交酯LLA联合接枝处理的新方法对纳米羟基磷灰石(n-HA)进行表面改性, 然后将其与聚乳酸-羟基乙酸(PLGA)作不同比例复合(n-HA为3wt%、10wt%、20wt%及30wt%), 得到改性n-HA/PLGA复合材料(g-n-HA/PLGA)。将其与未改性n-HA及未改性n-HA/PLGA复合材料作对比检测。结果表明, 该联合处理方法是n-HA进行表面接枝改性的新型有效方法。且改性处理后的n-HA与未改性处理的n-HA相比, 能更好地在PLGA基体中分散均匀, 并能提高PLGA结晶能力和PLGA的力学性能。当改性处理后的n-HA添加量为10wt%时, 其复合材料抗弯强度和拉伸强度分别比未改性n-HA/PLGA提高14.4%和11.3%。该新型g-n-HA/PLGA复合材料有望用作骨折固定材料。

关键词: 纳米羟基磷灰石; 表面改性; 复合材料; PLGA

中图分类号:R318 文献标志码:A 文章编号:1000-324X(2013)07-0751-06

Preparation and Characterization of Nano-hydroxyapatite/PLGA Composites with Novel Surface-modified Nano-hydroxyapatite

JIANG Li-Xin^1,², JIANG Liu-Yun¹, MA Chi^1,², HAN Chong-Tao^1,², XU Li-Juan^1,², XIONG Cheng-Dong¹

1. Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China

2. Graduated University of the Chinese Academy of Sciences, Beijing 100049, China

Fund:Talent Training Project of West Light Foundation of Chinese Academy of Science; National Natural Science Foundation of China (31000440);

Abstract

Nano-hydroxyapatite (n-HA) was modified by a new method of combining silane coupling reagent (KH550) with surface-grafting L-lactide LLA. Then, the surface-modified n-HA (g-n-HA) was introduced into poly(lactic-co-glycolic acid) (PLGA) to prepare a series of g-n-HA/PLGA composites with the concentration of 3wt%, 10wt%, 20wt% and 30wt%. The properties of the g-n-HA/PLGA composites were characterized and compared with PLGA and n-HA/PLGA composites. The results show that n-HA is successfully modified by KH550 and L-LA. The g-n-HA particles could disperse more uniformly in PLGA matrix and promote PLGA to crystallize. The obtained g-n-HA/PLGA composites has better mechanical properties than those of n-HA/PLGA composites with the same amount of n-HA. Moreover, the bending and tensile strength of g-n-HA/PLGA composite containing 10wt% g-n-HA are 14.4% and 11.3% which is higher than that of pure PLGA, respectively. Therefore, the g-n-HA/PLGA composite is promising for bone fracture internal fixation material in future.

Keyword: nano-hydroxyapatite (n-HA); surface modification; composite; PLGA

Show Figures

聚乳酸-羟基乙酸(PLGA)是由L-丙交酯和乙交酯两种单体共聚合而成的高分子共聚物, 是目前常用的骨折固定材料, 但单纯的PLGA材料作为骨折固定材料在临床应用中仍然存在一些缺点, 如力学强度不足, 降解酸性产物过多, 且缺乏成骨活性。随着纳米技术的出现, 将无机纳米粒子添加于PLGA基体中以改善其固有的缺陷已成为研究热点^{[ 1, 2]}。

纳米针状羟基磷灰石(n-HA)微晶在形态、晶体结构和结晶度上与人体骨组织的磷灰石相似, 具有良好的生物相容性和骨传导性, 是公认的性能良好的骨修复材料^{[ 3]}。但由于n-HA粒子粒径小极易团聚、亲水性好, 不易与疏水性PLGA基体界面相容, 导致复合材料力学性能不佳, 因而需要对n-HA粒子表面进行改性^{[ 4]}。近年来, 有关 n-HA的表面改性有聚多酸、硅烷偶联剂和十二烷醇等^{[ 5, 6, 7]}, 其中丙交酯接枝处理效果较好^{[ 8, 9]}, 即利用n-HA表面的羟基引发丙交酯开环聚合, 得到表面接枝有聚乳酸的n-HA, 从而改善其与PLGA复合的界面相容性。但通常将n-HA直接与丙交酯接枝时, 由于亲水性n-HA在疏水性溶剂中很难均匀稳定分散, 且n-HA本身表面的-OH活性不高, 因而不利于接枝反应, 以致复合后的材料力学性能不能有效提高, 尤其是n-HA以高含量复合时抗弯强度获得提高的报道甚少, 而抗弯强度是骨折固定材料的一个重要力学性能指标, 因而有必要探索n-HA的新型改性法以获得PLGA抗弯强度能有效提高的复合材料。

本研究采用新的改性方法对n-HA粒子进行表面处理, 即先将n-HA用硅烷偶联剂(KH550)处理, 再与丙交酯接枝处理, 一方面可以改善n-HA接枝前的表面疏水性, 以防止其团聚, 另一方面也可利用KH550的-NH₂引发丙交酯开环聚合, 以改善其接枝反应。将上述改性得到的n-HA以不同比例与PLGA复合, 以纯PLGA及未改性的n-HA/PLGA复合材料作为对照, 考察该新型改性法处理的n-HA在PLGA基体中的分散性、复合材料的热力学性能和力学性能。

1 材料和方法

1.1 原材料

n-HA粒子长径为100~120 nm, 短径为20~40 nm, PLGA(95/05)分子量为3.6×10⁵~3.9×10⁵, 均由本实验室自制; γ-氨丙基三乙氧基硅烷(KH550), 四川晨光工程设计院; L-丙交酯, Purac公司; 辛酸亚锡, 美国Sigma公司; 其它试剂都为分析纯。

1.2 n-HA的表面改性

将10 g n-HA超声分散于60 mL乙醇和水的混合液中, 加入含2 g KH550的50 mL乙醇和水(9:1)混合的水解液, 用NaOH溶液调节pH为9~10, 70℃下反应8 h, 离心并用热水洗涤3遍, 产物于130℃下真空干燥8 h, 记为KH550-n-HA。将KH550-n-HA超声分散于100 mL二甲苯中, 加入0.05 g 辛酸亚锡催化剂, 于氮气保护下138℃反应2 h后, 再加入100 mL含10 g丙交酯的二甲苯溶液, 继续反应18 h, 用二氯甲烷离心洗涤5遍, 于50℃下真空干燥24 h。最终改性产物记为g-n-HA。

1.3 g-n-HA/PLGA复合材料的制备

将g-n-HA粉末于二氯甲烷和乙醇混合液中超声分散后, 按质量分数分别为3wt%、10wt%、20wt%、30wt%的量加入PLGA的二氯甲烷溶液中, 超声搅拌4 h后用大量无水乙醇沉淀。将沉淀过滤并用无水乙醇洗涤3遍, 40℃真空干燥备用。复合材料记为g-n-HA/PLGA。同时按以上过程制备一系列同比例n-HA未经改性的n-HA/PLGA复合材料用于对比研究。

1.4 测试与表征

将KH550-n-HA、g-n-HA和n-HA粉末用美国Nicolet公司(6700)红外光谱仪进行测试; 将g-n-HA和n-HA粉末用X SAM-800型XPS对样品表面元素状态进行分析, 用Perkin-Elmer 7型热重分析仪在N₂气氛中以10℃/min速率从室温升至700℃, 测定样品失重率; 用JEM-100CX型电子显微镜和直观照片分别观察形貌及其在疏水性溶剂中的分散稳定性。

将g-n-HA/PLGA与n-HA/PLGA复合材料加工成型后, 取样品断面喷金后在扫描电子显微镜(SEM, S-520, 日本HITACHI公司)下观察其微观结构; 用差示扫描量热仪(DSC, Q20, 美国TA instruments公司)测试复合材料及纯PLGA的热力学性能; 采用万能材料试验机(SANSCMT4503, 中国深圳SANS公司)对复合材料及纯PLGA按GB/T1042-92标准测试弯曲及拉伸性能, 每个样品测5个平行样取平均值。

2 结果与讨论

2.1 n-HA的改性

2.1.1 IR分析

图1为n-HA、KH550-n-HA及g-n-HA的红外光谱图。从图可知, 未改性的n-HA(图1a)特征峰有PO₄^3- 吸收峰(962.0、1038.7、1091.5、471.8、565.1以及602.7 cm^-1)和-OH吸收峰(3570.1及630.6 cm^-1); 另外在1452和1413 cm^-1还出现双峰, 属CO₃^2-反对称伸缩峰, 表明CO₃^2-进入 HA晶格, 与文献报道相一致^{[ 10]}。对于KH550-n-HA样品(图1b), 相比于n-HA, PO₄^3- 吸收峰无明显变化, 而3570.1以及630.6 cm^-1处的-OH吸收峰变弱, 且在2931.8 cm^-1处出现C-H伸缩振动峰, 在3422.8 和692.3 cm^-1处分别出现了-NH₂的N-H的伸缩振动峰和弯曲振动峰, 表明KH550与n-HA之间存在化学键合作用, 即KH550已接枝在n-HA表面。g-n-HA样品(图1c)显示依然出现n-HA特征峰, 但692.3 cm^-1的-NH₂的N-H峰发生了轻微的偏移, 同时在2984.9、2938.2和2880.2 cm^-1处出现更强的C-H伸缩振动峰, 且在1751.7 cm^-1处出现酯羰基吸收峰^{[ 11, 12]}, 证明聚乳酸已接枝于n-HA表面, 且改性后的g-n-HA其主要化学组分并未发生改变。由此证明采用KH550和LLA联合处理法可对n-HA有效接枝。

	Figure Option View Download New Window
	图1 n-HA改性前后的红外光谱图Fig. 1 IR spectra of n-HA before and after modification(a) n-HA; (b) KH550-n-HA; (c) g-n-HA

2.1.2 XPS能谱分析

为进一步确证其接枝改性成功, 采用XPS对n-HA与g-n-HA进行了表面化学元素分析。图2和表1分别给出了改性前后的全扫描XPS能谱图和元素含量。从图可以看出, 改性前主要有Ca、P、O及C元素, 改性后还出现了Si、N元素, 证明KH550已接枝于n-HA表面; 从元素含量变化也可看出g-n-HA中新增了Si和N元素, 且C元素含量比改性前明显提高, 证明KH550和聚乳酸已成功接枝于n-HA表面^{[ 6]}, 这与红外分析结果一致。

	Figure Option View Download New Window
	图2 n-HA经表面改性前后的全扫描XPS能谱图Fig. 2 XPS spectra of n-HA before and after modification(a)n-HA; (b) g-n-HA

表1 表面改性前后n-HA粒子的元素分析(at%) Table 1 Contents of different elements of n-HA particles before (n-HA) and after (g-n-HA) modification(at%)

2.1.3 TGA测试

图3热失重曲线显示n-HA的失重率为4.703%, 这主要是由于n-HA表面的水分、结晶水以及HA晶格中的水造成的, 与文献报道数据基本一致^{[ 13]}。而g-n-HA的失重率为8.097%, 结合前面IR及XPS分析, 分析其失重主要是由接枝的KH550及聚乳酸在升温过程中燃烧造成的, 由此更定量说明该新型接枝改性确已在n-HA表面发生。

	Figure Option View Download New Window
	图3 n-HA改性前后的TGA曲线Fig. 3 TGA curves of HA before and after modification(a) n-HA; (b) g-n-HA

2.1.4 分散性观察

图4和图5是考察改性后n-HA在疏水性溶剂二氯甲烷中分散性的结果, 图4为n-HA和g-n-HA的TEM照片。照片显示n-HA改性后形貌尺寸略有变大, 为表面接枝包覆引起。从图5可看出, n-HA在30 min内已从二氯甲烷中逐渐沉淀完全, 而g-n-HA则在2 h内仍然保持良好的分散。这说明经表面改性的g-n-HA分散性明显改善, 将有助于其与PLGA在二氯甲烷溶液中进行均匀复合^{[ 14]}。

	Figure Option View Download New Window
	图4 n-HA改性前后的TEM照片Fig. 4 TEM micrographs of HA before and after modification(a) n-HA; (b) g-n-HA

	Figure Option View Download New Window
	图5 改性前后的n-HA 在二氯甲烷中分散不同时间点的照片Fig. 5 Photographs of n-HA (a) and g-n-HA (b) dispersed in dichloromethane at different stages

2.1.5 改性机理分析

通过以上分析, 该新型改性机理推测如下: 首先是偶联剂KH550在碱性水溶液中主要发生如下反应:H₂N(CH₂)₃Si(OCH₃)₃ + H₂O→H₂N(CH₂)₃Si(OH)₃ + CH₃OH

由于n-HA浆料具有较大的比表面积, 在溶液中其表面存在很多悬空键, 有大量活性中心, 可与水解后的偶联剂反应。其偶联结合方式有两种^{[ 6]}: 第一种是Si-OH与n-HA上的-OH、HPO₄^2-、PO₄^3-基团形成强的化学键; 第二种可能是硅羟基或氨基与n-HA表面的-OH、HPO₄^2-形成氢键。但由于产物经水热洗涤过多遍, 结合以上IR分析结果推测该新型改性可能以第一种结合方式为主, 即KH550连接在n-HA表面后, 再利用其末端氨基引发L-LA的开环聚合。整个改性过程如图6所示。

	Figure Option View Download New Window
	图6 n-HA表面改性的示意图Fig. 6 Illustration for the surface modification of n-HA

2.2 复合材料

2.2.1 SEM观察

由于纳米粒子在高聚物基体中的微观结构与复合材料的力学强度紧密相关, 故本研究观察了复合材料断面SEM形貌(图7)。从照片可知, 未经改性的n-HA纳米粒子在基质中的团聚现象严重(图中箭头所示), 且界面结合较差; 而改性处理后的g-n-HA粒子则具有更好的分散性和界面结合。n-HA采用直接接枝后含量为15wt%时在PLLA中的分散会出现大块团聚^{[ 15]}。相比之下, 本研究中的g-n-HA分散性明显改善, 说明所探索的新型改性方法能有效改善n-HA在PLGA中的分散性及界面相容性。

	Figure Option View Download New Window
	图7 n-HA/PLGA复合材料的断裂面SEM照片Fig. 7 Fracture surfaces of n-HA/PLGA composites(a)-(d): n-HA/PLGA; (A)-(D):g-n-HA/PLGA

2.2.2 DSC分析

对材料的DSC分析可以从微观上了解其结晶性能。表2数据显示, 复合材料的熔点 T_m和玻璃化温度 T_g都比纯PLGA低; 熔融焓 △H_m和结晶度 X_c都随着n-HA含量的增加呈递增趋势, 且添加相同量的n-HA时, g-n-HA/PLGA复合材料的 △H_m和 X_c都比n-HA/PLGA的大。这一方面是由于添加的n-HA起到了异相成核作用^{[ 16]}, 加快了PLGA成核的速度, 另一方面是由于加入n-HA后基质链段可以吸附在其表面有序排列, 提高结晶速率, 从而使结晶能力增强; 同时经改性的n-HA表面接枝的PLLA链段能更有效地与基质PLGA链段相互穿插缠绕, 使得界面结合强度增加, 从而使基质链段更易于吸附于n-HA粒子表面成核结晶, 此外, 改性后的n-HA粒子在PLGA基体中更好的分散性也可提高复合材料的结晶能力。显然, 复合材料结晶能力的提高也有利于其力学性能的提高。

表2 HA/PLGA复合材料的热力学性能 Table 2 Thermal properties of HA/PLGA nano-composites determined by DSC

2.2.3 力学性能测试

对于骨折固定材料来说, 材料的初始力学性能是临床应用中重要的指标。图8给出了两类复合材料的抗弯强度及拉伸强度随n-HA含量变化的曲线图。从图可知, n-HA/PLGA复合材料的抗弯强度和拉伸强度比不添加n-HA的纯PLGA要低, 且添加量越高, 强度越低, 未体现出纳米粒子对PLGA力学性能提高的效果。而g-n-HA/PLGA复合材料在添加量不超过10%时, 抗弯强度和拉伸强度均有提高, 当添加量为10wt%时达到最高值, 其抗弯强度和拉伸强度分别比不添加n-HA的PLGA提高了14.4%和11.3%。与文献报道相比^{[ 15]}, 本研究制备的g-n-HA添加量可更高, 力学性能增强效果也更明显, 可满足松质骨固定力学性能的要求。但添加量过高时, 力学性能反而比纯PLGA低, 这与纳米粒子增强聚合物力学性能的一般规律相符。

	Figure Option View Download New Window
	图8 HA/PLGA复合材料的力学强度Fig. 8 Mechanical properties of HA/PLGA composites(a) Bending strength; (b) Tensile strength

3 结论

1) 基于KH550的偶联剂作用及提供-NH₂与丙交酯开环聚合的特性, 采用联合接枝处理法对n-HA进行了表面改性, 经各种表征证实该联合处理法能有效对n-HA进行表面接枝, 是一种新型n-HA改性方法。

2) 将新型改性法处理得到的g-n-HA以不同质量比与PLGA复合后, 与未经改性的n-HA/PLGA复合材料相比, 前者更能在PLGA基体中均匀分散, 更有效提高PLGA结晶能力和力学性能。

3) 当改性得到的g-n-HA添加量达10wt%时, g-n-HA/PLGA复合材料抗弯强度及拉伸强度分别比纯PLGA提高了14.4%和11.3%, 有望用作骨折固定材料。

参考文献

View Option

[1]	Fiedler T, Belova I V, Murch GE, et al. Tailoring elastic properties of PLGA/TiO₂ biomaterials. Computational Materials Science, 2012, 61(8): 283-286. [本文引用:1] [JCR: 1.878]
[2]	Ebrahimian-Hosseinabadi M, Ashrafizadeh F, Etemadifar M, et al. Evaluating and modeling the mechanical properties of the prepared PLGA/nano-BCP composite scaffolds for bone tissue engineering. Journal of Materials Science & Technology, 2011, 27(12): 1105-1112. [本文引用:1] [JCR: 2.163]
[3]	Orlovskii V P, Komlev V S, Barinov S M. Hydroxyapatite and hydroxyapatite-based ceramics. Inorganic Materials, 2002, 38(10): 973-984. [本文引用:1] [JCR: 0.376]
[4]	Yang C, Cheng K, Weng W, et al. OTS-modified HA and its toughening effect on PLLA/HA porous composite. Journal of Materials Science: Materials in Medicine, 2009, 20(3): 667-672. [本文引用:1] [JCR: 2.141]
[5]	Liu Q, de Wijn JR, Bakker D, et al. Polyacids as bonding agents in hydroxyapatite polyester-ether (polyactiveTM 30/70) composites. Journal of Materials Science: Materials in Medicine, 1998, 9(1): 23-30. [本文引用:1] [JCR: 2.141]
[6]	LIAO Jian-Guo, WANG Xue-Jiang, ZUO Yi, et al. Surface modification of nano-hydroxyapatite with silane agent. Journal of Inorganic Materials, 2008, 23(1): 145-149. [本文引用:3] [JCR: 0.531] [CJCR: 1.106]
[7]	Borum-Nicholas L, Wilson Jr OC. Surface modification of hydroxyapatite. Part I. Dodecyl alcohol. Biomaterials, 2003, 24(21): 3671-3679. [本文引用:1]
[8]	Cui Y, Liu Y, Cui Y, et al. The nanocomposite scaffold of poly(lactide-co-glycolide) and hydroxyapatite surface-grafted with l-lactic acid oligomer for bone repair. Acta Biomaterialia, 2009, 5(7): 2680-2692. [本文引用:1] [JCR: 5.093]
[9]	于婷, 刘娅, 王宇, 等(YU Ting, et al). 改性纳米羟基磷灰石/PLGA复合材料的制备及生物活性. 高等学校化学学报(Chem. J. Chinese U. ), 2009, 30(7): 1439-1444. [本文引用:1] [JCR: 0.856] [CJCR: 0.949]
[10]	Jiang L Y, Li Y B, Zhang L, et al. Preparation and properties of a novel bone repair composite: nano-hydroxyapatite/chitosan/ carboxymethyl cellulose. Journal of Materials Science-Materials in Medicine, 2008, 19(3): 981-987. [本文引用:1] [JCR: 2.141]
[11]	Hong Z, Qiu X, Sun J, et al. Grafting polymerization of l-lactide on the surface of hydroxyapatite nano-crystals. Polymer, 2004, 45(19): 6699-6706. [本文引用:1] [JCR: 3.379]
[12]	Li J, Lu X L, Zheng Y F. Effect of surface modified hydroxyapatite on the tensile property improvement of HA/PLA composite. Applied Surface Science, 2008, 255(2): 494-497. [本文引用:1] [JCR: 2.112]
[13]	Tonsuaadu K, Peld M, Leskela T, et al. A themroanalytical study of synthetic carbonate-conatining apatites. Thermochimica Acta, 1995, 256(1): 55-65. [本文引用:1] [JCR: 1.989]
[14]	Wei J, Liu A, Chen L, et al. The surface modification of hydroxyapatite nanoparticles by the ring opening polymerization of γ-benzyl-L-glutamate N-carboxyanhydride. Macromolecular Bioscience, 2009, 9(7): 631-638. [本文引用:1] [JCR: 3.742]
[15]	Hong Z K, Zhang P B, He C L, et al. Nano-composite of poly (L-lactide) and surface grafted hydroxyapatite: mechanical properties and biocompatibility. Biomaterials, 2005, 26(32): 6296-6304. [本文引用:2] [JCR: 7.604]
[16]	LI Hai-Yan, TAN Ye-Qiang, ZHANG Lu, et al. Bio-filler from mussel shell: preparation and its effects on polypropylene composites properties. Journal of Inorganic Materials, 2012, 27(9): 977-983. [本文引用:1] [JCR: 0.531] [CJCR: 1.106]

2012

1.878

0.0

... 随着纳米技术的出现, 将无机纳米粒子添加于PLGA基体中以改善其固有的缺陷已成为研究热点^[1,2] ...

2011

2.163

0.0

Journal of Materials Science & Technology. 2011, 27(12):1105-1112

Evaluating and modeling the mechanical properties of the prepared PLGA/nano-BCP composite scaffolds for bone tissue engineering

1) Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran 2) Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran 3) Orthopedic Departments, School of Medicine, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran 4) Materials Science & Engineering School, Nanyang Technological University, 637819, Singapore

In this paper, preparation of nano-biphasic calcium phosphate (nBCP), mechanical behavior and load-bearing of poly (lactide-co-glycolide) (PLGA) and PLGA/nBCP are presented. The nBCP with composition of 63/37 (w/w) HA/β-TCP (hydroxyapatite/β-tricalcium phosphate) was produced by heating of bovine bone at 700°C. Composite scaffolds were made by using PLGA matrix and 10-50 wt% nBCP powders as reinforcement material. All scaffolds were prepared by thermally induced solid-liquid phase separation (TIPS) at -60°C under 4 Pa (0.04 mbar) vacuum. The results of elastic modulus testing were adjusted with Ishai-Cohen and Narkis models for rigid polymeric matrix and compared to each other. PLGA/nBCP scaffolds with 30 wt% nBCP showed the highest value of yield strength among the scaffolds. In addition, it was found that by increasing the nBCP in scaffolds to 50 wt%, the modulus of elasticity was highly enhanced. However, the optimum value of yield strength was obtained at 30 wt% nBCP, and the agglomeration of reinforcing particles at higher percentages caused a reduction in yield strength. It is clear that the elastic modulus of matrix has the significant role in elastic modulus of scaffolds, as also the size of the filler particles in the matrix.

In this paper, preparation of nano-biphasic calcium phosphate (nBCP), mechanical behavior and load-bearing of poly (lactide-co-glycolide) (PLGA) and PLGA/nBCP are presented. nBCP with composition of 63/37 HA/β-TCP was produced by heating of bovine bone at 700 °C. Composite scaffolds were made by using PLGA matrix and 10-50 wt.% nBCP powders as reinforcement material. All scaffolds were prepared by thermally induced solid – liquid phase separation (TIPS) at -60 °C under 0.04 mbar vacuum. The results of elastic modulus testing were adjusted with Ishai-Cohen and Narkis models for rigid polymeric matrix and compared to each other. PLGA/nBCP scaffolds with 30 wt.% nano-BCP showed the highest value of yield strength among the scaffolds. In addition, it was found that by increasing the nBCP in scaffolds to 50 wt.%, the modulus of elasticity were highly enhanced. However, the optimum value of yield strength was obtained at 30 wt.% nBCP; the agglomeration of reinforcing particles at higher percentages caused a reduction in yield strength. It is clear that the elastic modulus of matrix has the significant role in elastic modulus of scaffolds, as also the size of the filler particles in the matrix.

... 随着纳米技术的出现, 将无机纳米粒子添加于PLGA基体中以改善其固有的缺陷已成为研究热点^[1,2] ...

2002

0.376

0.0

Inorganic Materials. 2002, 38(10):973-984 DOI:10.1023/A:1020585800572

Hydroxyapatite and hydroxyapatite-based ceramics

1.Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences 2.Institute of Physicochemical Problems in Ceramic Science, Russian Academy of Sciences

Data are summarized on the synthesis of hydroxyapatite (HA) by wet-chemical processes, solid-state reactions, and hydrothermal treatment. The conditions for HA preparation via precipitation from solutions of calcium chloride, dibasic ammonium phosphate, and aqueous ammonia are discussed at length. Detailed analysis of the fabrication and properties of calcium-phosphate-based ceramics is presented. The techniques for producing dense and porous HA ceramics are considered. The fabrication and medical applications of HA granules are discussed. Data are presented on HA-based composites.

... 纳米针状羟基磷灰石(n-HA)微晶在形态、晶体结构和结晶度上与人体骨组织的磷灰石相似, 具有良好的生物相容性和骨传导性, 是公认的性能良好的骨修复材料^[3] ...

2009

2.141

0.0

Journal of Materials Science: Materials in Medicine. 2009, 20(3):667-672 DOI:10.1007/s10856-008-3604-1

OTS-modified HA and its toughening effect on PLLA/HA porous composite

1.Zhejiang University Department of Materials Science and Engineering Hangzhou Zhejiang 310027 People’s Republic of China 2.Harbin University of Commerce College of Food Science and Engineering Harbin Heilongjiang 150076 People’s Republic of China

In this paper, hydroxyapatite (HA) particles was modified with long-chain organic silane-Octadecyltrichlorosilane (OTS), and the modified particles were further used for preparing Poly(l-lactic acid) PLLA/HA porous composite. The modified particles were characterized by means of XRD, FTIR, and XPS techniques. Both XPS and FTIR results showed that OTS had been combined with HA, and the formation of P–O–Si bond, a covalent bond, on the HA particle surface was confirmed by XPS. OTS-modified HA particles were used to prepare porous composites by thermally induced phase separation method. The results showed that the composite had an interconnected pore structure with 100–300 μm macropores. With OTS dosage increasing during modification, the mechanical properties of PLLA/OTS-modified HA porous composites increased obviously. These results showed that OTS modification can effectively improve the interface compatibility between HA surface and PLLA.

... 但由于n-HA粒子粒径小极易团聚、亲水性好, 不易与疏水性PLGA基体界面相容, 导致复合材料力学性能不佳, 因而需要对n-HA粒子表面进行改性^[4] ...

1998

2.141

0.0

... 近年来, 有关 n-HA的表面改性有聚多酸、硅烷偶联剂和十二烷醇等^[5,6,7], 其中丙交酯接枝处理效果较好^[8,9], 即利用n-HA表面的羟基引发丙交酯开环聚合, 得到表面接枝有聚乳酸的n-HA, 从而改善其与PLGA复合的界面相容性 ...

2008

0.531

1.106

Journal of Inorganic Materials. 2008, 23(1):145-149 DOI:10.3724/SP.J.1077.2008.00145

Surface modification of nano-hydroxyapatite with silane agent

Research Center for Nano-Biomaterials, Analytical & Testing Center, Sichuan University, Chengdu 610064, China

Nano-hydroxyapatite (n-HA) was modified by using silane coupling reagent (KH-560), and the interfacial interactions between n-HA and KH-560 was also studied. Fourier transform infrared spectra (FT-IR) and X-ray photoelectron spectra (XPS) analyses show that the silane coupling molecular binds strongly to n-HA surface. Chemical bonding (Si--O--P) is formed by the reaction between Si--OH and HPO ^2-₄ group, and a similar interface effect exists between Si--OH and the hydroxyl group of HA. Surface modification of HA particles can improve the mechanical strength of the n-HA/polycarbonate (n-HA/PC) composites dramatically. SEM observation shows that modified HA particles uniformly distribute in the PC matrix. The results indicate that the interfacial interaction between surface-modified inorganic particles and polymer matrix is crucial for the improvement of the mechanical strength of the composites.

采用硅烷偶联剂(KH-560)对纳米羟基磷灰石(n-HA)表面进行处理, 并研究了n-HA与KH-560的界面作用. 傅立叶红外光谱(FT-IR)以及X光电子能谱(XPS)分析表明, 偶联剂在羟基磷灰石表面黏附, 其中硅羟基(Si--OH)与磷酸氢根(HPO ^2-₄)基团之间脱水形成稳定的Si--O--P化学键, 此外, 硅羟基与HA表面--OH间亦脱水形成化学键合. 偶联处理的HA与聚碳酸酯(PC)复合后, 复合材料的力学强度与未经处理的相比有明显提高. 扫描电子显微镜(SEM)结果显示, 经处理后的HA微粒在PC中分散均匀, 两者间结合紧密, 表明无机有机复合材料间良好的界面作用是提高复合材料力学强度的重要途径.

... 从元素含量变化也可看出g-n-HA中新增了Si和N元素, 且C元素含量比改性前明显提高, 证明KH550和聚乳酸已成功接枝于n-HA表面^[6], 这与红外分析结果一致 ...

... 其偶联结合方式有两种^[6]: 第一种是Si-OH与n-HA上的-OH、HPO₄^2-、PO₄^3-基团形成强的化学键 ...

2003

0.0

Part I. Dodecyl alcohol. Biomaterials. 2003, 24(21):3671-3679 DOI:10.1016/S0142-9612(03)00239-4

Surface modification of hydroxyapatite

Abstract

The influence of esterification reactions on the surface chemistry and colloid stability of hydroxyapatite (HAP) was studied by aging nanophase HAP in dodecyl alcohol at elevated temperatures (115°C and 190°C). The esterified HAP particles were characterized by X-ray diffraction, transmission electron microscopy, diffuse reflectance infra-red Fourier transform spectroscopy (DRIFTS), thermal gravimetric analysis, sedimentation time studies, and electrophoretic mobility (μ) measurements in water and ethyl alcohol. DRIFTS analysis revealed that the HAP surface was modified by dodecyl groups based on the appearance of C–H stretch vibrational modes at 2962, 2930, and 2860 cm⁻¹. Dodecyl alcohol modified HAP exhibited a larger TGA mass loss upon heating (up to 4.8%) compared to untreated HAP (2.5–3.2 wt%). Sedimentation studies revealed the following stability trends: HAP dispersed in water was approximately the same as esterified HAP in water (a few hours)

2009

5.093

0.0

Acta Biomaterialia. 2009, 5(7):2680-2692 DOI:10.1016/j.actbio.2009.03.024

The nanocomposite scaffold of poly(lactide-co-glycolide) and hydroxyapatite surface-grafted with l-lactic acid oligomer for bone repair

Abstract

Nanohydroxyapatite (op-HA) surface-modified with l-lactic acid oligomer (LAc oligomer) was prepared by LAc oligomer grafted onto the hydroxyapatite (HA) surface. The nanocomposite of op-HA/PLGA with different op-HA contents of 5, 10, 20 and 40 wt.% in the composite was fabricated into three-dimensional scaffolds by the melt-molding and particulate leaching methods. PLGA and the nanocomposite of HA/PLGA with 10 wt.% of ungrafted hydroxyapatite were used as the controls. The scaffolds were highly porous with evenly distributed and interconnected pore structures, and the porosity was around 90%. Besides the macropores of 100–300 μm created by the leaching of NaCl particles, the micropores (1–50 μm) in the pore walls increased with increasing content of op-HA in the composites of op-HA/PLGA. The op-HA particles could disperse more uniformly than those of pure HA in PLGA matrix. The 20 wt.% op-HA/PLGA sample exhibited the maximum mechanical strength, including bending strength (4.14 MPa) and compressive strength (2.31 MPa). The cell viability and the areas of the attached osteoblasts on the films of 10 wt.% op-HA/PLGA and 20 wt.% op-HA/PLGA were evidently higher than those on the other composites. For the animal test, there was rapid healing in the defects treated with 10 and 20 wt.% op-HA/PLGA, where bridging by a large bony callus was observed at 24 weeks post-surgery. There was non-union of radius defects implanted with PLGA and in the untreated group. This was verified by the Masson’s trichrome staining photomicrographs of histological analysis. All the data extrapolated that the composite with 10 and 20 wt.% op-HA exhibited better comprehensive properties and were the optimal composites for bone repairing.

2009

0.856

0.949

Chem. J. Chinese U.. 2009, 30(7):1439-1444

YU Ting

(于婷) , (刘娅) , (王宇) , (等) ( YU Ting

1. State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; 2. School of Public Health, Jilin University, Changchun 130021, China

The hydroxyapatite(HA) nanocrystals of 100—200 nm in length and 20—30 nm in width were hydrothermally synthesized by the reaction of phosphoric acid and calcium hydroxide. Lactic acid oligomer surface grafted HA(op-HA) nanoparticles were obtained by oligomeric lactic acid with a certain molecular weight grafting onto the HA surface to form a Ca carboxylate bond in the absence of any catalyst. The op-HA was further blended with poly(lactide-co-glycolide)(PLGA) to prepare the nanocomposite of op-HA/PLGA. FTIR, TGA, ESEM and EDX were used to analyze grafting reaction, the graft ratio of op-HA, surface topography and calcium deposition of the composites, respectively. The rabbit osteoblasts were seeded and cultured on the surface of composites in vitro. The cell morphology, adhesion, proliferation and gene expression were evaluated with FITC staining, NIH image J software and the analysis of real-time PCR, respectively. The results show that the graft ratio of op-HA is 8.3%(mass fraction). The op-HA/PLGA nanocomposite possessed more suitable surface properties, including roughness and plenty of calcium and phosphor. It exhibited better cell adhesion, spreading and proliferation of rabbit osteoblasts compared to pure PLGA. Its gene expression of Collagen-I, Bone Morphogenetic Protein 2(BMP-2) and Osteonectin were higher than that of PLGA. It indicated that the biocompatibility and osteogenic bioactivity of the op-HA/PLGA nanocomposite were improved obviously than that of the pure PLGA.

以低聚乳酸接枝改性的羟基磷灰石纳米粒子(op-HA)和聚丙交酯-乙交酯(PLGA)制备的生物可降解纳米复合材料(op-HA/PLGA)为研究对象, 采用FTIR, TGA, ESEM和EDX分析其接枝反应、接枝率、表面形貌和钙磷沉积情况, 通过在材料膜表面接种兔成骨细胞进行体外培养, 采用荧光染色、NIH Image J图像分析和Real-time PCR综合评价细胞在材料表面的形态、黏附面积比、增殖能力和基因表达水平, 以此评价新型骨修复纳米复合材料op-HA/PLGA的表面性质和生物活性. 研究结果表明, op-HA的表面接枝率为8.3%, 掺入至PLGA后可形成富含钙磷的粗糙表面, 促进成骨细胞的黏附、扩展和增殖, 提高Ⅰ型胶原蛋白(Collagen-Ⅰ)、骨形态蛋白-2(BMP-2)和骨连接蛋白(Osteonectin)的基因表达水平, 提高材料的钙磷沉积能力. op-HA/PLGA具有良好的细胞相容性和成骨活性.

2008

2.141

0.0

Journal of Materials Science-Materials in Medicine. 2008, 19(3):981-987 DOI:10.1007/s10856-007-3208-1

Preparation and properties of a novel bone repair composite: nano-hydroxyapatite/chitosan/ carboxymethyl cellulose

1.Research Center for Nano-Biomaterials, Analytical & Testing Center, Sichuan University, Chengdu, 610064 China

Nano-hydroxyapatite/chitosan/carboxymethyl cellulose (n-HA/CS/CMC) composites with weight ratios of 70/10/20, 70/15/15 and 70/20/10 were prepared through a co-solution method. The properties of the composites were characterized by means of burn-out test, IR, XRD, TEM and universal material testing machine. The degradation and bioactivity were also investigated by in vitro test in a simulated body fluid (SBF) for 8 weeks. The results showed that n-HA particles were dispersed uniformly in organic phase, and strong chemical interactions formed among the three phases. Moreover, the composites were similar to natural bone in morphology and size. In addition, the compressive strength was improved compared with n-HA/CS composite. The biodegradation rate was controllable by altering weight ratio of the CS/CMC. Meanwhile, the composites could induce apatite particles to deposit in SBF. All the above results indicate that the novel composites of n-HA/CS/CMC have a promising prospect used for bone repair materials in view of the good mechanical property, adjustable biodegradation rate and bioactivity in SBF. Additionally, the study would provide a good guide to exploit clinical application of natural cellulose.

... 另外在1452和1413 cm^-1还出现双峰, 属CO₃^2-反对称伸缩峰, 表明CO₃^2-进入 HA晶格, 与文献报道相一致^[10] ...

2004

3.379

0.0

Polymer. 2004, 45(19):6699-6706 DOI:10.1016/j.polymer.2004.07.036

Grafting polymerization of l-lactide on the surface of hydroxyapatite nano-crystals

Abstract

A novel method of grafting ring-opening polymerization of l-lactide (LLA) onto the surface of hydroxyapatite nano-particles (n-HAP) was developed. PLLA was directly connected onto the HAP surface through a chemical linkage. The PLLA-g-HAP particles could be stably dispersed in organic solvent such as chloroform for several weeks. The n-HAP particles still retained the original dimension and shape after the grafting of PLLA. Compared with the ³¹P MAS-NMR spectrum of pure HAP powders, there appeared a downfield displacement of 1.2 ppm in the spectrum of PLLA-g-HAP. Fourier transformation infrared (FT-IR) spectra further confirmed the existence of PLLA on the surface of PLLA-g-HAP. The amount of grafted polymer determined by thermal gravimetric analysis (TGA) was about 6% in weight. The tensile strength and elongation at break of the PLLA/PLLA-g-HAP composite containing 8 wt% of PLLA-g-HAP were 55 MPa and about 10–13%, respectively, while those of the PLLA/n-HAP composites were 40 MPa and 3–5%, respectively.

... 7 cm^-1处出现酯羰基吸收峰^[11,12], 证明聚乳酸已接枝于n-HA表面, 且改性后的g-n-HA其主要化学组分并未发生改变 ...

2008

2.112

0.0

... 7 cm^-1处出现酯羰基吸收峰^[11,12], 证明聚乳酸已接枝于n-HA表面, 且改性后的g-n-HA其主要化学组分并未发生改变 ...

1995

1.989

0.0

... 703%, 这主要是由于n-HA表面的水分、结晶水以及HA晶格中的水造成的, 与文献报道数据基本一致^[13] ...

2009

3.742

0.0

... 这说明经表面改性的g-n-HA分散性明显改善, 将有助于其与PLGA在二氯甲烷溶液中进行均匀复合^[14] ...

2005

7.604

0.0

Biomaterials. 2005, 26(32):6296-6304 DOI:10.1016/j.biomaterials.2005.04.018

Nano-composite of poly (L-lactide) and surface grafted hydroxyapatite: mechanical properties and biocompatibility

Abstract

In order to improve the bonding between hydroxyapatite (HAP) particles and poly(l-lactide) (PLLA), and hence to increase mechanical properties of the PLLA/HAP composite as potential bone substitute material, the HAP nano-particles were surface-grafted with PLLA and further blended with PLLA. The structure and properties of the composites were subsequently investigated by the mechanical property testing, the differential scanning calorimeter measurements (DSC), the scanning electron microscopy (SEM), the polarized optical microscopy (POM), and the cell culture. The PLLA molecules grafted on the HAP surfaces, as inter-tying molecules, played an important role in improving the adhesive strength between the particles and the polymer matrix. At a low content (∼4 wt%) of surface grafted-HAP (g-HAP), the PLLA/g-HAP nano-composites exhibited higher bending strength and impact energy than the pristine PLLA, and at a higher g-HAP content (e.g., 20 wt%), the modulus was remarkably increased. It implied that PLLA could be strengthened as well as toughened by g-HAP nano-particles. The results of biocompatibility test showed that the g-HAP existing in the PLLA composite facilitated both adhesion and proliferation of chondrocytes on the PLLA/g-HAP composite film.

... n-HA采用直接接枝后含量为15wt%时在PLLA中的分散会出现大块团聚^[15] ...

... 与文献报道相比^[15], 本研究制备的g-n-HA添加量可更高, 力学性能增强效果也更明显, 可满足松质骨固定力学性能的要求 ...

2012

0.531

1.106

Journal of Inorganic Materials. 2012, 27(9):977-983 DOI:10.3724/SP.J.1077.2012.11653

Bio-filler from mussel shell: preparation and its effects on polypropylene composites properties

(1. Department of Ocean Science and Engineering, Zhejiang University, Hangzhou 310058, China; 2. Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China)

Waste mussel shell stacking with a significant odor and toxicity which are hazardous to human constitutes a serious environmental hazard. For utilization of waste mussel shell resource, granule of mussel shell (YBCC) was prepared from waste mussel shell by removing cuticle, crushing, grinding and shearing emulsification and was introduced as a filler to reinforce polypropylene (PP). The characterization results of YBCC show that the mainly composition of YBCC is aragonite (CaCO₃) platelets and the particle size distribution range of YBCC powder is from 40 nm to 500 nm, the proportion of organic components of YBCC is about 2.04wt% and YBCC has a good thermal stability. The mechanical behavior of PP/YBCC composite shows a higher yield strain, yield strength, tensile strength and elongation at break than traditional commercial calcium carbonate (CMCC) filled PP. Yield strength of PP/YBCC composite with 3wt% YBCC is improved by about 11.1%. A small content (about 1wt%) of YBCC can promote the heterogeneous nucleation for PP crystallization and the formation β-crystalline PP. Using mussel shell for producing bio-filler is valuable for industrial production and practical application as fillers for reinforcing polymers.

以废弃贻贝壳为原料, 经去除角质层、粉碎、研磨、剪切乳化得到生物填料, 然后对聚丙烯(PP)进行充填. 研究分析了生物填料的物相组成、微观形貌、热稳定性和对其PP充填力学性能的影响. 实验结果表明, 制备的生物填料主要成分为文石碳酸钙, 成片状, 粒径大小约为40~500 nm, 有机物含量约为2.04wt%, 热稳定性良好. 生物填料(YBCC)对PP具有增强效果. 当填充比例为3wt%时, PP/(YBCC)复合材料屈服强度比PP提高了约11.1%; 对PP亦具有异相成核的作用, 可诱导形成?晶. 利用废弃物贻贝壳为原料生产的生物填料填充PP可降低材料成本, 提高力学性能和结晶性能, 具有广阔的应用前景.

... 这一方面是由于添加的n-HA起到了异相成核作用^[16], 加快了PLGA成核的速度, 另一方面是由于加入n-HA后基质链段可以吸附在其表面有序排列, 提高结晶速率, 从而使结晶能力增强 ...