聚合物调控下纳米磷灰石/聚乳酸原位复合材料研究
|
摘要
工业、交通、体育事业等的高速发展及全球人口老龄化程度加剧，使因疾病、外伤或老龄所致的骨组织缺损、缺失或功能障碍日益成为威胁人类健康的重大问题，其治疗也成为目前临床所面临的重点和难点。对于骨组织的修复和治疗，临床上一般可采用自体骨移植和异体骨移植，但这两种方法都存在一些问题：自体骨移植不可避免地给患者带来二次损伤，且来源匮乏；而异体骨移植可能因免疫排斥反应而导致植入失效甚至威胁患者生命，所以临床上越来越广泛地采用人工制备的生物医学材料作为骨修复或替代材料。
自然骨通过非常复杂的方式巧妙地将有机大分子与无机盐互相紧密地结合起来，实现了生物学和力学上的要求。从材料学的角度来看，人体骨可以看成是一种天然的无机物／高聚物复合材料。因此，根据骨的基本组成而制备的无机物／高聚物骨修复复合材料与单纯的陶瓷、金属材料或高分子材料相比，其物理性能和生物学性能均有不同程度的改善，显示了复合材料在应用上的优势。
聚乳酸(PLA)因其具有良好的生物相容性、生物可降解性、易加工性、无毒性、无刺激性等优点而在手术缝合线、骨折内固定、药物控释系统以及组织工程支架材料等生物医学领域有着较为广泛的应用。然而其细胞亲和力差，酸性降解产物会使局部酸度过大而出现非感染性炎症，缺乏生物活性。磷灰石是构成自然骨无机质的主要成分，生物活性好，能与骨形成牢固的骨性结合。但其脆性大，塑形难，和人体骨组织力学性能不相容。将磷灰石与聚乳酸复合，可以将二者优良性能充分地结合起来。于是，磷灰石／聚乳酸复合骨修复材料得到了广泛的关注。
骨的生物矿化过程实现了在分子水平上对其微结构的调控，通过有机大分子和无机矿物离子在界面处的相互作用和在分子水平上对晶体成核和生长的精细调控，将以胶原纤维为主的有机大分子与以骨磷灰石为主的无机盐紧密地结合起来，既加强了两相之间的界面结合，也调控了无机晶体的生长，实现了生物学和生物力学上的要求。这一过程的揭示为复合材料的制备提供了全新的思路，即通过有机物质从分子水平上调控无机晶体的生长来制备无机／有机高分子复合材料。
本研究以仿自然骨结构为出发点，利用聚乳酸的调控作用，采用原位合成法通过聚合物调控纳米磷灰石的生长来获得两相间均匀复合、存在化学键合且具有优良生物活性及其它生物学性能的纳米磷灰石／聚乳酸复合材料。
利用PLA分子终端的羧基和羟基以及PLA分子链中的羰基与Ca~(2+)的相互作用来调控磷灰石晶体的生长，原位合成了n-HA／PLA复合材料。结果表明，在形成复合材料的过程中，PLA分子中的羰基、羟基以及离解的羧基可能成为磷灰石晶体的成核位点，使磷灰石在PLA表面成核、生长，从而调控磷灰石晶体的形态和生长方向，而PLA的空间结构阻止了磷灰石晶体的进一步晶化或生长。得到的复合材料具有较好的均一性，基本实现了纳米尺度的复合；纳米磷灰石在复合材料中的含量可以调节，两相间存在一定的化学性键合和分子间作用力。然而，该种方法虽然能够通过PLA调控HA的生长，但聚乳酸分子链中只有终端羧基，其分子链中羰基与Ca~(2+)的作用力相对较弱，因而其调控能力是有限的，需要发展新的合成方法。
以过氧化氢为氧化剂，经紫外诱导将过氧基团引入到聚乳酸颗粒表面。结果表明，单位聚乳酸表面可以引入的过氧键的量可以通过氧化时间来控制。当单体溶液的浓度为15％、照射剂量为3000×100μJ／cm~2时，照射氧化50min时单位聚乳酸表面引入过氧键的量最多，大约为5.6×10~(-2)mmol／g，之后开始减少。随后，再在紫外照射下将甲基丙烯酸接枝聚合到聚乳酸表面，得到聚甲基丙烯酸修饰的聚乳酸材料(PMAA-PLA)，其接枝量在氧化时间、照射剂量及单体浓度相同时，随接枝时间的增加而增加。而接枝时间相同时，氧化时间越长接枝量越大。
PMAA-PLA表面的羧基在碱性条件下容易发生离解形成-COO~-离子，使PMAA-PLA微粒表面带上很高的负电荷。在磷酸氢二钠溶液中得到的PMAA-PLA为纳米微球，其平均粒度为133.1±2.3 nm，可以放置几周而没有什么变化。PMAA-PLA微球悬浮液的存在状态受到溶液pH值的影响，当pH=5时，微球的zeta电位的负值仍然很大(-79.8mV)；直到pH=3时，微球的zeta电位的绝对值才低于30mV，开始有PMAA-PLA沉淀析出。
利用PMAA-PLA分子中原有的羧基、羟基和羰基以及引入的羧基来调控磷灰石的生长合成了纳米磷灰石／P-PLA复合材料，通过红外光谱、X-射线衍射、扫描电镜、透射电镜、粒度分布测定与zeta电位仪以及X射线光电子能谱等对复合材料进行分析，结果表明在合成n-HA／P-PLA复合材料的过程中，PMAA-PLA可以调控磷灰石晶体的成核和生长从而控制磷灰石晶体的形态、尺寸、生长方向以及其在有机相中的分布，得到的纳米磷灰石／P-PLA复合材料中n-HA与PMAA-PLA两相间可能存在化学键合和分子间相互作用力。当该复合材料再与聚乳酸复合得到n-HA／PLA复合材料后，强化了磷灰石和PLA两相间以及PLA之间的结合，也保证了纳米磷灰石晶体在复合材料中的均匀分布和纳米级的尺寸也保证了复合材料的生物活性。
n-HA／PLA复合材料无论是在体内还是SBF溶液中，其表面都能形成骨磷灰石层，表明该复合材料具有良好的生物活性。同时，n-HA／PLA在生理环境中能够发生钙释放和钙沉积，进一步表明n-HA／PLA复合材料具有良好的生物活性和骨结合能力。
体内外降解实验表明复合材料无论在体内还是体外都是可降解的，体内降解速率大于体外。体内外的降解基本上都是简单的本体水解，体内降解速率较快是由于血液流动、酶的催化及应力作用所致。PLA降解过程中产生的酸性环境可被n-HA中和或缓冲，减弱了复合材料内层的自催化作用。体外降解实验中，前2周分子量下降较为迅速，之后降解较为缓慢，但重量的损失滞后一些。溶液的pH值降低缓慢，与复合材料中存在弱碱性的纳米磷灰石有关。
生物相容性评价实验结果表明：n-HA／PLA复合材料安全、无毒，无刺激性，无遗传毒性，无致敏作用，无任何不良组织反应，无排异反应，具有良好的生物活性和生物相容性。皮下植入2周时有纤维包囊形成，但随着植入时间的延长，纤维包囊逐渐变薄。
复合材料骨内植入后，发现材料具有促进新骨形成的能力，可与骨组织形成骨性结合，新生骨组织在材料周围是以膜内成骨方式形成。植入4周后，在材料和骨组织的界面处以及骨缺损区有新骨生成、成骨细胞活跃。12周时，界面处有大量的新骨形成，骨缺损区已基本被新骨修复。至于本研究中得到的纳米磷灰石／聚乳酸复合材料长期植入的情况如何还需进一步考察。
With the development of industry, transportation, sports and the aging of thepopulation, defection, losses and disfunction of bone tissues has gradually become aserious threat to public health and the clinical therapy to these diseases has attractedmuch research interest. Until now, autograft and allograft bone repair are used inclinics to restore bone defect. Autograft is the gold standard for bone repairing inclinics. But the disadvantages of autograft are obvious: limited resources, creatingsecond trauma and the possibility to induce donor tissue syndrome. Allograft maycause immuno-rejection and the risk to infect diseases from the donor. Therefore,artificial materials are used more and more in Clinics to replace bone defects.
By organizing organic materials and inorganic salt in a sophisticated way, naturalbone obtains its structure and physical strength. From a viewpoint of materialsscience, bone is a kind of natural composite composed of inorganic materials andpolymers. Therefore, as a material to restore defective bone, inorganicmaterials/polymer composites are better than pure ceramics, metals and polymersbecause the improvement in physical properties and biological properties.Composite showes its advantage as bone substitute.
Because of its excellent biocompatibility, biodegradability, feasibility ofprocessing, polylactic acid (PLA) has been used widely in the field of biomedicalmaterials field as surgical suture, fasten plate in bone fracture, drug controlled release system and scaffold in tissue engineering. However, it has the disadvantageof lack of bioactivity and poor cell compatibility, which results in non-infectiveinflammation due to the high local acidic concentration. Apatite is the main naturalinorganic component of bone with bioactivity, which combined with bone withstrong chemical bonding when implanted in bone tissue. But its disadvantage is thebrittleness, difficulty in processing and the incompatibility with bone in mechanicalproperty. If apatite is compounded with PLA, the composite will possess theirindividual advantages. Therefore, hydroxyapatie/poly(lactide)(HA/PLA) compositehas attracted much research interest.
Mineralization of bone realizes the modulation of bone microstructure inmolecular level. By the interaction of organic materials and inorganic materials onthe interlace and the precise modulation of crystal nucleation and growth inmolecular level, organic materials (mainly collagen) bond with salt (mainly boneapatite). The interface between them is strengthened and crystal growth is controlled,which satisfied the biological and biomechanical demand of bone. Theunderstanding of this process provides new ideas on the preparation of newcomposite, which is to prepare inorganic material/organic material composites bythe modulation of growth of inorganic crystal with organic materials in molecularlevel.
In this study, in situ synthesis method was used to prepare nano-HA/PLA(n-HA/PLA) composite by the modulation effect of PLA based on the structure ofnatural bone, in which two phases were evenly distributed with chemical bonding inbetween. And the obtained composite possesses good bioactivity and otherbiological properties.
Nano-HA/PLA was prepared with in situ synthesis by the interaction of theterminal carboxyl groups (-COOH) group and -OH group and carbonyl group insidePEA with calcium ions to modulate apatite growth. The results indicated that in theprocess of composite formation, the terminal COOH group, OH group and carbonylgroup in PLA might be the nucleation sites. Apatite nucleated and grew on the PLA surface and its morphology and growth direction were modulated by the PLA.Therefore, the further nucleation and growth of apatite was controlled by the 3-Dstructure of PLA. The composite obtained was homogenous with n-HA evenlydistributed in PLA matrix, which realized nano-sized HA composite. The content ofn-HA in the composite is controllable and chemical bonding and force of molecularinteraction was found between the two phases. However, the modulation ability ofPLA is limited because there is only terminal carboxyl group in PLA molecule andthe interaction between carbonyl in PLA and calcium ions is weak. New method isnedded to be developed.
The peroxide groups were introduced onto PLA particle surfaces viaphotooxidization with H_2O_2 oxidant. The results showed that the peroxide groups onPLA particle surfaces could be controlled by oxidation time, and the maximumcontent of peroxide groups produced on the PLA surfaces was about 5.6×10~(-2)mmol/g with energy of 3000×100μJ/cm~2 after 50min of oxidation. After 50min. thecontent of peroxide groups decreased. Then the PMAA was grafted onto the PLAsurface via UV induced polymerization and PMAA-modified PLA (PMAA-PLA)was obtained. The graft weight increased with the grafting time under the sameoxidation time, irradiation dose and monomer concentration. When grafting timewas the same. the grafting weight increased with the oxidation time.
The carboxyl groups (-COOH) on PMAA-PLA surface were easily ionized into-COO in alkaline aqueous solution, which resulted in PMAA-PLA microparticlesurface with high negative charge. PMAA-PLA nanosphere suspension with anaverage particle size of 133.1±2.3nm in Na_2HPO_4 aqueous solution was stable for afew weeks without any deposit. The absolute value of zeta potential of PMAA-PLAnanosphere suspension was affected by pH value of suspension system. When thepH value decreased to 5, PMAA-PLA nanosphere suspension still had high negativezeta potential (-79.8mV) with no deposit. Only when the pH decreased to 3.0. theabsolute value of zeta potential of PMAA-PLA nanosphere suspension was less than30mV and flocculent PMAA-PLA deposit could be observed.
Nano-hydroxyapatite/poly(lactide) (n-HA/P-PLA) composites were prepared bythe carboxylic groups, -OH groups and carbonyl groups on the PLA molecules andintroduced carboxylic groups of PMAA on PMAA-PLA controlling the growth ofapatite crystals. Several analyses about FTIR, XRD, TEM, SEM and XPS suggestedthat the PMAA-PLA could manipulate the nucleation and growth of n-HA crystals,control the morphology, size and growth orientation of n-HA crystals as well as theirdistribution over the organic phase. There might be chemical bonds and moleculesinteraction in obtained n-HA/P-PLA composites between the two phases. Theobtained n-HA/PLA composites synthesized by mixing n-HA/P-PLA compositeswith PLA not only strengthened combination between PLA molecules and twophases of HA and PLA but also guaranteed homogenous n-HA crystals distributionin n-HA/PLA composites and bioactivity of obtained composite.
Bone apatite could be formed on the surface of n-HA/PLA composites in vivo andin SBF, which indicated that n-HA/PLA composites had good bioactivity. Calciumrelease and calcium precipitation of n-HA/PLA composites in physiologicalenvironment further confirmed bioactivity and bone binding ability of n-HA/PLAcomposites.
The in vivo and in vitro experimental results showed that the n-HA/PLAcomposites could be degraded by simple hydrolyzation and the degradation rate invivo was quicker than in vitro because of blood fluidity, enzymatic activity and stressaction. The acidic environment due to the degradation of PLA could be neutralizedor buffered by n-HA, which lowered the intrinsic catalysis inside the composites.Molecular weight decreased quickly in 2 weeks in in vitro experiment, then itdecreased slower, but the loss of weight was lagged a little. The pH value reducedslower, which might be arised by alkalescent n-HA.
The results of biological evaluation in vivo suggested that the composites hadexcellent biocompatibility, biodegradability, bioactivity and osteogenicity. At 2weeks, there was a dense fibrous capsule surrounding the composites and the fibrouscapsule didn't become thicker with time. At 4 weeks, the newly formed immature bone grew along the surface of the composite and bone directly contacted with thesamples without intervening fibrous tissue. In undecalcified specimens, osteoblastsand osteoclasts were observed between the composite surface and lamellar bone(woven bone), and new bone formed which took on different structure andorientation from the old bone. The histological results of pure HA control rods wassimilar with that of the composite rods. After 1-2 weeks of implantation, new bonewrapping the implant was clearly visible. The investigation of long timeimplantation about the obtained n-HA/PLA composites needed to be studied further.
自然骨通过非常复杂的方式巧妙地将有机大分子与无机盐互相紧密地结合起来，实现了生物学和力学上的要求。从材料学的角度来看，人体骨可以看成是一种天然的无机物／高聚物复合材料。因此，根据骨的基本组成而制备的无机物／高聚物骨修复复合材料与单纯的陶瓷、金属材料或高分子材料相比，其物理性能和生物学性能均有不同程度的改善，显示了复合材料在应用上的优势。
聚乳酸(PLA)因其具有良好的生物相容性、生物可降解性、易加工性、无毒性、无刺激性等优点而在手术缝合线、骨折内固定、药物控释系统以及组织工程支架材料等生物医学领域有着较为广泛的应用。然而其细胞亲和力差，酸性降解产物会使局部酸度过大而出现非感染性炎症，缺乏生物活性。磷灰石是构成自然骨无机质的主要成分，生物活性好，能与骨形成牢固的骨性结合。但其脆性大，塑形难，和人体骨组织力学性能不相容。将磷灰石与聚乳酸复合，可以将二者优良性能充分地结合起来。于是，磷灰石／聚乳酸复合骨修复材料得到了广泛的关注。
骨的生物矿化过程实现了在分子水平上对其微结构的调控，通过有机大分子和无机矿物离子在界面处的相互作用和在分子水平上对晶体成核和生长的精细调控，将以胶原纤维为主的有机大分子与以骨磷灰石为主的无机盐紧密地结合起来，既加强了两相之间的界面结合，也调控了无机晶体的生长，实现了生物学和生物力学上的要求。这一过程的揭示为复合材料的制备提供了全新的思路，即通过有机物质从分子水平上调控无机晶体的生长来制备无机／有机高分子复合材料。
本研究以仿自然骨结构为出发点，利用聚乳酸的调控作用，采用原位合成法通过聚合物调控纳米磷灰石的生长来获得两相间均匀复合、存在化学键合且具有优良生物活性及其它生物学性能的纳米磷灰石／聚乳酸复合材料。
利用PLA分子终端的羧基和羟基以及PLA分子链中的羰基与Ca~(2+)的相互作用来调控磷灰石晶体的生长，原位合成了n-HA／PLA复合材料。结果表明，在形成复合材料的过程中，PLA分子中的羰基、羟基以及离解的羧基可能成为磷灰石晶体的成核位点，使磷灰石在PLA表面成核、生长，从而调控磷灰石晶体的形态和生长方向，而PLA的空间结构阻止了磷灰石晶体的进一步晶化或生长。得到的复合材料具有较好的均一性，基本实现了纳米尺度的复合；纳米磷灰石在复合材料中的含量可以调节，两相间存在一定的化学性键合和分子间作用力。然而，该种方法虽然能够通过PLA调控HA的生长，但聚乳酸分子链中只有终端羧基，其分子链中羰基与Ca~(2+)的作用力相对较弱，因而其调控能力是有限的，需要发展新的合成方法。
以过氧化氢为氧化剂，经紫外诱导将过氧基团引入到聚乳酸颗粒表面。结果表明，单位聚乳酸表面可以引入的过氧键的量可以通过氧化时间来控制。当单体溶液的浓度为15％、照射剂量为3000×100μJ／cm~2时，照射氧化50min时单位聚乳酸表面引入过氧键的量最多，大约为5.6×10~(-2)mmol／g，之后开始减少。随后，再在紫外照射下将甲基丙烯酸接枝聚合到聚乳酸表面，得到聚甲基丙烯酸修饰的聚乳酸材料(PMAA-PLA)，其接枝量在氧化时间、照射剂量及单体浓度相同时，随接枝时间的增加而增加。而接枝时间相同时，氧化时间越长接枝量越大。
PMAA-PLA表面的羧基在碱性条件下容易发生离解形成-COO~-离子，使PMAA-PLA微粒表面带上很高的负电荷。在磷酸氢二钠溶液中得到的PMAA-PLA为纳米微球，其平均粒度为133.1±2.3 nm，可以放置几周而没有什么变化。PMAA-PLA微球悬浮液的存在状态受到溶液pH值的影响，当pH=5时，微球的zeta电位的负值仍然很大(-79.8mV)；直到pH=3时，微球的zeta电位的绝对值才低于30mV，开始有PMAA-PLA沉淀析出。
利用PMAA-PLA分子中原有的羧基、羟基和羰基以及引入的羧基来调控磷灰石的生长合成了纳米磷灰石／P-PLA复合材料，通过红外光谱、X-射线衍射、扫描电镜、透射电镜、粒度分布测定与zeta电位仪以及X射线光电子能谱等对复合材料进行分析，结果表明在合成n-HA／P-PLA复合材料的过程中，PMAA-PLA可以调控磷灰石晶体的成核和生长从而控制磷灰石晶体的形态、尺寸、生长方向以及其在有机相中的分布，得到的纳米磷灰石／P-PLA复合材料中n-HA与PMAA-PLA两相间可能存在化学键合和分子间相互作用力。当该复合材料再与聚乳酸复合得到n-HA／PLA复合材料后，强化了磷灰石和PLA两相间以及PLA之间的结合，也保证了纳米磷灰石晶体在复合材料中的均匀分布和纳米级的尺寸也保证了复合材料的生物活性。
n-HA／PLA复合材料无论是在体内还是SBF溶液中，其表面都能形成骨磷灰石层，表明该复合材料具有良好的生物活性。同时，n-HA／PLA在生理环境中能够发生钙释放和钙沉积，进一步表明n-HA／PLA复合材料具有良好的生物活性和骨结合能力。
体内外降解实验表明复合材料无论在体内还是体外都是可降解的，体内降解速率大于体外。体内外的降解基本上都是简单的本体水解，体内降解速率较快是由于血液流动、酶的催化及应力作用所致。PLA降解过程中产生的酸性环境可被n-HA中和或缓冲，减弱了复合材料内层的自催化作用。体外降解实验中，前2周分子量下降较为迅速，之后降解较为缓慢，但重量的损失滞后一些。溶液的pH值降低缓慢，与复合材料中存在弱碱性的纳米磷灰石有关。
生物相容性评价实验结果表明：n-HA／PLA复合材料安全、无毒，无刺激性，无遗传毒性，无致敏作用，无任何不良组织反应，无排异反应，具有良好的生物活性和生物相容性。皮下植入2周时有纤维包囊形成，但随着植入时间的延长，纤维包囊逐渐变薄。
复合材料骨内植入后，发现材料具有促进新骨形成的能力，可与骨组织形成骨性结合，新生骨组织在材料周围是以膜内成骨方式形成。植入4周后，在材料和骨组织的界面处以及骨缺损区有新骨生成、成骨细胞活跃。12周时，界面处有大量的新骨形成，骨缺损区已基本被新骨修复。至于本研究中得到的纳米磷灰石／聚乳酸复合材料长期植入的情况如何还需进一步考察。
With the development of industry, transportation, sports and the aging of thepopulation, defection, losses and disfunction of bone tissues has gradually become aserious threat to public health and the clinical therapy to these diseases has attractedmuch research interest. Until now, autograft and allograft bone repair are used inclinics to restore bone defect. Autograft is the gold standard for bone repairing inclinics. But the disadvantages of autograft are obvious: limited resources, creatingsecond trauma and the possibility to induce donor tissue syndrome. Allograft maycause immuno-rejection and the risk to infect diseases from the donor. Therefore,artificial materials are used more and more in Clinics to replace bone defects.
By organizing organic materials and inorganic salt in a sophisticated way, naturalbone obtains its structure and physical strength. From a viewpoint of materialsscience, bone is a kind of natural composite composed of inorganic materials andpolymers. Therefore, as a material to restore defective bone, inorganicmaterials/polymer composites are better than pure ceramics, metals and polymersbecause the improvement in physical properties and biological properties.Composite showes its advantage as bone substitute.
Because of its excellent biocompatibility, biodegradability, feasibility ofprocessing, polylactic acid (PLA) has been used widely in the field of biomedicalmaterials field as surgical suture, fasten plate in bone fracture, drug controlled release system and scaffold in tissue engineering. However, it has the disadvantageof lack of bioactivity and poor cell compatibility, which results in non-infectiveinflammation due to the high local acidic concentration. Apatite is the main naturalinorganic component of bone with bioactivity, which combined with bone withstrong chemical bonding when implanted in bone tissue. But its disadvantage is thebrittleness, difficulty in processing and the incompatibility with bone in mechanicalproperty. If apatite is compounded with PLA, the composite will possess theirindividual advantages. Therefore, hydroxyapatie/poly(lactide)(HA/PLA) compositehas attracted much research interest.
Mineralization of bone realizes the modulation of bone microstructure inmolecular level. By the interaction of organic materials and inorganic materials onthe interlace and the precise modulation of crystal nucleation and growth inmolecular level, organic materials (mainly collagen) bond with salt (mainly boneapatite). The interface between them is strengthened and crystal growth is controlled,which satisfied the biological and biomechanical demand of bone. Theunderstanding of this process provides new ideas on the preparation of newcomposite, which is to prepare inorganic material/organic material composites bythe modulation of growth of inorganic crystal with organic materials in molecularlevel.
In this study, in situ synthesis method was used to prepare nano-HA/PLA(n-HA/PLA) composite by the modulation effect of PLA based on the structure ofnatural bone, in which two phases were evenly distributed with chemical bonding inbetween. And the obtained composite possesses good bioactivity and otherbiological properties.
Nano-HA/PLA was prepared with in situ synthesis by the interaction of theterminal carboxyl groups (-COOH) group and -OH group and carbonyl group insidePEA with calcium ions to modulate apatite growth. The results indicated that in theprocess of composite formation, the terminal COOH group, OH group and carbonylgroup in PLA might be the nucleation sites. Apatite nucleated and grew on the PLA surface and its morphology and growth direction were modulated by the PLA.Therefore, the further nucleation and growth of apatite was controlled by the 3-Dstructure of PLA. The composite obtained was homogenous with n-HA evenlydistributed in PLA matrix, which realized nano-sized HA composite. The content ofn-HA in the composite is controllable and chemical bonding and force of molecularinteraction was found between the two phases. However, the modulation ability ofPLA is limited because there is only terminal carboxyl group in PLA molecule andthe interaction between carbonyl in PLA and calcium ions is weak. New method isnedded to be developed.
The peroxide groups were introduced onto PLA particle surfaces viaphotooxidization with H_2O_2 oxidant. The results showed that the peroxide groups onPLA particle surfaces could be controlled by oxidation time, and the maximumcontent of peroxide groups produced on the PLA surfaces was about 5.6×10~(-2)mmol/g with energy of 3000×100μJ/cm~2 after 50min of oxidation. After 50min. thecontent of peroxide groups decreased. Then the PMAA was grafted onto the PLAsurface via UV induced polymerization and PMAA-modified PLA (PMAA-PLA)was obtained. The graft weight increased with the grafting time under the sameoxidation time, irradiation dose and monomer concentration. When grafting timewas the same. the grafting weight increased with the oxidation time.
The carboxyl groups (-COOH) on PMAA-PLA surface were easily ionized into-COO in alkaline aqueous solution, which resulted in PMAA-PLA microparticlesurface with high negative charge. PMAA-PLA nanosphere suspension with anaverage particle size of 133.1±2.3nm in Na_2HPO_4 aqueous solution was stable for afew weeks without any deposit. The absolute value of zeta potential of PMAA-PLAnanosphere suspension was affected by pH value of suspension system. When thepH value decreased to 5, PMAA-PLA nanosphere suspension still had high negativezeta potential (-79.8mV) with no deposit. Only when the pH decreased to 3.0. theabsolute value of zeta potential of PMAA-PLA nanosphere suspension was less than30mV and flocculent PMAA-PLA deposit could be observed.
Nano-hydroxyapatite/poly(lactide) (n-HA/P-PLA) composites were prepared bythe carboxylic groups, -OH groups and carbonyl groups on the PLA molecules andintroduced carboxylic groups of PMAA on PMAA-PLA controlling the growth ofapatite crystals. Several analyses about FTIR, XRD, TEM, SEM and XPS suggestedthat the PMAA-PLA could manipulate the nucleation and growth of n-HA crystals,control the morphology, size and growth orientation of n-HA crystals as well as theirdistribution over the organic phase. There might be chemical bonds and moleculesinteraction in obtained n-HA/P-PLA composites between the two phases. Theobtained n-HA/PLA composites synthesized by mixing n-HA/P-PLA compositeswith PLA not only strengthened combination between PLA molecules and twophases of HA and PLA but also guaranteed homogenous n-HA crystals distributionin n-HA/PLA composites and bioactivity of obtained composite.
Bone apatite could be formed on the surface of n-HA/PLA composites in vivo andin SBF, which indicated that n-HA/PLA composites had good bioactivity. Calciumrelease and calcium precipitation of n-HA/PLA composites in physiologicalenvironment further confirmed bioactivity and bone binding ability of n-HA/PLAcomposites.
The in vivo and in vitro experimental results showed that the n-HA/PLAcomposites could be degraded by simple hydrolyzation and the degradation rate invivo was quicker than in vitro because of blood fluidity, enzymatic activity and stressaction. The acidic environment due to the degradation of PLA could be neutralizedor buffered by n-HA, which lowered the intrinsic catalysis inside the composites.Molecular weight decreased quickly in 2 weeks in in vitro experiment, then itdecreased slower, but the loss of weight was lagged a little. The pH value reducedslower, which might be arised by alkalescent n-HA.
The results of biological evaluation in vivo suggested that the composites hadexcellent biocompatibility, biodegradability, bioactivity and osteogenicity. At 2weeks, there was a dense fibrous capsule surrounding the composites and the fibrouscapsule didn't become thicker with time. At 4 weeks, the newly formed immature bone grew along the surface of the composite and bone directly contacted with thesamples without intervening fibrous tissue. In undecalcified specimens, osteoblastsand osteoclasts were observed between the composite surface and lamellar bone(woven bone), and new bone formed which took on different structure andorientation from the old bone. The histological results of pure HA control rods wassimilar with that of the composite rods. After 1-2 weeks of implantation, new bonewrapping the implant was clearly visible. The investigation of long timeimplantation about the obtained n-HA/PLA composites needed to be studied further.
引文
1. Perry CR. Bone repair techniques, bone graft, and bone graft substitutes. Clinical Orthopaedics And Related Research 1999(360): 71-86.
2. Damien CJ, Parsons JR. Bone graft and bone graft substitutes: a review of current technology and applications. J Appl Biomater 1991; 2(3): 187-208.
3. Wen HB, Cut FZ, Feng QL, Li HD, Zhu XD. Microstructural Investigation Of The Early External Callus After Diaphyseal Fractures Of Human Long-Bone. Journal Of Structural Biology 1995; 114(2): 115-122.
4. Wen HB, Cui FZ, Zhu XD. Microstructural features of non-union of human humeral shaft fracture. Journal Of Structural Biology 1997; 119(3): 239-246.
5．师昌绪．材料科学技术百科全书，生物医学材料分支，中国大百科全书出版社，北京．1995．8．
6．李玉宝．《生物医学材料》．化学工业出版社2003．9．
7．李世普．《生物医学材料导论》，武汉工业大学出版社．2000．
8．梁芳慧，周廉．钛和钛合金生物活化研究现状．稀有金属材料与工程2003：32(4)：241-245．
9. Wen J, Leng Y, Chen JY, Zhang C. Chemical gradient in plasma-sprayed HA coatings. Biomaterials 2000; 21(13): 1339-1343.
10. Zheng XB, Huang MH, Ding CX. Bond strength of plasma-sprayed hydroxyapatite/Ti composite coatings. Biomaterials 2000; 21(8): 841-849.
11. Kim HM, Miyaji F, Kokubo T, Nishiguchi S, Nakamura T. Graded surface structure of bioactive titanium prepared by chemical treatment. Journal Of Biomedical Materials Research 1999; 45(2): 100-107.
12. Wen HB, de Wijn JR, Cut FZ, de Groot K. Preparation of calcium phosphate coatings on titanium implant materials by simple chemistry. Journal Of Biomedical Materials Research 1998; 41(2): 227-236.
13. Lu X, Leng Y, Zhang XD, Xu JR, Qin L, Chan CW. Comparative study of osteoconduction on micromachined and alkali-treated titanium alloy surfaces in vitro and in vivo. Biomaterials 2005; 26(14): 1793-1801.
14. Yang BC, Uchida M, Kim HM, Zhang XD, Kokubo T. Preparation of bioactive titanium metal via anodic oxidation treatment. Biomaterials 2004;25(6):1003-1010.
15. Spoerke ED, Stupp SI. Synthesis of a poly (L-lysine)-calcium phosphate hybrid on titanium surfaces for enhanced bioactivity. Biomaterials 2005; 26(25):5120-5129.
16. Lee JH, Ryu HS, Lee DS, Hong KS, Chang BS, Lee CK. Biomechanical and histomorphometric study on the bone-screw interface of bioactive ceramic-coated titanium screws. Biomaterials 2005;26(16):3249-3257.
17. Gross KA, Berndt CC. In-Vitro Testing Of Plasma-Sprayed Hydroxyapatite Coatings. Journal Of Materials Science-Materials In Medicine 1994; 5(4):219-224.
18. Kitsugi T, Yamamuro T, Nakamura T, Masanori O. Transmission Electron-Microscopy Observations At The Interface Of Bone And 4 Types Of Calcium-Phosphate Ceramics with Different Calcium Phosphorus Molar Ratios. Biomaterials 1995; 16(14): 1101-1107.
19. Yuan HP, Li YB, de Bruijn JD, de Groot K, Zhang XD. Tissue responses of calcium phosphate cement: a study in dogs. Biomaterials 2000; 21(12): 1283-1290.
20. Pioletti DP, Takei H, Lin T, Van Landuyt P, Ma QJ, Kwon SY, Sung KLP. The effects of calcium phosphate cement particles on osteoblast functions. Biomaterials 2000; 21(11): 1103-1114.
21. Mirtchi AA, Lemaitre J. Munting E. Calcium phosphate cements: action of setting regulators on the properties of the beta-tricalcium phosphate-monocalcium phosphate cements. Biomaterials 1989; 10(9): 634-8.
22．马祖伟，高长有，龚逸鸿，沈家骢．Ⅰ型胶原在聚-L-乳酸(PLLA)表面的化学接枝和涂层及其对软骨细胞生长的促进作用．高等学校化学学报2004；25(4)：749-752．
23．张其清，刘玲蓉．医用组织引导再生材料的发展现状及发展方向综述．中国修复重建外科杂志1997；11(6)：365-367．
24. Ruszczak Z. Effect of collagen matrices on dermal wound healing. Adv Drug Deliv Rev 2003; 55(12): 1595-611.
25. Lee CH, Singla A, Lee Y. Biomedical applications of collagen. International Journal Of Pharmaceutics 2001; 221(1-2): 1-22.
26. Lewis G. Properties of acrylic bone cement: State of the art review. Journal Of Biomedical Materials Research 1997; 38(2): 155-182.
27. Kulkarni RK, Pani KC, Neuman C, Leonard F. Polylactic acid for surgical implants. Arch Surg 1966; 93(5): 839-43.
28．陈俊民．药用高分子材料学．第一版，北京：中国医药科技出版社．2004．
29. Bostman O, Pihlajamaki H. Clinical biocompatibility of biodegradable orthopaedic implants for internal fixation: a review. Biomaterials 2000; 21(24): 2615-2621.
30. Meinig RP, Rahn B, Perren SM, Gogolewski S. Bone regeneration with resorbable polymeric membranes: Treatment of diaphyseal bone defects in the rabbit radius with poly(L-lactide) membrane. A pilot study. Journal Of Orthopaedic Trauma 1996; 10(3):178-190.
31．王远亮，潘君，蔡绍皙．组织工程研究的进展．生物化学与生物物理进展2000：27(4)：365-367．
32. Ajioka M, Enomoto K, Suzuki K, Yamaguchi A. Basic Properties Of Polylactic Acid Produced By The Direct Condensation Polymerization Of Lactic-Acid. Bulletin Of The Chemical Society Of Japan 1995; 68(8): 2125-2131.
33. Cerrai P, Tricoli M. Block-Copolymers From L-Lactide And Poly(Ethylene Glycol) Through A Noncatalyzed Route. Makromolekulare Chemic-Rapid Communications 1993; 14(9): 529-538.
34．马克昌，冯刊，朱太咏，郭建刚．骨生理学，河南医科大学出版社．2000．
35. Ducheyne P, Qiu Q. Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function. Biomaterials 1999; 20(23-24): 2287-2303.
36. IshaugRiley SL, Crane GM, Gurlek A, Miller MJ, Yasko AW, Yaszemski MJ, Mikos AG. Ectopic bone formation by marrow stromal osteoblast transplantation using poly(DL-lactic-co-glycolic acid) foams implanted into the rat mesentery. Journal Of Biomedical Materials Research 1997; 36(1): 1-8.
37．袁华，陈宁，吕晓迎，郑步中，宋晓陵．天然羟基磷灰石-壳聚糖复合材料修复骨缺损的实验研究．口腔医学2005；25(2)：65-67．
38．文学军．多孔轻基磷灰石陶瓷一胶原复合材料研究，四川大学硕士学位论文．1992．
39. Liu YH. Zhang QQ, Weng J, Zhang XD. Promotive effect of collagen in porous HA ceramics. Biomedical Materials Research in the Far East(I), eds Xingdong Zhang and Yoshito Ikada, Kobunshi Kankokai, Inc., Kyoto, Japan 1993: 161-162.
40. Stjohn KR. Zardiackas LD, Terry RC, Teasdall RD, Cooke SE, Mitias HM. Histological And Electron-Microscopic Analysis Of Tissue-Response To Synthetic Composite Bone-Graft In The Canine. Journal Of Applied Biomaterials 1995; 6(2): 89-97.
41．田卫东，李声伟，邓楠等．纤维蛋白粘合剂与羟基磷灰石复合人工骨的实验研究．中国口腔种植学杂志1998；3(4)：170-173．
42. Bonfield W. Hydroxyapatite-reinforced polyethylene as an analogical material for bone replacement. Ann NY Acad Sci 1998; 523: 173-177.
43. Bonfield W, Doyle C, Tanner KE. In vivo evaluation of hydroxyapatite reinforced polyethylene composites. Biological Performance of Biomaterials. Elsvier, Amsterdam 1986: 153-159.
44. Li DM, Zhang SZ, Chen T, et al. Experimental study of the biocompatible and osteoinductive behavior of the hydroxyapatite/ultra-high molecular weight polyethtlene composite. Chin J Plast Surg 2004; 20(3): 180-183.
45．严永刚，李玉宝，汪建新，冯建清，黄玫，deGroot K．聚酰胺-66／羟基磷灰石复合材料的制备和性能研究．塑料工业2000：28(3)：38-40．
46. Wet J, Hong H, Wu L, He Y, Li YB. Preliminary investigation of bioactivity of nano biocomposite. Journal Of Materials Science-Materials In Medicine 2007; 18(3): 529-533.
47. Zhang X, Li YB, Zuo Y, Lv GY, Mu YH, Li H. Morphology, hydrogen-bonding and crystal linity of nano-hydroxyapatite/polyamide 66 biocomposites. Composites Part A-Applied Science And Manufacturing 2007;38(3):843-848.
48. Wet J, Li YB, Lau KT. Preparation and characterization ofa nano apatite/polyamide(6) bioactive composite. Composites Part B-Engineering 2007;38(3):301-305.
49. Zhang X, Li YB, Zuo Y, Lv GY, Mu YH. Influences of the crystallization behavior of n-HA reinforced PA66 biocomposite on its mechanical properties. Eco-Materials Processing & Design Vii. Zurich-Uetikon: Trans Tech Publications Ltd; 2006. p 898-901.
50. Zhang L. Li YB, Wang X J, Wet J, Peng XL. Studies on the porous scaffold made of the nano-HA/PA66 composite. Journal Of Materials Science 2005;40(1): 107-110.
51．万涛，闫玉华，陈波等．PMMA／HA-GF复合材料．中国有色金属学报2002；12(5)：935-939．
52. Zheng YD, Wang Y J, Chen XF, et al. Studies of Poly(vinylalcohol)/Hydroxylapatite Hydrogels Compounds for Cartilage Implantation. J Biomed Eng 2003; 20(3):401-403.
53．卢华定，蔡道章，刘青，王迎军，郑裕东．聚乙烯醇／羟基磷灰石复合水凝胶移植修复兔膝关节软骨缺损．中国矫形外科杂志2004；12(21-22)：1701-1703．
54．魏杰．纳米类骨磷灰石晶体及其与聚酰胺复合骨修复材料研究，博士学位论文．
55. Sato K, Kogure T, Kumagai Y, Tanaka J. Crystal orientation of hydroxyapatite induced by ordered carboxyl groups. Journal Of Colloid And Interface Science 2001; 240(1): 133-138.
56．姚晖，杜昶，杨韶华，崔福斋，雷涛．纳米羟晶／胶原仿生骨修复兔颅颌骨缺损的实验研究．透析与人工器官2000；11：5-8．
57. Zhai Y. Cui FZ. Recombinant human-like collagen directed growth of hydroxyapatite nanocrystals. Journal Of Crystal Growth 2006;291(1): 202-206.
58. Liao S, Watari F, Uo M, Obkawa S, Tamura K, Wang W, Cui FZ. The preparation and characteristics of a carbonated hydroxyapatite/collagen composite at room temperature. Journal Of Biomedical Materials Research Part B-Applied Biomaterials 2005; 74B(2): 817-821.
59. Zhai Y, Cui FZ, Wang Y. Formation of nano-hydroxyapatite on recombinant human-like collagen fibrils. Current Applied Physics 2005; 5(5): 429-432.
60. Liao SS, Cui FZ. In vitro and in vivo degradation of mineralized collagen-based composite scaffold: Nanohydroxyapatite/collagen/poly(L-lactide). Tissue Engineering 2004; 10(1-2): 73-80.
61. Zhang L J, Feng XS, Liu HG, Qian D J, Zhang L, Yu XL, Cui FZ. Hydroxyapatite/collagen composite materials formation in simulated body fluid environment. Materials Letters 2004;58(5):719-722.
62．冯庆玲，崔福斋，张伟．纳米羟基磷灰石／胶原骨修复材料．中国医学科学院学报2002：24(2)：124-128．
63. Zhou DS, Zhao KB, Li Y, Cui FZ, Lee IS. Repair of segmental defecits with nano-hydroxyapatite/collagen/PLA composite combined with mesenchymal stem cells. Journal Of Bioactive And Compatible Polymers 2006; 21(5): 373-384.
64. Li XM, Feng QL, Cui FZ. In vitro degradation of porous nano-hydroxyapatite/collagen/PLLA scaffold reinforced by chitin fibres. Materials Science & Engineering C-Biomimetic And Supramolecular Systems 2006;26(4):716-720.
65. Liao S, Tamura K, Zhu YH, Wang W, Uo M, Akasaka T, Cui FZ, Watari F. Human neutrophils reaction to the biodegraded nano-hydroxyapatite/collagen and nano-hydroxyapatite/collagen/poly(L-lactic acid) composites. Journal Of Biomedical Materials Research Part A 2006;76A(4):820-825.
66．林晓艳．高强度纳米羟基磷灰石／胶原仿骨材料研究，博士学位论文．
67. Lin XY. Li XD, Fan HS, Xiao YM, Lu J, Zhang XD. Comparative investigation of coprecipitation and in situ synthesis of nanohydroxyapatite/collagen composite. Bioceramics 17. Zurich-Uetikon: Trans Tech Publications Ltd; 2005. p 839-842.
68. Lin XY. Li XO. Fan HS, Wen XT, Lu H, Zhang XD. In situ synthesis of bone-like apatite/collagen nano-composite at low temperature. Materials Letters 2004; 58(27-28): 3569-3572.
69．徐国富，牟申周，廖素三，Watari F．碳酸化羟基磷灰石／胶原(nCHAC)生物复合材料的室温制备及表征．材料导报2006；20(8)：140-148．
70. Tampieri A, Celotti G, Landi E, Sandri M, Roveri N, Falini G. Biologically inspired synthesis of bone-like composite: Self-assembled collagen fibers/hydroxyapatite nanocrystals. Journal Of Biomedical Materials Research Part A 2003;67A(2):618-625.
71. Roveri N, Falini G, Sidoti MC, Tampieri A, Landi E, Sandri M, Parma B. Biologically inspired growth of hydroxyapatite nanocrystals inside self-assembled collagen fibers. Materials Science & Engineering C-Biomimetic And Supramolecular Systems 2003; 33(3): 441-446.
72. Kikuchi M, Itoh S, Ichinose S, Shinomiya K, Tanaka J. Self-organization mechanism in a bone-like hydroxyapatite/collagen nanocomposite synthesized in vitro and its biological reaction in vivo. Biomaterials 2001; 22(13): 1705-1711.
73. Itoh S, Kikuchi M, Koyama Y, Matumoto HN, Takakuda K, Shinomiya K, Tanaka J. Development of a novel biomaterial, hydroxyapatite/collagen (HAp/Col) composite for medical use. Bio-Medical Materials And Engineering 2005; 15(1-2):29-41.
74. Kikuchi M, Ikoma T, Itoh S, Matsumoto HN, Koyama Y, Takakuda K, Shinomiya K, Tanaka J. Biomimetic synthesis of bone-like nanocomposites using the self-organization mechanism of hydroxyapatite and collagen. Composites Science And Technology 2004;64(6):819-825.
75. Itoh S. Kikuchi M, Takakuda K, Nagaoka K, Koyama Y, Tanaka J, Shinomiya K. Implantation study of a novel hydroxyapatite/collagen (HAp/Col) composite into weight-bearing sites of dogs. Journal Of Biomedical Materials Research 2002;63(5):507-515.
76. Kikuchi M. Matsumoto HN, Yamada T, Koyama Y, Takakuda K, Tanaka J, Glutaraldehyde cross-linked hydroxyapatite/collagen self-organized nanocomposites. Biomaterials 2004;25(1): 63-69.
77. John A, Hong L, Ikada Y, Tabata Y. A trial to prepare biodegradable collagen-hydroxyapatite composites for bone repair. Journal Of Biomaterials Science-Polymer Edition 2001; 12(6): 689-705.
78. Yamaguchi I, Tokuchi K, Fukuzaki H, Koyama Y, Takakuda K, Monma H, Tanaka T. Preparation and microstructure analysis of chitosan/hydroxyapatite nanocomposites. Journal Of Biomedical Materials Research 2001; 55(1): 20-27.
79. Rusu VM, Ng CH, Wilke M, Tiersch B, Fratzl P, Peter MG. Size-controlled hydroxyapatite nanoparticles as self-organized organic-in organic composite materials. Biomaterials 2005; 26(26): 5414-5426.
80. Hu QL, Li BQ, Wang M, Shen JC. Preparation and characterization of biodegradable chitosan/hydroxyapatite nanocomposite rods via in situ hybridization: A potential material as internal fixation of bone fracture. Biomaterials 2004;25(5): 779-785.
81. Zhang L, Li YB, Yang AP, Peng XL, Wang XJ, Zhang X. Preparation and in vitro investigation of chitosan/nano-hydroxyapatite composite used as bone substitute materials. Journal Of Materials Science-Materials in Medicine 2005; 16(3): 213-219.
82．李保强，胡巧玲，汪茫，沈家骢．原位复合法制备层状结构的壳聚糖／羟基磷灰石纳米材料．高等学校化学学报2004；25(10)：1949-1952．
83. Jie W, Li Y. Tissue engineering scaffold material of nano-apatite crystals and polyamide composite. European Polymer Journal 2004;40(3):509-5[5.
84. Wei J, Li YB, Chen WQ, Zuo Y. A study on nano-composite of hydroxyapatite and polyamide. Journal Of Materials Science 2003; 38(15): 3303-3306.
85. Bonfield W, Wang M, Tanner KE. Interfaces in analogue biomaterials. Acta Materialia 1998; 46(7): 2509-2518.
86. Bomber M. Ward IM, McGregor W, Tanner KE, Bonfield W. Hydroxyapatite/ polypropylene composite: A novel bone substitute material. Journal Of Materials Science Letters 2001; 20(22): 2049-2051.
87. Uskokovic PS, Tang CY, Tsui CP, Ignjatovic N, Uskokovic DP. Micromechanical properties ofa hydroxyapatite/poly-L-lactide biocomposite using nanoindentation and modulus mapping. Journal Of The European Ceramic Society 2007;27(2-3):1559-1564.
88. Verheyen C, Klein C, Deblieckhogervorst JMA, Wolke JGC, Vanblitterswijn CA, Degroot K. Evaluation Of Hydroxylapatite Poly(L-Lactide)Composites-Physicochemical Properties. Journal Of Materials Science-Materials In Medicine 1993; 4(1): 58-65.
89. Verheyen C, Dewijn JR. Vanblitterswijk CA, Degroot K, Rozing PM. Hydroxylapatite Poly(L-Lactide) Composites-An Animal Study On Push-Out Strengths And Interface Histology. Journal Of Biomedical Materials Research 1993;27(4):433-444.
90. Verheyen C, Dhert WJA, Petit PLC, Rozing PM, Degroot K. Invitro Study On The integrity Of A Hydroxylapatite Coating When Challenged With Staphylococci. Journal Of Biomedical Materials Research 1993;27(6):775-781.
91．郭晓东，郑启新，杜靖远，全大萍，阎玉华，李世普，李香亮．可吸收羟基磷灰石／聚DL-乳酸骨折内固定材料机械强度和生物降解性研究．中国生物医学工程学报2001：20(1)：23-27．
92．全大萍，卢泽俭，李世普，袁润章．聚DL乳酸／轻基磷灰石复合材料((Ⅰ)：制备与力学性能．中国生物医学土程学报2001；20(6)：485-488．
93．薄颖慧，廖凯荣，卢泽俭，郑臣谋．聚乳酸／羟基磷灰石复合材料的研究Ⅰ．超细微羟基磷灰石的合成及表面处理．中山大学学报(自然科学版)1999；38(3)：43-47．
94．张胜民，李世普，曹献英，王欣宇等．聚乳酸自修饰羟基基磷灰石／聚乳酸复合内固定 材料：Ⅱ．抗弯性能与溶胀度．《2002年材料科学与工程新进展》，北京：冶金工业出版社 2003：4：230-233．
95. Zhang RY, Ma PX. Poly(alpha-hydroxyl acids) hydroxyapatite porous composites for bone-tissue engineering. Ⅰ. Preparation and morphology. Journal Of Biomedical Materials Research 1999; 44(4): 446-455.
96．全大萍，江昕，李世普．聚乳酸及其复合材料的研究概况．武汉工业大学学报1996；18(2)：114-117．
97. Calandrelli L, Immirzi B, Malinconico M, Volpe MG, Oliva A, Della Ragione F. Preparation and cbaracterisation of composites based on biodegradable polymers for "in vivo" application. Polymer 2000;41 (22):8027-8033.
98．张弛，陈峥嵘，林建平，张光健．聚乳酸涂层的多孔羟基磷灰石负载软骨细胞移植修复兔关节软骨缺损．上海医科大学学报2000；37(2)：83-86．
99. Kasuga T, Ota Y, Nogami M, Abe Y. Preparation and mechanical properties of polylactic acid composites containing hydroxyapatite fibers. Biomaterials 2001; 22(1): 19-23.
100. Ignjatovic N, Savic V, Najman S, Plavsic M, Uskokovic D. A study of HAp/PLLA composite as a substitute for bone powder, using FT-IR spectroscopy. Biomaterials 2001; 22(6): 571-575.
101. Ignjatovic N, Tomic S, Dakic M, Miljkovic M, Plavsic M, Uskokovic D. Synthesis and properties of hydroxyapatite/poly-L-lactide composite biomaterials. Biomaterials 1999:20(9):809-816.
102. Najman S, Savic V, Djordjevic L, Ignjatovic N, Uskokovic D. Biological evaluation of hydroxyapatite/poly-L-lactide (HAp/PLLA) composite biomaterials with poly-L-lactide of different molecular weights intraperitoneally implanted into mice. Bio-Medical Materials And Engineering 2004; 14(1): 61-70.
103. Ignjatovic N, Delijic K, Vukcevic M, Uskokovic D. The designing of properties of hydroxyapatite/poly-I-lactide composite biomaterials by hot pressing. Zeitschrift Fur Metallkunde 2001; 92(2): 145-149.
104. Sujovrujic E, Ignjatovic N, Uskokovic D. Gamma irradiation processing of hydroxyapatite/poly-L-lactide composite biomaterial. Radiation Physics And Chemistry 2003; 67(3-4):375-379.
105. Ignjatovic N, Plavsic M, Najman S, Savic V, Uskokovic D. Analysis of in vivo substitution of bone tissue by HAp/PLLA composite biomaterial with PLLA of different molecular weights using FTIR spectroscopy. Trends In Advanced Materials And Processes. Zurich-Uetikon: Trans Tech Publications Ltd; 2000. p 143-150.
106. Ignjatovic N, Plavsic M, Uskokovic D. Hydroxyapatite/poly-L-lactide (collagen) biocomposite with poly-L-lactide of different molecular weights, Advanced Engineering Materials 2000; 2(8): 511-514.
107. Ignjatovic N, Suijovrujic E, Budinski-Simendic J, Krakovsky I, Uskokovic D. Evaluation of hot-pressed hydroxyapatite/poly-L-lactide composite biomaterial characteristics. Journal Of Biomedical Materials Research Part B-Applied Biomaterials 2004; 71 B(2):284-294.
108. Ignjatovic N, Uskokovic D. Synthesis and application of hydroxyapatite/polylactide composite biomaterial. Applied Surface Science 2004; 238(1-4):314-319.
109. Ignjatovic N, Uskokovic D. Molecular spectroscopy analysis of the substitution of bone tissue by HAp/PLLA composite biomaterial. Spectroscopy-An International Journal 2004; 18(4): 553-565.
110. Shikinami Y. Kawarada H. Potential application of a triaxial three-dimensional fabric (3-DF) as an implant. Biomaterials 1998; 19(7-9):617-635.
111. Shikinami Y, Matsusue Y, Nakamura T. The complete process of bioresorption and bone replacement using devices made of forged composites of raw hydroxyapatite particles/poly L-lactide (F-u-HA/PLLA). Biomaterials 2005; 26(27): 5542-5551.
112. Shikinami Y, Okuno M. Bioresorbable devices made of forged composites of hydroxyapatite (HA) particles and poly-L-lactide (PLLA): Part Ⅰ. Basic characteristics. Biomaterials 1999;20(9):859-877.
113. Shikinami Y, Okuno M. Bioresorbable devices made of forged composites of hydroxyapatite (HA) particles and poly L-lactide (PLLA). Part Ⅱ: practical properties of miniscrews and miniplates. Biomaterials 2001; 22(23): 3197-3211.
114. Shikinami Y, Okuno M. Mechanical evaluation of novel spinal interbody fusion cages made of bioactive, resorbable composites. Biomaterials 2003; 24(18): 3161-3170.
115. Furukawa T, Matsusue Y, Yasunaga T, Nakagawa Y, Okada Y, Shikinami Y, Okuno M, Nakamura T. Histomorphometric study on high-strength hydroxyapatite/poly(L-lactide) composite rods for internal fixation of bone fractures. Journal Of Biomedical Materials Research 2000;50(3):410-419.
116. Furukawa T, Matsusue Y, Yasunaga T, Nakagawa Y, Shikinami Y, Okuno M, Nakamura T. Bone bonding ability of a new biodegradable composite for internal fixation of bone fractures. Clinical Orthopaedics And Related Research 2000(379): 247-258.
117. Furukawa T, Matsusue Y, Yasunaga T, Shikinami Y, Okuno M, Nakamura T. Biodegradation behavior of ultra-high-strength hydroxyapatite/poly(L-lactide) composite rods for internal fixation of bone fractures. Biomaterials 2000; 21(9):889-898.
118. Hojo Y, Kotani Y, Ito M, Abumi K, Kadosawa T, Shikinami Y, Minami A. A biomechanical and histological evaluation of a bioresorbable lumbar interbody fusion cage. Biomaterials 2005; 26(15): 2643-2651.
119. Hasegawa M, Sudo A, Shikinami Y, Uchida A. Biological performance of a three-dimensional fabric as artificial cartilage in the repair of large osteochondral defects in rabbit. Biomaterials 1999; 20(20): 1969-1975.
120. Hasegawa S, Ishii S, Tamura J, Furukawa T, Neo M, Matsusue Y, Shikinami Y, Okuno M, Nakamura T. A 5-7 year in vivo study of high-strength hydroxyapatite/poly(L-lactide) composite rods for the internal fixation of bone fractures. Biomaterials 2006; 27(8):1327-1332.
121. Hasegawa S, Neo M, Tamura J, Goto K, Takemoto M, Shikinami Y, Saito M, Nakamura T. In vivo evaluation of a porous hydroxyapatite/poly-D,L-lactide composite for use as bone substitutes and scaffolds for bone tissue engineering. Cytotherapy 2006;8:61-61.
122. Hasegawa S, Tamura J, Neo M, Fujibayashi S, Goto K, Shikinami Y, Okazaki K, Nakamura T. In vivo evaluation of porous hydroxyapatite/poly D/L-lactide composite for bone substitutes and scaffolds. Bioceramics 18, Pts 1 And 2. Zurich-Uetikon: Trans Tech Publications Ltd; 2006. p 1311-1314.
123. Hasegawa S, Tamura J, Neo M, Goto K, Shikinami Y, Saito M, Kita M, Nakamura T. In vivo evaluation of a porous hydroxyapatite/poly-DL-lactide composite for use as a bone substitute. Journal Of Biomedical Materials Research Part A 2005;75A(3):567-579.
124. Hasegawa S, Tamura J, Neo M, Goto K, Shikinami Y, Saito M, Nakamura Y. In vivo evaluation of porous hydroxyapatite/poly D/L-lactide composite for bone substitute and scaffold. Bioceramics 17. Zurich-Uetikon: Trans Tech Publications Ltd; 2005. p 769-772.
125. Bleach NC, Nazhat SN, Tanner KE, Kellomaki M, Tormala P. Effect of filler content on mechanical and dynamic mechanical properties of particulate biphasic calcium phosphate-polylactide composites. Biomaterials 2002; 23(7): 1579-1585.
126. Verheyen C, Dewijn JR, Vanblitterswijk CA, Degroot K. Evaluation Of Hydroxylapatite Poly(L-Lactide) Composites-Mechanical-Behavior. Journal Of Biomedical Materials Research 1992; 26(10): 1277-1296.
127. Zhang SM, Li SP, Yan YH, Wan T, Jiang X, Han CR, Song XP. Surface modification of hydroxyapatite by using gamma-aminopropyl silane. Journal Of Wuhan University Of Technology-Materials Science Edition 2001; 16(3): 37-38.
128．全大萍，李世普，袁润章，廖凯荣，卢泽俭，王海华．聚DL一丙交酯／羟基磷灰石(PDLLA／HA)复合材料Ⅱ：硅烷偶联剂处理羟基磷灰石表面的作用研究．复合材料学报2000；17(4)：114-118．
129．张胜民，李世普，闰玉华，陈晓明．羟基磷灰石颗粒表面改性研究．材料科学与工艺2001；9：404-406．
130．姚晖，杜昶，杨韶华，崔福斋，雷涛．纳米羟晶／胶原仿生骨修复兔颅颌骨缺损的实验研究．透析与人工器官2000：11：5-8．
131. Deng XM, Hao JY, Wang CS. Preparation and mechanical properties of nanocomposites of poly(O,L-lactide) with Ca-deficient hydroxyapatite nanocrystals. Biomaterials 2001: 22(21): 2867-2873.
132．程俊秋，段可，翁杰，张兴栋．多孔纳米羟基磷灰石-聚乳酸复合材料的制备及其界面研究．化学研究与应用2001；13(5)：517-520．
133. Hone ZK, Qiu XY, Sun JR, Deng MX, Chen XS, Jing XB. Grafting polymerization of L-lactide on the surface of hydroxyapatite nano-crystals. Polymer 2004; 45(19):6699-6706.
134. Suljovrujic E, Ignjatovic N, Uskokovic D, Mitric M, Mitrovic M, Tomic S. Radiation-induced degradation of hydroxyapatite/poly L-lactide composite biomaterial. Radiation Physics And Chemistry 2007;76(4):722-728.
135. Balac I, Uskokovic PS, Ignjatovic N, Aleksic R, Uskokovic D. Stress analysis in hydroxyapatite/poly-L-lactide composite biomaterials. Computational Materials Science 2001;20(2):275-283.
136. Ajdukovic Z, Najman S, Dordevic LJ, Savic V, Mihailovic D, Petrovic D, Ignjatovic N, Uskokovic D. Repair of bone tissue affected by osteoporosis with hydroxyapatite-poly-L-lactide (HAp-PLLA) with and without blood plasma. Journal Of Biomaterials Applications 2005;20(2):179-190.
137. Nikcevic I, Maravic D, Ignjatovic N, Mitric M, Makovec D, Uskokovic D. The formation and characterization of nanocrystalline phases by mechanical milling of biphasic calcium phosphate/poly-L-lactide biocomposite. Materials Transactions 2006;47(12):2980-2986.
138. Fukuda A, Kato K, Hasegawa M, Hirata H, Sudo A, Okazaki K, Tsuta K, Shikinami Y, Uchida A. Enhanced repair of large osteochondral defects using a combination of artificial cartilage and basic fibroblast growth factor. Biomaterials 2005;26(20):4301-4308.
139. Ishii S, Tamura J, Furukawa T, Nakamura T, Matsusue Y, Shikinami Y, Okuno M. Long-term study of high-strength hydroxyapatite/poly(L-lactide) composite rods for the internal fixation of bone fractures: A 2-4-year follow-up study in rabbits. Journal Of Biomedical Materials Research Part B-Applied Biomaterials 2003;66B(2):539-547.
140. Kadoya K, Kotani Y, Abumi K, Takada T, Shimamoto N, Shikinami Y, Kadosawa T, Kaneda K. Biomechanical and morphologic evaluation of a three-dimensional fabric sheep artificial intervertebral disc-In vitro and in vivo analysis. Spine 2001; 26(14):1562-1569.
141. Kotani Y, Abumi K, Shikinami Y, Takada T, Kadoya K, Shimamoto N, Ito M, Kadosawa T, Fujinaga T, Kaneda K. Artificial intervertebral disc replacement using bioactive three-dimensional fabric-Design, development, and preliminary animal study. Spine 2002;27(9):929-935.
142. Kotani Y, Abumi K, Shikinami Y, Takahata M, Kadoya K, Kadosawa T, Minami A, Kaneda K. Two-year observation of artificial intervertebral disc replacement: results after supplemental ultra-high strength bioresorbable spinal stabilization. Journal Of Neurosurgery 2004:100(4):337-342.
143. Kotani Y, Cunningham BW, Abumi K, Dmitriev AE, Ito M, Hu N, Shikinami Y, McAfee PC, Minami A. Multidirectional flexibility analysis of cervical artificial disc reconstruction: in vitro human cadaveric spine model. Journal Of Neurosurgery-Spine 2005;2(2):188-194.
144. Totoribe K, Matsumoto M, Goel VK, Yang SJ, Tajima N, Shikinami Y. Comparative biomechanical analysis of a cervical cage made of an unsintered hydroxyapatite particle and poly-L-lactide composite in a cadaver model. Spine 2003;28(10): 1010-1014.
145. Yasunaga T, Matsusue Y, Furukawa T, Shikinami Y, Okuno M, Nakamura T. Bonding behavior of ultrahigh strength unsintered hydroxyapatite particles/poly(L-lactide) composites to surface of tibial cortex in rabbits. Journal Of Biomedical Materials Research 1999; 42(3): 412-419.
146．郭晓东，郑启新，杜靖远，曾晖，全大萍，闫玉华，李世普．可吸收HA／PDLLA内固定材料组织相容性观察．武汉工业大学学报1998；20(4)：28-31．
147．郭晓东，郑启新，杜靖远，全大萍．羟基磷灰石／聚DL-乳酸复合材料在不同植入部位降解机制研究．中国生物医学工程学报2001；20(3)：200-205．
148. VanderMeer SAT, DeWijn JR, Wolke JGC. The influence of basic filler materials on the degradation of amorphous D-and L-lactide copolymer. Journal Of Materials Science-Materials In Medicine 1996; 7(6): 359-361.
149．全大萍，廖凯荣，卢泽俭，王海华．聚dl-丙交酯/羟基磷灰石复合材料Ⅲ．体内外降解性能研究．功能高分子学报2000；13(3)：41-45．
150．廖凯荣，赵剑豪，罗丙红，卢泽俭．聚乳酸／羟基磷灰石复合材料的研究Ⅲ．聚(D，L-乳酸)／羟基磷灰石复合材料的体外降解行为．中山大学学报(自然科学版)2001；40(1)：44-46．
151. Heidemann W, Jeschkeit S, Ruffieux K, Fischer JH, Wagner M, Kruger G, Wintermantel E, Gerlach KL. Degradation of poly(D,L)lactide implants of calciumphosphates with or without addition in vivo. Biomaterials 2001;22(17):2371-2381.
152. Weng J, Wang M, Chen JY. Plasma-sprayed calcium phosphate particles with high bioactivity and their use in bioactive scaffolds. Biomaterials 2002;23(13):2623-2629.
153. Mann S. Molecular Tectonics In Biomineralization And Biomimetic Materials Chemistry. Nature 1993;365(6446):499-505.
154. Mann S, Archibald DD, Didymus JM, Douglas T, Heywood BR, Meldrum FC, Reeves NJ. Crystallization At Inorganic-Organic Interfaces-Biominerals And Biomimetic Synthesis. Science 1993; 261(5126): 1286-1292.
155. Spanos N, Koutsoukos PG. Hydroxyapatite precipitation on a carboxylated vinyl chloride-vinyl acetate copolymer. Journal Of Materials Science 2001; 36(3): 573-578.
156. Sato K, Kumagai Y, Tanaka T. Apatite formation on organic monolayers in simulated body environment. Journal Of Biomedical Materials Research 2000; 50(1): 16-20.
157. Yuan XY, Mak AFT, Li JL. Formation of bone-like apatite on poly(L-lactic acid) fibers by a biomimetic process. Journal Of Biomedical Materials Research 2001; 57(1): 140-150.
158. Zhang RY, Ma PX. Porous poly(L-lactic acid)/apatite composites created by biomimetic process. Journal Of Biomedical Materials Research 1999; 45(4): 285-293.
159. Kato K, Eika Y, Ikada Y. In situ hydroxyapatite crystallization for the formation of hydroxyapatite/polymer composites. Journal Of Materials Science 1997; 32(20): 5533-5543.
160. Nagata F, Miyajima T, Yokogawa Y. Surfactant-free preparation of poly(lactic acid)/hydroxyapatite microspheres. Chemistry Letters 2003; 32(9):784-785.
161. Xiao YM, Zhao HC, Fan HS, Wang XL, Gun LK, Li XD, Zhang XD. A novel way to prepare nano-hydroxyapatite/poly(D,L-lactide)composite. Pricm 5: The Fifth Pacific Rim International Conference On Advanced Materials And Processing, Pts 1-5. Zurich-Uetikon: Trans Tech Publications Ltd; 2005. p 2383-2386.
1. Bostman O, Viljanen J, Salminen S, Pihlajamaki H. Response of articular cartilage and subchondral bone to internal fixation devices made of poly-L-lactide: a histomorphometric and microradiographic study on rabbits. Biomaterials 2000; 21(24): 2553-2560.
2. Bostman O, Pihlajamaki H. Clinical biocompatibility of biodegradable orthopaedic implants for internal fixation: a review. Biomaterials 2000; 21(24): 2615-2621.
3. Zhang XC, McAuley KB, Goosen MFA. Towards Prediction Of Release Profiles Of Antibiotics From Coated Poly(Dl-Lactide)Cylinders. Journal Of Controlled Release 1995: 34(2): 175-179.
4. Pineda LM, Busing M, Meinig RP, Gogolewski S. Bone regeneration with resorbable polymeric membranes. 3. Effect of poly(L-lactide) membrane pore size on the bone healing process in large detects. Journal Of Biomedical Materials Research 1996: 31(3): 385-394.
5. Meinig RP, Rahn B, Perren SM, Gogolewski S. Bone regeneration with resorbable polymeric membranes: Treatment of diaphyseal bone defects in the rabbit radius with poly(L-lactide) membrane. A pilot study. Journal Of Orthopaedic Trauma 1996;10(3): 178-190.
6．王远亮，潘君，蔡绍皙．组织工程研究的进展．生物化学与生物物理进展2000；27(4)：365-367．
7．王勤，路岩，张娟．以聚乳酸为载体的药物释放及动物疗效学的研究．中国生物医学工程学报1995；14(1)：11-14．
8．李玉宝．《生物医学材料》．化学工业出版社2003．9．
9．全大萍，江昕，李世普．聚乳酸及其复合材料的研究概况．武汉工业大学学报1996；18(2)：114-117．
10. Crane GM, Ishaug SL, Mikos AG. Bone Tissue Engineering. Nature Medicine 1995; 1(12):1322-1324.
11. Calandrelli L, Immirzi B, Malinconico M, Volpe MG, Oliva A, Della Ragione F. Preparation and characterisation of composites based on biodegradable polymers for "in vivo" application. Polymer 2000; 41(22): 8027-8033.
12. Kasuga T, Ota Y, Nogami M, Abe Y. Preparation and mechanical properties of polylactic acid composites containing hydroxyapatite fibers. Biomaterials 2001; 22(1):19-23.
13. Najman S, Savic V, Djordjevic L, Ignjatovic N, Uskokovic D. Biological evaluation of hydroxyapatite/poly-L-lactide (HAp/PLLA) composite biomaterials with poly-L-lactide of different molecular weights intraperitoneally implanted into mice. Bio-Medical Materials And Engineering 2004; 14(1):61-70.
14. Ignjatovic N, Delijic K, Vukcevic M, Uskokovic D. Microstructure and mechanical properties of hot-pressed hydroxyapatite/poly-L-lactide biomaterials. Bioceramics. Zurich-Uetikon: Trans Tech Publications Ltd; 2000. p 737-740.
15. Ignjatovic N, Delijic K, Vukcevic M, Uskokovic D. The designing of properties of hydroxyapatite/poly-l-lactide composite biomaterials by hot pressing. Zeitschrift Fur Metallkunde 2001; 92(2): 145-149.
16. Ignjatovic N, Ninkov P, Ajdukovic Z, Vasijevic-Radovic D, Uskokovic D. Biphasic calcium phosphate coated with poly-D,L-lactide-co-glycolide biomaterial as a bone substitute. Journal Of The European Ceramic Society 2007;27(2-3):1589-1594.
17. Ignjatovic N, Plavsic M, Uskokovic D. Hydroxyapatite/poly-L-lactide (collagen) biocomposite with poly-L-lactide of different molecular weights. Advanced Engineering Materials 2000; 2(8): 511-514.
18. Ignjatovic N, Savic V, Najman S, Plavsic M, Uskokovic D. A study of HAp/PLLA composite as a substitute for bone powder, using FT-IR spectroscopy. Biomaterials 2001; 22(6): 571-575.
19. Ignjatovic N, Suijovrujic E, Budinski-Simendic J, Krakovsky I, Uskokovic D. Evaluation of hot-pressed hydroxyapatite/poly-L-lactide composite biomaterial characteristics. Journal Of Biomedical Materials Research Part B-Applied Biomaterials 2004;71B(2):284-294.
20. Ignjatovic N, Tomic S, Dakic M, Miljkovic M, Plavsic M, Uskokovic D. Synthesis and properties of hydroxyapatite/poly-L-lactide composite biomaterials. Biomaterials 1999; 20(9): 809-816.
21. Ignjatovic N, Uskokovic D. Synthesis and application of hydroxyapatite/polylactide composite biomaterial. Applied Surface Science 2004;238(1-4):314-319.
22. Shikinami Y, Kawarada H. Potential application ofa triaxial three-dimensional fabric (3-DF) as an implant. Biomaterials 1998; 19(7-9):617-635.
23. Shikinami Y, Matsusue Y, Nakamura T. The complete process of bioresorption and bone replacement using devices made of forged composites of raw hydroxyapatite particles/poly L-lactide (F-u-HA/PLLA). Biomaterials 2005;26(27):5542-5551.
24. Shikinami Y, Okuno M. Bioresorbable devices made of forged composites of hydroxyapatite (HA) particles and poly-L-lactide (PLLA): Part Ⅰ. Basic characteristics. Biomaterials 1999;20(9):859-877.
25. Shikinami Y, Okuno M. Bioresorbable devices made of forged composites of hydroxyapatite (HA) particles and poly L-lactide (PLLA). Part Ⅱ: practical properties of miniscrews and miniplates. Biomaterials 2001 ;22(23):3197-3211.
26. Shikinami Y, Okuno M. Mechanical evaluation of novel spinal interbody fusion cages made of bioactive, resorbable composites. Biomaterials 2003;24(18):3161-3170.
27．郭晓东，郑启新，杜靖远，全大萍，阎玉华，李世普，李香亮．可吸收羟基磷灰石／聚 DL-乳酸骨折内固定材料机械强度和生物降解性研究．中国生物医学工程学报2001；20(1)：23-27．
28．张弛，陈峥嵘，林建平，张光健．聚乳酸涂层的多孔羟基磷灰石负载软骨细胞移植修复兔关节软骨缺损．上海医科大学学报2000；37(2)：83-86．
29．廖凯荣，罗力力，薄颖慧等．聚左旋乳酸及其复合体系的非等温结晶动力学．中山大学学报(自然科学版)1998；37(4)：71-75．
30．薄颖慧，廖凯荣，卢泽俭，郑臣谋．聚乳酸／羟基磷灰石复合材料的研究Ⅰ．超细微羟基磷灰石的合成及表面处理．中山大学学报(自然科学版)1999；38(3)：43-47．
31．程俊秋，段可，翁杰，张兴栋．多孔纳米羟基磷灰石-聚乳酸复合材料的制备及其界面研究．化学研究与应用2001；13(5)：517-520．
32. Zhang RY, Ma PX. Poly(alpha-hydroxyl acids) hydroxyapatite porous composites for bone-tissue engineering. Ⅰ. Preparation and morphology. Journal Of Biomedical Materials Research 1999;44(4):446-455.
33. Verheyen C, Dewijn JR, Vanblitterswijk CA, Degroot K. Evaluation Of Hydroxylapatite Poly(L-Lactide) Composites-Mechanical-Behavior. Journal Of Biomedical Materials Research 1992;26(10):1277-1296.
34. Verheyen C, Klein C, Deblieckhogervorst JMA, Wolke JGC, Vanblitterswijn CA, Degroot K. Evaluation Of Hydroxylapatite Poly(L-Lactide) Composites-Physicochemical Properties. Journal Of Materials Science-Materials In Medicine 1993;4(1):58-65.
35. Mann S. Molecular Tectonics In Biomineralization And Biomimetic Materials Chemistry. Nature 1993; 365(6446): 499-505.
36. Mann S, Archibald DD, Didymus JM, Douglas T, Heywood BR, Meldrum FC, Reeves NJ. Crystallization At Inorganic-Organic Interfaces-Biominerals And Biomimetic Synthesis. Science 1993; 261(5126): 1286-1292.
37. Kato K, Eika Y, Ikada Y. In situ hydroxyapatite crystallization for the formation of hydroxyapatite/polymer composites. Journal Of Materials Science 1997; 32(20): 5533-5543.
38. Spanos N, Koutsoukos PG. Hydroxyapatite precipitation on a carboxylated vinyl chloride-vinyl acetate copolymer. Journal Of Materials Science 2001; 36(3): 573-578.
39. Sato K, Kogure T, Kumagai Y, Tanaka J. Crystal orientation of hydroxyapatite induced by ordered carboxyl groups. Journal Of Colloid And Interface Science 2001; 240(1): 133-138.
40. Sato K, Kumagai Y, Tanaka T. Apatite formation on organic monolayers in simulated body environment. Journal Of Biomedical Materials Research 2000;50(1):16-20.
41. Nagata F, Miyajima T, Yokogawa Y. Surfactant-free preparation of poly(lactic acid)/hydroxyapatite microspheres. Chemistry Letters 2003;32(9):784-785.
42. Yuan XY, Mak AFT, Li JL. Formation of bone-like apatite on poly(L-lactic acid) fibers by a biomimetic process. Journal Of Biomedical Materials Research 2001; 57(1): 140-150.
43. Zhang RY, Ma PX. Porous poly(L-lactic acid)/apatite composites created by biomimetic process. Journal Of Biomedical Materials Research 1999; 45(4): 285-293.
44. Xiao YM, Zhao HC, Fan HS, Wang XL, Guo LK, Li XD, Zhang XD. A novel way to prepare nano-hydroxyapatite/poly(D,L-lactide) composite. Pricm 5: The Fifth Pacific Rim International Conference On Advanced Materials And Processing, Pts 1-5. Zurich-Uetikon: Trans Tech Publications Ltd; 2005. p 2383-2386.
45．魏杰．纳米类骨磷灰石晶体及其与聚酰胺复合骨修复材料研究，博士学位论文．
46. Kister G, Cassanas G, Vert M. Effects of morphology, conformation and configuration on the IR and Raman spectra of various poly(lactic acid)s. Polymer 1998; 39(2): 267-273.
47. Rusu VM, Ng CH, Wilke M, Tiersch B, Fratzl P, Peter MG. Size-controlled hydroxyapatite nanoparticles as self-organized organic-in organic composite materials. Biomaterials 2005; 26(26): 5414-5426.
1. Mann S. Molecular Tectonics In Biomineralization And Biomimetic Materials Chemistry. Nature 1993; 365(6446): 499-505.
2. Mann S, Archibald DD, Didymus JM, Douglas T, Heywood BR, Meldrum FC, Reeves NJ. Crystallization At Inorganic-Organic Interfaces-Biominerals And Biomimetic Synthesis. Science 1993; 261(5126): 1286-1292.
3. Kato K, Eika Y, Ikada Y. In situ hydroxyapatite crystallization for the formation of hydroxyapatite/polymer composites. Journal Of Materials Science 1997. 32(20): 5533-5543.
4. Sato K, Kogure 7: Kumagai Y, Tanaka J. Crystal orientation of hydrogyapatite induced by ordered carboxyl groups. Journal Of Colloid And Interface Science 2001; 240(1): 133-138.
5. Sato K, Kumagai Y, Tanaka T. Apatite formation on organic monolayers in simulated body environment. Journal Of Biomedical Materials Research 2000; 50(1): 16-20.
6. Spanos N, Koutsoukos PG. Hydroxyapatite precipitation on a carboxylated vinyl chloride-vinyl acetate copolymer. Journal Of Materials Science 2001; 36(3): 573-578.
7. Nagata F, Miyajima T, Yokogawa Y. Surfactant-free preparation of poly(lactic acid)/hydroxyapatite microspheres. Chemistry Letters 2003;32(9):784-785.
8. Yuan XY, MakAFT, Li JL. Formation of bone-like apatite on poly(L-lactic acid) fibers by a biomimetic process. Journal Of Biomedical Materials Research 2001; 57(1): 140-150.
9. Zhang RY, Ma PX. Porous poly(L-lactic acid)/apatite composites created by biomimetic process. Journal Of Biomedical Materials Research 1999; 45(4): 285-293.
10. Xiao YM, Zhao HC, Fan HS, Wang XL, Guo LK, Li XD, Zhang XD. A novel way to prepare nano-hydroxyapatite/poly(D,L-lactide) composite. Pricm 5: The Fifth Pacific Rim International Conference On Advanced Materials And Processing, Pts 1-5. Zurich-Uetikon: Trans Tech Publications Ltd; 2005. p 2383-2386.
11. Xiao YM, Li DX, Fan HS, Li XD, Gu ZW, X. D. Z. Preparation of nano-HA/PLA composite by modified-PLA for controlling the growth of HA crystals. Materials Letters 2006; 61(1): 59-62.
12. Ma ZW, Gao CY, Ji JA, Shen JC. Protein immobilization on the surface of poly-L-lactic acid films for improvement of cellular interactions. European Polymer Journal 2002; 38(11): 2279-2284.
13. Fujimoto K, Takebayashi Y, Inoue H, Ikada Y. Ozone-Induced Graft-Polymerization Onto Polymer Surface. Journal Of Polymer Science Part A-Polymer Chemistry 1993; 31(4): 1035-1043.
14. Suh H, Hwang YS, Lee JE, Han CD, Park JC. Behavior of osteoblasts on a type Ⅰ atelocollagen grafted ozone oxidized poly L-lactic acid membrane. Biomaterials 2001; 22(3): 219-230.
15. Frew JE, Jones J, Scholes G. Spectrophotometric determination of hydrogen peroxide and organic, hydroperoxides at low concentrations in aqueous solution. Analytica Chimica Acta 1983; 155: 139-150.
16．董文艺，杜红．过氧化氢氧化法的原理及对有机物的去除．中国农村水利水电 2004;2:47-48.
17. Stefan MI, Bolton JR. Mechanism of the degradation of 1,4-dioxane in dilute aqueous solution using the UV hydrogen peroxide process. Environmental Science & Technology 1998;32(11):1588-1595.
18. Esplugas S, Gimenez J, Contreras S, Pascual E, Rodriguez M. Comparison of different advanced oxidation processes for phenol degradation. Water Research 2002; 36(4): 1034-1042.
19. Kister G, Cassanas G, Vert M. Effects of morphology, conformation and configuration on the IR and Raman spectra of various poly(lactic acid)s. Polymer 1998;39(2):267-273.
20．魏杰．纳米类骨磷灰石晶体及其与聚酰胺复合骨修复材料研究，博士学位论文．
21. Wang X J, Li YB, Wei J, de Groot K. Development of biomimetic nano-hydroxyapatite/poly(hexamethylene adipamide) composites. Biomaterials 2002; 23(24): 4787-4791.
22. Jie W, Li Y. Tissue engineering scaffold material ofnano-apatite crystals and polyamide composite. European Polymer Journal 2004;40(3):509-515.
23．朱埗瑶，赵振国等．界面化学基础．北京：化学工业出版社1999：257-258．
24. Malvern Instruments Ltd. Zetasizer Nano Series User Manual (2004). printed in England MRK0499-01: 16.2.
25．邵鑫，田军，薛群基等．有机-无机纳米复合材料的合成、性质及应用前景．材料导报2001；15(1)：50-53．
1．俞梦孙，蒋大宗．中国生物医学工程的今天与明天，生物医学工程学丛书．天津科技翻译出版公司，天津1998年．
2．王慧明，李梵，王模堂等．四种骨替代材料的人成骨细胞生物相容性研究．中国生物医学工程学学报1996；15(3)：239-244．
3．杨晓芳．生物材料生物相容性评价研究进展．生物医学工程2001；18(1)：123-128．
4. Dee KC, Bizios R. Mini-review: Proactive biomaterials and bone tissue engineering. Biotechnology And Bioengineering 1996;50(4):438-442.
5. McKay GC, Macnair R, MacDonald C, Grant MH. Interactions of orthopaedic metals with an immortalized rat osteoblast cell line. Biomaterials 1996; 17(13): 1339-1344.
6．郭晓东，郑启新，杜靖远，全大萍．羟基磷灰石／聚DL-乳酸复合材料在不同植入部位降解机制研究．中国生物医学工程学报2001；20(3)：200-205．
7．刘建伟，赵强，万昌秀．医用聚乳酸体内降解机理及应用研究进展．航天医学与医学工程2001；14(4)：308．
8. Therin M. Christel P, Li SM, Garreau H, Vert M. Invivo Degradation Of Massive Poly(Alpha-Hydroxy Acids)-Validation Of Invitro Findings. Biomaterials 1992; 13(9): 594-600.
9. Vert M, Li SM, Garreau H. Attempts to map the structure and degradation characteristics of aliphatic polyesters derived from lactic and glycolic acids. J Biomater Sci Polym Ed 1994: 6(7): 639-49.
10. Spenlehauer G, Vert M, Benoit JP, Boddaert A. In vitro and in vivo degradation ofpoly(D,L lactide/glycolide) type microspheres made by solvent evaporation method. Biomaterials 1989; 10(8): 557-63.
11. Therin M. Christel P. Li S, Garreau H, Vert M. In vivo degradation of massive poly(alpha-hydroxy acids): validation of in vitro findings. Biomaterials 1992; 13(9):594-600.
12. Grizzi I, Garreau H, Li S, Vert M. Hydrolytic degradation of devices based on poly(DL-lactic acid) size-dependence. Biomaterials 1995; 16(4): 305-11.
13. Schmitt EA, Flanagan DR, Linhardt RJ. Importance Of Distinct Water Environments In The Hydrolysis Of Poly(Dl-Lactide-Co-Glycolide). Macromolecules 1994; 27(3):743-748.
14. Zhang XC, Wyss UP, Pichora D, Goosen MFA. An Investigation Of Poly(Lactic Acid) Degradation. Journal Of Bioactive And Compatible Polymers 1994; 9(1): 80-100.
15. Liu Q, de Wijn JR, Bakker D, van Toledo M, van Blitterswijk CA. Polyacids as bonding agents in hydroxyapatite polyester-ether(Polyactive (TM) 30/70) composites. Journal Of Materials Science-Materials In Medicine 1998; 9(1): 23-30.
16．郭晓东，郑启新，杜靖远，曾晖，全大萍，闫玉华，李世普．可吸收HA／PDLLA内固定材料组织相容性观察．武汉工业大学学报1998；20(4)：28-31．
17. Rizzi SC, Heath DT, Coombes AGA, Bock N, Textor M, Downes S. Biodegradable polymer/hydroxyapatite composites: Surface analysis and initial attachment of human osteoblasts. Journal Of Biomedical Materials Research 2001; 55(4): 475-486.
18．郭晓东，郑启新，杜靖远，全大萍，阎玉华，李世普，李香亮．可吸收羟基磷灰石／聚DL-乳酸骨折内固定材料机械强度和生物降解性研究．中国生物医学工程学报2001；20(1)：23-27．
19．赵建华，廖维宏，王远亮，潘君，柳峰．消旋聚乳酸／羟基磷灰石／脱钙骨基质的制备及其体外降解特性研究．中华修复重建外科杂志2003；17(1)：61-64．
20. Shackelford JF. Bioceramics-Current status and future trends. Bioceramics. Zurich-Uetikon: Transtec Publications Ltd; 1999. p 99-106.
21. Hench LL. Bioceramics: From concept to clinic. J Atn Ceram Soc 1991: 74: 1487-1510.
22．李玉宝．《生物医学材料》．化学工业出版社2003．9．
23．师昌绪．材料科学技术百科全书，生物医学材料分支，中国大百科全书出版社．北京．1995．8．
24．顾汉卿，徐国风．《生物医学材料学》，生物医学工程学丛书．天津科技翻译出版社，天津．1993年．
25. Hench LL, Wilson J. Surface-active biomaterials. Science 1984;226(4675):630-6.
26. Hench LL, Polak JM. Third-generation biomedical materials. Science 2002:295(5557):1014.
27. Ducheyne P. Qiu Q. Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function. Biomaterials 1999;20(23-24):2287-2303.
28. Knaack D, Goad MEP, Aiolova M. Rey C, Tofighi A, Chakravarthy P. Lee DD. Resorbable calcium phosphate bone substitute. Journal Of Biomedical Materials Research 1984: 43(4): 399-409.
29. Germine M. Parsons JR. Deconvoluted X-ray diffraction analysis of bone and mixtures of bone and particulate hydroxyapatite. J Biomed Mater Res 1988; 22(A1 Suppl): 55-67.
30. Lampin M. WarocquierClerout R, Legris C, Degrange M, SigotLuizard MF. Correlation between substratum roughness and wettability, cell adhesion, and cell migration. Journal Of Biomedical Materials Research 1997; 36(1): 99-108.
31. Kokubo T. Miyaji F, Kim HM, Nakamura T. Spontaneous formation of bonelike apatite layer on chemically treated titanium metals. Journal Of The American Ceramic Society 1996; 79(4): 1127-1129.
32. Hench L, Splinter R, Greenlee T, al. e. Bonding mechanisms at the interface of ceramic prosthetic materials. J Biomed Eng 1971; 2: 117-141.
33. Kay MI, Young RA, Posner AS. Crystal Structure Of Hydroxyapatite. Nature 1964: 204: 1050-2.
34. Oyane A, Nakanishi K, Kim HM, Miyaji F, Kokubo T, Soga N, Nakamura T. Sol-gel modification of silicone to induce apatite-forming ability. Biomaterials 1999; 20(1): 79-84.
35. Nishio K, Neo M, Akiyama H, Nishiguchi S, Kim HM, Kokubo T, Nakamura T. The effect of alkali-and heat-treated titanium and apatite-formed titanium on osteoblastic differentiation of bone marrow cells. Journal Of Biomedical Materials Research 2000:52(4):652-661.
36. de Sena LA, Rocha NCC, Andrade MC, Soares GA. Bioactivity assessment of titanium sheets electrochemically coated with thick oxide film. Surface & Coatings Technology 2003:166(2-3):254-258.
37. Ni J. Wang M. In vitro evaluation of hydroxyapatite reinforced po yhydroxybutyrate composite. Materials Science & Engineering C-Biomimetic And Supramolecular Systems 2002; 20(1-2):101-109.
38. Li PJ, Degroot K. Calcium-Phosphate Formation Within Sol-Gel Prepared Titania In-Vitro And In-Vivo. Journal Of Biomedical Materials Research 1993; 27(12): 1495-1500.
39. Bunker BC, Rieke PC, Tarasevich BJ, Campbell AA, Fryxell GE, Graff GL, Song L, Liu J, Virden JW, McVay GL. Ceramic Thin-Film Formation On Functionalized Interfaces Through Biomimetic Processing. Science 1994;264(5155):48-55.
40. Nakamura T, Yamamuro T, Higashi S, Kokubo T, Itoo S. A new glass-ceramic for bone replacement: evaluation of its bonding to bone tissue. J Biomed Mater Res 1985; 19(6): 685-98.
41. Rhee SH, Tanaka J. Effect of citric acid on the nucleation of hydroxyapatite in a simulated body fluid. Biomaterials 1999;20(22):2155-2160.
42. Bigi A, Boanini E, Panzavolta S, Roveri N. Biomimetic growth of hydroxyapatite on gelatin films doped with sodium polyacrylate. Biomacromolecules 2000;1(4):752-756.
43．张胜民．HA／PLA复合生物材料界面的分子设计、构建与相关性能，博士学位论文．
44．杨志明．组织工程基础与临床．四川科学技术出版社，成都，2000年．
45. Knabe C, Gildenhaar R, Berger G, Ostapowicz W, Fitzner R, Radlanski RJ, Gross U. Morphological evaluation of osteoblasts cultured on different calcium phosphate ceramics. Biomaterials 1997; 18(20): 1339-1347.
46. Mullermai CM, Stupp SI, Voigt C, Gross U. Nanoapatite And Organoapatite Implants In Bone-Histology And Ultrastructure Of The Interface. Journal Of Biomedical Materials Research 1995;29(1):9-18.
47. Gross U, Brandes J, Strunz V, Bab I, Sela J. The ultrastructure of the interface between a glass ceramic and bone. J Biomed Mater Res 1981;15(3):291-305.
48. Kwong CH, Burns WB, Cheung HS. Solubilization ofhydroxyapatite crystals by murine bone cells, macrophages and fibroblasts. Biomaterials 1989;10(9):579-84.
49. Ajioka M, Enomoto K, Suzuki K, Yamaguchi A. Basic Properties Of Polylactic Acid Produced By The Direct Condensation Polymerization Of Lactic-Acid. Bulletin Of The Chemical Society Of Japan 1995;68(8):2125-2131.
50．李孝红，袁明龙，熊成东等．聚乳酸及其共聚物的合成和在生物医学上的应用．高分子通报1999：1：24-32．
51．阮狄克，沈根标，邹宏恩等．可吸收聚乳酸植入材料的实验观察．中华骨科杂志1994；14(6)：370-373．
52．郑谦，魏世成，赵宗林等．可吸收DL—聚乳酸夹板行额面部骨折内固定的实验研究．华西口腔医学杂志1996；14(4)：254-257．
53. Bos RR, Boering G, Rozema FR, Leenslag JW. Resorbable poly(L-lactide) plates and screws for the fixation ofzygomatic fractures. J Oral Maxillofac Surg 1987;45(9):751-3.
54. Leenslag JW, Pennings AJ, Bos RR, Rozema FR, Boering G. Resorbable materials of poly(L-lactide). Ⅵ. Plates and screws for internal fracture fixation. Biomaterials 1987; 8(1): 70-3.
55. Viljanen J, Kinnunen J, Bondestam S, MajolaA, Rokkanen P, Tormala P. Bone changes after experimental osteotomies fixed with absorbable self-reinforced poly-L-lactide screws or metallic screws studied by plain radiographs, quantitative computed tomography and magnetic resonance imaging. Biomaterials 1995; 16(17):1353-8.
56. Majola A, Vainionpaa S, Vihtonen K, Mero M, Vasenius J, Tormala P, Rokkanen P. Absorption, biocompatibility, and fixation properties of polylactic acid in bone tissue: an experimental study in rats. Clin Orthop Relat Res 1991(268): 260-9.
57. Pihlajamaki H, Bostman O, Hirvensalo E, Tormala P, Rokkanen P. Absorbable Pins Of Self-Reinforced Poly-L-Lactic Acid For Fixation Of Fractures And Osteotomies. Journal Of Bone And Joint Surgery-British Volume 1992; 74(6): 853-857.
58. Pistner H, Gutwald R, Ordung R, Reuther J, Muhling J. Poly(L-Lactide)-A Long-Term Degradation Study In-Vivo. I. Biological Results. Biomaterials 1993; 14(9):671-677.
59. Asanami S, Shimono K, Kaneda S. Transient hypothermia induces micronuclei in mice. Mutation Research-Genetic Toxicology And Environmental Mutagenesis 1998; 413(1): 7-14.
60. Przybojewska B. An evaluation of the genotoxic properties of some chosen dyes using the micronucleus test in vivo. Mutation Research-Genetic Toxicology 1996;367(2):93-97.
61. Witt KL, Gulati DK, Kaur P, Shelby MD. Phenolphthalein-Induction Of Micronucleated Erythrocytes In Mice. Mutation Research-Genetic Toxicology 1995;341 (3):151-160.
62. Kulkarni RK, Pani KC, Neuman C, Leonard F. Polylactic acid for surgical implants. Arch Surg 1966; 93(5): 839-43.
63. Matsusue Y, Yamamuro T, Oka M, Shikinami Y, Hyon SH, Ikada Y. Invitro And Invivo Studies On Bioabsorbable Ultrahigh-Strength Poly(L-Lactide) Rods. Journal Of Biomedical Materials Research 1992; 26(12): 1553-1567.
64．全大萍，廖凯荣，卢泽俭，王海华．聚dl-丙交酯／羟基磷灰石复合材料Ⅲ．体内外降解性能研究．功能高分子学报2000；13(3)：41-45．
65. Damien CJ, Ricci JL, Christel P, Alexander H, Patat JL. Formation Of A Calcium Phosphate-Rich Layer On Absorbable Calcium-Carbonate Bone-Graft Substitutes. Calcified Tissue International 1994;55(2):151-158.
66. Johnson KD, Frierson KE, Keller TS, Cook C, Scheinberg R, Zerwekh J, Meyers L, Sciadini MF. Porous ceramics as bone graft substitutes in long bone defects: A biomechanical, histological, and radiographic analysis. Journal Of Orthopaedic Research 1996; 14(3): 351-369.
67. Oguchi H, Ishikawa K, Mizoue K, Seto K, Eguchi G. Long-Term Histological-Evaluation Of Hydroxyapatite Ceramics In Humans. Biomaterials 1995; 16(1):33-38.
68. Pettis GY, Kaban LB, Glowacki J. Tissue response to composite ceramic hydroxyapatite/demineralized bone implants. J Oral Maxillofac Surg 1990; 48(10): 1068-74.
69. Neo M, Kotani S, Fujita Y, Nakamura T, Yamamuro T, Bando Y, Ohtsuki C, Kokubo T. Differences In Ceramic Bone Interface Between Surface-Active Ceramics And Resorbable Ceramics-A Study By Scanning And Transmission Electron-Microscopy. Journal Of Biomedical Materials Research 1992; 26(2): 255-267.
70. de Groot K, Klein CAPT, Wolke JGC, et al.. Handbook of bioactive ceramics: Chemistry of calcium phosphate bioceramics. CRC Press, Boca Raton, Florida, 1990.
71. Dahlin C, Linde A, Gottlow J, Nyman S. Healing of bone defects by guided tissue regeneration. Plast Reconstr Surg 1988; 81(5): 672-6.
72. Urist MR, McLean FC. Recent Advances In Physiology Of Bone. I. J Bone Joint Surg Am 1963; 45: 1305-13.
2. Damien CJ, Parsons JR. Bone graft and bone graft substitutes: a review of current technology and applications. J Appl Biomater 1991; 2(3): 187-208.
3. Wen HB, Cut FZ, Feng QL, Li HD, Zhu XD. Microstructural Investigation Of The Early External Callus After Diaphyseal Fractures Of Human Long-Bone. Journal Of Structural Biology 1995; 114(2): 115-122.
4. Wen HB, Cui FZ, Zhu XD. Microstructural features of non-union of human humeral shaft fracture. Journal Of Structural Biology 1997; 119(3): 239-246.
5．师昌绪．材料科学技术百科全书，生物医学材料分支，中国大百科全书出版社，北京．1995．8．
6．李玉宝．《生物医学材料》．化学工业出版社2003．9．
7．李世普．《生物医学材料导论》，武汉工业大学出版社．2000．
8．梁芳慧，周廉．钛和钛合金生物活化研究现状．稀有金属材料与工程2003：32(4)：241-245．
9. Wen J, Leng Y, Chen JY, Zhang C. Chemical gradient in plasma-sprayed HA coatings. Biomaterials 2000; 21(13): 1339-1343.
10. Zheng XB, Huang MH, Ding CX. Bond strength of plasma-sprayed hydroxyapatite/Ti composite coatings. Biomaterials 2000; 21(8): 841-849.
11. Kim HM, Miyaji F, Kokubo T, Nishiguchi S, Nakamura T. Graded surface structure of bioactive titanium prepared by chemical treatment. Journal Of Biomedical Materials Research 1999; 45(2): 100-107.
12. Wen HB, de Wijn JR, Cut FZ, de Groot K. Preparation of calcium phosphate coatings on titanium implant materials by simple chemistry. Journal Of Biomedical Materials Research 1998; 41(2): 227-236.
13. Lu X, Leng Y, Zhang XD, Xu JR, Qin L, Chan CW. Comparative study of osteoconduction on micromachined and alkali-treated titanium alloy surfaces in vitro and in vivo. Biomaterials 2005; 26(14): 1793-1801.
14. Yang BC, Uchida M, Kim HM, Zhang XD, Kokubo T. Preparation of bioactive titanium metal via anodic oxidation treatment. Biomaterials 2004;25(6):1003-1010.
15. Spoerke ED, Stupp SI. Synthesis of a poly (L-lysine)-calcium phosphate hybrid on titanium surfaces for enhanced bioactivity. Biomaterials 2005; 26(25):5120-5129.
16. Lee JH, Ryu HS, Lee DS, Hong KS, Chang BS, Lee CK. Biomechanical and histomorphometric study on the bone-screw interface of bioactive ceramic-coated titanium screws. Biomaterials 2005;26(16):3249-3257.
17. Gross KA, Berndt CC. In-Vitro Testing Of Plasma-Sprayed Hydroxyapatite Coatings. Journal Of Materials Science-Materials In Medicine 1994; 5(4):219-224.
18. Kitsugi T, Yamamuro T, Nakamura T, Masanori O. Transmission Electron-Microscopy Observations At The Interface Of Bone And 4 Types Of Calcium-Phosphate Ceramics with Different Calcium Phosphorus Molar Ratios. Biomaterials 1995; 16(14): 1101-1107.
19. Yuan HP, Li YB, de Bruijn JD, de Groot K, Zhang XD. Tissue responses of calcium phosphate cement: a study in dogs. Biomaterials 2000; 21(12): 1283-1290.
20. Pioletti DP, Takei H, Lin T, Van Landuyt P, Ma QJ, Kwon SY, Sung KLP. The effects of calcium phosphate cement particles on osteoblast functions. Biomaterials 2000; 21(11): 1103-1114.
21. Mirtchi AA, Lemaitre J. Munting E. Calcium phosphate cements: action of setting regulators on the properties of the beta-tricalcium phosphate-monocalcium phosphate cements. Biomaterials 1989; 10(9): 634-8.
22．马祖伟，高长有，龚逸鸿，沈家骢．Ⅰ型胶原在聚-L-乳酸(PLLA)表面的化学接枝和涂层及其对软骨细胞生长的促进作用．高等学校化学学报2004；25(4)：749-752．
23．张其清，刘玲蓉．医用组织引导再生材料的发展现状及发展方向综述．中国修复重建外科杂志1997；11(6)：365-367．
24. Ruszczak Z. Effect of collagen matrices on dermal wound healing. Adv Drug Deliv Rev 2003; 55(12): 1595-611.
25. Lee CH, Singla A, Lee Y. Biomedical applications of collagen. International Journal Of Pharmaceutics 2001; 221(1-2): 1-22.
26. Lewis G. Properties of acrylic bone cement: State of the art review. Journal Of Biomedical Materials Research 1997; 38(2): 155-182.
27. Kulkarni RK, Pani KC, Neuman C, Leonard F. Polylactic acid for surgical implants. Arch Surg 1966; 93(5): 839-43.
28．陈俊民．药用高分子材料学．第一版，北京：中国医药科技出版社．2004．
29. Bostman O, Pihlajamaki H. Clinical biocompatibility of biodegradable orthopaedic implants for internal fixation: a review. Biomaterials 2000; 21(24): 2615-2621.
30. Meinig RP, Rahn B, Perren SM, Gogolewski S. Bone regeneration with resorbable polymeric membranes: Treatment of diaphyseal bone defects in the rabbit radius with poly(L-lactide) membrane. A pilot study. Journal Of Orthopaedic Trauma 1996; 10(3):178-190.
31．王远亮，潘君，蔡绍皙．组织工程研究的进展．生物化学与生物物理进展2000：27(4)：365-367．
32. Ajioka M, Enomoto K, Suzuki K, Yamaguchi A. Basic Properties Of Polylactic Acid Produced By The Direct Condensation Polymerization Of Lactic-Acid. Bulletin Of The Chemical Society Of Japan 1995; 68(8): 2125-2131.
33. Cerrai P, Tricoli M. Block-Copolymers From L-Lactide And Poly(Ethylene Glycol) Through A Noncatalyzed Route. Makromolekulare Chemic-Rapid Communications 1993; 14(9): 529-538.
34．马克昌，冯刊，朱太咏，郭建刚．骨生理学，河南医科大学出版社．2000．
35. Ducheyne P, Qiu Q. Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function. Biomaterials 1999; 20(23-24): 2287-2303.
36. IshaugRiley SL, Crane GM, Gurlek A, Miller MJ, Yasko AW, Yaszemski MJ, Mikos AG. Ectopic bone formation by marrow stromal osteoblast transplantation using poly(DL-lactic-co-glycolic acid) foams implanted into the rat mesentery. Journal Of Biomedical Materials Research 1997; 36(1): 1-8.
37．袁华，陈宁，吕晓迎，郑步中，宋晓陵．天然羟基磷灰石-壳聚糖复合材料修复骨缺损的实验研究．口腔医学2005；25(2)：65-67．
38．文学军．多孔轻基磷灰石陶瓷一胶原复合材料研究，四川大学硕士学位论文．1992．
39. Liu YH. Zhang QQ, Weng J, Zhang XD. Promotive effect of collagen in porous HA ceramics. Biomedical Materials Research in the Far East(I), eds Xingdong Zhang and Yoshito Ikada, Kobunshi Kankokai, Inc., Kyoto, Japan 1993: 161-162.
40. Stjohn KR. Zardiackas LD, Terry RC, Teasdall RD, Cooke SE, Mitias HM. Histological And Electron-Microscopic Analysis Of Tissue-Response To Synthetic Composite Bone-Graft In The Canine. Journal Of Applied Biomaterials 1995; 6(2): 89-97.
41．田卫东，李声伟，邓楠等．纤维蛋白粘合剂与羟基磷灰石复合人工骨的实验研究．中国口腔种植学杂志1998；3(4)：170-173．
42. Bonfield W. Hydroxyapatite-reinforced polyethylene as an analogical material for bone replacement. Ann NY Acad Sci 1998; 523: 173-177.
43. Bonfield W, Doyle C, Tanner KE. In vivo evaluation of hydroxyapatite reinforced polyethylene composites. Biological Performance of Biomaterials. Elsvier, Amsterdam 1986: 153-159.
44. Li DM, Zhang SZ, Chen T, et al. Experimental study of the biocompatible and osteoinductive behavior of the hydroxyapatite/ultra-high molecular weight polyethtlene composite. Chin J Plast Surg 2004; 20(3): 180-183.
45．严永刚，李玉宝，汪建新，冯建清，黄玫，deGroot K．聚酰胺-66／羟基磷灰石复合材料的制备和性能研究．塑料工业2000：28(3)：38-40．
46. Wet J, Hong H, Wu L, He Y, Li YB. Preliminary investigation of bioactivity of nano biocomposite. Journal Of Materials Science-Materials In Medicine 2007; 18(3): 529-533.
47. Zhang X, Li YB, Zuo Y, Lv GY, Mu YH, Li H. Morphology, hydrogen-bonding and crystal linity of nano-hydroxyapatite/polyamide 66 biocomposites. Composites Part A-Applied Science And Manufacturing 2007;38(3):843-848.
48. Wet J, Li YB, Lau KT. Preparation and characterization ofa nano apatite/polyamide(6) bioactive composite. Composites Part B-Engineering 2007;38(3):301-305.
49. Zhang X, Li YB, Zuo Y, Lv GY, Mu YH. Influences of the crystallization behavior of n-HA reinforced PA66 biocomposite on its mechanical properties. Eco-Materials Processing & Design Vii. Zurich-Uetikon: Trans Tech Publications Ltd; 2006. p 898-901.
50. Zhang L. Li YB, Wang X J, Wet J, Peng XL. Studies on the porous scaffold made of the nano-HA/PA66 composite. Journal Of Materials Science 2005;40(1): 107-110.
51．万涛，闫玉华，陈波等．PMMA／HA-GF复合材料．中国有色金属学报2002；12(5)：935-939．
52. Zheng YD, Wang Y J, Chen XF, et al. Studies of Poly(vinylalcohol)/Hydroxylapatite Hydrogels Compounds for Cartilage Implantation. J Biomed Eng 2003; 20(3):401-403.
53．卢华定，蔡道章，刘青，王迎军，郑裕东．聚乙烯醇／羟基磷灰石复合水凝胶移植修复兔膝关节软骨缺损．中国矫形外科杂志2004；12(21-22)：1701-1703．
54．魏杰．纳米类骨磷灰石晶体及其与聚酰胺复合骨修复材料研究，博士学位论文．
55. Sato K, Kogure T, Kumagai Y, Tanaka J. Crystal orientation of hydroxyapatite induced by ordered carboxyl groups. Journal Of Colloid And Interface Science 2001; 240(1): 133-138.
56．姚晖，杜昶，杨韶华，崔福斋，雷涛．纳米羟晶／胶原仿生骨修复兔颅颌骨缺损的实验研究．透析与人工器官2000；11：5-8．
57. Zhai Y. Cui FZ. Recombinant human-like collagen directed growth of hydroxyapatite nanocrystals. Journal Of Crystal Growth 2006;291(1): 202-206.
58. Liao S, Watari F, Uo M, Obkawa S, Tamura K, Wang W, Cui FZ. The preparation and characteristics of a carbonated hydroxyapatite/collagen composite at room temperature. Journal Of Biomedical Materials Research Part B-Applied Biomaterials 2005; 74B(2): 817-821.
59. Zhai Y, Cui FZ, Wang Y. Formation of nano-hydroxyapatite on recombinant human-like collagen fibrils. Current Applied Physics 2005; 5(5): 429-432.
60. Liao SS, Cui FZ. In vitro and in vivo degradation of mineralized collagen-based composite scaffold: Nanohydroxyapatite/collagen/poly(L-lactide). Tissue Engineering 2004; 10(1-2): 73-80.
61. Zhang L J, Feng XS, Liu HG, Qian D J, Zhang L, Yu XL, Cui FZ. Hydroxyapatite/collagen composite materials formation in simulated body fluid environment. Materials Letters 2004;58(5):719-722.
62．冯庆玲，崔福斋，张伟．纳米羟基磷灰石／胶原骨修复材料．中国医学科学院学报2002：24(2)：124-128．
63. Zhou DS, Zhao KB, Li Y, Cui FZ, Lee IS. Repair of segmental defecits with nano-hydroxyapatite/collagen/PLA composite combined with mesenchymal stem cells. Journal Of Bioactive And Compatible Polymers 2006; 21(5): 373-384.
64. Li XM, Feng QL, Cui FZ. In vitro degradation of porous nano-hydroxyapatite/collagen/PLLA scaffold reinforced by chitin fibres. Materials Science & Engineering C-Biomimetic And Supramolecular Systems 2006;26(4):716-720.
65. Liao S, Tamura K, Zhu YH, Wang W, Uo M, Akasaka T, Cui FZ, Watari F. Human neutrophils reaction to the biodegraded nano-hydroxyapatite/collagen and nano-hydroxyapatite/collagen/poly(L-lactic acid) composites. Journal Of Biomedical Materials Research Part A 2006;76A(4):820-825.
66．林晓艳．高强度纳米羟基磷灰石／胶原仿骨材料研究，博士学位论文．
67. Lin XY. Li XD, Fan HS, Xiao YM, Lu J, Zhang XD. Comparative investigation of coprecipitation and in situ synthesis of nanohydroxyapatite/collagen composite. Bioceramics 17. Zurich-Uetikon: Trans Tech Publications Ltd; 2005. p 839-842.
68. Lin XY. Li XO. Fan HS, Wen XT, Lu H, Zhang XD. In situ synthesis of bone-like apatite/collagen nano-composite at low temperature. Materials Letters 2004; 58(27-28): 3569-3572.
69．徐国富，牟申周，廖素三，Watari F．碳酸化羟基磷灰石／胶原(nCHAC)生物复合材料的室温制备及表征．材料导报2006；20(8)：140-148．
70. Tampieri A, Celotti G, Landi E, Sandri M, Roveri N, Falini G. Biologically inspired synthesis of bone-like composite: Self-assembled collagen fibers/hydroxyapatite nanocrystals. Journal Of Biomedical Materials Research Part A 2003;67A(2):618-625.
71. Roveri N, Falini G, Sidoti MC, Tampieri A, Landi E, Sandri M, Parma B. Biologically inspired growth of hydroxyapatite nanocrystals inside self-assembled collagen fibers. Materials Science & Engineering C-Biomimetic And Supramolecular Systems 2003; 33(3): 441-446.
72. Kikuchi M, Itoh S, Ichinose S, Shinomiya K, Tanaka J. Self-organization mechanism in a bone-like hydroxyapatite/collagen nanocomposite synthesized in vitro and its biological reaction in vivo. Biomaterials 2001; 22(13): 1705-1711.
73. Itoh S, Kikuchi M, Koyama Y, Matumoto HN, Takakuda K, Shinomiya K, Tanaka J. Development of a novel biomaterial, hydroxyapatite/collagen (HAp/Col) composite for medical use. Bio-Medical Materials And Engineering 2005; 15(1-2):29-41.
74. Kikuchi M, Ikoma T, Itoh S, Matsumoto HN, Koyama Y, Takakuda K, Shinomiya K, Tanaka J. Biomimetic synthesis of bone-like nanocomposites using the self-organization mechanism of hydroxyapatite and collagen. Composites Science And Technology 2004;64(6):819-825.
75. Itoh S. Kikuchi M, Takakuda K, Nagaoka K, Koyama Y, Tanaka J, Shinomiya K. Implantation study of a novel hydroxyapatite/collagen (HAp/Col) composite into weight-bearing sites of dogs. Journal Of Biomedical Materials Research 2002;63(5):507-515.
76. Kikuchi M. Matsumoto HN, Yamada T, Koyama Y, Takakuda K, Tanaka J, Glutaraldehyde cross-linked hydroxyapatite/collagen self-organized nanocomposites. Biomaterials 2004;25(1): 63-69.
77. John A, Hong L, Ikada Y, Tabata Y. A trial to prepare biodegradable collagen-hydroxyapatite composites for bone repair. Journal Of Biomaterials Science-Polymer Edition 2001; 12(6): 689-705.
78. Yamaguchi I, Tokuchi K, Fukuzaki H, Koyama Y, Takakuda K, Monma H, Tanaka T. Preparation and microstructure analysis of chitosan/hydroxyapatite nanocomposites. Journal Of Biomedical Materials Research 2001; 55(1): 20-27.
79. Rusu VM, Ng CH, Wilke M, Tiersch B, Fratzl P, Peter MG. Size-controlled hydroxyapatite nanoparticles as self-organized organic-in organic composite materials. Biomaterials 2005; 26(26): 5414-5426.
80. Hu QL, Li BQ, Wang M, Shen JC. Preparation and characterization of biodegradable chitosan/hydroxyapatite nanocomposite rods via in situ hybridization: A potential material as internal fixation of bone fracture. Biomaterials 2004;25(5): 779-785.
81. Zhang L, Li YB, Yang AP, Peng XL, Wang XJ, Zhang X. Preparation and in vitro investigation of chitosan/nano-hydroxyapatite composite used as bone substitute materials. Journal Of Materials Science-Materials in Medicine 2005; 16(3): 213-219.
82．李保强，胡巧玲，汪茫，沈家骢．原位复合法制备层状结构的壳聚糖／羟基磷灰石纳米材料．高等学校化学学报2004；25(10)：1949-1952．
83. Jie W, Li Y. Tissue engineering scaffold material of nano-apatite crystals and polyamide composite. European Polymer Journal 2004;40(3):509-5[5.
84. Wei J, Li YB, Chen WQ, Zuo Y. A study on nano-composite of hydroxyapatite and polyamide. Journal Of Materials Science 2003; 38(15): 3303-3306.
85. Bonfield W, Wang M, Tanner KE. Interfaces in analogue biomaterials. Acta Materialia 1998; 46(7): 2509-2518.
86. Bomber M. Ward IM, McGregor W, Tanner KE, Bonfield W. Hydroxyapatite/ polypropylene composite: A novel bone substitute material. Journal Of Materials Science Letters 2001; 20(22): 2049-2051.
87. Uskokovic PS, Tang CY, Tsui CP, Ignjatovic N, Uskokovic DP. Micromechanical properties ofa hydroxyapatite/poly-L-lactide biocomposite using nanoindentation and modulus mapping. Journal Of The European Ceramic Society 2007;27(2-3):1559-1564.
88. Verheyen C, Klein C, Deblieckhogervorst JMA, Wolke JGC, Vanblitterswijn CA, Degroot K. Evaluation Of Hydroxylapatite Poly(L-Lactide)Composites-Physicochemical Properties. Journal Of Materials Science-Materials In Medicine 1993; 4(1): 58-65.
89. Verheyen C, Dewijn JR. Vanblitterswijk CA, Degroot K, Rozing PM. Hydroxylapatite Poly(L-Lactide) Composites-An Animal Study On Push-Out Strengths And Interface Histology. Journal Of Biomedical Materials Research 1993;27(4):433-444.
90. Verheyen C, Dhert WJA, Petit PLC, Rozing PM, Degroot K. Invitro Study On The integrity Of A Hydroxylapatite Coating When Challenged With Staphylococci. Journal Of Biomedical Materials Research 1993;27(6):775-781.
91．郭晓东，郑启新，杜靖远，全大萍，阎玉华，李世普，李香亮．可吸收羟基磷灰石／聚DL-乳酸骨折内固定材料机械强度和生物降解性研究．中国生物医学工程学报2001：20(1)：23-27．
92．全大萍，卢泽俭，李世普，袁润章．聚DL乳酸／轻基磷灰石复合材料((Ⅰ)：制备与力学性能．中国生物医学土程学报2001；20(6)：485-488．
93．薄颖慧，廖凯荣，卢泽俭，郑臣谋．聚乳酸／羟基磷灰石复合材料的研究Ⅰ．超细微羟基磷灰石的合成及表面处理．中山大学学报(自然科学版)1999；38(3)：43-47．
94．张胜民，李世普，曹献英，王欣宇等．聚乳酸自修饰羟基基磷灰石／聚乳酸复合内固定 材料：Ⅱ．抗弯性能与溶胀度．《2002年材料科学与工程新进展》，北京：冶金工业出版社 2003：4：230-233．
95. Zhang RY, Ma PX. Poly(alpha-hydroxyl acids) hydroxyapatite porous composites for bone-tissue engineering. Ⅰ. Preparation and morphology. Journal Of Biomedical Materials Research 1999; 44(4): 446-455.
96．全大萍，江昕，李世普．聚乳酸及其复合材料的研究概况．武汉工业大学学报1996；18(2)：114-117．
97. Calandrelli L, Immirzi B, Malinconico M, Volpe MG, Oliva A, Della Ragione F. Preparation and cbaracterisation of composites based on biodegradable polymers for "in vivo" application. Polymer 2000;41 (22):8027-8033.
98．张弛，陈峥嵘，林建平，张光健．聚乳酸涂层的多孔羟基磷灰石负载软骨细胞移植修复兔关节软骨缺损．上海医科大学学报2000；37(2)：83-86．
99. Kasuga T, Ota Y, Nogami M, Abe Y. Preparation and mechanical properties of polylactic acid composites containing hydroxyapatite fibers. Biomaterials 2001; 22(1): 19-23.
100. Ignjatovic N, Savic V, Najman S, Plavsic M, Uskokovic D. A study of HAp/PLLA composite as a substitute for bone powder, using FT-IR spectroscopy. Biomaterials 2001; 22(6): 571-575.
101. Ignjatovic N, Tomic S, Dakic M, Miljkovic M, Plavsic M, Uskokovic D. Synthesis and properties of hydroxyapatite/poly-L-lactide composite biomaterials. Biomaterials 1999:20(9):809-816.
102. Najman S, Savic V, Djordjevic L, Ignjatovic N, Uskokovic D. Biological evaluation of hydroxyapatite/poly-L-lactide (HAp/PLLA) composite biomaterials with poly-L-lactide of different molecular weights intraperitoneally implanted into mice. Bio-Medical Materials And Engineering 2004; 14(1): 61-70.
103. Ignjatovic N, Delijic K, Vukcevic M, Uskokovic D. The designing of properties of hydroxyapatite/poly-I-lactide composite biomaterials by hot pressing. Zeitschrift Fur Metallkunde 2001; 92(2): 145-149.
104. Sujovrujic E, Ignjatovic N, Uskokovic D. Gamma irradiation processing of hydroxyapatite/poly-L-lactide composite biomaterial. Radiation Physics And Chemistry 2003; 67(3-4):375-379.
105. Ignjatovic N, Plavsic M, Najman S, Savic V, Uskokovic D. Analysis of in vivo substitution of bone tissue by HAp/PLLA composite biomaterial with PLLA of different molecular weights using FTIR spectroscopy. Trends In Advanced Materials And Processes. Zurich-Uetikon: Trans Tech Publications Ltd; 2000. p 143-150.
106. Ignjatovic N, Plavsic M, Uskokovic D. Hydroxyapatite/poly-L-lactide (collagen) biocomposite with poly-L-lactide of different molecular weights, Advanced Engineering Materials 2000; 2(8): 511-514.
107. Ignjatovic N, Suijovrujic E, Budinski-Simendic J, Krakovsky I, Uskokovic D. Evaluation of hot-pressed hydroxyapatite/poly-L-lactide composite biomaterial characteristics. Journal Of Biomedical Materials Research Part B-Applied Biomaterials 2004; 71 B(2):284-294.
108. Ignjatovic N, Uskokovic D. Synthesis and application of hydroxyapatite/polylactide composite biomaterial. Applied Surface Science 2004; 238(1-4):314-319.
109. Ignjatovic N, Uskokovic D. Molecular spectroscopy analysis of the substitution of bone tissue by HAp/PLLA composite biomaterial. Spectroscopy-An International Journal 2004; 18(4): 553-565.
110. Shikinami Y. Kawarada H. Potential application of a triaxial three-dimensional fabric (3-DF) as an implant. Biomaterials 1998; 19(7-9):617-635.
111. Shikinami Y, Matsusue Y, Nakamura T. The complete process of bioresorption and bone replacement using devices made of forged composites of raw hydroxyapatite particles/poly L-lactide (F-u-HA/PLLA). Biomaterials 2005; 26(27): 5542-5551.
112. Shikinami Y, Okuno M. Bioresorbable devices made of forged composites of hydroxyapatite (HA) particles and poly-L-lactide (PLLA): Part Ⅰ. Basic characteristics. Biomaterials 1999;20(9):859-877.
113. Shikinami Y, Okuno M. Bioresorbable devices made of forged composites of hydroxyapatite (HA) particles and poly L-lactide (PLLA). Part Ⅱ: practical properties of miniscrews and miniplates. Biomaterials 2001; 22(23): 3197-3211.
114. Shikinami Y, Okuno M. Mechanical evaluation of novel spinal interbody fusion cages made of bioactive, resorbable composites. Biomaterials 2003; 24(18): 3161-3170.
115. Furukawa T, Matsusue Y, Yasunaga T, Nakagawa Y, Okada Y, Shikinami Y, Okuno M, Nakamura T. Histomorphometric study on high-strength hydroxyapatite/poly(L-lactide) composite rods for internal fixation of bone fractures. Journal Of Biomedical Materials Research 2000;50(3):410-419.
116. Furukawa T, Matsusue Y, Yasunaga T, Nakagawa Y, Shikinami Y, Okuno M, Nakamura T. Bone bonding ability of a new biodegradable composite for internal fixation of bone fractures. Clinical Orthopaedics And Related Research 2000(379): 247-258.
117. Furukawa T, Matsusue Y, Yasunaga T, Shikinami Y, Okuno M, Nakamura T. Biodegradation behavior of ultra-high-strength hydroxyapatite/poly(L-lactide) composite rods for internal fixation of bone fractures. Biomaterials 2000; 21(9):889-898.
118. Hojo Y, Kotani Y, Ito M, Abumi K, Kadosawa T, Shikinami Y, Minami A. A biomechanical and histological evaluation of a bioresorbable lumbar interbody fusion cage. Biomaterials 2005; 26(15): 2643-2651.
119. Hasegawa M, Sudo A, Shikinami Y, Uchida A. Biological performance of a three-dimensional fabric as artificial cartilage in the repair of large osteochondral defects in rabbit. Biomaterials 1999; 20(20): 1969-1975.
120. Hasegawa S, Ishii S, Tamura J, Furukawa T, Neo M, Matsusue Y, Shikinami Y, Okuno M, Nakamura T. A 5-7 year in vivo study of high-strength hydroxyapatite/poly(L-lactide) composite rods for the internal fixation of bone fractures. Biomaterials 2006; 27(8):1327-1332.
121. Hasegawa S, Neo M, Tamura J, Goto K, Takemoto M, Shikinami Y, Saito M, Nakamura T. In vivo evaluation of a porous hydroxyapatite/poly-D,L-lactide composite for use as bone substitutes and scaffolds for bone tissue engineering. Cytotherapy 2006;8:61-61.
122. Hasegawa S, Tamura J, Neo M, Fujibayashi S, Goto K, Shikinami Y, Okazaki K, Nakamura T. In vivo evaluation of porous hydroxyapatite/poly D/L-lactide composite for bone substitutes and scaffolds. Bioceramics 18, Pts 1 And 2. Zurich-Uetikon: Trans Tech Publications Ltd; 2006. p 1311-1314.
123. Hasegawa S, Tamura J, Neo M, Goto K, Shikinami Y, Saito M, Kita M, Nakamura T. In vivo evaluation of a porous hydroxyapatite/poly-DL-lactide composite for use as a bone substitute. Journal Of Biomedical Materials Research Part A 2005;75A(3):567-579.
124. Hasegawa S, Tamura J, Neo M, Goto K, Shikinami Y, Saito M, Nakamura Y. In vivo evaluation of porous hydroxyapatite/poly D/L-lactide composite for bone substitute and scaffold. Bioceramics 17. Zurich-Uetikon: Trans Tech Publications Ltd; 2005. p 769-772.
125. Bleach NC, Nazhat SN, Tanner KE, Kellomaki M, Tormala P. Effect of filler content on mechanical and dynamic mechanical properties of particulate biphasic calcium phosphate-polylactide composites. Biomaterials 2002; 23(7): 1579-1585.
126. Verheyen C, Dewijn JR, Vanblitterswijk CA, Degroot K. Evaluation Of Hydroxylapatite Poly(L-Lactide) Composites-Mechanical-Behavior. Journal Of Biomedical Materials Research 1992; 26(10): 1277-1296.
127. Zhang SM, Li SP, Yan YH, Wan T, Jiang X, Han CR, Song XP. Surface modification of hydroxyapatite by using gamma-aminopropyl silane. Journal Of Wuhan University Of Technology-Materials Science Edition 2001; 16(3): 37-38.
128．全大萍，李世普，袁润章，廖凯荣，卢泽俭，王海华．聚DL一丙交酯／羟基磷灰石(PDLLA／HA)复合材料Ⅱ：硅烷偶联剂处理羟基磷灰石表面的作用研究．复合材料学报2000；17(4)：114-118．
129．张胜民，李世普，闰玉华，陈晓明．羟基磷灰石颗粒表面改性研究．材料科学与工艺2001；9：404-406．
130．姚晖，杜昶，杨韶华，崔福斋，雷涛．纳米羟晶／胶原仿生骨修复兔颅颌骨缺损的实验研究．透析与人工器官2000：11：5-8．
131. Deng XM, Hao JY, Wang CS. Preparation and mechanical properties of nanocomposites of poly(O,L-lactide) with Ca-deficient hydroxyapatite nanocrystals. Biomaterials 2001: 22(21): 2867-2873.
132．程俊秋，段可，翁杰，张兴栋．多孔纳米羟基磷灰石-聚乳酸复合材料的制备及其界面研究．化学研究与应用2001；13(5)：517-520．
133. Hone ZK, Qiu XY, Sun JR, Deng MX, Chen XS, Jing XB. Grafting polymerization of L-lactide on the surface of hydroxyapatite nano-crystals. Polymer 2004; 45(19):6699-6706.
134. Suljovrujic E, Ignjatovic N, Uskokovic D, Mitric M, Mitrovic M, Tomic S. Radiation-induced degradation of hydroxyapatite/poly L-lactide composite biomaterial. Radiation Physics And Chemistry 2007;76(4):722-728.
135. Balac I, Uskokovic PS, Ignjatovic N, Aleksic R, Uskokovic D. Stress analysis in hydroxyapatite/poly-L-lactide composite biomaterials. Computational Materials Science 2001;20(2):275-283.
136. Ajdukovic Z, Najman S, Dordevic LJ, Savic V, Mihailovic D, Petrovic D, Ignjatovic N, Uskokovic D. Repair of bone tissue affected by osteoporosis with hydroxyapatite-poly-L-lactide (HAp-PLLA) with and without blood plasma. Journal Of Biomaterials Applications 2005;20(2):179-190.
137. Nikcevic I, Maravic D, Ignjatovic N, Mitric M, Makovec D, Uskokovic D. The formation and characterization of nanocrystalline phases by mechanical milling of biphasic calcium phosphate/poly-L-lactide biocomposite. Materials Transactions 2006;47(12):2980-2986.
138. Fukuda A, Kato K, Hasegawa M, Hirata H, Sudo A, Okazaki K, Tsuta K, Shikinami Y, Uchida A. Enhanced repair of large osteochondral defects using a combination of artificial cartilage and basic fibroblast growth factor. Biomaterials 2005;26(20):4301-4308.
139. Ishii S, Tamura J, Furukawa T, Nakamura T, Matsusue Y, Shikinami Y, Okuno M. Long-term study of high-strength hydroxyapatite/poly(L-lactide) composite rods for the internal fixation of bone fractures: A 2-4-year follow-up study in rabbits. Journal Of Biomedical Materials Research Part B-Applied Biomaterials 2003;66B(2):539-547.
140. Kadoya K, Kotani Y, Abumi K, Takada T, Shimamoto N, Shikinami Y, Kadosawa T, Kaneda K. Biomechanical and morphologic evaluation of a three-dimensional fabric sheep artificial intervertebral disc-In vitro and in vivo analysis. Spine 2001; 26(14):1562-1569.
141. Kotani Y, Abumi K, Shikinami Y, Takada T, Kadoya K, Shimamoto N, Ito M, Kadosawa T, Fujinaga T, Kaneda K. Artificial intervertebral disc replacement using bioactive three-dimensional fabric-Design, development, and preliminary animal study. Spine 2002;27(9):929-935.
142. Kotani Y, Abumi K, Shikinami Y, Takahata M, Kadoya K, Kadosawa T, Minami A, Kaneda K. Two-year observation of artificial intervertebral disc replacement: results after supplemental ultra-high strength bioresorbable spinal stabilization. Journal Of Neurosurgery 2004:100(4):337-342.
143. Kotani Y, Cunningham BW, Abumi K, Dmitriev AE, Ito M, Hu N, Shikinami Y, McAfee PC, Minami A. Multidirectional flexibility analysis of cervical artificial disc reconstruction: in vitro human cadaveric spine model. Journal Of Neurosurgery-Spine 2005;2(2):188-194.
144. Totoribe K, Matsumoto M, Goel VK, Yang SJ, Tajima N, Shikinami Y. Comparative biomechanical analysis of a cervical cage made of an unsintered hydroxyapatite particle and poly-L-lactide composite in a cadaver model. Spine 2003;28(10): 1010-1014.
145. Yasunaga T, Matsusue Y, Furukawa T, Shikinami Y, Okuno M, Nakamura T. Bonding behavior of ultrahigh strength unsintered hydroxyapatite particles/poly(L-lactide) composites to surface of tibial cortex in rabbits. Journal Of Biomedical Materials Research 1999; 42(3): 412-419.
146．郭晓东，郑启新，杜靖远，曾晖，全大萍，闫玉华，李世普．可吸收HA／PDLLA内固定材料组织相容性观察．武汉工业大学学报1998；20(4)：28-31．
147．郭晓东，郑启新，杜靖远，全大萍．羟基磷灰石／聚DL-乳酸复合材料在不同植入部位降解机制研究．中国生物医学工程学报2001；20(3)：200-205．
148. VanderMeer SAT, DeWijn JR, Wolke JGC. The influence of basic filler materials on the degradation of amorphous D-and L-lactide copolymer. Journal Of Materials Science-Materials In Medicine 1996; 7(6): 359-361.
149．全大萍，廖凯荣，卢泽俭，王海华．聚dl-丙交酯/羟基磷灰石复合材料Ⅲ．体内外降解性能研究．功能高分子学报2000；13(3)：41-45．
150．廖凯荣，赵剑豪，罗丙红，卢泽俭．聚乳酸／羟基磷灰石复合材料的研究Ⅲ．聚(D，L-乳酸)／羟基磷灰石复合材料的体外降解行为．中山大学学报(自然科学版)2001；40(1)：44-46．
151. Heidemann W, Jeschkeit S, Ruffieux K, Fischer JH, Wagner M, Kruger G, Wintermantel E, Gerlach KL. Degradation of poly(D,L)lactide implants of calciumphosphates with or without addition in vivo. Biomaterials 2001;22(17):2371-2381.
152. Weng J, Wang M, Chen JY. Plasma-sprayed calcium phosphate particles with high bioactivity and their use in bioactive scaffolds. Biomaterials 2002;23(13):2623-2629.
153. Mann S. Molecular Tectonics In Biomineralization And Biomimetic Materials Chemistry. Nature 1993;365(6446):499-505.
154. Mann S, Archibald DD, Didymus JM, Douglas T, Heywood BR, Meldrum FC, Reeves NJ. Crystallization At Inorganic-Organic Interfaces-Biominerals And Biomimetic Synthesis. Science 1993; 261(5126): 1286-1292.
155. Spanos N, Koutsoukos PG. Hydroxyapatite precipitation on a carboxylated vinyl chloride-vinyl acetate copolymer. Journal Of Materials Science 2001; 36(3): 573-578.
156. Sato K, Kumagai Y, Tanaka T. Apatite formation on organic monolayers in simulated body environment. Journal Of Biomedical Materials Research 2000; 50(1): 16-20.
157. Yuan XY, Mak AFT, Li JL. Formation of bone-like apatite on poly(L-lactic acid) fibers by a biomimetic process. Journal Of Biomedical Materials Research 2001; 57(1): 140-150.
158. Zhang RY, Ma PX. Porous poly(L-lactic acid)/apatite composites created by biomimetic process. Journal Of Biomedical Materials Research 1999; 45(4): 285-293.
159. Kato K, Eika Y, Ikada Y. In situ hydroxyapatite crystallization for the formation of hydroxyapatite/polymer composites. Journal Of Materials Science 1997; 32(20): 5533-5543.
160. Nagata F, Miyajima T, Yokogawa Y. Surfactant-free preparation of poly(lactic acid)/hydroxyapatite microspheres. Chemistry Letters 2003; 32(9):784-785.
161. Xiao YM, Zhao HC, Fan HS, Wang XL, Gun LK, Li XD, Zhang XD. A novel way to prepare nano-hydroxyapatite/poly(D,L-lactide)composite. Pricm 5: The Fifth Pacific Rim International Conference On Advanced Materials And Processing, Pts 1-5. Zurich-Uetikon: Trans Tech Publications Ltd; 2005. p 2383-2386.
1. Bostman O, Viljanen J, Salminen S, Pihlajamaki H. Response of articular cartilage and subchondral bone to internal fixation devices made of poly-L-lactide: a histomorphometric and microradiographic study on rabbits. Biomaterials 2000; 21(24): 2553-2560.
2. Bostman O, Pihlajamaki H. Clinical biocompatibility of biodegradable orthopaedic implants for internal fixation: a review. Biomaterials 2000; 21(24): 2615-2621.
3. Zhang XC, McAuley KB, Goosen MFA. Towards Prediction Of Release Profiles Of Antibiotics From Coated Poly(Dl-Lactide)Cylinders. Journal Of Controlled Release 1995: 34(2): 175-179.
4. Pineda LM, Busing M, Meinig RP, Gogolewski S. Bone regeneration with resorbable polymeric membranes. 3. Effect of poly(L-lactide) membrane pore size on the bone healing process in large detects. Journal Of Biomedical Materials Research 1996: 31(3): 385-394.
5. Meinig RP, Rahn B, Perren SM, Gogolewski S. Bone regeneration with resorbable polymeric membranes: Treatment of diaphyseal bone defects in the rabbit radius with poly(L-lactide) membrane. A pilot study. Journal Of Orthopaedic Trauma 1996;10(3): 178-190.
6．王远亮，潘君，蔡绍皙．组织工程研究的进展．生物化学与生物物理进展2000；27(4)：365-367．
7．王勤，路岩，张娟．以聚乳酸为载体的药物释放及动物疗效学的研究．中国生物医学工程学报1995；14(1)：11-14．
8．李玉宝．《生物医学材料》．化学工业出版社2003．9．
9．全大萍，江昕，李世普．聚乳酸及其复合材料的研究概况．武汉工业大学学报1996；18(2)：114-117．
10. Crane GM, Ishaug SL, Mikos AG. Bone Tissue Engineering. Nature Medicine 1995; 1(12):1322-1324.
11. Calandrelli L, Immirzi B, Malinconico M, Volpe MG, Oliva A, Della Ragione F. Preparation and characterisation of composites based on biodegradable polymers for "in vivo" application. Polymer 2000; 41(22): 8027-8033.
12. Kasuga T, Ota Y, Nogami M, Abe Y. Preparation and mechanical properties of polylactic acid composites containing hydroxyapatite fibers. Biomaterials 2001; 22(1):19-23.
13. Najman S, Savic V, Djordjevic L, Ignjatovic N, Uskokovic D. Biological evaluation of hydroxyapatite/poly-L-lactide (HAp/PLLA) composite biomaterials with poly-L-lactide of different molecular weights intraperitoneally implanted into mice. Bio-Medical Materials And Engineering 2004; 14(1):61-70.
14. Ignjatovic N, Delijic K, Vukcevic M, Uskokovic D. Microstructure and mechanical properties of hot-pressed hydroxyapatite/poly-L-lactide biomaterials. Bioceramics. Zurich-Uetikon: Trans Tech Publications Ltd; 2000. p 737-740.
15. Ignjatovic N, Delijic K, Vukcevic M, Uskokovic D. The designing of properties of hydroxyapatite/poly-l-lactide composite biomaterials by hot pressing. Zeitschrift Fur Metallkunde 2001; 92(2): 145-149.
16. Ignjatovic N, Ninkov P, Ajdukovic Z, Vasijevic-Radovic D, Uskokovic D. Biphasic calcium phosphate coated with poly-D,L-lactide-co-glycolide biomaterial as a bone substitute. Journal Of The European Ceramic Society 2007;27(2-3):1589-1594.
17. Ignjatovic N, Plavsic M, Uskokovic D. Hydroxyapatite/poly-L-lactide (collagen) biocomposite with poly-L-lactide of different molecular weights. Advanced Engineering Materials 2000; 2(8): 511-514.
18. Ignjatovic N, Savic V, Najman S, Plavsic M, Uskokovic D. A study of HAp/PLLA composite as a substitute for bone powder, using FT-IR spectroscopy. Biomaterials 2001; 22(6): 571-575.
19. Ignjatovic N, Suijovrujic E, Budinski-Simendic J, Krakovsky I, Uskokovic D. Evaluation of hot-pressed hydroxyapatite/poly-L-lactide composite biomaterial characteristics. Journal Of Biomedical Materials Research Part B-Applied Biomaterials 2004;71B(2):284-294.
20. Ignjatovic N, Tomic S, Dakic M, Miljkovic M, Plavsic M, Uskokovic D. Synthesis and properties of hydroxyapatite/poly-L-lactide composite biomaterials. Biomaterials 1999; 20(9): 809-816.
21. Ignjatovic N, Uskokovic D. Synthesis and application of hydroxyapatite/polylactide composite biomaterial. Applied Surface Science 2004;238(1-4):314-319.
22. Shikinami Y, Kawarada H. Potential application ofa triaxial three-dimensional fabric (3-DF) as an implant. Biomaterials 1998; 19(7-9):617-635.
23. Shikinami Y, Matsusue Y, Nakamura T. The complete process of bioresorption and bone replacement using devices made of forged composites of raw hydroxyapatite particles/poly L-lactide (F-u-HA/PLLA). Biomaterials 2005;26(27):5542-5551.
24. Shikinami Y, Okuno M. Bioresorbable devices made of forged composites of hydroxyapatite (HA) particles and poly-L-lactide (PLLA): Part Ⅰ. Basic characteristics. Biomaterials 1999;20(9):859-877.
25. Shikinami Y, Okuno M. Bioresorbable devices made of forged composites of hydroxyapatite (HA) particles and poly L-lactide (PLLA). Part Ⅱ: practical properties of miniscrews and miniplates. Biomaterials 2001 ;22(23):3197-3211.
26. Shikinami Y, Okuno M. Mechanical evaluation of novel spinal interbody fusion cages made of bioactive, resorbable composites. Biomaterials 2003;24(18):3161-3170.
27．郭晓东，郑启新，杜靖远，全大萍，阎玉华，李世普，李香亮．可吸收羟基磷灰石／聚 DL-乳酸骨折内固定材料机械强度和生物降解性研究．中国生物医学工程学报2001；20(1)：23-27．
28．张弛，陈峥嵘，林建平，张光健．聚乳酸涂层的多孔羟基磷灰石负载软骨细胞移植修复兔关节软骨缺损．上海医科大学学报2000；37(2)：83-86．
29．廖凯荣，罗力力，薄颖慧等．聚左旋乳酸及其复合体系的非等温结晶动力学．中山大学学报(自然科学版)1998；37(4)：71-75．
30．薄颖慧，廖凯荣，卢泽俭，郑臣谋．聚乳酸／羟基磷灰石复合材料的研究Ⅰ．超细微羟基磷灰石的合成及表面处理．中山大学学报(自然科学版)1999；38(3)：43-47．
31．程俊秋，段可，翁杰，张兴栋．多孔纳米羟基磷灰石-聚乳酸复合材料的制备及其界面研究．化学研究与应用2001；13(5)：517-520．
32. Zhang RY, Ma PX. Poly(alpha-hydroxyl acids) hydroxyapatite porous composites for bone-tissue engineering. Ⅰ. Preparation and morphology. Journal Of Biomedical Materials Research 1999;44(4):446-455.
33. Verheyen C, Dewijn JR, Vanblitterswijk CA, Degroot K. Evaluation Of Hydroxylapatite Poly(L-Lactide) Composites-Mechanical-Behavior. Journal Of Biomedical Materials Research 1992;26(10):1277-1296.
34. Verheyen C, Klein C, Deblieckhogervorst JMA, Wolke JGC, Vanblitterswijn CA, Degroot K. Evaluation Of Hydroxylapatite Poly(L-Lactide) Composites-Physicochemical Properties. Journal Of Materials Science-Materials In Medicine 1993;4(1):58-65.
35. Mann S. Molecular Tectonics In Biomineralization And Biomimetic Materials Chemistry. Nature 1993; 365(6446): 499-505.
36. Mann S, Archibald DD, Didymus JM, Douglas T, Heywood BR, Meldrum FC, Reeves NJ. Crystallization At Inorganic-Organic Interfaces-Biominerals And Biomimetic Synthesis. Science 1993; 261(5126): 1286-1292.
37. Kato K, Eika Y, Ikada Y. In situ hydroxyapatite crystallization for the formation of hydroxyapatite/polymer composites. Journal Of Materials Science 1997; 32(20): 5533-5543.
38. Spanos N, Koutsoukos PG. Hydroxyapatite precipitation on a carboxylated vinyl chloride-vinyl acetate copolymer. Journal Of Materials Science 2001; 36(3): 573-578.
39. Sato K, Kogure T, Kumagai Y, Tanaka J. Crystal orientation of hydroxyapatite induced by ordered carboxyl groups. Journal Of Colloid And Interface Science 2001; 240(1): 133-138.
40. Sato K, Kumagai Y, Tanaka T. Apatite formation on organic monolayers in simulated body environment. Journal Of Biomedical Materials Research 2000;50(1):16-20.
41. Nagata F, Miyajima T, Yokogawa Y. Surfactant-free preparation of poly(lactic acid)/hydroxyapatite microspheres. Chemistry Letters 2003;32(9):784-785.
42. Yuan XY, Mak AFT, Li JL. Formation of bone-like apatite on poly(L-lactic acid) fibers by a biomimetic process. Journal Of Biomedical Materials Research 2001; 57(1): 140-150.
43. Zhang RY, Ma PX. Porous poly(L-lactic acid)/apatite composites created by biomimetic process. Journal Of Biomedical Materials Research 1999; 45(4): 285-293.
44. Xiao YM, Zhao HC, Fan HS, Wang XL, Guo LK, Li XD, Zhang XD. A novel way to prepare nano-hydroxyapatite/poly(D,L-lactide) composite. Pricm 5: The Fifth Pacific Rim International Conference On Advanced Materials And Processing, Pts 1-5. Zurich-Uetikon: Trans Tech Publications Ltd; 2005. p 2383-2386.
45．魏杰．纳米类骨磷灰石晶体及其与聚酰胺复合骨修复材料研究，博士学位论文．
46. Kister G, Cassanas G, Vert M. Effects of morphology, conformation and configuration on the IR and Raman spectra of various poly(lactic acid)s. Polymer 1998; 39(2): 267-273.
47. Rusu VM, Ng CH, Wilke M, Tiersch B, Fratzl P, Peter MG. Size-controlled hydroxyapatite nanoparticles as self-organized organic-in organic composite materials. Biomaterials 2005; 26(26): 5414-5426.
1. Mann S. Molecular Tectonics In Biomineralization And Biomimetic Materials Chemistry. Nature 1993; 365(6446): 499-505.
2. Mann S, Archibald DD, Didymus JM, Douglas T, Heywood BR, Meldrum FC, Reeves NJ. Crystallization At Inorganic-Organic Interfaces-Biominerals And Biomimetic Synthesis. Science 1993; 261(5126): 1286-1292.
3. Kato K, Eika Y, Ikada Y. In situ hydroxyapatite crystallization for the formation of hydroxyapatite/polymer composites. Journal Of Materials Science 1997. 32(20): 5533-5543.
4. Sato K, Kogure 7: Kumagai Y, Tanaka J. Crystal orientation of hydrogyapatite induced by ordered carboxyl groups. Journal Of Colloid And Interface Science 2001; 240(1): 133-138.
5. Sato K, Kumagai Y, Tanaka T. Apatite formation on organic monolayers in simulated body environment. Journal Of Biomedical Materials Research 2000; 50(1): 16-20.
6. Spanos N, Koutsoukos PG. Hydroxyapatite precipitation on a carboxylated vinyl chloride-vinyl acetate copolymer. Journal Of Materials Science 2001; 36(3): 573-578.
7. Nagata F, Miyajima T, Yokogawa Y. Surfactant-free preparation of poly(lactic acid)/hydroxyapatite microspheres. Chemistry Letters 2003;32(9):784-785.
8. Yuan XY, MakAFT, Li JL. Formation of bone-like apatite on poly(L-lactic acid) fibers by a biomimetic process. Journal Of Biomedical Materials Research 2001; 57(1): 140-150.
9. Zhang RY, Ma PX. Porous poly(L-lactic acid)/apatite composites created by biomimetic process. Journal Of Biomedical Materials Research 1999; 45(4): 285-293.
10. Xiao YM, Zhao HC, Fan HS, Wang XL, Guo LK, Li XD, Zhang XD. A novel way to prepare nano-hydroxyapatite/poly(D,L-lactide) composite. Pricm 5: The Fifth Pacific Rim International Conference On Advanced Materials And Processing, Pts 1-5. Zurich-Uetikon: Trans Tech Publications Ltd; 2005. p 2383-2386.
11. Xiao YM, Li DX, Fan HS, Li XD, Gu ZW, X. D. Z. Preparation of nano-HA/PLA composite by modified-PLA for controlling the growth of HA crystals. Materials Letters 2006; 61(1): 59-62.
12. Ma ZW, Gao CY, Ji JA, Shen JC. Protein immobilization on the surface of poly-L-lactic acid films for improvement of cellular interactions. European Polymer Journal 2002; 38(11): 2279-2284.
13. Fujimoto K, Takebayashi Y, Inoue H, Ikada Y. Ozone-Induced Graft-Polymerization Onto Polymer Surface. Journal Of Polymer Science Part A-Polymer Chemistry 1993; 31(4): 1035-1043.
14. Suh H, Hwang YS, Lee JE, Han CD, Park JC. Behavior of osteoblasts on a type Ⅰ atelocollagen grafted ozone oxidized poly L-lactic acid membrane. Biomaterials 2001; 22(3): 219-230.
15. Frew JE, Jones J, Scholes G. Spectrophotometric determination of hydrogen peroxide and organic, hydroperoxides at low concentrations in aqueous solution. Analytica Chimica Acta 1983; 155: 139-150.
16．董文艺，杜红．过氧化氢氧化法的原理及对有机物的去除．中国农村水利水电 2004;2:47-48.
17. Stefan MI, Bolton JR. Mechanism of the degradation of 1,4-dioxane in dilute aqueous solution using the UV hydrogen peroxide process. Environmental Science & Technology 1998;32(11):1588-1595.
18. Esplugas S, Gimenez J, Contreras S, Pascual E, Rodriguez M. Comparison of different advanced oxidation processes for phenol degradation. Water Research 2002; 36(4): 1034-1042.
19. Kister G, Cassanas G, Vert M. Effects of morphology, conformation and configuration on the IR and Raman spectra of various poly(lactic acid)s. Polymer 1998;39(2):267-273.
20．魏杰．纳米类骨磷灰石晶体及其与聚酰胺复合骨修复材料研究，博士学位论文．
21. Wang X J, Li YB, Wei J, de Groot K. Development of biomimetic nano-hydroxyapatite/poly(hexamethylene adipamide) composites. Biomaterials 2002; 23(24): 4787-4791.
22. Jie W, Li Y. Tissue engineering scaffold material ofnano-apatite crystals and polyamide composite. European Polymer Journal 2004;40(3):509-515.
23．朱埗瑶，赵振国等．界面化学基础．北京：化学工业出版社1999：257-258．
24. Malvern Instruments Ltd. Zetasizer Nano Series User Manual (2004). printed in England MRK0499-01: 16.2.
25．邵鑫，田军，薛群基等．有机-无机纳米复合材料的合成、性质及应用前景．材料导报2001；15(1)：50-53．
1．俞梦孙，蒋大宗．中国生物医学工程的今天与明天，生物医学工程学丛书．天津科技翻译出版公司，天津1998年．
2．王慧明，李梵，王模堂等．四种骨替代材料的人成骨细胞生物相容性研究．中国生物医学工程学学报1996；15(3)：239-244．
3．杨晓芳．生物材料生物相容性评价研究进展．生物医学工程2001；18(1)：123-128．
4. Dee KC, Bizios R. Mini-review: Proactive biomaterials and bone tissue engineering. Biotechnology And Bioengineering 1996;50(4):438-442.
5. McKay GC, Macnair R, MacDonald C, Grant MH. Interactions of orthopaedic metals with an immortalized rat osteoblast cell line. Biomaterials 1996; 17(13): 1339-1344.
6．郭晓东，郑启新，杜靖远，全大萍．羟基磷灰石／聚DL-乳酸复合材料在不同植入部位降解机制研究．中国生物医学工程学报2001；20(3)：200-205．
7．刘建伟，赵强，万昌秀．医用聚乳酸体内降解机理及应用研究进展．航天医学与医学工程2001；14(4)：308．
8. Therin M. Christel P, Li SM, Garreau H, Vert M. Invivo Degradation Of Massive Poly(Alpha-Hydroxy Acids)-Validation Of Invitro Findings. Biomaterials 1992; 13(9): 594-600.
9. Vert M, Li SM, Garreau H. Attempts to map the structure and degradation characteristics of aliphatic polyesters derived from lactic and glycolic acids. J Biomater Sci Polym Ed 1994: 6(7): 639-49.
10. Spenlehauer G, Vert M, Benoit JP, Boddaert A. In vitro and in vivo degradation ofpoly(D,L lactide/glycolide) type microspheres made by solvent evaporation method. Biomaterials 1989; 10(8): 557-63.
11. Therin M. Christel P. Li S, Garreau H, Vert M. In vivo degradation of massive poly(alpha-hydroxy acids): validation of in vitro findings. Biomaterials 1992; 13(9):594-600.
12. Grizzi I, Garreau H, Li S, Vert M. Hydrolytic degradation of devices based on poly(DL-lactic acid) size-dependence. Biomaterials 1995; 16(4): 305-11.
13. Schmitt EA, Flanagan DR, Linhardt RJ. Importance Of Distinct Water Environments In The Hydrolysis Of Poly(Dl-Lactide-Co-Glycolide). Macromolecules 1994; 27(3):743-748.
14. Zhang XC, Wyss UP, Pichora D, Goosen MFA. An Investigation Of Poly(Lactic Acid) Degradation. Journal Of Bioactive And Compatible Polymers 1994; 9(1): 80-100.
15. Liu Q, de Wijn JR, Bakker D, van Toledo M, van Blitterswijk CA. Polyacids as bonding agents in hydroxyapatite polyester-ether(Polyactive (TM) 30/70) composites. Journal Of Materials Science-Materials In Medicine 1998; 9(1): 23-30.
16．郭晓东，郑启新，杜靖远，曾晖，全大萍，闫玉华，李世普．可吸收HA／PDLLA内固定材料组织相容性观察．武汉工业大学学报1998；20(4)：28-31．
17. Rizzi SC, Heath DT, Coombes AGA, Bock N, Textor M, Downes S. Biodegradable polymer/hydroxyapatite composites: Surface analysis and initial attachment of human osteoblasts. Journal Of Biomedical Materials Research 2001; 55(4): 475-486.
18．郭晓东，郑启新，杜靖远，全大萍，阎玉华，李世普，李香亮．可吸收羟基磷灰石／聚DL-乳酸骨折内固定材料机械强度和生物降解性研究．中国生物医学工程学报2001；20(1)：23-27．
19．赵建华，廖维宏，王远亮，潘君，柳峰．消旋聚乳酸／羟基磷灰石／脱钙骨基质的制备及其体外降解特性研究．中华修复重建外科杂志2003；17(1)：61-64．
20. Shackelford JF. Bioceramics-Current status and future trends. Bioceramics. Zurich-Uetikon: Transtec Publications Ltd; 1999. p 99-106.
21. Hench LL. Bioceramics: From concept to clinic. J Atn Ceram Soc 1991: 74: 1487-1510.
22．李玉宝．《生物医学材料》．化学工业出版社2003．9．
23．师昌绪．材料科学技术百科全书，生物医学材料分支，中国大百科全书出版社．北京．1995．8．
24．顾汉卿，徐国风．《生物医学材料学》，生物医学工程学丛书．天津科技翻译出版社，天津．1993年．
25. Hench LL, Wilson J. Surface-active biomaterials. Science 1984;226(4675):630-6.
26. Hench LL, Polak JM. Third-generation biomedical materials. Science 2002:295(5557):1014.
27. Ducheyne P. Qiu Q. Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function. Biomaterials 1999;20(23-24):2287-2303.
28. Knaack D, Goad MEP, Aiolova M. Rey C, Tofighi A, Chakravarthy P. Lee DD. Resorbable calcium phosphate bone substitute. Journal Of Biomedical Materials Research 1984: 43(4): 399-409.
29. Germine M. Parsons JR. Deconvoluted X-ray diffraction analysis of bone and mixtures of bone and particulate hydroxyapatite. J Biomed Mater Res 1988; 22(A1 Suppl): 55-67.
30. Lampin M. WarocquierClerout R, Legris C, Degrange M, SigotLuizard MF. Correlation between substratum roughness and wettability, cell adhesion, and cell migration. Journal Of Biomedical Materials Research 1997; 36(1): 99-108.
31. Kokubo T. Miyaji F, Kim HM, Nakamura T. Spontaneous formation of bonelike apatite layer on chemically treated titanium metals. Journal Of The American Ceramic Society 1996; 79(4): 1127-1129.
32. Hench L, Splinter R, Greenlee T, al. e. Bonding mechanisms at the interface of ceramic prosthetic materials. J Biomed Eng 1971; 2: 117-141.
33. Kay MI, Young RA, Posner AS. Crystal Structure Of Hydroxyapatite. Nature 1964: 204: 1050-2.
34. Oyane A, Nakanishi K, Kim HM, Miyaji F, Kokubo T, Soga N, Nakamura T. Sol-gel modification of silicone to induce apatite-forming ability. Biomaterials 1999; 20(1): 79-84.
35. Nishio K, Neo M, Akiyama H, Nishiguchi S, Kim HM, Kokubo T, Nakamura T. The effect of alkali-and heat-treated titanium and apatite-formed titanium on osteoblastic differentiation of bone marrow cells. Journal Of Biomedical Materials Research 2000:52(4):652-661.
36. de Sena LA, Rocha NCC, Andrade MC, Soares GA. Bioactivity assessment of titanium sheets electrochemically coated with thick oxide film. Surface & Coatings Technology 2003:166(2-3):254-258.
37. Ni J. Wang M. In vitro evaluation of hydroxyapatite reinforced po yhydroxybutyrate composite. Materials Science & Engineering C-Biomimetic And Supramolecular Systems 2002; 20(1-2):101-109.
38. Li PJ, Degroot K. Calcium-Phosphate Formation Within Sol-Gel Prepared Titania In-Vitro And In-Vivo. Journal Of Biomedical Materials Research 1993; 27(12): 1495-1500.
39. Bunker BC, Rieke PC, Tarasevich BJ, Campbell AA, Fryxell GE, Graff GL, Song L, Liu J, Virden JW, McVay GL. Ceramic Thin-Film Formation On Functionalized Interfaces Through Biomimetic Processing. Science 1994;264(5155):48-55.
40. Nakamura T, Yamamuro T, Higashi S, Kokubo T, Itoo S. A new glass-ceramic for bone replacement: evaluation of its bonding to bone tissue. J Biomed Mater Res 1985; 19(6): 685-98.
41. Rhee SH, Tanaka J. Effect of citric acid on the nucleation of hydroxyapatite in a simulated body fluid. Biomaterials 1999;20(22):2155-2160.
42. Bigi A, Boanini E, Panzavolta S, Roveri N. Biomimetic growth of hydroxyapatite on gelatin films doped with sodium polyacrylate. Biomacromolecules 2000;1(4):752-756.
43．张胜民．HA／PLA复合生物材料界面的分子设计、构建与相关性能，博士学位论文．
44．杨志明．组织工程基础与临床．四川科学技术出版社，成都，2000年．
45. Knabe C, Gildenhaar R, Berger G, Ostapowicz W, Fitzner R, Radlanski RJ, Gross U. Morphological evaluation of osteoblasts cultured on different calcium phosphate ceramics. Biomaterials 1997; 18(20): 1339-1347.
46. Mullermai CM, Stupp SI, Voigt C, Gross U. Nanoapatite And Organoapatite Implants In Bone-Histology And Ultrastructure Of The Interface. Journal Of Biomedical Materials Research 1995;29(1):9-18.
47. Gross U, Brandes J, Strunz V, Bab I, Sela J. The ultrastructure of the interface between a glass ceramic and bone. J Biomed Mater Res 1981;15(3):291-305.
48. Kwong CH, Burns WB, Cheung HS. Solubilization ofhydroxyapatite crystals by murine bone cells, macrophages and fibroblasts. Biomaterials 1989;10(9):579-84.
49. Ajioka M, Enomoto K, Suzuki K, Yamaguchi A. Basic Properties Of Polylactic Acid Produced By The Direct Condensation Polymerization Of Lactic-Acid. Bulletin Of The Chemical Society Of Japan 1995;68(8):2125-2131.
50．李孝红，袁明龙，熊成东等．聚乳酸及其共聚物的合成和在生物医学上的应用．高分子通报1999：1：24-32．
51．阮狄克，沈根标，邹宏恩等．可吸收聚乳酸植入材料的实验观察．中华骨科杂志1994；14(6)：370-373．
52．郑谦，魏世成，赵宗林等．可吸收DL—聚乳酸夹板行额面部骨折内固定的实验研究．华西口腔医学杂志1996；14(4)：254-257．
53. Bos RR, Boering G, Rozema FR, Leenslag JW. Resorbable poly(L-lactide) plates and screws for the fixation ofzygomatic fractures. J Oral Maxillofac Surg 1987;45(9):751-3.
54. Leenslag JW, Pennings AJ, Bos RR, Rozema FR, Boering G. Resorbable materials of poly(L-lactide). Ⅵ. Plates and screws for internal fracture fixation. Biomaterials 1987; 8(1): 70-3.
55. Viljanen J, Kinnunen J, Bondestam S, MajolaA, Rokkanen P, Tormala P. Bone changes after experimental osteotomies fixed with absorbable self-reinforced poly-L-lactide screws or metallic screws studied by plain radiographs, quantitative computed tomography and magnetic resonance imaging. Biomaterials 1995; 16(17):1353-8.
56. Majola A, Vainionpaa S, Vihtonen K, Mero M, Vasenius J, Tormala P, Rokkanen P. Absorption, biocompatibility, and fixation properties of polylactic acid in bone tissue: an experimental study in rats. Clin Orthop Relat Res 1991(268): 260-9.
57. Pihlajamaki H, Bostman O, Hirvensalo E, Tormala P, Rokkanen P. Absorbable Pins Of Self-Reinforced Poly-L-Lactic Acid For Fixation Of Fractures And Osteotomies. Journal Of Bone And Joint Surgery-British Volume 1992; 74(6): 853-857.
58. Pistner H, Gutwald R, Ordung R, Reuther J, Muhling J. Poly(L-Lactide)-A Long-Term Degradation Study In-Vivo. I. Biological Results. Biomaterials 1993; 14(9):671-677.
59. Asanami S, Shimono K, Kaneda S. Transient hypothermia induces micronuclei in mice. Mutation Research-Genetic Toxicology And Environmental Mutagenesis 1998; 413(1): 7-14.
60. Przybojewska B. An evaluation of the genotoxic properties of some chosen dyes using the micronucleus test in vivo. Mutation Research-Genetic Toxicology 1996;367(2):93-97.
61. Witt KL, Gulati DK, Kaur P, Shelby MD. Phenolphthalein-Induction Of Micronucleated Erythrocytes In Mice. Mutation Research-Genetic Toxicology 1995;341 (3):151-160.
62. Kulkarni RK, Pani KC, Neuman C, Leonard F. Polylactic acid for surgical implants. Arch Surg 1966; 93(5): 839-43.
63. Matsusue Y, Yamamuro T, Oka M, Shikinami Y, Hyon SH, Ikada Y. Invitro And Invivo Studies On Bioabsorbable Ultrahigh-Strength Poly(L-Lactide) Rods. Journal Of Biomedical Materials Research 1992; 26(12): 1553-1567.
64．全大萍，廖凯荣，卢泽俭，王海华．聚dl-丙交酯／羟基磷灰石复合材料Ⅲ．体内外降解性能研究．功能高分子学报2000；13(3)：41-45．
65. Damien CJ, Ricci JL, Christel P, Alexander H, Patat JL. Formation Of A Calcium Phosphate-Rich Layer On Absorbable Calcium-Carbonate Bone-Graft Substitutes. Calcified Tissue International 1994;55(2):151-158.
66. Johnson KD, Frierson KE, Keller TS, Cook C, Scheinberg R, Zerwekh J, Meyers L, Sciadini MF. Porous ceramics as bone graft substitutes in long bone defects: A biomechanical, histological, and radiographic analysis. Journal Of Orthopaedic Research 1996; 14(3): 351-369.
67. Oguchi H, Ishikawa K, Mizoue K, Seto K, Eguchi G. Long-Term Histological-Evaluation Of Hydroxyapatite Ceramics In Humans. Biomaterials 1995; 16(1):33-38.
68. Pettis GY, Kaban LB, Glowacki J. Tissue response to composite ceramic hydroxyapatite/demineralized bone implants. J Oral Maxillofac Surg 1990; 48(10): 1068-74.
69. Neo M, Kotani S, Fujita Y, Nakamura T, Yamamuro T, Bando Y, Ohtsuki C, Kokubo T. Differences In Ceramic Bone Interface Between Surface-Active Ceramics And Resorbable Ceramics-A Study By Scanning And Transmission Electron-Microscopy. Journal Of Biomedical Materials Research 1992; 26(2): 255-267.
70. de Groot K, Klein CAPT, Wolke JGC, et al.. Handbook of bioactive ceramics: Chemistry of calcium phosphate bioceramics. CRC Press, Boca Raton, Florida, 1990.
71. Dahlin C, Linde A, Gottlow J, Nyman S. Healing of bone defects by guided tissue regeneration. Plast Reconstr Surg 1988; 81(5): 672-6.
72. Urist MR, McLean FC. Recent Advances In Physiology Of Bone. I. J Bone Joint Surg Am 1963; 45: 1305-13.