纳米羟基磷灰石骨修复复合材料的研究进展

羟基磷灰石（Hydroxyapatite，HA）是一种性能良好的骨修复材料，但是由于脆性而限制了它在承力部位的应用。天然骨本身是纳米羟基磷灰石（Nanohydroxyapatite，n．HA）和胶原的复合材料，从仿生的角度看，n—HA与其它材料复合可以提高生物相容性和力学性能。目前研究的纳米羟基磷灰石复合材料可分为两类：非降解的纳米羟基磷灰石复合材料和可降解的纳米羟基磷灰石复合材料。前者包括n—HA/聚乙烯、n-HA／尼龙以及n—HA／聚丙烯酸。后者主要有n—HA与胶原、明胶、壳聚糖、聚乳酸和聚酸酐等的复合材料。本文详细综述了近年来纳米羟基磷灰石复合材料的制备、力学性能以及生物学性能的研究进展。     

电纺纳米羟基磷灰石/聚酯酰胺复合支架材料的制备及其细胞相容性

背景：采用静电纺丝技术将功能性无机纳米微粒复合高分子超细纤维,形成类细胞外基质结构和功能的复合支架材料是骨组织工程支架领域一个新的研究方向。 目的：通过静电纺丝法构建纳米羟基磷灰石/脂肪族聚酯酰胺复合纤维支架材料,并初步考察其细胞相容性。 方法：以静电纺丝法制备纳米羟基磷灰石/脂肪族聚酯酰胺超细纤维支架材料,通过扫描电镜、原子能谱等表面形貌的物相分析,进行细胞在复合材料上的形态学观察。 结果与结论：通过静电纺丝法成功制备出纳米羟基磷灰石/脂肪族聚酯酰胺超细纤维复合材料,成骨细胞直接培养于材料上呈现良好生长行为,初步证实了复合支架材料的细胞相容性。说明静电纺丝技术在构建类骨细胞外基质结构和功能的仿生复合材料方面具有独特优势,电纺超细纤维复合材料有望成为新型的骨组织工程支架。     

纳米羟基磷灰石复合支架材料的研究与应用

背景：羟基磷灰石具有良好的生物相容性和生物活性,被广泛应用于骨组织的修复与替代技术,但脆性大限制了其在承载部位骨替换中的应用。 目的：对纳米羟基磷灰石复合支架材料的研究现状与进展进行综述。 方法：分别以英文检索词“nano-hydroxyapatite(nano-HA),composites”;中文检索词“纳米羟基磷灰石,复合材料”,应用计算机检索中国期刊网全文检索库(CNKI)及PubMed数据库1995-01/2010-10 有关文章,纳入纳米羟基磷灰石复合材料的文献。排除与研究目的无关和内容重复者。保留33篇文献做进一步分析。 结果与结论：随着纳米技术的发展,纳米羟基磷灰石复合支架材料中复合成分得以不断优化,能比较好的模仿天然骨和细胞外基质的结构特点,证明了其优越性,但仍需要进一步优化制备方法,增强纳米羟基磷灰石和生物高分子界面的结合,使复合材料的力学、加工性能和生物性能达到最佳契合点,从而达到临床使用的要求。     

注射型纳米羟基磷灰石/聚酰胺生物活性骨修复材料的研究

利用羟基磷灰石纳米晶体与聚酰胺66复合，构成新型生物活性骨修复材料，探讨用于不规则骨缺损修复的注射型纳米复合人工骨的生物学特性及骨组织修复能力。对该材料进行X射线衍射分析、凝结时间、凝结强度等研究及动物实验研究，评价该材料的组织相容性和缺损骨组织的修复能力。结果表明该材料的X射线衍射谱与羟基磷灰石／聚酰胺复合材料的X射线衍射谱相同；液固比为0．5时复合材料易于注射；在生理盐水或血液中的凝固时间为25～30min；在生理盐水中固化48h后，抗压强度为37MPa。植入后牙槽嵴表面软组织愈合良好，实验侧牙槽嵴修复高度明显大于对照侧；组织形态学观察，4周时材料周围未见有成骨迹象，16周时材料被包裹并在与其相连的区域出现成骨早期的片状结缔组织。研究证实，以一定的复合比例构成的纳米羟基磷灰石／聚酰胺66复合材料组织相容性良好，可以注射方式实现对不规则骨缺损的修复。     

原位法制备羟基磷灰石/聚乳酸纳米复合材料的体外生物学研究

通过羟基磷灰石/聚乳酸(HA/PLLA)纳米复合材料在模拟体液(SBF)中的浸泡实验评价该材料的生物学性能。测试发现HA/PLLA纳米复合材料在浸泡过程中SBF的pH值呈现下降趋势,HA的存在缓冲了PLLA的酸性;复合材料表面有类骨磷灰石层沉积,并有"蚕茧状"类骨磷灰石颗粒和夹有短棒状晶体的片状晶体簇生成;同时复合材料的降解导致表面形成大量蜂巢状多孔。因此原位法制备的HA/PLLA纳米复合材料具有较好的生物活性和可降解性。     

纳米羟基磷灰石复合人工骨材料的研究进展

近年来,随着材料科学的发展,人工骨材料的构建与合成有了突破性的进展。纳米羟基磷灰石是自然骨的天然组分,具备良好的骨传导性、诱导性及生物相容性,因而被广泛应用于人工骨材料的构建中;但单纯的羟基磷灰石作为人工骨材料时由于其强度低、韧性差、体内降解速率缓慢等特性受到一定程度的制约。因此,对纳米羟基磷灰石与其他材料进行多相复合以尽可能的模拟正常骨组织结构或赋予其一定的特殊性能是当前人工骨领域的研究热点。本文从纳米羟基磷灰石支架材料、具备特殊性能的复合人工骨材料的研究现状等方面做一综述。     

新型聚乳酸与纳米羟基磷灰石复合人工骨的性能测试研究

目的　通过原位聚合法制备新型的聚乳酸与纳米羟基磷灰石复合材料,找到两者复合的最佳配比,从而得到理想的人工骨移植材料。 方法　采用原位聚合法按一定的配比（纳米羟基磷灰石质量分数分别为0,10%,20%,30%,40%)聚乳酸与纳米羟基磷灰石复合人工骨,对这类新型的人工骨进行性能测试,通过抗弯,抗压,弹性模量,电镜扫描,体外降解实验,观测该人工骨的力学性能、微观结构、纳米羟基磷灰石在聚乳酸中的分散情况以及复合材料的降解性能。 结果　（1）力学测试显示：随着n-HA含量的增加,复合材料的拉伸强度逐渐减少。复合材料的弯曲强度在n-HA微粒的质量分数为20%时弯曲强度出现峰值(156.8 MPa)。复合材料的弯曲模量随着n-HA微粒质量分数的增加而增大。（2）SEM扫描显示：纯PDLLA材料断裂表面较平整;在n-HA含量为10%时出现大量的韧窝, 明显的粗糙断裂面;在n-HA含量为20%断裂表面凹凸不平,形成大量的韧窝;在n-HA含量为30%以上时断口又变得越来越平整,尚有许多小的韧窝。（3）体外降解实验显示：随着降解时间的延长,降解液的pH值均逐渐降低,复合材料的力学性能也逐渐的产生一定的衰减。 结论　当n-HA含量为20%时,该人工骨复合材料有着更好的力学性能和降解性能,筛选出该种新型人工骨的最佳配比,制备出性能良好的PDLLA/n-HA复合人工骨材料。     

纳米羟基磷灰石膜聚氨酯复合材料的体内组织相容性

背景：纳米羟基磷灰石与聚氨酯复合材料在体外实验中具有良好的相容性。 目的：验证纳米羟基磷灰石膜聚氨酯复合材料在大鼠体内的组织相容性。 方法：将18只SD大鼠随机分为复合材料组、聚氨酯组和对照组,复合材料组和聚氨酯组分别将纳米羟基磷灰石膜聚氨酯复合材料、聚氨酯植入大鼠背部肌肉内,对照组仅作切开缝合,未植入任何材料。 结果与结论：①大体观察：术后12周,各组切口与周围皮肤几乎无界限,聚氨酯组及复合材料组囊壁与材料融合较好,对照组皮肤已恢复正常。②组织学观察：术后4,8,12周,聚氨酯组及复合材料组切口周围组织中淋巴细胞数、中性粒细胞数及毛细血管量均高于对照组(P < 0.05),复合材料组切口周围组织中淋巴细胞数、中性粒细胞数及毛细血管量均少于聚氨酯组(P < 0.05)。证实纳米羟基磷灰石膜聚氨酯复合材料具有较好的组织相容性。     

纳米羟基磷灰石及其复合物修复骨缺损的研究与应用

背景：羟基磷灰石是骨组织工程公认的骨修复替代材料,而纳米羟基磷灰石具有与天然骨更为相似的结构特征。 目的：介绍纳米羟基磷灰石及其复合物的制备方法及特点,了解其在骨缺损修复中的应用情况。 方法：以“Nano-hydroxyapatite,bone defects,bone tissue engineering”为检索词,检索Pubmed数据库;以“纳米羟基磷灰石,骨缺损,骨组织工程”为检索词,检索CNKI数据库。文献检索语种限制为英文和中文。纳入纳米羟基磷灰石修复骨缺损的研究,纳米羟基磷灰石与一种或两种以上复合材料修复骨缺损的研究,以及骨组织工程中纳米羟基磷灰石研究的文章。最终纳入29篇符合标准的文献。 结果与结论：纳米羟基磷灰石可促进新骨形成,且新骨形成量大,具有较好的生物降解性、骨引导性。与天然或非天然材料复合,克服了自身脆性和弱的机械性等缺点,可以加速骨界面愈合。目前研究证实纳米羟基磷灰石在骨缺损的修复中发挥重要的作用,与其他材料复合后将有助于骨缺损的治疗,制备出特定功能的纳米仿生智能材料将是骨组织修复材料的未来发展方向。     

纳米羟基磷灰石仿生骨材料的研究进展

纳米羟基磷灰石仿生骨材料因其与天然骨结构和成分相近,已成为组织工程领域研究的热点之一。介绍了纳米羟基磷灰石的各种制备方法及其复合材料的合成方法,并对纳米羟基磷灰石复合材料的特性进行了说明。通过将纳米羟基磷灰石表面修饰改性后,其复合材料有着广阔的应用前景,可用于修复骨缺损,也可以作为药物载体治疗肿瘤。对近年来纳米羟基磷灰石仿生骨材料的研究进展进行了综述。     

Evaluation of the osteoconductive potential of poly(propylene carbonate)/nano-hydroxyapatite composites mimicking the osteogenic niche for bone augmentation

Nano-hydroxyapatite (n-HA) reinforced poly(propylene carbonate) (PPC) composites were prepared for bone repair and reconstruction. The effects of reinforcement on the morphology, mechanical properties and biological performance of n-HA/PPC composites were investigated. The surface morphology and mechanical properties of the composites were characterized by scanning electron microscopy (SEM) and universal material testing machine. The analytical data showed that good incorporation and dispersion of n-HA crystals could be obtained in the PPC matrix at a 30:70 weight ratio. With the increase of n-HA content, the tensile strength increased and the fracture elongation rate decreased. In vitro cell culture revealed that the composite was favorable template for cell attachment and growth. In vivo implantation in femoral condyle defects of rabbits confirmed that the n-HA/PPC composite had good biocompatibility and gradual biodegradability, exhibiting good performance in guided bone regeneration. The results demonstrates that the incorporation of n-HA crystals into PPC matrix provides a practical way to produce biodegradable and cost-competitive composites mimicking the osteogenic niche for bone augmentation.     

Preparation and properties of nano-hydroxyapatite/PCL-PEG-PCL composite membranes for tissue engineering applications

Nano-hydroxyapatite (n-HA)/poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) composite membranes were prepared by solvent casting and evaporation method. The structure and properties of the membranes were investigated by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), water contact angle measurements, in vitro hydrolytic degradation, mechanical test, and cell culture. The effect of n-HA content on physical-chemical properties of the n-HA/PCEC composite membranes was studied. The results showed that the shape and size of micropores of the composite membranes changed with n-HA content increased; the tensile strength decreased with the increase of n-HA content. The osteoblast cell was cultured on the membranes, good cell attachment and growth manner were observed after postseeding for 1 day. MTT assays showed that the n-HA/PCEC membranes had no negative effect on the cell viability and proliferation. These results suggested that the obtained n-HA/PCEC composite membranes in this study might have prospective applications in tissue engineering field.     

Development of biomimetic nano-hydroxyapatite/poly(hexamethylene adipamide) composites

In this study, acicular nano-hydroxyapatite (n-HA) was used to make a new biomimetic composite with polyamide (poly hexamethylene adipamide) by a unique technique. The physical and chemical characteristics of the composites were tested. It was found that these synthesized n-HA crystals were similar to bone apatite in size, phase composition and crystal structure. The biomimetic n-HA crystals were uniformly distributed in the polymer matrix and its content can reach 65%, close to that in natural bone. Chemical binding between inorganic n-HA and polyamide was investigated and discussed. The mechanical properties of the composites were found to match well with those of natural bone.     

Employing the cyclophosphate to accelerate the degradation of nano-hydroxyapatite/poly(amino acid) (n-HA/PAA) composite materials

Owing to the good degradability and biocompatibility of polyphosphoesters (PPEs), the aim of the current study was to investigate a novel degradable composite of nano-hydroxyapatite/poly(amino acid) (n-HA/PAA) with cyclophosphate (CPE) via in situ melting polymerization to improve the degradation of n-HA/PAA. The structure of each composite was characterized via Fourier transform infrared spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The degradation properties were studied in terms of the weight loss and pH in a phosphate-buffered saline (PBS) solution, while the surface morphology was examined using a scanning electron microscope-energy dispersive spectrometer (SEM-EDS) after soaking the surface in simulated body fluid (SBF). The cell proliferation, cell adhesion, and alkaline phosphatase (ALP) activity were used for the analysis of cytocompatibility. The weight loss results showed that the n-HA/PAA composite was 9.98 wt%, weighed after soaking in the PBS solution for 12 weeks, whereas the nano-hydroxyapatite/polyphosphoester-amino acid (n-HA/PPE-AA) composite was 46.94 wt%. The pH of the composites was in a suitable range between 6.64 to 7.06 and finally stabilized at 7.39. The SEM and EDS results revealed the formation of an apatite-like layer on the surface of the n-HA/PPE-AA composites after soaking in SBF for one week. The cell counting Kit 8 (CCK-8) assay of the cell culture in the leaching liquid of the n-HA/PPE-AA composites exhibited non-cytotoxicity and high-proliferation, and the cell adhesion showed the well spreading and normal phenotype extension of the cells on the n-HA/PPE-AA composites surface. Concurrently, the co-culture results of the composites and cells confirmed that the n-HA/PPE-AA composites exhibited a higher ALP activity. In summary, the results demonstrated that the n-HA/PPE-AA composites had a controllable degradation property, good bioactivity, and cytocompatibility.     

丝素蛋白对纳米羟基磷灰石晶体生长的调控作用

背景：前期研究表明丝素蛋白含量对丝素蛋白/纳米羟基磷灰石复合材料性能与结构有一定影响。 目的：观察丝素蛋白含量对纳米羟基磷灰石晶体生长的调控作用。 方法：采用物理化学方法制备出含0,10%,20%,30%,40%丝素蛋白的丝素蛋白/纳米羟基磷灰石复合物,通过热重分析仪、傅里叶红外光谱仪、透射电镜、X射线粉末衍射仪分析丝素蛋白含量对纳米羟基磷灰石晶体生长的调控作用。 结果与结论：丝素蛋白的加入对纳米羟基磷灰石晶体的成核和生长具有明显调控作用：在纳米羟基磷灰石晶粒沿c轴高度择优生长,长径比增大,形貌由短棒状调控为针状。丝素蛋白含量对纳米羟基磷灰石晶体的成核和生长影响微弱,但对晶粒在丝素蛋白基质的有序排布有明显的调控作用：当丝素含量为10%和20%时,纳米羟基磷灰石晶粒呈放射状有序排布;丝素含量为30%和40%时,纳米羟基磷灰石晶粒无序团聚,说明30%含量是丝素蛋白与纳米羟基磷灰石的饱和吸附临界点。     

Fabrication of mineralized polymeric nanofibrous composites for bone graft materials

Poly-L-lactic acid (PLLA) and PLLA/collagen (50% PLLA+50% collagen; PLLA/Col) nanofibers were fabricated using electrospinning. Mineralization of these nanofibers was processed using a modified alternating soaking method. The structural properties and morphologies of mineralized PLLA and PLLA/Col nanofibers were investigated using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and contact angle measurements. Human bone-derived osteoblasts were cultured on the materials for up to 1 week to assess the biological properties of the nanofibrous composites. Cell attachment on these nanocomposites was also tested within 1 h of culture at room temperature. The mechanical properties of the cell-nanocomposite constructs were determined using tensile testing. From our results, the bone-like nano-hydroxyapatite (n-HA) was successfully deposited on the PLLA and PLLA/Col nanofibers. We observed that the formation of n-HA on PLLA/Col nanofibers was faster and significantly more uniform than on pure PLLA nanofibers. The n-HA significantly improved the hydrophilicity of PLLA/Col nanofibers. From the results of cell attachment studies, n-HA deposition enhanced the cell capture efficacy at the 20-minute time point for PLLA nanofibers. The E-modulus values for PLLA+n-HA with cells (day 1 and day 4) were significantly higher than for PLLA+n-HA without cells. Based on these observations, we have demonstrated that n-HA deposition on nanofibers is a promising strategy for early cell capture.     

Morphological and X-ray diffraction studies of crystalline hydroxyapatite-reinforced polycaprolactone

Morphological and mechanical properties of hydroxyapatite (HAP)-reinforced polycaprolactone (PCL) were studied. The objective was to examine how morphological features alter the bulk mechanical properties in our laboratory-synthesized HAP-reinforced PCL. HAP crystals were synthesized by hydrolysis of mixtures of calcium and phosphate salts in the laboratory with wet chemical methods. The properties of the commercially available hydroxyapatite (HAP(1)) are compared with that of laboratory-synthesized hydroxyapatite (HAP(2)). The HAP crystals and composition were characterized using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectrometry (FTIR). The HAP(1) and HAP(2) crystals were dispersed into polymers to examine the mechanical behavior of bioactive composites, and the interfacial interactions between the polymer and HAP crystals are addressed. The FTIR results confirmed that the two forms of HAP crystals are consistent in terms of the functional chemical groups. The wide angle X-ray diffraction study was performed to determine the crystallinity of the bioactive composites. It was observed that the crystallinty of HAP-filled PCL steadily increased as the filler concentration increased. Generally, HAP(2) has a particle size considerably smaller than HAP(1) and the composite derived had higher modulus than conventional HAP-filled polymers. This increase in modulus is attributed to better interfacial interaction. Bioresorbability tests performed on HAP particles found that the synthesized HAP had higher resorption rates. It is clear that the mechanical properties are influenced by the particle size and therefore by the processing method used.     

Porous nano-hydroxyapatite/poly(vinyl alcohol) composite hydrogel as artificial cornea fringe: characterization and evaluation in vitro

A nano-hydroxyapatite/poly(vinyl alcohol) (n-HA/PVA) composite hydrogel was employed as artificial cornea fringe to improve biocompatibility for the firm fixation between material and surrounding host tissues. The morphology and swelling behavior, as well as mechanical strength of the fringes were characterized. The results showed that the n-HA/PVA fringes had interconnective porous structure, high water content and good mechanical properties. With the aid of cell culture observed by inverted microscopy, scanning electron microscopy (SEM) and MTT test, it was concluded that PVA hydrogel modified with n-HA can improve biocompatibility and has no negative effects on the corneal fibroblasts in vitro. These findings indicate that the porous n-HA/PVA fringe can allow invasion and proliferation of cells, and can function as a fringe for artificial cornea.     

Preparation and characterization of nano-hydroxyapatite/chitosan/konjac glucomannan composite

Nano-hydroxyapatite (n-HA)/chitosan (CS)/konjac glucomannan (KGM) composite was prepared by coprecipitation method and investigated by thermal gravitivity/differentiate thermal analysis, Fourier transform infrared spectroscopy, X-ray diffraction, inductively coupled plasma emission spectroscopy, scanning electron microscopy, and energy dispersive X-ray analyzer. The analyses showed that the three phases of n-HA, CS, and KGM combined closely to each other. Further, in vitro tests were conducted to investigate the degradation and bioactivity of the composite. During immersion in simulated body fluid (SBF), pores appeared and a new substance containing Ca and P formed on the surface of the composite. Also, the concentration of Ca and P in SBF changed and weight loss of the composite was observed during time. The composite revealed a high degradation in SBF. Evidently, the new composite has a potential to be used as a carrier of implantable drug delivery system. The biodegradation rate and route could be different from CS and KGM, which will provide an opportunity to control the degradation rate or drug releasing rate by simply adjusting the ratio of CS and KGM.     

Effects of crystalline phase on the biological properties of collagen–hydroxyapatite composites

The objective of this study was to investigate the effects of spatial structure and crystalline phase on the biological performance of collagen–hydroxyapatite (Col–HA) composite prepared by biomineralization crystallization. Two types of Col–HA composites were prepared using mineralization crystallization (MC composites) and pre-crystallization (PC composites), respectively. Structural characteristics were analyzed by scanning electron microscopy and transmission electron microscopy. Surface elemental compositions were measured by electron spectroscopy for chemical analysis (ESCA). These composites were used in in vivo repair of bone defects. The effects of the crystalline phase on the biological performance of Col–HA composites were investigated using radionuclide bone scan, histopathology and morphological observation. It was observed that in MC composites, HA was located on the surface of the collagen fibers and aggregated into crystal balls, whereas HA in PC composites was scattered among the collagen fibers. ESCA showed that phosphorus and calcium were 8.99% and 17.56% on MC composite surface, compared with 4.39% and 5.86% on the PC composite surface. In vivo bone defect repair experiments revealed that radionuclide uptake was significantly higher in the area implanted with the PC composite than in the contralateral area implanted with the MC composite. Throughout the whole repair process, the PC composite proved to be superior to the MC composite with regard to capillary-forming capacity and the amount of newly formed bone tissue. So it could be concluded that HA placement on collagen fibers affected the biological performance of Col–HA composites. Pre-crystallization made HA scattered among collagen fibers, creating a better structure for bone defect repair in comparison with MC Col–HA composites.