纳米相羟基磷灰石/胶原复合材料研究进展

综述羟基磷灰石(hydroxyapatite,HA)/胶原复合材料的研究进展,着重阐述自组装纳米相羟基磷灰石/胶原复合材料的制作方法、结构特点、体内植入后修复骨缺损的效果及降解过程。基于仿生学设计的纳米相羟基磷灰石/胶原复合材料,其HA纳米晶体约50～100nm,HA的C-轴沿胶原纤维排列,形成片状包绕胶原纤维束,HA和胶原分子之间为牢固的化学键性结合,为自组装的纳米结构,和自然骨中钙化的胶原相同。复合材料体内植入后降解和骨替代的过程与骨的改建过程相似。纳米相羟基磷灰石/胶原复合材料具有生物降解性高、表面能大、生物活性好、生物相容性好等特点,作为骨修复和重建材料具有更好的前景。     

纳米羟基磷灰石/胶原药物载体的制备

以湿法制备出平均粒径为50nm的羟基磷灰石粉体，并采用超声分散，将纳米羟基磷灰石分散在酸溶的胶原稀溶液中。测试结果显示，羟基磷灰石在胶原溶液中形成了稳定的分散体系，该分散体系的稳定性与体系的pH值以及羟基磷灰石和胶原的相对浓度有关。     

魔芋葡甘聚糖/纳米羟基磷灰石/胶原复合材料构建组织工程椎间盘纤维环支架

BACKGROUND: Tissue-engineered transplantation technique has become an ideal therapeutic regimen for degenerative disc diseases through reconstituting the biological functions of the degenerated intervertebral discs.     

纳米羟基磷灰石复合材料研究进展

综述了近年来纳米羟基磷灰石复合材料研究进展,并对各种方法进行了简单比较。     

胶原羟基磷灰石（C／HA）组织埋藏

我们采用自制的Ｉ型胶原和羟基磷灰石做家兔皮下组织埋藏，分别在一个月和一个半月取出，组织切片证明应用胶原组比对照组的羟基磷灰石间的纤维结缔组织多，成纤维细胞浸润多，微血管丰富。炎症反应消失，无脱粒现象，结果证明胶原和羟基磷灰石联合植入组织比单用羟基磷灰石好。     

胶原/羟基磷灰石复合材料的制备及用于骨缺损修复的研究现状

通过模拟天然骨的结构,制备胶原/羟基磷灰石复合材料,与天然骨具有相似的组成、结构和性能,并具有良好的生物活性和生物降解性。本文就胶原/羟基磷灰石复合材料的制备方法、仿生形成机制、表征手段及骨缺损修复的应用等进行综述,并展望其未来发展方向。     

羟基磷灰石复合材料的研究进展

目的:本文综述了羟基磷灰石(HA)复合材料的最新进展和研究近况,并简略探讨了它们的今后发展方向.     

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。     

羟基磷灰石/胶原-聚乳酸三维多孔框架材料的制备成形及分析

目的：合成新型的复合生物材料框架作为骨组织工程研究的细胞外基质材料。方法：本研究采用材料学自组装技术的原理，以Ⅰ型胶原蛋白为分子模板，引导钙磷盐在液相中的矿化，制备具有天然骨基质层状结构的羟基磷灰石／胶原复合材料，并以热致分相法制备了羟基磷灰石／胶原-聚乳酸复合三维多孔框架。结果：羟基磷灰石／胶原复合材料具有与天然骨基质相似的成分与结构，加入聚乳酸制备成三维多孔框架，孔隙直径界于50um-300um。结论：羟基磷灰石／胶原-聚乳酸复合三维多孔框架可能作为骨组织工程良好的细胞外基质材料。     

纳米羟基磷灰石/Ⅰ型胶原/壳聚糖复合支架材料的制备与优化

目的制备适合于骨组织工程的高强度纳米羟基磷灰石/Ⅰ型胶原/壳聚糖复合支架材料。方法用原位合成法代替传统的直接分散法,以胶原和壳聚糖为模板原位合成羟基磷灰石,再用冷冻干燥法使材料成型,制成可用于骨组织工程的多孔支架材料。结果制备的材料孔隙率高,孔的连通性好,材料中羟基磷灰石结晶度更小,表面能大,与有机物基底结合紧密,也能为成骨细胞的粘附提供更多的活性位点。结论用紫外辐照对材料进行处理,能使其抗压性能得到提高。制备的支架材料适用于骨组织工程。     

Glutaraldehyde cross-linked hydroxyapatite/collagen self-organized nanocomposites

To control the mechanical properties and biodegradability of self-organized hydroxyapatite/collagen (HAp/Col) nanocomposites, cross-linkage was introduced into the composites with glutaraldehyde (GA). The HAp/Col composite suspensions, prepared by a simultaneous titration method and aged for 3h, were cross-linked with the reagents for 10min under vigorous stirring. The precipitates obtained were filtrated and compacted by dehydration under a uniaxial pressure. The particle size distribution, 3-point bending strength, contained water amount and swelling ratio of the composites were examined as a function of cross-linkage amount; the biodegradability was estimated by animal tests using rabbits. As regards the cross-linked composites, no long-rage alignment of HAp crystals along collagen molecules was found with a transmission electron microscope, suggesting that the cross-linking reagents suppressed their long-range self-organization mechanism. The 3-point bending strength increased with the GA content and took a maximal value at 1.35mmol/g(col). The animal tests indicated no toxicity and osteoclastic resorption with good osteoconductivity. The resorption rate was decreased with increasing GA concentration. These results suggest that GA cross-linkage controls mechanical properties and resorption rate without reducing high biocompatibility of the composite.     

FT-IR study for hydroxyapatite/collagen nanocomposite cross-linked by glutaraldehyde

FT-IR analysis was performed for the hydroxyapatite (HAp)/collagen (COL) nanocomposite cross-linked by glutaraldehyde (GA). The amide bands I, II and III from COL matrix, and phosphate and carbonate bands from HAp were identified. The amide B band arising from C–H stretching mode showed a sensitive conformation by the degree of cross-linking. The amide I band showed a complicate conformational change by the degree of cross-linking. The characteristic amide I band at 1685 cm⁻¹, which is known as an aging parameter in the biological bone, did not show a monotonous tendency by the degree of cross-linking. The relative contents of the organics in the cross-linked HAp/COL nanocomposite were evaluated as an integration ratio between the amide I band at 1600–1700 cm⁻¹ and PO₄³⁻ band at 900–1200 cm⁻¹. The increase of the organics content by the cross-linking is enabled by the further organization of Ca²⁺ ions of HAp crystals in HAp/COL nanocomposite. The complicate conformational behavior in the amide I, II and III bands seems to be affected by the cross-linking induced directional arrangement of HAp/COL nanocomposite fibrils.     

羟基磷灰石／胶原人工骨在创伤后骨缺损修复中的初步研究

目的评估羟基磷灰石，胶原（hydroxyapatite/collagen，HAC）人工骨在创伤后骨缺损修复中的临床效果。方法48例创伤后四肢骨骨折患者，无其他病史，分为2组。试验组25例，其中男性15例，女性10例，年龄22～82岁，平均年龄45.3岁。对照组患者23例，其中男性13例，女性10例，年龄21～81岁，平均年龄46岁。对所有患者进行骨折切开复位，选择合适的内固定。试验组于固定后，在骨缺损处、骨髓腔、骨折线周围直接植骨，羟基磷灰石，胶原人工骨修复材料植入量0.4～4.0g不等。对照组不植入羟基磷灰石，胶原人工骨。结果两组46例病例获随访。试验组中2例失随访，余23例患者无局部或全身不良反应，骨折均达临床愈合。X线片显示,术后1～3个月材料植入区与缺损周围的骨组织间界限模糊，有新骨形成，3～6个月材料植入区内有明显的新骨长入，人工骨与骨组织融合，骨缺损基本修复。对照组3例延迟愈合和1例骨折不愈合患者在功能上恢复较差；试验组与对照组比较具有统计学意义，P〈0．05。结论胶原，羟基磷灰石人工骨具有良好的材料，细胞界面，使材料本身更具备与骨键合的能力。其三维多孔结构便于骨组织的长入，生物降解性有利于骨组织的改建和塑形，具有良好的临床应用前景。     

Preparation and microstructure analysis of chitosan/hydroxyapatite nanocomposites.

Chitosan/hydroxyapatite (HAp) composites with a homogeneous nanostructure have been prepared by a co-precipitation method. According to TEM observations, HAp crystallites in the composites formed elliptic aggregations 230 nm in length and 50 nm in width. The typical length of the aggregations corresponded approximately to that of a chitosan molecule. The size of the constituent HAp crystallites was found to be predominantly 30 nm in length and 10 nm in width, and the c-axes were well aligned in parallel with the chitosan molecules in the respective aggregations. The growth of the HAp crystallites is considered to occur at nucleation sites, most probably forming the complexes with amino groups on chitosan with calcium ions. The compact composites obtained have been found to be mechanically flexible, and this flexibility has been improved further by heating at 120 degrees C for 20 min in an autoclave with saturated steam pressure.     

Biomedical nanocomposites of hydroxyapatite/polycaprolactone obtained by surfactant mediation

The composite approach to combining bioactive ceramic and degradable polymer is a promising strategy in the development of bone regenerative matrices. Moreover, in the fabrication of composites, the nanoscale organization of each component should improve the level of structural integration as well as the resultant mechanical and biological properties. The aim of this study was to develop a novel nanocomposite system consisting of hydroxyapatite (HA) and poly(epsilon-caprolactone) (PCL), wherein the HA nanoparticles were uniformly dispersed within the PCL matrix. The strategy was based on applying an amphiphilic surfactant, oleic acid in this case, between the HA and PCL. Oleic acid, which belongs to the fatty acid family and is generally noncytotoxic at the levels used in this study, is believed to mediate the interaction between the hydrophilic HA and hydrophobic PCL. With the mediation of oleic acid, the HA nanoparticles were distributed uniformly within the PCL matrix on the nanoscale (distributed particle size of less than 1 microm), which is in marked contrast to the conventionally mixed HA-PCL composite, in which the HA particles were severely agglomerated. The developed nanocomposite had significantly higher mechanical strength than did the conventional composite and the pure PCL. Moreover, the osteoblastic cells showed a better proliferation behavior on the nanocomposite than on the conventional composite. This HA-PCL nanocomposite mediated by oleic acid is expected to be useful in the bone regeneration field. Moreover, this methodology is applicable to the nanocomposite processing of other biomedical materials.     

Three-dimensional porous hydroxyapatite/collagen composite with rubber-like elasticity

A three-dimensional porous hydroxyapatite/collagen (HAp/Col) composite with a random pore structure was fabricated using freeze-drying processes; the self-organized HAp/Col nanocomposite with a weight ratio of 80.5:19.5, freeze-dried, was kneaded in 100 mM sodium phosphate buffer, frozen at ?20°C and freeze-dried. The cross-linkage of Col molecules was introduced dehydrothermally at 140°C in vacuo. The porous composite had a porosity of 94.7% with pore sizes between 200 and 500 μm. The compressive stress for the wet porous composite in phosphate buffer saline (PBS) was gradually decreased during 20 days incubation with a small amount of weight loss. The cyclic and time-course compression tests showed good repeatability of stress and well-recovery of its height, and caused no collapse of the porous composite. The implantation of the porous composite in rat bone holes showed the biodegradable property and new bone formation occurred in the pores without inflammatory response. The porous composite fabricated has good flexibility and rubber-like elasticity, and is a promising bone regenerative material.     

Three-dimensional porous hydroxyapatite/collagen composite with rubber-like elasticity

A three-dimensional porous hydroxyapatite/collagen (HAp/Col) composite with a random pore structure was fabricated using freeze-drying processes; the self-organized HAp/Col nanocomposite with a weight ratio of 80.5:19.5, freeze-dried, was kneaded in 100 mM sodium phosphate buffer, frozen at -20 degrees C and freeze-dried. The cross-linkage of Col molecules was introduced dehydrothermally at 140 degrees C in vacuo. The porous composite had a porosity of 94.7% with pore sizes between 200 and 500 microm. The compressive stress for the wet porous composite in phosphate buffer saline (PBS) was gradually decreased during 20 days incubation with a small amount of weight loss. The cyclic and time-course compression tests showed good repeatability of stress and well-recovery of its height, and caused no collapse of the porous composite. The implantation of the porous composite in rat bone holes showed the biodegradable property and new bone formation occurred in the pores without inflammatory response. The porous composite fabricated has good flexibility and rubber-like elasticity, and is a promising bone regenerative material.     

Osteocalcin enhances bone remodeling around hydroxyapatite/collagen composites

The effect of osteocalcin (OC), an extracellular bone matrix protein, on bone healing around hydroxyapatite/collagen composites was investigated. Cylindrical nanocrystalline hydroxyapatite implants of 2.5-mm diameter containing 2.5% biomimetically mineralized collagen type I were inserted press-fit into the tibial head of adult Wistar rats. To one implant group, 10 mug/g OC was added. Six specimens per group were analyzed at 2, 7, 14, 28, and 56 days. After 14 days, newly formed woven bone had reached the implant surface of the OC implants whereas a broad fibrous interface could still be observed around controls. Woven bone was formed directly around both implant groups after 28 days and had been replaced partially by lamellar bone around the OC implants only. No significant differences in total bone contact were seen between both groups after 56 days. The higher number of phagocytosing cells and osteoclasts characterized immunohistochemically with ED1, cathepsin D, and tartate-resistant alkaline phosphatase around the OC implants at the early stages of bone healing suggests an earlier onset of bone remodeling. The earlier and increased expression of bone-specific matrix proteins and multifunctional adhesion proteins (osteopontin, bone sialoprotein, CD44) at the interface around the OC implants indicates that OC may accelerate bone formation and regeneration. This study supports the observations from in vitro studies that OC activates both osteoclasts and osteoblasts during early bone formation.     

羟基磷灰石/壳聚糖生物复合材料的制备研究进展

羟基磷灰石/壳聚糖复合材料因其生物相容性和合适的力学性能逐渐成为骨替代材料研究的热点。本文综述了羟基磷灰石/壳聚糖复合材料的研究现状,探讨了其特点、制备和性能。并在此基础上提出了此类材料今后的发展方向：三相复合材料和电、磁学性能的研究。