新型有序纳米介孔生物活性玻璃的不同浓度浸提液对成骨细胞影响的研究

目的评价新型有序纳米介孔生物活性玻璃（80SMBG）的浸提浓度对成骨细胞的影响。方法采用大鼠成骨细胞体外培养,按细胞增殖度法,取0.25%、0.5%、1%、2%、4%共五种浓度的80SMBG浸提培养液进行检测,分别于3、4、5天用倒置显微镜观察细胞生长情况;用四唑盐（MTT）比色法计数计算细胞相对增殖度,用6级毒性分类法评级;用偶氮偶联法（PNPP）染色,分析碱性磷酸酶活性的变化。结果 80SMBG浸提液在高浓度时轻度抑制细胞增殖,促进细胞分化;低浓度促进细胞增殖,轻度抑制细胞分化。结论 80SMBG的体外生物活性较高,对体液微环境的影响轻微,细胞相容性好,作为骨组织修复替代材料或骨组织工程支架材料具有较高的研究和应用价值。     

新型有序纳米介孔生物活性玻璃在模拟体液中的表面生物活性研究

目的评价新型行序纳米介孔生物活性玻璃（80SMBG）的体外生物活性及其对体液环境的影响。方法以Novabone为对照,利用模拟人体体液体外浸泡实验（SBF）的方法和扫描电镜（SEM）、等离子发射光谱仪（ICP）pH仪等技术,比较80SMBG与Novabone体外生成类似于天然骨中无机矿物的羟基磷灰石（HA）的能力,分析SBF中各离子浓度、pH值的变化情况。结果80SMBG在SBF中浸泡4h表面即有羟基磷灰石（HA）生成,浸泡1～4hSBF中Ca、P、Si的离子浓度迅速达到峰值,8h后逐渐降低直至稳定,pH仅在7．40～7．65范围内变化。结论80SMBG的体外生物活性更高,对体液微环境的影响更轻微,作为骨组织修复替代材料或骨组织工程支架材料具有较高的研究和应用价值。     

介孔二氧化硅纳米颗粒的生物相容性

背景：介孔二氧化硅纳米颗粒具有很多优异的物理性质,在生物医学领域应用广泛,但目前对其生物相容性研究不足。 目的：综述国内外对介孔二氧化硅纳米颗粒生物相容性的研究进展。 方法：检索PubMed、EMBASE、万方、CNKI、维普、中国生物医学数据库有关介孔二氧化硅纳米颗粒细胞毒性和动物毒性的相关文献。 结果与结论：介孔二氧化硅纳米颗粒可通过内吞作用被细胞摄取,其可能通过在细胞内产生活性氧化物导致细胞毒性;介孔二氧化硅纳米颗粒致细胞毒作用与介孔二氧化硅纳米颗粒浓度、颗粒尺寸、表面活性剂去除方式、细胞种类有关。介孔二氧化硅纳米颗粒在动物体内主要富集在肝脏和脾脏,尿液和粪便是其主要排泄途径;介孔二氧化硅纳米颗粒在体内局部生物相容性良好,而大剂量介孔二氧化硅纳米颗粒经腹腔注射或静脉注射可导致严重全身反应。介孔二氧化硅纳米颗粒在体外和体内均显示出较好的生物相容性,但其安全性仍需进一步研究。     

生物活性玻璃／胶原蛋白倦酸丝氨酸复合支架材料的制备及其细胞相容性探讨

通过冷冻干燥方法制备出仿生型多孔结构的溶胶一凝胶生物活性玻璃（t36）／胶原蛋白（00L）／磷酸丝氨酸（PS）支架材料，并评价了小鼠胚胎成骨细胞系细胞在BG、BG-COL、BG-COL-PS支架材料上的生长、黏附、增殖情况。MTT法测结果显示，细胞在材料表面贴附、增殖良好，且细胞在BG-COL-PS支架材料生长增殖要明显好于BG-COL、BG支架材料。BG-COL-PS支架材料有可能成为一种新型的骨组织工程支架材料。     

生物活性玻璃/胶原蛋白/磷酸丝氨酸复合支架材料的制备及其细胞相容性探讨

通过冷冻干燥方法制备出仿生型多孔结构的溶胶-凝胶生物活性玻璃(BG)/胶原蛋白(COL)/磷酸丝氨酸(PS)支架材料,并评价了小鼠胚胎成骨细胞系细胞在BG、BG-COL、BG-COL-PS支架材料上的生长、黏附、增殖情况。MTT法测结果显示,细胞在材料表面贴附、增殖良好,且细胞在BG-COL-PS支架材料生长增殖要明显好于BG-COL、BG支架材料。BG-COL-PS支架材料有可能成为一种新型的骨组织工程支架材料。     

介孔-大孔生物活性玻璃的合成及其生物活性**◆

背景：多孔生物活性玻璃材料具有较大的比表面积、孔隙率以及贯通的孔道结构,可以加速羟基磷灰石沉积的动力学速率从而提高材料诱导形成新骨的能力。 目的：利用有机酸替代无机酸来合成新型介孔-大孔生物活性玻璃。 方法：将柠檬酸和P123加入到无水乙醇中,在室温下搅拌2 h至溶液澄清。依次加入正硅酸乙酯、四水硝酸钙和三磷酸乙酯,继续搅拌24 h。将所得溶胶倒入培养皿中,在室温下放置7 d,之后高温下烧结除去有机物模板。 结果与结论：①利用有机酸所制备的材料具有大孔结构,拥有较大的比表面积、孔隙率和孔径。②合成的介孔-大孔生物活性玻璃在人工模拟体液中可以诱导形成含碳羟基磷灰石,表现出了较好的生物活性,有望成为一种具有发展前景的骨缺损修复替代材料。     

新型改性聚乳酸与成骨细胞相容性的研究

探讨了成骨细胞与新型生物可降解材料乙二胺改性聚乳酸(EMPLA)的细胞相容性。在PLA、EMPLA及玻璃(对照组)上培养成骨细胞,采用细胞形态学观察法和细胞增殖法,在相差显微镜下观察细胞在上生长情况;分别于1、2、4、6d用MTT法记数,绘制生长曲线图。实验结果表明EMPLA组的成骨细胞比PLA组和对照组的形态好,增殖快,说明EMPLA比PLA表现出更好的细胞相容性,EMPLA在生物医学,特别是在组织工程领域存在着广泛的应用性。     

钛合金表面新型生物玻璃/纳米羟基磷灰石涂层的细胞相容性评价

目的为检验前期制备的新型生物玻璃／纳米羟基磷灰石涂层的细胞相容性。方法在本实验中，采用L929成纤维细胞在涂层浸提液中的培养，检测了涂层的细胞毒性，采用人体骨髓基质干细胞存涂层上的培养，检测了涂层对人体骨髓基质下细胞增殖和代谢的影响。结果低于浓度的涂层浸提液（〈10％）埘L929细胞增殖具有促进作用，而高浓度的涂层浸提液（〉50％）对L929细胞的增殖具有抑制作用，其中100％的涂层浸提液对L929细胞的增殖抑制比例为20.9％，在细胞毒性分级中处于合格范围内。结论在培养早期，人体骨髓基质干细胞在涂层表面的增殖要优于对照组，涂层显示出良好的细胞相容性。由于合格的细胞毒性和良好的细胞相容性，该涂层的钛合金具有作为骨植入物的应用潜力。     

新型纳米纤维支架的细胞生物相容性

背景：高孔隙率聚己内酯纳米纤维支架具有适合血管平滑肌细胞黏附、增殖的多级孔径结构,具有良好的细胞生物相容性。 目的：探讨高孔隙率聚己内酯静电纺丝纳米纤维支架的细胞相容性。 方法：根据支架的制作工艺不同分为传统支架组、新型纳米纤维支架组两组,另设单纯细胞组为对照组。采用组织块贴壁法体外原代培养兔主动脉平滑肌细胞并进行传代,用3~6代细胞作为实验用种子细胞。应用WST-1法测定平滑肌细胞黏附率、增殖力,光镜及扫描电镜观察细胞形态,评估支架的细胞生物相容性。 结果与结论：高孔隙率聚己内酯纳米纤维支架对细胞形态无明显影响,新型支架上的种子细胞黏附、增殖及代谢活性情况较传统支架好。提示,高孔隙率聚己内酯静电纺丝纳米纤维支架具有较高的细胞相容性。     

生物活性玻璃对鼠成骨细胞体外增殖的形态学研究

通过在培养液内加入生物活性玻璃,观察生物活性玻璃对成骨细胞增殖的影响。将生物活性玻璃晶体溶于DMEM培养液内,测定其中的Na、Ca、P、Si 4种离子的浓度。以对照组培养液和实验组培养液分别培养鼠成骨细胞,观察成骨细胞生长形态,测定成骨细胞生长指数并绘制生长曲线,动态观察细胞内甲肷的形态,观察细胞超微结构。结果表明:Si离子的浓度在实验培养液内是对照培养液的26.12%(P<0.01),Ca是88.03%(P<0.01),P是73.23%(P<0.01),Na的浓度无差异(P>0.05)。大体细胞形态:开始2天内实验组细胞胞体较对照组大,随时间延长,实验组成骨细胞比对照组密度高。动态观察细胞内甲肷:实验组较对照组成骨细胞增殖活跃,其定量指标即细胞生长指数在培养第2天,即出现明显的差异(P<0.01),随时间延长差异越明显,两条生长曲线呈分离趋势。细胞超微结构:实验组成骨细胞内比对照组有较多的粗面内质网、线粒体和核糖体。说明生物活性玻璃可促进成骨细胞增殖。     

Bioactive glasses with improved processing. Part 1. Thermal properties,ion release and apatite formation

Bioactive glasses, particularly Bioglass® 45S5, have been used to clinically regenerate human bone since the mid-1980s; however, they show a strong tendency to undergo crystallization upon heat treatment, which limits their range of applications. Attempts at improving their processing (by reducing their tendency to crystallize) have included increasing their silica content (and thus their network connectivity), incorporating intermediate oxides or reducing their phosphate content, all of which reduce glass bioactivity. Therefore, bioactive glasses known for their good processing (e.g. 13–93) are considerably less bioactive. Here, we investigated if the processing of 45S5 bioactive glass can be improved while maintaining its network connectivity and phosphate content. The results show that, by increasing the calcium:alkali cation ratio, partially substituting potassium for sodium (thereby making use of the mixed alkali effect) and adding small amounts of fluoride, bioactive glasses can be obtained which have a larger processing window (suggesting that they can be processed more easily, allowing for sintering of scaffolds or drawing into fibres) while degrading readily and forming apatite in aqueous solution within a few hours.     

溶胶-凝胶生物活性玻璃/胶原复合多孔支架的力学性能研究

目的研究溶胶-凝胶生物活性玻璃/胶原组织工程支架的力学性能及降解性能,为胶原基复合支架的进一步应用,提供理论基础。方法以纳米溶胶-凝胶生物活性玻璃为添加相,利用冷冻干燥法制备了4种溶胶-凝胶生物活性玻璃/胶原基复合多孔组织工程支架。结果(1)溶液中胶原纤维的聚集状态,制备出具有直径约为400～600nm的粗胶原纤维束支架材料,这种粗胶原纤维束对改善胶原基组织工程支架的力学强度和减慢其降解速度具有重要作用,其中胶原与生物活性玻璃质量比为40∶60时,具有最高的抗压强度(1.5469±0.0995)MPa。(2)利用FTIR和Raman等技术综合分析研究了溶胶-凝胶生物活性玻璃对胶原蛋白的二级结构的影响,当复合材料中胶原含量小于20%时,胶原蛋白二级结构破坏严重。结论当胶原与生物活性玻璃质量比为40∶60时,所制备的复合支架具有最好的抗压性能和降解性能,为进一步应用提供了研究基础。     

Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function

Surface reactivity is one of the common characteristics of bone bioactive ceramics. It contributes to their bone bonding ability and their enhancing effect on bone tissue formation. During implantation, reactions occur at the material-tissue interface that lead to time-dependent changes in the surface characteristics of the implant material and the tissues at the interface. This review describes some of the current concepts regarding the surface reactivity of bone bioactive materials and its effect on attachment, proliferation, differentiation and mineralization of bone cells.     

介孔生物玻璃对人骨髓间充质干细胞早期黏附增殖行为的影响*

目的制备具有高度有序介孔结构的介孔生物玻璃,研究人骨髓间充质干细胞（hBMSCs）在其表面黏附、铺展、增殖等早期细胞生物学行为。方法通过溶胶凝胶法制备介孔生物玻璃（MBG）;接种人骨髓间充质干细胞（hBMSCs）于不同组材料表面共培养,采用四唑盐比色法（MTT）分析其对细胞增殖的影响,绘制增殖曲线;使用DAPI染核,在荧光显微镜下观测材料表面的细胞粘附情况;利用扫描电子显微镜（SEM）直接观察细胞在材料表面的铺展形态。结果在4h和12h,MBG能够显著促进hBMSCs在其表面的黏附;同时,第1~7d,MBG表面的细胞增殖数量显著多于没有介孔结构的普通生物玻璃（NBG）表面的细胞增殖数;在24h内的荧光显微镜观察下,MBG表面在早期有更多的hBMSCs黏附;在第1、4、7d SEM的观察下,MBG表面的细胞能够更均匀的分布并覆盖材料。结论具有有序介孔结构的介孔生物玻璃能够促进人骨髓间充质干细胞在其表面的早期黏附、铺展和增殖,具有更好的生物活性。     

Ab initio molecular dynamics simulations of structural changes associated with the incorporation of fluorine in bioactive phosphate glasses

Phosphate-based bioactive glasses containing fluoride ions offer the potential of a biomaterial which combines the bioactive properties of the phosphate glass and the protection from dental caries by fluoride. We conduct accurate first-principles molecular dynamics simulations of two compositions of fluorinated phosphate-based glass to assess its suitability as a biomaterial. There is a substantial amount of F–P bonding and as a result the glass network will be structurally homogeneous on medium-range length scales, without the inhomogeneities which reduce the bioactivity of other fluorinated bioactive glasses. We observe a decrease in the network connectivity with increasing F content, caused by the replacement of bridging oxygen atoms by non-bridging fluorine atoms, but this decrease is small and can be opposed by an increase in the phosphate content. We conclude that the structural changes caused by the incorporation of fluoride into phosphate-based glasses will not adversely affect their bioactivity, suggesting that fluorinated phosphate glasses offer a superior alternative to their silicate-based counterparts.     

In vitro bioactivity and degradation of polycaprolactone composites containing silicate fillers

In spite of numerous publications on the potential use of combinations of polycaprolactone (PCL)/bioactive fillers for bone regeneration, little information exists on the assessment of solid, nonporous composites prepared via solventless routes and consisting of unmodified, slowly degrading homopolymer with relatively low amounts of reactive fillers such as bioglass or calcium silicate (CS). Thus, composites of PCL with commercial CS and a bioactive glass (BG45S5) at 30wt.% were produced by melt mixing in a twin screw extruder. Neat fillers, PCL and their composites were immersed in simulated body fluid (SBF) and phosphate buffer saline and tested for in vitro bioactivity and degradation, respectively, over a 4 month period. Testing methods included scanning electron microscopy with energy dispersive X-ray analysis, X-ray diffraction (XRD), elemental analysis and weight and pH changes before and after immersion. Experiments with neat fillers indicated fast growth of calcium phosphate minerals having different textures; they included clusters and globules of mineral precipitates as well as needle-shaped nanosized crystallites and possibly other calcium phosphate structures with varying Ca/P ratio. The bioactive glass composite initially showed fast growth of the precipitated minerals and partial surface coverage after 1 week, whereas in the CS composite, growth and surface coverage increased as a function of immersion time (over a period of 4 weeks) in the SBF solution. XRD results showed early appearance (1 week) of hydroxyapatite for both types of composites with differences attributed to different dissolution rates and different surface reactions of the fillers. Both fillers appeared to enhance the hydrolytic degradation of the matrix. Overall, the limited observed bioactivity of both composites within the test period may be related to the hydrophobicity of the matrix, insufficient ionic activity since SBF was not replenished and the relatively low content of the low surface areas fillers. Optimization of filler properties, such as surface/volume ratio, surface chemistry and size range, appears as a most important factor that would provide, at the required high filler volume fractions, a balance of melt processability and bioactivity.