可注射性硫酸钙/羟基磷灰石骨替代物抗压强度的影响因素

目的分析可注射性硫酸钙／羟基磷灰石骨替代物抗压强度的影响因素。方法用材料力学测试机，①测定含10％、20％、30％、40％、50％质量HA的α-半水硫酸钙分别与欧乃派克按照0．4ml／g的液固比混合后的抗压强度；②测定含40％质量HA的α-半水硫酸钙与欧乃派克按照液固比分别为0．350、0．375、0．400、0．425、0．450或0．475混合后的抗压强度；③测定含40％质量HA的α-半水硫酸钙按照0．4ml／g的液固比与不同的固化液即欧乃派克或蒸馏水混合后的抗压强度。结果当增加液固比，提高羟基磷灰石含量时可注射性硫酸钙／羟基磷灰石骨替代物抗压强度下降，使用固化液欧乃派克或蒸馏水对其抗压强度的影响无显著性差异。结论对可注射性硫酸钙／羟基磷灰石骨替代物抗压强度通过改变影响因素可以满足临床操作的要求。     

复合纳米人工骨的注射、凝固及其机械性能研究

目的 构建半水硫酸钙和纳米羟基磷灰石为主的复合人工骨材料并对其注射性能、凝固性能和机械强度的影响因素进行考察.方法 测试不同液固比条件下复合材料的注射特性,25℃和37℃时分别测试不同液固比、不同二水硫酸钙促凝剂条件下的材料初、终凝时间和压缩强度,均与纯硫酸钙作对比.结果 液固比0.50以上时注射性能满意.无论何种液/固比,复合材料的凝固时间均较硫酸钙延长,37℃下的凝固时间较25℃下延长.一定范围内促凝剂用量过大或过小均使凝固时间延长.液固比越大或促凝剂用量越高,材料压缩强度越低.纳米磷灰石含量增大则材料强度降低.结论 合理掌握纳米磷灰石的比例,液固比和促凝剂的用量,是开发可注射纳米人工骨的关键.     

可塑型生物活性骨修复材料的制备及性能表征

背景：国外研制的可注射性硫酸钙骨替代材料具有操作简便、生物相容性好、能够注射入骨缺损处、原位固化、适应骨缺损进行塑形等优点,但价格昂贵。 目的：研究以α-半水硫酸钙为主要成分可塑型骨修复材料的最佳制备参数,并对其性能进行研究和表征。 方法：使用汽热法制备粉末,将α-半水硫酸钙粉末与透明质酸钠固化液分别按液固比0.2,0.25,0.3,0.35,0.4 mL/g混合,制备可注射人工骨材料,检测其注射性能、凝固时间和抗压强度;根据检测结果选择最佳液固比0.3 mL/g,在α-半水硫酸钙粉末中分别加入质量分数为1%,2%,3%的二水硫酸钙粉末,制备可注射人工骨材料,检测其注射性能、凝固时间和抗压强度,同时检测可注射骨材料的生物安全性。将液固比为     0.3 mL/g并加入2%二水硫酸钙制备的可注射人工骨材料植入巴马小型猪胸骨缺损模型,植入后8,16,24周进行组织学观察。 结果与结论：α-半水硫酸钙粉末与透明质酸钠固化液液固比为0.3 mL/g,加入质量分数2%二水硫酸钙粉末制备的可注射人工骨材料,初凝时间为4.0-5.0 min,终凝时间为8.0-9.0 min,抗压强度(8.93±0.23) MPa,具备良好的注射性能,符合临床要求的凝固时间及作为非负重骨缺损修复要求的抗压强度,并具有良好的生物安全性。动物植入实验表明可注射人工骨材料通过自身降解,可为新生骨的爬行替代提供空间,具有一定的成骨活性。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

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。     

纳米羟基磷灰石/壳聚糖/半水硫酸钙为可注射骨组织工程支架材料的可行性

背景：前期实验采用仿生学原理制备了可注射性纳米羟基磷灰石/壳聚糖/半水硫酸钙复合材料,但其与骨髓间充质干细胞的生物相容性还不十分清楚。目的：探讨纳米羟基磷灰石/壳聚糖/半水硫酸钙作为注射型骨组织工程支架材料的可行性。方法：将第3代兔骨髓间充质干细胞与可注射纳米羟基磷灰石/壳聚糖/半水硫酸钙支架复合培养,作为实验组;以单纯接种培养的骨髓间充质干细胞为对照组,倒置显微镜下观察细胞生长情况,MTT法检测细胞增殖,扫描电镜观察细胞在材料表面生长与增殖。将纳米羟基磷灰石/壳聚糖/半水硫酸钙支架埋植在家兔背部肌袋内,埋植后2,4,6,8周进行病理学观察。结果与结论：实验组细胞生长、增殖良好,与对照组无明显差异。支架埋植后2周,材料周围有中等量中性粒细胞、淋巴细胞和巨细胞浸润,可见小血管与纤维母细胞增生,材料已被炎性细胞分割、围绕散碎;埋植后4周,可见少量淋巴细胞、纤维母细胞聚集,炎症反应进一步消退,肌纤维排列、形态正常;埋植后6周,材料周围炎症反应轻微,组织水肿不明显;埋植后8周,炎症反应基本消退,材料基本降解完成,肌纤维形态基本正常。表明纳米羟基磷灰石/壳聚糖/半水硫酸钙复合物具有良好的细胞相容性和生物降解性,可作为注射型支架材料。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

nHA/α-CSH复合植骨材料的研制及其固化时间和抗压强度测定

目的构建纳米羟基磷灰石(nHA)/α型半水硫酸钙(α-CSH)复合植骨材料并对其固化性能和机械强度进行观测。方法测试不同液/固比、不同二水硫酸钙(CSD)促凝剂含量条件下复合植骨材料的固化时间和压缩强度,并进行X线衍射(XRD)和扫描电镜(ESM)观察。结果复合骨水泥的固化时间随着nHA的增加而增加,随着CSD的增加而降低。含20%nHA、80%α-CSH的骨修复材料固化时间为(169±36)min;而含5%nHA、20%CSD、75%α-CSH的骨修复材料固化时间为(6±1.1)min。抗压强度随着nHA的增加而降低。纯α-CSH的平均压缩强度为(12.3±2.4)MPa,而含20%nHA、80%α-CSH的骨修复材料为(4.8±0.6)MPa。XRD检测显示固化后α-CSH转化为CSD,没有其他物质生成。ESM显示固化后nHA镶嵌在了CSD的晶体结构上,呈两相结构。结论通过调节nHA、α-CSH和促凝剂CSD的含量可以控制复合骨水泥的固化时间和机械强度,为临床应用提供适宜条件。     

纳米羟基磷灰石/羧甲基壳聚糖-海藻酸钠复合骨水泥的性能

背景：目前普遍使用的黏合剂对粉碎骨折块进行黏合复位或多或少都存在一些缺陷。 目的：研制具有黏接骨骼作用的生物活性骨水泥。 方法：应用共沉淀法制备纳米羟基磷灰石/羧甲基壳聚糖-海藻酸钠复合材料作为骨水泥的固相粉体,将柠檬酸衍生物配制成溶液作为液相。通过优化实验,从骨水泥的固化时间、抗压强度、抗拉强度、抗稀散性等方面确定最佳配比。 结果与结论：纳米羟基磷灰石/羧甲基壳聚糖-海藻酸钠质量比为65/35,其中羧甲基壳聚糖和海藻酸钠质量比为4∶1时复合成粉体,并按固液比为1.0∶0.5(g∶mL)调拌后形成的骨水泥呈膏状,塑形性和抗稀散性能良好,固化时间12~18 min,抗压强度为(4.5±2.1) MPa。体外黏接猪股骨头抗拉强度在不同室温下无显著性差异无显著性意义(P > 0.05),固化后2 h的抗拉强度达到24 h的94%。骨水泥为多孔状结构,孔径为100~300 μm,纳米羟基磷灰石分布较均匀。提示制备的纳米羟基磷灰石/羧甲基壳聚糖-海藻酸钠复合骨水泥具有良好的生物活性、适当的力学强度以及较好的黏合强度。     

载药复合纳米人工骨的注射、凝固、抗稀散性及药物缓释放的性能研究

目的 考察纳米羟基磷灰石(n-HA)的载药情况,并复合α-半水硫酸钙(CSH)构建复合人工骨材料,比较载药与未载药的复合人工骨的各方面性能,以及对复合材料的药物缓释放情况进行考察.方法 用离子交换法把阿莫西林载入n-HA中,与未载药的n-HA用UV-vis和TEM进行对比检测.再分别以质量比1:1与CSH复合,并对两组复合人工骨的各方面性能进行对比考察.把复合材料浸泡于生理盐水,每天更新浸泡液,测试骨水泥中药物的释放效果.结果 n-HA可有效地运载入阿莫西林.载药组的注射性能优于未载药组,凝固时间、抗稀散性相差不大.药物在浸泡数天内持续释放.结论 n-HA可以作为药物缓释放载体,以质量比1:1与CSH构建复合人工骨材料,其注射性能、凝固时间、抗稀散性均能符合临床要求.     

纳米羟基磷灰石/细菌纤维素复合组织工程支架的细胞毒性和生物相容性

背景:天津大学材料学院利用仿生学方法制备的纳米羟基磷灰石/细菌纤维素复合支架材料,具有与天然骨相似的结构和性能。目的:研究纳米羟基磷灰石/细菌纤维素复合组织工程支架的细胞毒性和生物相容性。方法:1急性全身性毒性实验:将纳米羟基磷灰石/细菌纤维素材料浸提液与生理盐水分别注射至昆明小鼠腹腔,注射24,48,72 h记录小鼠体质量。2致敏实验:在日本大耳白兔背部皮下分别注射纳米羟基磷灰石/细菌纤维素材料浸提液与生理盐水,72 h内观察注射部位水肿及红斑情况,间隔14 d后再次行激发实验。3热源实验:在日本大耳白兔耳缘静脉注射纳米羟基磷灰石/细菌纤维素材料浸提液,注射后检测体温变化。4溶血实验:在稀释的兔抗凝血中分别加入纳米羟基磷灰石/细菌纤维素材料浸提液、生理盐水与蒸馏水。5将第3代兔骨髓间充质干细胞与纳米羟基磷灰石/细菌纤维素材料共培养,观察材料表面细胞增殖、生长及黏附状态。结果与结论:纳米羟基磷灰石/细菌纤维素复合支架材料无急性全身毒性、无致敏性、无热源反应、无溶血反应,该支架材料具有三维网络结构,骨髓间充质干细胞在材料表面生长、增殖及黏附良好,表明纳米羟基磷灰石/细菌纤维素复合支架材料具有良好的生物相容性与细胞相容性。     

多孔结构对碳酸化羟基磷灰石骨水泥溶解度的影响

目的探讨碳酸化羟基磷灰石骨水泥中多孔结构存在的意义及其对溶解性能的影响.方法合成能原位固化形成多孔结构的碳酸化羟基磷灰石骨水泥,并通过扫描电镜和模拟体液浸泡实验,观察其孔隙结构和失重率变化.结果多孔碳酸化羟基磷灰石骨水泥固化后的孔隙率为42%,平均孔径为153μm,孔之间以90μm左右的连通孔互相贯通,孔隙结构与松质骨相似.碳酸化羟基磷灰石的多孔结构增加了其比表面积,利于体液循环.经模拟体液浸泡后,其失重率的改变比普通型碳酸化羟基磷灰石骨水泥明显增加,二者差异显著.结论碳酸化羟基磷灰石骨水泥内部的多孔结构能促进其体外溶解.     

In vitro properties of a chitosan-bonded hydroxyapatite bone-filling paste.

A possible bone substitute material for dental treatment was developed and tested. The material is composed of powdered hydroxyapatite (HA), ZnO and CaO, kneaded into a chitosan sol to make a quick-hardening paste. A composition was found which showed neutral pH, short setting time, and relatively high compressive strength. The use of such a paste for the treatment of periodontal defects or the augmentation of edentulous alveolar ridges may alleviate problems now associated with the implantation of particulate HA, such as early migration of particles and recontouring of the implant.     

骨移植体及骨移植替代物在体内的血管化

探讨了骨移植体及骨移植替代物在体内血管化的机理、意义及过程,以更好地促进骨缺损移植修复的效果.通过对近期有关文献所作相关研究的综述,总结出各类骨移植体及骨移植替代物体内血管化的特点及影响因素.骨移植体及骨移植替代物体内血管化过程是移植手段能够奏效的重要保障.组织工程化人工骨作为一种日益重要的骨移植替代物,进一步提高其在体内的血管化进程,是更好发挥其生命活力的关键.     

Novel injectable calcium phosphate/chitosan composites for bone substitute materials

In this study, a novel injectable bone substitute material was developed which consists of chitosan, citric acid and glucose solution as the liquid phase, and tricalcium phosphate powder as the solid phase. This material was moldable because of its paste consistency after mixing. We used four groups of cement to investigate the mechanical properties and biocompatibility of the new biomaterial in vitro, which were named group A (10% citric acid), B (15% citric acid), C (20% citric acid) and D (25% citric acid). The setting times of the cements were 5-30 min. X-ray diffraction analysis showed that the products were hydroxyapatite (HA) and dicalcium phosphate anhydrous. When the concentration of citric acid was increased, the compressive strength of specimen increased. Through the simulated body fluid test, we observed the material was bioactive. Group D could induce Ca and P ions to deposit the surface group D quickly. These results indicated that the concentration of citric acid in the liquid component affected the mechanical properties and bioactivity of cements. The cell cultivation test showed that the cytocompatibility of the new biomaterial was good. The method for preparing the novel bone substitute material is simple. The starting material is more readily available and cheaper than HA, poly(methyl methacrylate), and so on. The cement could have good prospects for medical application.     

New bioactive glass-ceramic: synthesis and application in PMMA bone cement composites

In present study, a new composition of glass-ceramic was synthesized based on the Na2O-CaO-SiO2-P2O5 glass system. Heat treatment of glass powder was carried out in 2 stages: 600 °C as the nucleation temperature and different temperature on crystallization at 850, 950 and 1000 °C. The glass-ceramic heat-treated at 950 °C was selected as bioactive filler in commercial PMMA bone cement; (PALACOS? LV) due to its ability to form 2 high crystallization phases in comparison with 850 and 1000 °C. The results of this newly glass-ceramic filled PMMA bone cement at 0-16 wt% of filler loading were compared with those of hydroxyapatite (HA). The effect of different filler loading on the setting properties was evaluated. The peak temperature during the polymerization of bone cement decreased when the liquid to powder (L/P) ratio was reduced. The setting time, however, did not show any trend when filler loading was increased. In contrast, dough time was observed to decrease with increased filler loading. Apatite morphology was observed on the surface of the glass-ceramic and selected cement after bioactivity test.     

Polymorphonuclear neutrophil response to hydroxyapatite particles,implication in acute inflammatory reaction

Hydroxyapatite (HA) is widely used as a bone substitute or coating biomaterial in bone diseases or prosthesis metal parts. The release of HA particles induces an inflammatory response and, if uncontrolled, could result in implant loss. Among the hallmarks of such inflammatory response is early recruitment of the polymorphonuclear cells (PMNs). The purpose of this work is to investigate the response of PMNs following exposure to HA in terms of secreted mediators. Our study shows that HA particles increase the release of pro-inflammatory mediators such as interleukin-1α, as well as chemotactic factors such as interleukin-8, macrophage inflammatory protein-1α and macrophage inflammatory protein-1β. HA also induces an increase in matrix metalloproteinase 9 expression. Taken together, our data demonstrate for the first time that HA is capable of activating PMNs, a phenomenon that could potentially contribute to the onset of implant-associated inflammation.     

医用磷酸钙骨水泥的制备及性能的实验研究

探索了磷酸四钙（Ca4（PO4）2O，TTCP）的制备，并合成了磷酸钙骨水泥（CPC），对CPC固化时间、引起浸泡液pH值的变化、抗压强度、产物物相组成及微观结构进行了研究。结果表明：在真空条件下、1500℃下煅烧6h可制得TTCP，并含有少量CaO。CPC初凝时间为4min、终凝时间为15min，浸泡1d和7d后的抗压强度分别为20MPa和35MPa，浸泡液的pH值在6．4～8．9之间变化，这些性能均符合临床用CPC的性能要求。CPC水化产物为片状或针状羟基磷灰石（Ca5（PO4）3OH，HA），相互交错呈连续分布的网状结构，这种结构有利于材料强度的提高。实验研制的CPC材料可用于骨缺损的修复治疗。     

Bioresorbable composite bone paste using polysaccharide based nano hydroxyapatite

Aim of this study concerns to the development of bioresorbable composite materials for bone repair and regeneration. Despite nano hydroxyapatite (HA) has wide range of medical applications, particles mobilization and slow resorbable nature limits its use in certain applications particularly, periodontal and alveolar ridge augmentation. To enhance its usage, we have prepared HA composite bone paste with a natural polysaccharide, chitosan, using wet chemical method at low temperature. The prepared composites were analyzed by various physicochemical methods and suggesting that the nano HA crystallites are well intact with the chitosan macromolecules. FT-IR results are indicating the existence of hydroxyl and amide groups in addition to the characteristic peaks of nano HA in the composite paste. The physical nature of paste form implies that it would be highly beneficial for the particle immobilization upon implantation. In vitro physiological stability and solubility of the composite was performed in phosphate buffered saline under physiological condition and found that the rate of resorbability of composite was quite higher than nano HA. These findings suggest that the HA/chitosan composites may have a great impact on human health care systems as bioresorbable bone substitute.     

Effects of additives on the rheological properties and injectability of a calcium phosphate bone substitute material

An injectable calcium phosphate bone substitute material has been prepared by mixing amorphous calcium phosphate (ACP) and dicalcium phosphate dihydrate (DCPD) for use in noninvasive surgery, and the influence of additives, such as disodium hydrogen phosphate, polyethylene glycol (PEG), glycerin, and citric acid, on the rheological properties and injectability of the ACP + DCPD cement system have been studied in this work. Novel approach of thixotropy measurement has been used to characterize the stability of the pastes. The results show that the injectability and the setting time can be augmented by the addition of disodium phosphate solution to the paste but reduced by the addition of PEG 200, glycerin, or citric acid to the paste. This study suggests that the injectability and the setting time of the ACP + DCPD bone substitute material can be balanced, and the injectable calcium phosphate bone substitute material with satisfied fluidity and injectability for clinical operation can be prepared by optimizing the additives and their concentrations, according to different clinical requirements.