Biological Evaluation of α-TCP/TTCP Composite Bone Cement

tricalcium phosphate(α TCP)/tetracalcium phosphate(TTCP) composite bone cement had good hydration characteristic.In our system,α TCP/TTCP powder mixture was mixed with water at a powder/liquid (P/L) ratio of 1.50g·mL -1 .The setting time could be adjusted,the maximum compressive strength was 45.36MPa,and the hydration product was hydroxyapatite (HAP).In vitro biological simulated experiments indicate that α TCP/TTCP bone cement has α certain dissolubility.The hardened product is mainly HAP after soaking in simulated body fluid (SBF) for 10 weeks.The results of in vitro test and animal experiments and SEM analyses show that no local or general toxicity response,no muscle stimulation,no haemolysis,no cruor,no inflammatory reaction and no exclusion response are caused by α TCP/TTCP cement, which can be contributed to bone tissue spreading and impinging.α TCP/TTCP cement hydrated and hardened continually in vivo.The materials fused with host bone together with implanting time prolonging.Therefore,it is believed that α TCP/TTCP composite bone cement has a high biocompatibility and bioactivity,a certain biodegradation and good osteogenesis as well.

Osteogenesis Capacity of a Novel BMP/α-TCP Bioactive Composite Bone Cement

To improve the osteogenesis ability of a-tricalcium phosphate (α-TCP) bone cement, a novel BMP/ α-TCP composite bone cement was prepared. By measuring the setting time and compressive strength, the hydration characteristic of bone cement was evaluated. Animal experiments including histological observation, radiographic investigation as well as digital image analyses reveal the difference of osteogenesis ability among BMP,a-TCP bone cement and BMP/α-TCP composite bone cement. Results show that α-TCP bone cement possesses excellent hydration and setting properties as well as high mechanical property. Comparison experiments show that BMP/ α-TCP composite bone cement has a stronger osteogenesis ability. The gross observation of the implant site does not exhibit any inflammation or necrosis. Histological analyses reveal that the material has good osteointegration with host bone, and new bone formation is detected within the materials, which are degrading. Strong osteogenesis ability of the composite is due to not only the excellent osteoconductive potential but also the osteoinductive potential contributed by active BMP releasing and the material degradation. Large skull defect could be well-healed by filling BMP/α-TCP composite bone cement. This novel material proves itself to be an absorbable and bioactive bone cement with an osteogenesis ability. Key words α-tricalcium phosphate (α-TCP) - bone morphogenetic proteins (BMP) - bone cement - osteogenesis - osteoinductivity - bone tissue engineering Funded by 863 Hi-Tech Research and Development Program of China (2002AA326080) and the Fund for Outstanding Young Teacher of the Education Ministry of China(2002123)

复合α-TCP透磷灰石骨水泥材料的生物相容性研究

目的:观察复合α-TCP透磷灰石骨水泥的生物相容性,为该复合骨水泥的临床应用提供动物组织学实验依据。方法:在β-TCP+MCPM骨水泥的基础上添加α-TCP,得到一种改进型透磷灰石骨水泥。以传统的透磷灰石骨水泥为对照组,对其进行体外溶血试验、热源试验、急性毒性试验、皮肤过敏试验、肌内植入试验。结果:α-TCP透磷灰石骨水泥的溶血率<5%,无热源性、无毒性、无皮肤过敏,植入肌肉后无明显炎症反应。结论:α-TCP的透磷灰石骨水泥具有良好的生物相容性和安全性,可作为体内骨替换材料。

Osteogenic lithium-doped brushite cements for bone regeneration

This study investigated the osteogenic performance of new brushite cements obtained from Li+-dopedβ-tricalcium phosphate as a promising strategy for bone regeneration.Lithium(Li+)is a promising trace element to encourage the migration and proliferation of adipose-derived stem cells(hASCs)and the osteogenic differentiation-related gene expression,essential for osteogenesis.In-situ X-ray diffraction(XRD)and in-situ 1H nuclear magnetic resonance(1H NMR)measurements proved the precipitation of brushite,as main phase,and monetite,indicating that Li+favored the formation of monetite under certain conditions.Li+was detected in the remaining pore solution in significant amounts after the completion of hydration.Isothermal calorimetry results showed an accelerating effect of Li+,especially for low concentration of the setting retarder(phytic acid).A decrease of initial and final setting times with increasing amount of Li+was detected and setting times could be well adjusted by varying the setting retarder concentration.The cements presented compressive mechanical strength within the ranges reported for cancellous bone.In vitro assays using hASCs showed normal metabolic and proliferative levels.The immunodetection and gene expression profile of osteogenic-related markers highlight the incorporation of Li+for increasing the in vivo bone density.The osteogenic potential of Li-doped brushite cements may be recommended for further research on bone defect repair strategies.

Metal-Doped Brushite Cement for Bone Regeneration

For the past several years,calcium phosphate cement was used in the biomedical applications.Outstanding biocompatibility,good bioactivity,self-setting qualities,minimum setting degree,appropriate toughness,and simple shape to accommodate any difficult geometry are among their most notable attributes.Calcium phosphate has some types and brushite is one of the most attractive mineral for bone repair application.Brushite is extensively employed in filling fractures and trauma treatments as a bone substituted material.This kind of material can potentially be used as a medicine delivery device.The replacement of metal,such as magnesium,zinc,and strontium ions,into the calcium phosphate structure is a major research topic these days.Brushite cement has low mechanical strength and quick setting rate.It is possible to produce biomaterials with higher mechanical characteristics.By adding metal that are great potential in controlling cellular density when included into biomaterials.As a result,it is a successful method to develop quite well regenerative medicine.This paper provides a detailed summary of the present achievements of metal-doped brushite cement for bone repair and healing process.The major purpose of this work is to give a simple but thorough analysis of current successes in brushite cement doped with Zn,Mg,Sr,and other ions as well as to highlight new advancements and prospects.The impact of metal replacement on cement physical and chemical properties,including microstructure,setting time,injectability,mechanical property,and ion release,is explored.The metal-doped cement has osteogenesis,angiogenesis,and antibacterial properties,as well as their prospective utility as drug carriers,also considered.

生物活性离子改性透钙磷石骨水泥的生物和理化性能

背景:透钙磷石骨水泥作为一种骨替代和骨填充材料,因其具有良好的生物相容性、骨传导性等优点,尤其是相比于其他磷酸钙类骨水泥具有更好的生物降解能力,在骨修复方面有重要应用价值,但也因其存在机械性能不足、固化反应快及注射性能差等问题的限制,目前一般只能用于非负重区骨的修复。目的:探讨生物活性离子(金属离子和非金属离子)改性透钙磷石骨水泥,以期拓展使用范围。方法:利用Pub Med、Science Direct和中国知网、万方数据库检索2018-2023年发表的文献,中文检索词为“金属离子,铁,铜,锶,镁,锌,非金属离子,改性,骨,透钙磷石骨水泥”;英文检索词为“metal ion,iron,Fe,copper,Cu,strontium,Sr,magnesium,Mg,zinc,Zn,non-metal ion,modification,bone,Brushite Cements”。通过阅读标题、摘要对所得文献进行初筛,排除重复及内容不相关文献,最终纳入64篇文献进行综述。结果与结论:(1)生物活性离子影响透钙磷石骨水泥水化反应过程,不同离子以离子取代的方式掺入透钙磷石骨水泥晶体结构中,改变了骨水泥晶体形态,引起凝固时间、注射性、抗压强度等理化性能改变。(2)离子改性的透钙磷石骨水泥因不同的晶体结构而产生不同的离子释放效应,不同类型离子具有如促血管生成/成骨、抗菌及抗肿瘤等特性而发挥作用,此外,透钙磷石骨水泥具有良好的生物降解性,这对于各离子性能的发挥具有极大优势。(3)不同离子改性透钙磷石骨水泥理化性能影响如下:铁、铜、锶、镁、锌、银、钴可延长凝固时间;锶、镁可提高注射性能;铜、锶、镁、银、硅可增强抗压强度;能同时改善透钙磷石骨水泥以上3种理化性能的离子有锶、镁;良好的理化性能是临床应用的前提,故离子改善透钙磷石骨水泥的凝固时间、注射性及抗压强度等性能对骨水泥的研究应用具有重要意义。(4)不同离子改性透钙磷石骨水泥生物性能影响如下:铜、锶、镁、锌、钴、锂、硅、硒具有促血管生成/成骨效应;铁、铜、镁、锌、银具有抗菌特性;镁离子具有抗炎特性;铜、硒具有抗肿瘤性。(5)综上所述,镁离子能改善透钙磷石骨水泥凝固时间、注射性和抗压强度,同时具有促新生血管生成/成骨及抗菌性,对合并感染的骨缺损治疗具有良好应用前景;此外,铜还具有抗肿瘤特性,因此铜离子在感染、肿瘤引起的骨缺损治疗方面有巨大潜力;只是目前相关研究仍处于基础研究阶段,不同离子掺杂浓度和合成条件等对透钙磷石骨水泥理化性能的影响需进一步探索,同时对于生物性能影响也需更长期的研究观察。

一种改进型透磷灰石骨水泥的初步研究

为了改善透磷灰石骨水泥的性能,使其更适用于临床,在传统透磷灰石骨水泥的基础上引入了α-TCP,测定了其理化性质,并进行了肌肉植入实验。α-TCP的引入延长了透磷灰石骨水泥的固化时间,提高了骨水泥的抗溃散能力,在一定程度上提高了透磷灰石骨水泥的pH值。植入肌肉实验对照表明,植入初期均有轻微炎症,含α-TCP骨水泥的炎症略轻,植入后期炎症反应均消失。

可注射载Co/Fe/Cu透钙磷石的制备及其抗菌性能

以含Co、Fe、Cu三种离子的磷酸钙为原料,制备载Co、Fe、Cu可注射透钙磷石骨水泥(CFC-Bru)。对CFC-Bru的固化时间、可注射、抗溃散、显微结构、降解性、抗菌性及细胞相容性等进行评价。结果表明:CFC-Bru固化时间约30 min;可注射系数达90%;抗溃散性良好;主晶型为透钙磷石和磷酸二氢钙;表面形貌于对照组变化显著。平板抑菌实验显示CFC-Bru对大肠杆菌、金色葡萄球菌和铜绿杆菌的抑菌直径分别达到了11、15和25 mm;肉汤抑菌实验表明,材料浓度为10 mg/mL时可完全抑制铜绿杆菌生长;为20 mg/mL时可完全抑制大肠杆菌生长;为50 mg/mL时可完全抑制金色葡萄球菌生长。细胞实验显示,CFC-Bru对人成骨肉瘤MG-63无细胞毒性;材料与细胞复合培养3和7天后,细胞可在其表面黏附,生长。该材料具有作为抗菌骨修复材料应用的潜力。

氟化钠对掺锶透钙磷石骨水泥成骨活性的影响

探究掺入不同质量氟化钠至锶透钙磷石骨水泥对理化性能及成骨活性的影响。以二水合磷酸氢钙与碳酸钙为原料制备β-磷酸三钙,以氯化锶为原料制备掺锶透钙磷石骨水泥,考察将氟化钠按不同质量比(0.5wt%、1.0wt%、1.5wt%)制备的掺氟锶透钙磷石骨水泥微观形貌、元素含量、物相形式及抗压强度,MTT法检测细胞增殖,并对其碱性磷酸酶(ALP)和骨保护素OPG mRNA表达进行检测。掺氟锶透钙磷石骨水泥抗压强度低于单一掺锶透钙磷石骨水泥(P>0.05),当氟化钠质量比为1.5wt%时促进MC3T3-E1的增殖及ALP效果最好,1.0wt%时显著促进OPG蛋白表达。

可注射载钽透钙磷石制备及其显影增强性能

背景:由于透钙磷石骨水泥与人体骨组织成分接近,造成二者在X射线下难以区分,不利于临床应用,但目前关注于提高透钙磷石显影性能的研究较少。目的:制备载钽透钙磷石骨水泥可注射材料,探究载钽对透钙磷石骨水泥可注射性、微观结构、显影性能、抗压强度、细胞相容性等的影响。方法:将β-磷酸钙与磷酸二氢钙以摩尔比为1∶1的比例混合,制备透钙磷石骨水泥基质粉体;向粉体中分别加入质量分数0%,1%,3%和5%的氧化钽,制成骨水泥固相;将骨水泥固相与含壳聚糖的柠檬酸固化液按比例混合,制备载不同量氧化钽的可注射透钙磷石骨水泥。检测4组骨水泥材料的固化时间、可注射性、微观形貌、晶相组成、化学基团、显影性能、抗压强度、可降解性、细胞相容性。结果与结论:①随着加入氧化钽比例的增加,骨水泥的固化时间逐渐延长,并保持了良好的抗溃散性与可注射性;②氧化钽的加入未明显改变透钙磷石骨水泥的晶相结构与基团组成,但显著改变了材料的表面形貌;③氧化钽的加入提升了透钙磷石骨水泥的抗压强度,但却降低了其降解速率;④随着加入氧化钽比例的增加,骨水泥材料的显影性能逐渐增强;⑤载不同量氧化钽的可注射透钙磷石骨水泥无细胞毒性,MG63细胞可在其表面正常黏附与增殖;⑥结果表明,载氧化钽的可注射透钙磷石骨水泥具有良好的可注射性、显影性能、抗压强度、可降解性及细胞相容性。