Calcium phosphate cements for bone engineering and their biological properties

Calcium phosphate cements （CPCs） are frequently used to repair bone defects. Since their discovery in the 1980s, extensive research has been conducted to improve their properties, and emerging evidence supports their increased application in bone tissue engineering. Much effort has been made to enhance the biological performance of CPCs, including their biocompatibility, osteoconductivity, osteoinductivity, biodegradability, bioactivity, and interactions with cells. This review article focuses on the major recent developments in CPCs, including 3D printing, injectability, stem cell delivery, growth factor and drug delivery, and pre- vascularization of CPC scaffolds via co-culture and tri-culture techniques to enhance angiogenesis and osteogenesis.

Macrophages in Degradation of Calcium Phosphate Compound Artificial Bone： An in vitro Study

The isolated mice peritoneal macrophages in degradation of calcium phosphate compound artificial bone - collagen/hydroxylapatite (CHA). hydroxylapatite (HA), beta-tricalcium phosphate (TCP) ceramics, have been studied by use of both Ca++, P concentration assay in cultured supernatant and scanning electron microscopy (SEM). The solubility of Ca++ . composition of materials increased more significantly when macrophages were inoculated than when macrophages were not seeded (P< 0.001), and it was shown that the ground materials were wrapped and phagocytized or resorbed extracellularly by macrophages under SEM, suggesting that macrophages could mediate the degradation of calcium phosphate compound artificial bone by phagocytizing and/or degrading extracellularly.

Preparation and Compressive Strength of Calcium Phosphate Bone Cement Containing N,O-carboxymethyl Chitosan

N, O-carboxymethyl chitosan （ CMCTS ）, a kind of biodegradable organic substance, was added to calcium phosphate bone cement （CPC） to prodnce a composite more similar in composition to human bone. The compressive strength of the new material was inereased by 10 times compared with conventional CPC.

Bone tissue engineering via nanostructured calcium phosphate biomaterials and stem cells

Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate （CAP） biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review： nanostructured calcium phosphate cement （CPC）; nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/ morphology, differentiation and in vivo bone regeneration. Several trends can be seen： （i） nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; （ii） the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; （iii） nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; （iv） combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and （v） cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments.

Augmentation of Pedicle Screw Fixation with Calcium Phosphate Cement

To determine whether a biodegradable calcium phosphate cement(CPC) provides significant augmentation of pedicle screw fixation or not,an in vitro biomechanical study was carried out to evaluate the biomechanical effect of CPC in the restoration and augmentation of pedicle screw fixation.Axial pullout test and cyclic bending resistance test were employed in the experiment,and polymethylmethacrylate (PMMA) was chosen as control.The results demonstrate that the pullout strengths following CPC restoration and augmentation are 74% greater on an average than those of the control group,but less than those of PMMA restoration group and augmentation group respectively (increased by 126% versus control).In cyclic bending resistance test,the CPC augmented screws are found to withstand a greater number of cycles or greater loading with less displacement before loosening,but the augmentation effect of PMMA is greater than that of CPC.

antagomir-30d转染BMSCs联合CPC支架材料的异位成骨作用

目的:构建antagomir-30d/种子细胞骨髓间充质干细胞(BMSCs)/磷酸钙骨水泥(CPC)复合物,并将该复合物植入裸鼠皮下,研究antagomir-30d促进体内骨形成的作用。方法:将转染有150 nmol/L antagomir-30d、NC的BMSCs以及未经转染的空白BMSCs转移到CPC支架进行孵育,后植入到BALB/c-nu裸鼠皮下,以此研究裸鼠异位成骨。术后2、4、8周分别取出植入体。2周时,取出植入体,提取RNA进行RT-PCR检测,分析成骨基因碱性磷酸酶(ALP)、骨钙素(OC)以及Runt相关转录因子2(RUNX2)mRNA表达情况。此外,4周和8周的植入体分别进行苦味酸品红组织学染色和组织形态学分析新骨形成的情况。结果:植入2周RT-PCR结果显示,各成骨基因mRNA水平的表达量中转染有antagomir-30d组最高,并显著高于另外2组(P<0.05)。组织学染色结果表明,植入后4周,antagomir-30d组有少量新骨形成,而另外2组则少有新骨形成。组织形态学分析显示,新骨面积百分比antagomir-30d组为1.28%±0.19%。植入后8周,3组均可见明显新骨形成,但antagomir-30d组新骨形成量明显大于NC组及空白对照组(P<0.05),各组新骨面积百分比分别为17.79%±1.15%,1.82%±0.53%,2.33%±0.52%。结论:antagomir-30d可诱导裸鼠体内异位成骨,antagomir-30d/BMSCs/CPC复合物有希望作为组织工程复合物用于颌骨骨缺损及其他类型骨缺损的修复。

Preparation of new tissue engineering bone-CPC/PLGA composite and its application in animal bone defects

To investigate the feasibility of implanting the biocomposite of calcium phosphate cement(CPC)/polylactic acid-polyglycolic acid(PLGA) into animals for bone defects repairing,the biocomposite of CPC/PLGA was prepared and its setting time,compressive strength,elastic modulus,pH values,phase composition of the samples,degradability and biocompatibility in vitro were tested.The above-mentioned composite implanted with bone marrow stromal cells was used to repair defects of the radius in rabbits.Osteogenesis was histomorphologically observed by using an electron-microscope.The results show that compared with the CPC,the physical and chemical properties of CPC/PLGA composite have some differences in which CPC/PLGA composite has better biological properties.The CPC/PLGA composite combined with seed cells is superior to the control in terms of the amount of new bones formed after CPC/PLGA composite is implanted into the rabbits,as well as the speed of repairing bone defects.The results suggest that the constructed CPC/PLGA composite basically meets the requirements of tissue engineering scaffold materials and that the CPC/PLGA composite implanted with bone marrow stromal cells may be a new artificial bone material for repairing bone defects because it can promote the growth of bone tissues.

Injectable bone cements:What benefits the combination of calcium phosphates and bioactive glasses could bring?

Out of the wide range of calcium phosphate(CaP)biomaterials,calcium phosphate bone cements(CPCs)have attracted increased attention since their discovery in the 1980s due to their valuable properties such as bioactivity,osteoconductivity,injectability,hardening ability through a low-temperature setting reaction and moldability.Thereafter numerous researches have been performed to enhance the properties of CPCs.Nonetheless,low mechanical performance of CPCs limits their clinical application in load bearing regions of bone.Also,the in vivo resorption and replacement of CPC with new bone tissue is still controversial,thus further improvements of high clinical importance are required.Bioactive glasses(BGs)are biocompatible and able to bond to bone,stimulating new bone growth while dissolving over time.In the last decades extensive research has been performed analyzing the role of BGs in combination with different CaPs.Thus,the focal point of this review paper is to summarize the available research data on how injectable CPC properties could be improved or affected by the addition of BG as a secondary powder phase.It was found that despite the variances of setting time and compressive strength results,desirable injectable properties of bone cements can be achieved by the inclusion of BGs into CPCs.The published data also revealed that the degradation rate of CPCs is significantly improved by BG addition.Moreover,the presence of BG in CPCs improves the in vitro osteogenic differentiation and cell response as well as the tissue-material interaction in vivo.

应用人造骨(CPC)修复骨缺损33例近期随访报告

[目的]自固化磷酸钙(CPC)为非陶瓷型羟基磷灰石类人造骨材料,它解决了长期困扰骨科的骨缺损修复这一难题。[方法]选用国产CPC修复骨缺损33例,年龄7~43岁,平均23.2岁。骨缺损部位为股骨上端、肱骨上端及股骨颈部、指骨、股骨下段、胫骨上端。骨缺损范围为1 cm×0.5 cm×0.5 cm^15 cm×3 cm×2 cm。骨缺损病因为动脉瘤样骨囊肿及纤维结构不良、非骨化性纤维瘤、骨瘤及骨软骨瘤、骨巨细胞瘤及组织性黄色肉芽肿。修复方法是彻底病灶清除,石炭酸、酒精灭活瘤细胞,彻底止血,CPC填充,封闭骨窗。[结果]CPC固化时间在15~30 m in,平均20 m in。临床使用后未见明显局部和全身不良反应,3个月后逐渐出现降解。随访最长30个月,最短13个月,平均22.5个月,随访X线片示CPC与宿主骨直接愈合,接触紧密无间隙、无脱落。[结论]CPC是骨缺损修复的理想材料。

CPC提高椎体钉固定强度的体外实验研究

目的探讨磷酸钙骨水泥(calcium phosphate cement,CPC)强化骨质疏松椎体钉后穿透单侧椎体皮质固定的可行性。方法选用新鲜成人尸体胸腰段骨质疏松标本24个,实验组为骨水泥(PMMA)和磷酸钙骨水泥灌注后椎体钉穿透单侧椎体皮质固定;对照组为无骨水泥强化,螺钉穿透双侧椎体皮质固定。应用螺钉拔出实验,记录螺钉最大拔出力并观察椎体破坏形态。结果三组拉出力值PMMA组(811.19±188.58N)、CPC组(541.89±101.44N)、对照组(374.21±77.66N)差异有显著性,P<0.01。分别增加122%±56%和50%±37%。对照组(8例)螺钉拔出破坏时均为螺钉抽出,在8例PMMA强化椎体中所有椎体均有不同程度骨折。而在8例CPC强化椎体中仅1例发生椎体骨折。结论应用CPC强化骨质疏松椎体钉简化手术步骤、增加手术安全性是可行的。

载辛伐他汀PLGA/CPC支架材料复合BMSCs修复大鼠颅骨缺损的实验研究

目的:探讨载辛伐他汀PLGA/CPC支架材料复合骨髓间充质干细胞(BMSCs)构建组织工程骨,修复大鼠颅骨临界尺寸骨缺损的可行性以及效果。方法:24只雄性大鼠随机均分为3组;在大鼠颅骨人字缝两侧各做一直径5mm的骨缺损。每组16个骨缺损再随机分为:载辛伐他汀PLGA/CPC/BMSCs(Brdu标记的BMSCs)组(n=4);载辛伐他汀PLGA/CPC组(n=4);单纯PLGA/CPC组(n=4)以及空白对照组(n=4)。术后4、8、12周取标本分别进行大体观察,HE染色及免疫组织化学染色来评价骨再生情况。结果:术后4、8、12周组织学观察表明载辛伐他汀PLGA/CPC/BMSCs组的成骨质量和速度明显优于其他3组,免疫组化结果显示载辛伐他汀PLGA/CPC/BMSCs组骨钙素(OC)阳性表达IOD值明显高于其他3组。结论:载辛伐他汀PLGA/CPC支架材料复合BMSCs可以诱导大鼠颅骨临界尺寸骨缺损内的新骨形成,成骨质量优于其他3组,而且可以明显缩短骨愈合时间。

不同配方CPC/DBM/rhBMP-2复合材料的抗压性能和超微结构特征

目的:探讨脱钙骨基质颗粒(DBM)/磷酸钙骨水泥(CPC)/重组人骨形成蛋白-2(rhBMP-2)复合材料的抗压性能和超微结构特征,找出该复合材料的最佳配方.方法:预制兔DBM,用吸附法将rhBMP-2与DBM复合后,再按不同的质量比与CPC复合.复合材料行体外抗压强度测定和扫描电镜观察.结果:DBM的质量比在0.2～0.4的范围内,复合材料中存在较多100μm以上的不规则裂隙.DBM的质量比≤0.1时,材料内部的大部分间隙<100μm.DBM的质量比≥0.5时,DBM和CPC丧失结合及塑型能力.随DBM质量比的增加,材料抗压极限强度递减,质量比为0.1,0.2,0.3,0.4的抗压极限强度分别为(8.12±0.79)MPa,(5.46±1.13)MPa,(5.13±1.18)Mpa和(1.49±0.61)MPa.各组数据经方差分析,差异具有统计学意义(P<0.05),其中质量比为0.2,0.3,两组比较差异无统计学意义(P>0.05),而(1.49±0.61)MPa小于人体松质骨的平均抗压强度.结论:随着DBM质量比的增加,孔隙越丰富而材料力学强度逐渐降低.DBM质量比为0.2～0.3的复合材料可用于修复低承重部位松质骨的骨缺损.

rhBMP-2/CPC对骨质疏松骨缺损的治疗作用的研究

目的探讨磷酸钙骨水泥复合rhBMP-2对骨质疏松骨缺损的治疗作用。方法以卵巢切除法对10只成年山羊去势，低钙膳食6个月后建立骨质疏松模型；手术去除每只动物L2、L4椎体部分侧方骨质，造成约5mm×10mm×10mm大小骨缺损，将动物随机分成2组，一组植入rhBMP-2／CPC作为实验组，另一组植入CPC作为对照组；术后1周、9周分别采用双能X线吸收骨密度仪检测手术椎体骨密度、CT三维成像观察骨缺损愈合情况，术后9周手术椎体进行生物力学检测，制作椎体不脱钙切片进行骨组织计硅学分析。结果术后骨密度榆测实验组与对照组间差异无显著性，但实验组在骨缺损愈合状况、骨小梁微结构及骨牛物力学性能等方面均显著优于对照组。结论应用rhBMP-2／CPC能改善局部骨质疏松，促进骨质疏松骨缺损愈合，达到治疗骨质疏松骨折骨缺损的目的。

不同载药方式对载三氧化二砷(As_2O_3)磷酸钙骨水泥(CPC)固化时间和抗压强度的影响

目的探讨不同载药方式对载三氧化二砷(arsenic trioxide,As2O3)磷酸钙骨水泥(calcium phosphate cement,CPC)固化时间和抗压强度的影响。方法将As2O3粉末与CPC粉末的混合物或载As2O3壳聚糖微球与CPC粉末的混合物加入固化液制备载药CPC。分别在不同固化液和固液比的条件下,测定载药CPC的固化时间及抗压强度。结果固化液为4%磷酸氢二钠(Na2HPO4)时,无论CPC直接荷载As2O3或复合载As2O3壳聚糖微球,CPC的固化时间都有明显延长。CPC直接荷载As2O3时,药物含量和固液比越大,其固化时间也越长。将固化液改进为含柠檬酸混合溶液后,复合载药微球的CPC的固化时间延长不明显。直接荷载As2O3使CPC的抗压强度有所下降,而固化液的改进和壳聚糖微球的复合则能显著提高CPC的抗压强度。结论相比直接荷载As2O3的CPC,复合载As2O3壳聚糖微球的CPC具有更好的生物力学性能,并在固化液改进后能维持适宜的固化时间。

优化配方的CPC/DBM/rhBMP-2复合材料在体内的超微结构和组织学特征

目的探讨磷酸钙骨水泥(CPC)/脱钙骨基质颗粒(DBM)/重组人骨形成蛋白-2(rhBMP-2)复合材料在骨内的超微结构和组织学特征,评价该材料的成骨性能。方法预制兔DBM,按0.2的DBM质量比制作CPC/DBM/rhBMP-2复合材料。将复合材料(A组,n=12)、CPC(B组,n=10)、医用骨水泥(C组,n=7)分别植入兔股骨髁部骨缺损,在植入后第6、12、24周取材进行组织学和扫描电镜观察。结果术后第6周,A组中复合材料-骨界面模糊,宿骨发出纤维连续通过界面,编织骨样结构开始向材料内部长入。第12周,A组中血管和成骨细胞在复合材料内部生长,产生新骨。第24周,A组中骨缺损已修复,形成骨性连接,材料大部分被新骨替代。B组术后第6周CPC-骨界限清晰,未见新骨向材料内部长入,第24周骨缺损部位仍为CPC填充,材料内部未见新骨出现。C组材料直至第24周尚未与宿骨形成任何连接。A组材料在成骨细胞活性、血管化程度和新骨生长速度方面均优于B组。结论将DBM质量比为0.2的复合材料植入骨缺损内可以促进细胞、血管、新骨的长入,且易降解及被自体骨替代。

自固化磷酸钙人工骨(CPC)修复骨肿瘤骨缺损的初步临床应用

目的评价自固化磷酸钙人工骨(CPC)治疗骨肿瘤骨缺损早期临床效果。方法对23例骨肿瘤患者行病灶刮除、国产CPC填塞修补术。患者年龄8～45岁,平均24.3岁。术后血液免疫学及X线检查,随访1～2年。结果CPC固化时间在15～30min,平均20min。临床使用后未见明显局部和全身不良反应,6个月后逐渐出现降解。随访X线片示CPC与宿主骨直接愈合,与原骨界面间接触紧密无间隙,骨缺损处解剖形状完全恢复。结论自固化磷酸钙人工骨(CPC)生物相容性良好,是肿瘤性骨缺损修复的理想材料。

自固化磷酸钙人工骨(CPC)载药妥布霉素体外抗菌活性评价

目的 :评价自固化磷酸钙骨水泥 ,(calciumphosphatecementCPC)载药妥布霉素的体外抗菌活性。方法 :载药妥布霉素的CPC浸入磷酸盐缓冲液中 ,其浸液用慢性骨髓炎常见的致病菌金黄色葡萄球菌、表皮葡萄球菌、大肠杆菌、绿脓杆菌进行药敏试验。结果 :这种载药系统的浸液在体外具有极强的抗菌活性 ,并且其抗菌活性至少能够持续 8周 ,而对照组 (不含妥布霉素的棒 )并没有抗菌作用。结论 :这表明这种载药体系在体外治疗骨髓炎感染的常见细菌是有效的。

钛框架/CPC/BMP复合人工骨的钙磷碳变化规律

为了解决磷酸钙骨水泥(CPC)/骨形态发生蛋白(BMP)植入体强度低的缺陷,提出一种钛框架/CPC/BMP复合结构的植入体,参考犬桡骨半月形断面及尺寸,利用计算机辅助设计与加工方法完成了相似形状的钛框架设计与制造,并将糊状CPC填充晾干后植入犬桡骨部位.通过动物实验,分析研究了钙磷碳的变化规律,得出了植入体钙磷碳变化模型.研究表明:植入体内的碳含量按二次抛物线增长,钙和磷的含量按线性规律递减,钙磷比则保持稳定;钛框架上有孔处的钙磷碳变化效率明显高于无孔处的变化效率.研究结果不仅为设计钛框架的形状提供了依据,而且证实了这种植入体的钛框架在不明显影响降解速度的条件下具有较好的支撑作用,因此扩大了CPC的临床应用范围.

自固化磷酸钙人工骨(CPC)治疗骨肿瘤骨缺损

目的 评价自固化磷酸钙人工骨 (CPC)治疗骨肿瘤骨缺损临床效果。方法 对 5 9例骨肿瘤患者在硬膜外麻醉或相应其他麻醉下行病灶搔刮、CPC填塞修补术 ;术后血液免疫学及X线或CT检查 ,随访 1～ 2 .5年。结果 骨缺损破坏区CPC与宿主骨直接愈合 ;CPC在一年多完全转化成宿主骨 ,相融性好 ,与原骨界面间无间隙、无分离 ,骨缺损处解剖形状完全恢复。肿瘤无复发。结论 自固化磷酸钙人工骨 (CPC)细胞生物相容性良好 。

髓芯减压联合骨形成蛋白活性诱导棒植入术治疗早期股骨头坏死的效果

目的探讨髓芯减压联合骨形成蛋白(BMP)活性诱导棒植入术治疗早期股骨头坏死的效果。方法回顾性分析2018年6月至2022年6月收治的116例早期股骨头坏死患者,按照不同的手术方式分为髓芯减压联合BMP活性诱导棒组(BMP组)和同种异体骨组。BMP组60例,采用髓芯减压联合BMP活性诱导棒植入术治疗。同种异体骨组56例,采用髓芯减压联合同种异体骨打压植骨术治疗。对比两组患者术前、术后6个月和术后1年的髋关节Harris评分、疼痛视觉模拟评分(VAS)的差异,并对患者术后1年疗效和股骨头存活率进行比较。结果所有患者均获得随访,两组患者术前VAS评分、Harris评分差异无统计学意义(P>0.05),术后6个月、1年时两组患者VAS评分、Harris评分均显著改善,且BMP组优于同种异体骨组,差异有统计学意义(P<0.05)。术后1年时,BMP组Harris髋关节评分优良率高于同种异体骨组,差异有统计学意义(P<0.05);BMP组股骨头存活率高于同种异体骨组,差异有统计学意义(P<0.05)。结论髓芯减压联合BMP活性诱导棒植入术治疗早期股骨头坏死早期具有疗效,能够加速诱导新骨生成,提高新骨质量,为股骨头提供生物力学支撑,有效避免股骨头塌陷,且生物相容性好、能够在体内降解吸收,值得在临床上推广。