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.

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.

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.

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.

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.

Reconstruction of orbital defect in rabbits with composite of calcium phosphate cement and recombinant human bone morphogenetic protein-2

Background Calcium phosphate cement （CPC） is a biocompatible and osteoconductive bone substitute, and recombinant human bone morphogenetic protein-2 （rhBMP-2） has strong osteoinductibility, therefore we developed a composite bone substitute with CPC and rhBMP-2 and evaluate its reconstruction effect in rabbit orbital defect.Methods Thirty-six rabbits were randomly divided into two groups and a 5 mmx5 mmx2 mm bone defect in the infraorbital rim was induced by surgery in each orbit （72 orbits in all）. The orbital defects were treated with pure CPC or composite of CPC and rhBMP-2. The osteogenesis ability of different bone substitute was evaluated by gross observation, histological examination, histomorphometrical evaluation, compressive load-to-failure testing, and scanning electron microscope （SEM）.Results Gross observation showed that both bone substitutes were safe and effective for reconstruction of orbital defect. However, histological examination, histomorphometrical evaluation and SEM showed that CPC/rhBMP-2 group had faster speed in new bone formation and degradation of substitute material than CPC group. Compressive load-to-failure testing showed that CPC/rhBMP-2 group had stronger compressive strength than CPC group at every stage with significant difference （P ＜0.05）.Conclusion Composite of CPC/rhBMP-2 is an ideal bioactive material for repairing orbital defect, with good osteoconductibility and osteoinductibility.

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。

Injectable nanofiber-reinforced bone cement with controlled biodegradability for minimally-invasive bone regeneration

Injectable materials show their special merits in regeneration of damaged/degenerated bones in minimally-invasive approach.Injectable calcium phosphate bone cement(CPC)has attracted broad attention for its bioactivity,as compared to non-degradable polymethyl methacrylate cement.However,its brittleness,poor anti-washout property and uncontrollable biodegradability are the main challenges to limit its further clinical application mainly because of its stone-like dense structure and fragile inorganic-salt weakness.Herein,we developed a kind of injectable CPC bone cement with porous structure and improved robustness by incorporating poly(lactide-co-glycolic acid)(PLGA)nanofiber into CPC,with carboxymethyl cellulose(CMC)to offer good injectability as well as anti-wash-out capacity.Furthermore,the introduction of PLGA and CMC also enabled a formation of initial porous structure in the cements,where PLGA nanofiber endowed the cement with a dynamically controllable biodegradability which provided room for cell movement and bone ingrowth.Inter-estingly,the reinforced biodegradable cement afforded a sustainable provision of Ca^(2+)bioactive components,together with its porous structure,to improve synergistically new bone formation and osteo-integration in vivo by using a rat model of femur condyle defect.Further study on regenerative mechanisms indicated that the good minimally-invasive bone regeneration may come from the synergistic enhanced osteogenic effect of calcium ion enrichment and the improved revascularization capacity contributed from the porosity as well as the lactic acid released from PLGA nanofiber.These results indicate the injectable bone cement with high strength,anti-washout property and controllable biodegradability is a promising candidate for bone regeneration in a minimally-invasive approach.

弯角椎体成形聚甲基丙烯酸甲酯骨水泥注射治疗骨质疏松性椎体压缩骨折的临床研究

目的:研究弯角椎体成形(PCVP)聚甲基丙烯酸甲酯骨水泥(PMMA)注射治疗骨质疏松性椎体压缩骨折(OVCF)的临床效果。方法:选择2020年1月—2022年5月江西省新余市北湖医院收治的OVCF患者84例,按随机数字表法将其分为两组。两组患者均行PCVP治疗,磷酸钙骨水泥(CPC)组采用CPC作为填充物,PMMA组采用PMMA作为填充物。比较两组伤椎椎体前缘高度、Cobb角、疼痛程度、术中透视次数、骨水泥灌注量及渗漏率。结果:术后,PMMA组视觉疼痛模拟评分(VAS)低于CPC组(P<0.05);两组间伤椎椎体前缘高度、Cobb角、术中透视次数、骨水泥灌注量及骨水泥渗漏率差异无统计学意义(P>0.05)。结论:在PCVP术中,PMMA或CPC注射治疗OVCF均可恢复椎体高度,纠正后凸畸形,但PMMA注射治疗患者近期疼痛缓解效果更佳,且不增加骨水泥渗漏发生率。

磷酸钙骨水泥的体内外显影性能优化

为了优化磷酸钙骨水泥(CPC)的体内显影性能,便于临床医师通过X射线辅助注射,从而防止材料在宿主体内的不当移位,本研究通过引入临床安全性高、适用范围广的显影剂——欧乃派克,提升CPC在X光下的衬度。分别考察了不同显影剂添加量下,CPC在离体骨内、大型动物体内的显影效果。发现60%含量下的欧乃派克能基本满足临床对骨修复材料衬度的要求。该研究证明欧乃派克能显著提升CPC的显影性,有助于进一步提升其临床应用价值,为开发功能更完善的可注射骨修复材料提供了实验依据。

Bioactive calcium and mangnesium phosphate bone adhesive for enhanced vascularization and bone regeneration

Bone adhesive is a promising material for the treatment of bone fractures,which is helpful for the fast and effective reduction and fixation of broken bones.However,the existing adhesives bond weakly to bone tissues,and are non-absorbable,or hard to cure under wet conditions.Herein,inspired by the cement-based adhesive used in the industry field,we report a bioactive calcium and magnesium phosphate bone adhesive(MPBA)with the properties of facile preparation,robust adhesion,and bioactive.MPBA is equipped with similar strength to cancellous bones and shows reliable bonding performance for various interfaces,such as Ti6Al4V,Al2O3,and poly(ether-ether-ketone).MPBA achieves excellent bonding ability for the above interfaces with the bonding strengths of 2.28±0.47,2.32±0.15,and 1.44±0.38 MPa,respectively.Besides,it also shows reliable fixation ability for bovine bone surfaces.The bonding behavior to materials and bones suggests that MPBA could be used for both fracture treatment and implant fixation.Meanwhile,MPBA possesses good biological activity,which could promote the vascularization process and osteogenic differentiation.Finally,in vivo experiments confirmed MPBA can effectively restore bone strength and promote bone regeneration.

Local treatment of osteoporosis with alendronate-loaded calcium phosphate cement

Background A new treatment strategy is to target specific areas of the skeletal system that are prone to clinically significant osteoporotic fractures.We term this strategy as the ＂local treatment of osteoporosis＂.The study was performed to investigate the effect of alendronate-loaded calcium phosphate cement （CPC） as a novel drug delivery system for local treatment of osteoorosis.Methods An in vitro study was performed using CPC fabricated with different concentrations of alendronate （ALE,0,2,5,10 weight percent （wt％））.The microstructure,setting time,infrared spectrum,biomechanics,drug release,and biocompatibility of the composite were measured in order to detect changes when mixing CPC with ALE.An in vivo study was also performed using 30 Sprague-Dawley rats randomly divided into six groups：normal,Sham （ovariectomized （OVX） ＋ Sham）,CPC with 2％ ALE,5％ALE,and 10％ ALE groups.At 4 months after the implantation of the composite,animals were sacrificed and the caudal vertebrae （levels 4-7） were harvested for micro-CT examination and biomechanical testing.Results The setting time and strength of CPC was significantly faster and greater than the other groups.The ALE release was sustained over 21 days,and the composite showed good biocompatibility.In micro-CT analysis,compared with the Sham group,there was a significant increase with regard to volumetric bone mineral density （BMD） and trabecular number （Tb.N） in the treated groups （P ＜0.05）.Trabecular spacing （Tb.Sp） showed a significant increase in the Sham group compared to other groups （P ＜0.01）.However,trabecular thickness （Tb.Th） showed no significant difference among the groups.In biomechanical testing,the maximum compression strength and stiffness of trabecular bone in the Sham group were lower than those in the experimental groups.Conclusions The ALE-loaded CPC displayed satisfactory properties in vitro,which can reverse the OVX rat vertebral trabecular bone microarchitecture and biomechanical properties in vivo.

Sudoku of porous, injectable calcium phosphate cements – Path to osteoinductivity

With the increase of global population,people’s life expectancy is growing as well.Humans tend to live more active lifestyles and,therefore,trauma generated large defects become more common.Instances of tumour resection or pathological conditions and complex orthopaedic issues occur more frequently increasing necessity for bone substitutes.Composition of calcium phosphate cements(CPCs)is comparable to the chemical structure of bone minerals.Their ability to self-set and resorb in vivo secures a variety of potential applications in bone regeneration.Despite the years-long research and several products already reaching the market,finding the right properties for calcium phosphate cement to be osteoinductive and both injectable and suitable for clinical use is still a sudoku.This article is focused on injectable,porous CPCs,reviewing the latest developments on the path toward finding osteoinductive material,which is suitable for injection.

Effect of surgical factors on the augmentation of cementinjectable cannulated pedicle screw fixation by a novel calcium phosphate-based nanocomposite

Bone cement-augmented pedicle screw system demonstrates great efficacy in spinal disease treatments. However, the intrinsic drawbacks associated with clinically used polymethylmethacrylate (PMMA) cement demands for new bone cement formulations. On the basis of our previous studies, a novel injectable and biodegradable calcium phosphate-based nanocomposite (CPN) for the augmentation of pedicle screw fixation was systematically evaluated for its surgical feasibility and biomechanical performance by simulated and animal osteoporotic bone models, and the results were compared with those of clinical PMMA cement. ASTM-standard solid foam and open-cell foam models and decalcified sheep vertebra models were employed to evaluate the augmentation effects of CPN on bone tissue and on the cement-injected cannulated pedicle screws (CICPs) placed in osteoporotic bone. Surgical factors in CICPs application, such as injection force, tapping technique, screw diameter, and pedicle screw loosening scenarios, were studied in comparison with those in PMMA. When directly injected to the solid foam model, CPN revealed an identical augmentation effect to that of PMMA, as shown by the similar compressive strengths (0.73 ± 0.04 MPa for CPN group vs. 0.79 ± 0.02 MPa for PMMA group). The average injection force of CPN at approximately 40-50 N was higher than that of PMMA at approximately 20 N. Although both values are acceptable to surgeons, CPN revealed a more consistent injection force pattern than did PMMA. The dispersing and anti-pullout ability of CPN were not affected by the surgical factors of tapping technique and screw diameter. The axial pullout strength of CPN evaluated by the decalcified sheep vertebra model revealed a similar augmentation level as that of PMMA (1351.6 ± 324.2 N for CPN vs. 1459.7 ± 304.4 N for PMMA). The promising results of CPN clearly suggest its potential for replacing PMMA in CICPs augmentation application and the benefits of further study and development for clinical uses.

Tissue-engineered calcium phosphate cement in rabbit femoral condylar bone defects

Background Calcium phosphate cement （CPC） is a favorable bone-graft substitute, with excellent biocompatibility and osteoconductivity. However, its reduced osteoinductive ability may limit the utility of CPC. To increase its osteoinductive potential, this study aimed to prepare tissue-engineered CPC and evaluate its use in the repair of bone defects. The fate of transplanted seed cells in vivo was observed at the same time. Methods Tissue-engineered CPC was prepared by seeding CPC with encapsulated bone mesenchymal stem cells （BMSCs） expressing recombinant human bone morphogenetic protein-2 （rhBMP-2） and green fluorescent protein （GFP）. Tissue-engineered CPC and pure CPC were implanted into rabbit femoral condyle bone defects respectively. Twelve weeks later, radiographs, morphological observations, histomorphometrical evaluations, and in vivo tracing were performed. Results The radiographs revealed better absorption and faster new bone formation for tissue-engineered CPC than pure CPC. Morphological and histomorphometrical evaluations indicated that tissue-engineered CPC separated into numerous small blocks, with active absorption and reconstruction noted, whereas the residual CPC area was larger in the group treated with pure CPC. In the tissue-engineered CPC group, in vivo tracing revealed numerous cells expressing both GFP and rhBMP-2 that were distributed in the medullar cavity and on the surface of bony trabeculae. Conclusion Tissue-engineered CPC can effectively repair bone defects, with allogenic seeded cells able to grow and differentiate in vivo after transplantation.

Preparation, Fundamental Characteristics and Biosafety Evalution of Compound rhBMP-2/CPC

To stndy the fundamental characteristics and biosafety of the compound bone morphogenetic protein （ BMP ） and rhBMP- 2/CPC , and to provide a theoretical basis for the compound biologically active artificial bone made of calcium phosphate cement （CPC） and bone morphogenetic protein, simplex CPC was taken as the control group, and the compound with the blending ratio of 1g CPC to 5mg rhBMP-2 was taken as the experimentation group to determine the setting time, compressive, strength, acute toxicological and sub acute toxicological properties. The osteogenic characteristic of compound rhBMP- 2/CPC was measured by making animal model of radio discontinuous defect. The setting time of the two groups meets the clinical requirements, and the compressive strength of the solidified body of bone cement increases along with increasing the immersion time. Compound rhBMP- 2/ CPC has a favorable ostengenic characteristic for animal model of radio discontinuous deject. The fundamental characteristics of the compound rhBMP- 2 phosphate bone cement are basically the same as that of CPC, and also have a favorable biosafety and osteogenesis.

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。

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.

Factors influencing the drug release from calcium phosphate cements

Thanks to their biocompatibility,biodegradability,injectability and self-setting properties,calcium phosphate cements(CPCs)have been the most economical and effective biomaterials of choice for use as bone void fillers.They have also been extensively used as drug delivery carriers owing to their ability to provide for a steady release of various organic molecules aiding the regeneration of defective bone,including primarily antibiotics and growth factors.This review provides a systematic compilation of studies that reported on the controlled release of drugs from CPCs in the last 25 years.The chemical,compositional and microstructural characteristics of these systems through which the control of the release rates and mechanisms could be achieved have been discussed.In doing so,the effects of(i)the chemistry of the matrix,(ii)porosity,(iii)additives,(iv)drug types,(v)drug concentrations,(vi)drug loading methods and(vii)release media have been distinguished and discussed individually.Kinetic specificities of in vivo release of drugs from CPCs have been reviewed,too.Understanding the kinetic and mechanistic correlations between the CPC properties and the drug release is a prerequisite for the design of bone void fillers with drug release profiles precisely tailored to the application area and the clinical picture.The goal of this review has been to shed light on these fundamental correlations.

磷酸钙骨水泥载药核心的块型重组合异种骨体内缓释及修复兔长段感染性骨缺损的研究

目的 寻找抗感染的块型重组合异种骨制备工艺简便的药物缓释方式 ,一期修复感染性长段骨缺损。方法 将载药的自凝固磷酸钙骨水泥 (calcium phosphate cement,CPC)分 4柱置入块型重组合异种骨 (massivereconstituted bone xenograft,MRBX) ,制成 CPC载药核心的块型重组合异种骨 (CPC- MRBX)。用 18只成年大白兔行体内缓释实验。按照术后 1、2、5、10、15、2 0、2 5、30和 35 d分为 9组 ,每组 2只。将 CPC- MRBX植入兔骶棘肌肌袋中 ,按各时间点测定动物的血药浓度 ,并从植骨处取软组织测定植骨区周围的药物浓度。动物模型采用兔股骨感染长段骨缺损模型 ,共 4 0只。外固定架位于膝上 1.5～ 2 .0 cm ,邻近截骨处的固定针距离截骨端 0 .5～ 0 .8cm,针道方向垂直于股骨前外侧面 ,并在植入材料后适当加压。实验组 (n=2 5 )用 CPC- MRBX修复 ,对照组 (n=15 )将自体骨段回植。术后观察动物饮食、活动和伤口的变化 ;在 4、8、16和 2 4周分别行影像学、组织学观察两组骨愈合情况。 结果 CPC- MRBX的制备过程在常温、常压下顺利完成 ,体内药物缓释实验显示组织中有效药物浓度可以维持 30 d左右 ,同时血药浓度无明显增高。动物模型的固定方法可靠 ,术后实验组动物一般情况可。术后 4 d动物能够正常站立 ,X线片示?