Methods for improving drug release from poly(methyl)methacrylate bone cement

Poly(methylmethacrylate) (PMMA) is a widely used material with both dental and orthopaedic applications. The acrylic cement is produced by the combination of polymethylacrylate beads with methylmethacrylate monomer. After polymerisation, a heterogeneous and porous matrix is formed which can be used to deliver therapeutic agents. In this work, the release of antibiotic, growth hormone and serum albumin is demonstrated. The mechanism is similar for all agents; a rapid release followed by a slow continuous release. The quantity of drug released depends upon the formulation of both the PMMA and the drug. The polymer-to-monomer ratio can greatly affect the ratio of drug release; increased polymer-to-monomer ratio leads to increased release of antibiotic. Optimum release is achieved if a crystalline formulation of the drug is used rather than a fine powder. Experimental methods to improve the drug release performance of bone cements are presented.     

Antibiotic-releasing porous polymethylmethacrylate/gelatin/antibiotic constructs for craniofacial tissue engineering

An antibiotic-releasing porous polymethylmethacrylate (PMMA) construct was developed to maintain the bony space and prime the wound site in the initial step of a two-stage regenerative medicine approach toward reconstructing significant bony or composite craniofacial tissue defects. Porous PMMA constructs incorporating gelatin microparticles (GMPs) were fabricated by the sequential assembly of GMPs, the antibiotic colistin, and a clinically used bone cement formulation of PMMA powder and methylmethacrylate liquid. PMMA/gelatin/antibiotic constructs with varying gelatin incorporation and drug content were investigated to elucidate the relationship between material composition and construct properties (porosity and drug release kinetics). The porosity of PMMA/gelatin/antibiotic constructs ranged between 7.6 ± 1.8% and 38.4 ± 1.4% depending on the amount of gelatin incorporated and the drug solution added for gelatin swelling. The constructs released colistin over 10 or 14 days with an average release rate per day above 10 μg/ml. The porosity and in vitro colistin release kinetics of PMMA/gelatin/antibiotic constructs were tuned by varying the material composition and fabrication parameters. This study demonstrates the potential of gelatin-incorporating PMMA constructs as a functional space maintainer for both promoting tissue healing/coverage and addressing local infections, enabling better long-term success of the definitive regenerated tissue construct.     

Optimized elution of daptomycin from polymethylmethacrylate beads

We demonstrate that xylitol can be added to polymethylmethacrylate (PMMA) bone cement to enhance the elution of daptomycin in terms of both the peak and sustained release of antibiotic. We also demonstrate that a PMMA-xylitol formulation optimized for daptomycin can be used to enhance the elution of both vancomycin and gentamicin.     

Contrasting effects of physical wear on elution of two antibiotics from orthopedic cement

The use of antibiotics as a supplement to bone cement for the purposes of providing a local release of antibiotics is common practice in arthroplasty surgery and the kinetics of elution of the antibiotics in such systems have been investigated previously. However, in these previous studies no account was taken of the potential effects that wear may have on the elution kinetics of the antibiotic. Here, we have modified an existing wear testing rig to allow the simultaneous study of the elution kinetics of bone cement samples containing antibiotics being subjected to immersion only and immersion and conjoint wear. The results show contrasting effects with two commonly used antibiotics. Bone cement containing daptomycin showed no substantial change in antibiotic elution due to wear, while cement containing gentamicin (the most commonly used antibiotic in this application) in contrast demonstrated a substantial reduction in the rate of antibiotic elution when wear was applied. Scanning electron microscopy revealed a possible explanation for these diverse results, due to wear-induced "sealing" of the surface in conjunction with the crystal morphology of the antibiotic.     

In vitro activities of daptomycin-, vancomycin-, and teicoplanin-loaded polymethylmethacrylate against methicillin-susceptible, methicillin-resistant, and vancomycin-intermediate strains of Staphylococcus aureus

The objective of this study was to evaluate the antibacterial effects of polymethylmethacrylate (PMMA) bone cements loaded with daptomycin, vancomycin, and teicoplanin against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-intermediate Staphylococcus aureus (VISA) strains. Standardized cement specimens made from 40 g PMMA loaded with 1 g (low-dose), 4 g (middle-dose) or 8 g (high-dose) antibiotics were tested for elution characteristics and antibacterial activities. The patterns of release of antibiotics from the cement specimens were evaluated using in vitro broth elution assay with high-performance liquid chromatography. The activities of broth elution fluid against different Staphylococcus aureus strains (MSSA, MRSA, and VISA) were then determined. The antibacterial activities of all the tested antibiotics were maintained after being mixed with PMMA. The cements loaded with higher dosages of antibiotics showed longer elution periods. Regardless of the antibiotic loading dose, the teicoplanin-loaded cements showed better elution efficacy and provided longer inhibitory periods against MSSA, MRSA, and VISA than cements loaded with the same dose of vancomycin or daptomycin. Regarding the choice of antibiotics for cement loading in the treatment of Staphylococcus aureus infection, teicoplanin was superior in terms of antibacterial effects.     

Release of gentamicin and vancomycin from temporary human hip spacers in two-stage revision of infected arthroplasty

AIM: Evaluation of the delivery of gentamicin and vancomycin from polymethylmethacrylate (PMMA) spacers before and after implantation for the treatment of total hip replacement infections. METHODS: Twenty industrially produced spacers containing gentamicin (1.9%) were utilized. Vancomycin (2.5%) mixed with PMMA cement was used to fill holes drilled in the cement of 14 of the 20 spacers immediately before implantation. The spacers were removed from 20 patients 3-6 months after implantation and then immersed in phosphate buffer at 37 degrees C for 10 days. Antibiotic concentrations were determined by fluorescence polarization immunoassay. RESULTS: Gentamicin and vancomycin were still present in all the spacers removed from the patients. The release of gentamicin alone and in combination with vancomycin was in the range 0.05%-0.4% of the initial amount present, whereas the release of vancomycin was in the range 0.8%-3.3%. The release kinetics showed a similar pattern for both drugs. After a high initial release of drug, a reduced, but constant, elution was observed over the next few days. CONCLUSIONS: The delivery of gentamicin and vancomycin from PMMA cement was high initially, with sustained release over several months. Incorporation of vancomycin into the surface of the spacers permitted spacers to be prepared with multiple antibiotics present and without adversely affecting the release kinetics of the agents. The gentamicin-vancomycin combination shows potential for the treatment of infection following total hip replacement in specific patients.     

Understanding drug release from poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) gels.

Experimental and mathematical studies were performed to understand the release mechanism of small molecular weight compounds from poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) polymer gels (trademarked Pluronic by BASF Corp.) of various concentrations. Studies of the diffusion coefficient of solutes in the polymer gels were performed using a novel technique to predict movement of drugs within the gel as release occurs. Studies were also performed to determine the diffusion coefficient of water in the polymer gel, as it is this parameter that controls the dissolution rate of the polymer, and in turn, the drug release rate. A model was formulated and solved numerically to determine the controlling release mechanism. By parameter modification, this algorithm for determining the overall mass of drug released from a drug loaded gel can be used for a number of drugs and for a wide range of initial polymer concentrations. Drug release data were obtained with a novel experimental setup and were used to verify the accuracy of the overall solution of the model. The results of the model indicate that although the rate of polymer dissolution ultimately controls the drug release, about 5% of the release is due to diffusion at the gel/liquid interface, giving rise to a slightly non-linear release. It was also found that agitation speed greatly affects the dissolution rates of these polymer gels.     

两种抗生素复合骨水泥体外药物释放的规律

目的：观察抗生素复合骨水泥体外释药规律，以及有效的检测方法。 方法：实验于2005-10／2006—01在解放军第四二五医院外二科完成。将骨水泥固体相分别与万古霉素和庆大霉素按照1：25（g：mg）的比例混合，再按2g：10mL：50mg（固相：液相：抗生素）比例加入骨水泥液相，搅拌成糊状，注入模具中铸型，采用K—B制片扩散法，对两种抗生素各浓度梯度的抑菌环直径平均值与药物浓度之间的关系进行相关分析。以金黄色葡萄球菌为敏感细菌，检测1，3，5，7，10，14，22，26，30d9个时间点抗生素骨水泥制件浸泡液，观察骨水泥中抗生素的释放效果，并根据结果绘制释药曲线，计算释药效率。 结果：①万古霉素浓度-抑菌环直径标准方程Y=2．71＋5．59X（r=0．989），庆大霉素浓度-抑菌环直径Y=0．17＋7．87X（r=0．977）。②骨水泥早期爆发释药，中期平稳释药，26d释药浓度大于对应细菌最低抑菌浓度。骨水泥释药复合Higuchi方程。30d抗生素释放率分别是83．73％和89．38％。 结论：①骨水泥具有缓释模型特点，为感染性人工髋关节翻修术中的应用提供实验依据。②K—B法可简单有效检测抗生素骨水泥的释药效果。     

Cultured skin loaded with tetracycline HCl and chloramphenicol as dermal delivery system: mathematical evaluation of the cultured skin containing antibiotics.

Dermal patches consisting of cultured human skin with antibiotics, which have a protective effect on wound skin as well as a preventative effect on second infection of the skin, were prepared and mathematically analyzed as a new drug delivery system (DDS) that can be applied to serious skin defects such as severe burns. In the present study, a three-dimensional cultured human skin model (living skin equivalent-high, LSE-high) was used as a cultured skin membrane and tetracycline HCl (TC-HCl) and chloramphenicol (CP) were used as antibiotics. At first, antibiotics were entrapped in the LSE-high from the dermal side through culture medium in order to obtain a drug-loaded LSE-high. The antibiotic release from the drug-loaded LSE-high was then examined and the resulting release data were used to calculate the effective diffusion coefficient of the antibiotics (D(LSE)) and initial loading concentration of the antibiotics (C0) in the LSE-high. The release profile of TC-HCl was represented by general diffusion-limited kinetics, whereas an initial burst effect was found in the release profile of CP. Therefore, the burst effect was taken into account for analyzing the release profile of CP. Stripped skin excised from hairless rats was used as a wound model, and the antibiotic permeation through the skin from aqueous solution was examined and evaluated using differential equations for Fick's second law of diffusion to obtain the effective diffusion coefficient of the antibiotics in the wound skin (D(skin)). Furthermore, the antibiotic permeation profile through the excised stripped skin from the drug-loaded LSE-high was measured and theoretically evaluated by Fick's second law of diffusion with previously obtained parameters (C0, D(LSE), D(skin)) using a newly constructed two- or three-layered diffusion model. The calculated concentrations of TC-HCl and CP in the upper epidermis of the model wound skin were over their minimum inhibitory concentration (MIC) for several hours against various bacteria, suggesting that this dosage system is useful for the treatment of severe burns. In addition, the present analytical method and diffusion model, with the drug-loaded LSE-high and stripped rat skin, are useful tools for evaluating this new DDS.     

In vitro evaluation of antibiotic diffusion from antibiotic-impregnated biodegradable beads and polymethylmethacrylate beads.

Antibiotic-impregnated beads are used in the dead bone space following debridement surgery to deliver local, high concentrations of antibiotics. Polymethylmethacrylate (PMMA), 2,000-molecular-weight (MW) polylactic acid (PLA), Poly(DL-lactide)-coglycolide (PL:CG; 90:10, 80:20, and 70:30), and the combination 2,000-MW PLA-70:20 PL:CG were individually mixed with clindamycin, tobramycin, or vancomycin. Beads were placed in 1 ml of phosphate-buffered saline (PBS) and incubated at 37 degrees C. The PBS was changed daily, and the removed PBS samples were stored at -70 degrees C until the antibiotic in each sample was determined by microbiological disk diffusion assay. Nondissolving PMMA beads with tobramycin and clindamycin had concentrations well above breakpoint sensitivity concentrations (i.e., the antibiotic concentrations at the transition point between bacterial killing and resistance to the antibiotic) for more than 90 days, but vancomycin concentrations dropped by day 12. ALl PLA, PL:CG, and the 2,000-MW PLA-70:30 PL:CG biodegradable beads release high concentrations of all the antibiotics in vitro for the period of time needed to treat bone infections (i.e., 4 to 8 weeks). Antibiotic-loaded PLA and PL:CG beads have the advantage of better antibiotic elution and the ability to biodegradable (thereby averting the need for secondary surgery for bead removal) compared to the PMMA beads presently used in the clinical setting.     

Strength of cement-metal interfaces in fatigue: comparison of smooth, porous and precoated specimens

Radiographic follow-up studies of cemented total hip arthroplasty have shown that failure of the cement-metal interface of the femoral component is as high as 25% at 10 years. Recent analyses of clinically successful cemented femoral components obtained in toto with the surrounding cement and femurs after many years of in-vivo service have suggested that the mechanism of the initiation of failure of fixation of cemented femoral components is debonding at the cement-metal interface. Since this critical interface is subjected primarily to cyclic loading, the evaluation of different surface preparations should be studied in fatigue, not static testing. In the current study, several contemporary methods for increasing the strength of the cement-metal interface were evaluated by testing the interfacial fatigue pushout strength under varying conditions of cyclic loading. The effect of a smooth 'implant finish' surface, a surface coated with polymethylmethacrylate (PMMA precoated surface), a combination of a textured surface with PMMA precoat, and a porous titanium mesh coated surface were examined. Precoating the metal with a thin film of PMMA significantly increased the number of compressive fatigue loading cycles required for failure of the cement-metal interface under cyclic loading compared to a smooth, uncoated surface. Adding indentations to the surface and then precoating with PMMA further significantly increased the fatigue life of the cement-metal interface. The strongest interface in fatigue was the titanium fibermesh-cement interface.     

In vitro testing of antimicrobial activity of bone cement

The purpose of this study was to establish a reliable and cost-effective microplate proliferation assay for in vitro antimicrobial testing of bone cement samples. Cement samples devoid of antimicrobial agents, loaded with 2% gentamicin or with different concentrations of high-porosity silver, were incubated in a 96-well microplate with several staphylococcal, Pseudomonas aeruginosa, and Enterococcus faecium isolates exhibiting different susceptibilities to gentamicin. After being rinsed, the samples were brought into a soy medium in which adherent cells on the cement surface either were killed by the antimicrobial surface or started to release clonal counterparts. The medium was monitored in real time by recording a time proliferation curve for each well. Microplate testing revealed no antibacterial effect of plain bone cement. The antibacterial activity of gentamicin-loaded bone cement was shown by the microplate test to depend on the gentamicin susceptibilities of the strains. The effect of high-porosity silver was dose dependent. Bactericidal activity against all tested strains was found for bone cement loaded with 1% high-porosity silver. The accuracy of this new proliferation assay was shown by the high correlation between the types of proliferation curves and antibiotic susceptibility. In contrast to routine agar diffusion testing, it assesses the dynamic response of microorganisms to antimicrobial agents in biomaterials and allows high-throughput screening and detection of antimicrobial properties of poorly water-soluble compounds like silver.     

In vitro measurement of the time-related efficacy of gentamicin sulfate release from bone cements

BACKGROUND: The aim of the present study was to establish an in vitro microbiologic monitoring system which measures the dynamics of antibiotic release from acrylic bone cement and its antibacterial efficacy. METHODS: Palacos R and Orthofix R cements containing gentamicin sulfate were tested. The in vitro elution dynamics was analyzed by plate diffusion method during a 1-year period after mixing. High but rapidly decreasing antibiotic levels were detected within the 1st week, resulting in an almost steadily low concentration by the end of the 1st month. After 1 year, it was still possible to demonstrate the inhibitory effect of the drug from both cements. Comparison of the time-related release between the antibiotics failed to find any statistically significant differences. CONCLUSION: The method described is a useful and reproducible technique for the in vitro measurement of the inhibitory activity of antibiotic released from bone cements.     

聚甲基丙烯酸甲酯骨水泥与Cortoss骨水泥生物力学性能及聚合温度比较

背景:聚甲基丙烯酸甲酯骨水泥是其最常用的一种填充材料,但由于其存在聚合时放热、单体毒性等缺点,所以目前出现了以Cortoss为代表的生物新型骨水泥.目的:对比两种骨水泥在体外的力学性能.方法:将聚甲基丙烯酸甲酯与新型骨水泥Cortoss按照ISO5833:2002标准分别制作成抗压及抗弯模型,将制作的模型使用生物力学机测试两种骨水泥的抗弯及抗压模量,同时在制模过程中测量骨水泥聚合温度.结果与结论:与聚甲基丙烯酸甲酯骨水泥比较,Cortoss骨水泥在聚合过程中最高温度较低、抗压强度较强、抗弯模量降低,差异均有显著性意义(P < 0.05),而抗弯强度间差异无显著性意义(P > 0.05).说明Cortoss生物力学强度优于聚甲基丙烯酸甲酯骨水泥,由于Cortoss在聚合时放热较少,所以其用于手术时有较好的安全性.     

Antibiotic-Loaded Synthetic Calcium Sulfate Beads for Prevention of Bacterial Colonization and Biofilm Formation in Periprosthetic Infections

Periprosthetic infection (PI) causes significant morbidity and mortality after fixation and joint arthroplasty and has been extensively linked to the formation of bacterial biofilms. Poly(methyl methacrylate) (PMMA), as a cement or as beads, is commonly used for antibiotic release to the site of infection but displays variable elution kinetics and also represents a potential nidus for infection, therefore requiring surgical removal once antibiotics have eluted. Absorbable cements have shown improved elution of a wider range of antibiotics and, crucially, complete biodegradation, but limited data exist as to their antimicrobial and antibiofilm efficacy. Synthetic calcium sulfate beads loaded with tobramycin, vancomycin, or vancomycin-tobramycin dual treatment (in a 1:0.24 [wt/wt] ratio) were assessed for their abilities to eradicate planktonic methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis relative to that of PMMA beads. The ability of the calcium sulfate beads to prevent biofilm formation over multiple days and to eradicate preformed biofilms was studied using a combination of viable cell counts, confocal microscopy, and scanning electron microscopy of the bead surface. Biofilm bacteria displayed a greater tolerance to the antibiotics than their planktonic counterparts. Antibiotic-loaded beads were able to kill planktonic cultures of 10⁶ CFU/ml, prevent bacterial colonization, and significantly reduce biofilm formation over multiple days. However, established biofilms were harder to eradicate. These data further demonstrate the difficulty in clearing established biofilms; therefore, early preventive measures are key to reducing the risk of PI. Synthetic calcium sulfate loaded with antibiotics has the potential to reduce or eliminate biofilm formation on adjacent periprosthetic tissue and prosthesis material and, thus, to reduce the rates of periprosthetic infection.     

The effect of a thin coating of polymethylmethacrylate on the torsional fatigue strength of the cement-metal interface.

Recent studies have established that a mechanism of initiation of failure of fixation of cemented femoral components is debonding of the cement-metal interface. Other studies have shown that the torsional forces induced by stair climbing and rising from a chair are very high. Thus, the interface between the femoral prosthesis and the bone cement in total hip arthroplasty (THA) is required to transmit high torsional loads from the metal to the cement in a cyclic shear mode many times per year. These torsional loads likely contribute to the debonding. This study evaluated the efficacy of a thin layer of polymethylmethacrylate (PMMA) precoating in increasing the torsional fatigue strength of the cement-metal interface. Fatigue studies were performed on 15 specimens. Each specimen was tested with and without PMMA precoating. The PMMA precoat significantly and substantially increased the torsional fatigue strength of the cement-metal interface. Thus, PMMA precoating is likely to be a clinical advantage in maintaining the long-term integrity of the cement-prosthesis interface.     

不同充填材料应用于经皮椎体成形术的效果及影像特征

背景:现在应用于治疗骨质疏松性压缩骨折的填充材料主要为聚甲基丙烯酸,但聚甲基丙烯酸为永久性异物,不能促进骨再生,随着时间的延长机械性能有下降的可能,学者们正在积极寻找新型的填充材料替代聚甲基丙烯酸.目的:观察不同充填材料在骨质疏松压缩骨折山羊模型上行经皮椎体成形术的效果及影像表现.方法:应用适当的机械压力造成骨质疏松山羊三节段椎体骨折模型,在G形臂X射线机监视下,选取骨折椎体行经皮椎体成形术,分别充填聚甲基丙烯酸、自固化磷酸钙人工骨和重组人骨形态发生蛋白2/自固化磷酸钙人工骨.结果与结论:①12只山羊36个椎体的经皮椎体成形术均成功,3种材料的充填量差异无显著性意义(P>0.05),均为(3.5±1.8)mL;聚甲基丙烯酸推注阻力较大,可操作时间短,术中显影较好,自固化磷酸钙人工骨和重组人骨形态发生蛋白2/自固化磷酸钙人工骨推注阻力较小,可操作时间长;无渗漏占位.②术后第2天CT扫描结果显示,3种充填材料不规则分布于椎体内,呈斑片状高密度影,36个椎体中有6个椎体出现渗漏,其中4例系聚甲基丙烯酸所致,1例系自固化磷酸钙人工骨所致,1例系重组人骨形态发生蛋白2/自固化磷酸钙人工骨所致.③扫描电镜观察示聚甲基丙烯酸组所有材料与宿主骨之间不能紧密结合,自固化磷酸钙人工骨和重组人骨形态发生蛋白2/自固化磷酸钙人工骨和宿主骨均紧密结合,无界膜形成.结果提示重组人骨形态发生蛋白2/自固化磷酸钙人工骨具有可操作性长,发生骨替代时间较短,有利于永久性重建脊柱稳定性.     

材料表面发热范围温度升高对于内植物相关感染的预防

目的观察在动物实验中,内植物材料表面温度发热范围升高能否降低内植物相关感染率。方法在兔背部两侧皮下各植入1个无菌组织笼子,内放置骨水泥包裹的发热体,两周后,注入金黄色葡萄球菌,分别给予材料表面发热和不发热,抽取组织液测定细菌浓度及计算感染率,测定白细胞浓度。结果在发热组,组织笼子感染率为34.4%（11/32）;组织笼子内白细胞计数在发热组升高。在未发热组,实验结束时,感染率为75.0%（24/32）;在未感染组织笼子内白细胞计数第一天后白细胞计数不再增高。感染组织笼子内白细胞计数达到105/μl,但是成活细胞仅有50%左右。结论材料表面发热范围的温度升高能够降低内植物材料相关感染率。     

A new bioactive bone cement consisting of BIS-GMA resin and bioactive glass powder.

We have developed a bioactive bone cement consisting of silane-treated CaO-SiO 2-P 2O 5-CaF 2 glass powder as the filling particles and bisphenol-a-glycidyl methacrylate (BIS-GMA) diluted with triethylene-glycol dimethacrylate (TEGDMA) as the organic matrix. Histological examination demonstrated direct bonding between the cement and bone along the circumference of the cement at 4 weeks after implantation in rat tibia. The compressive strength and toughness of the cement were two and four times greater than those of polymethylmethacrylate (PMMA) cement, respectively. The inflammatory reaction of the skin caused by the new cement was not as intense as that for PMMA 3 days after subcutaneous implantation. This new cement may be applicable as a bioactive bone cement with high mechanical strength.     

磷酸钙骨水泥对股骨颈骨折内固定辅强作用的组织学评价

背景:将磷酸钙骨水泥作为一种内固定辅强材料可提高骨折固定的稳定性,特别是对伴有骨质疏松、骨质较脆弱的骨折可发挥长期良好的固定作用。目的:从组织学方向分析磷酸钙骨水泥对股骨颈骨折内固定的辅强作用,并同非辅强及聚甲基丙烯酸甲酯辅强进行对比评估。设计:随机对照、重复观察、开放性实验。单位:吉林大学第一医院骨科与基本外科,吉林大学基础医学院病理室,日本爱知医科大学整形外科。材料:实验于1999-01/2004-01在吉林省洮南市医院、吉林大学、日本爱知医科大学完成。选用45只成熟中国绵羊,平均年龄12.5个月,随机分成3组:非辅强组、磷酸钙骨水泥辅强组、聚甲基丙烯酸甲酯辅强组,15只/组。分别于术后3,6,12周取材,每个时间点5只/组。磷酸钙骨水泥由粉剂和固化液组成(粉剂包括75%α-磷酸三钙、18%磷酸四钙、5%磷酸氢钙和2%Hydroxyapatite;固化液包括5%sodiumchondroitinsulphate、12%sodiumsuccinate和83%水),粉液比为3∶1。聚甲基丙烯酸甲酯骨水泥包括97.4%methylmethacrylate、2.6%Ndimethyl-para-toluidine和hydroquinone。方法:①将各组绵羊采用pentobarbitalsodium静脉麻醉后,进行截骨、钻孔、攻丝和固定。截骨部位均在右股骨颈基底部,用2枚直径4mm松质骨螺钉经大转子下固定。骨水泥则在螺钉拧入前填充。②磷酸钙骨水泥辅强组向孔中注射调配好粉剂和固化液比例的磷酸钙骨水泥,聚甲基丙烯酸甲酯辅强组向孔中注射聚甲基丙烯酸甲酯骨水泥,非辅强组不给予任何材料。③各组标本首先进行最大载荷测试,然后均在40%,70%,90%,100%乙醇中梯度脱水、染色、聚甲基丙烯酸甲酯包埋。最后用锯切片机沿股骨颈方向连续切片,厚度为150～200μm。硬组织切片在接触显微X线照相机上进行拍摄,分别于术后3,6,12周显微镜下观察各组标本骨水泥周围新骨形成情况及宿主骨的改变。主要观察指标:术后不同时间各组骨水泥周围新骨形成情况及宿主骨的变化。结果:实验选用45只成熟中国绵羊,全部进入结果分析。术后不同时间各组骨水泥周围新骨形成情况及宿主骨的变化:①非辅强组:术后3周在螺钉周围产生少量纤维组织,且宿主骨骨床有显微破坏,但显微破坏在术后6及12周时可见修复。②磷酸钙骨水泥辅强组:术后3,6,12周磷酸钙骨水泥充满于螺钉和宿主骨之间,而且磷酸钙骨水泥表面有新骨形成,在新骨和磷酸钙骨水泥之间没有纤维组织介入。在术后12周可见大量新骨形成,且见许多骨小管。③聚甲基丙烯酸甲酯辅强组:术后3周在骨床与聚甲基丙烯酸甲酯之间产生大量纤维组织,可见明显骨吸收,术后6及12周尤为明显。结论:由于磷酸钙骨水泥具有良好的组织相容性、骨传导性及自身改建能力,因此对股骨颈骨折提供了长期有益的辅强作用。