大段异体骨移植钻孔携带抗生素骨水泥释放抗生素的效果研究

目的观察大段异体骨移植钻孔携带抗生素骨水泥释放抗生素特性可行性及浓度。方法取24只大白兔随机抽签法分为A、B、C、D组,每组6只建立兔胫骨骨缺损模型,将异体骨分别用直径1.2、1.5、1.8、2.0mm钻头钻24个骨孔,并测量异体骨的表面积和孔的内表面积,用40 g骨水泥固相与液相混合后加入2 g万古霉素粉剂,分别填塞至异体骨的钻孔内,植入兔骨缺损处固定,在术后1、3、7、14、21、30天用注射器抽取0.3 m L生理盐水并通过放置的引流管进行冲洗,所得冲洗液用高效液相色谱仪测出的抗生素浓度。并求出异体骨的表面积与相应抗生素骨水泥的表面积的比值。结果 4组抗生素在兔体内持续平均释放时间在30天以上,A组抗生素提洗量在30天低于最小抑菌浓度,该异体骨的表面积与相应抗生素骨水泥的表面积的比值为5.8∶1,B组接近最小抑菌浓度,该异体骨的表面积与相应抗生素骨水泥的表面积的比值为4.2∶1,C,D组的洗提量高于最小抑菌浓度差异有显著性意义(0.05),该异体骨的表面积与相应抗生素骨水泥的表面积的比值分别为3.2∶1和2.7∶1。结论大段异体骨移植钻孔携带抗生素骨水泥抗生素析出释放,在实验的30天中,异体骨表面积与相应抗生素骨水泥表面积的比值为为1∶3.2和1∶2.7时,万古霉素的释放量始终维持在高于有效的抗菌浓度。     

硫酸钙/庆大霉素抗生素释放系统的抗生素释放规律*

目的探讨新型骨植入型抗生素释放系统硫酸钙/庆大霉素的抗生素释放特点。方法对研制的庆大霉素3%,5%含量的硫酸钙/庆大霉素抗生素释放系统进行抗生素洗提,应用高效液相色谱-蒸发光散射检测法(HPLC-ELSD)对不同时间点洗提液中庆大霉素含量进行测定,并与PMMA抗生素释放系统进行比较,观察抗生素释放特点。结果硫酸钙/庆大霉素抗生素释放系统与PMMA抗生素释放系释放时间分别为4周和2周,初期抗生素释放浓度高,相同时间点5%硫酸钙/庆大霉素释放系统抗生素释放量高于3%组,硫酸钙/庆大霉素组高于PMMA/庆大霉素组。结论硫酸钙/庆大霉素抗生素释放系统可降解,抗生素释放时间长,浓度高,优于PMMA抗生素释放系统。     

抗生素复合骨水泥洗脱特性的实验研究

目的探讨将2种抗生素混入骨水泥时抗生素释放特性的变化。方法骨水泥样品分为单一万古霉素组(40 g PMMA骨水泥中混入2 g万古霉素)、单一头孢他啶组(40 g PMMA骨水泥中混入2 g头孢他啶)和联合组(40 g PMMA骨水泥中混入2 g万古霉素+2 g头孢他啶),每组6个。抗生素骨水泥载体在体外用PBS缓冲液浸泡,取4 h、8 h、16 h、24 h、2 d、3 d、4 d、5 d、6 d、7 d、2周、3周、4周、6周样本,并应用高效液相色谱仪测定抗生素洗脱浓度。结果在为期6周的洗脱过程中,联合组万古霉素及头孢他啶在骨水泥载体中的洗脱浓度分别高于单一万古霉素组和单一头孢他啶组(P<0.05)。结论2种抗生素添加于骨水泥载体中,可更好地发挥其功效。     

不同品牌骨水泥中抗生素的释放特性研究

目的探讨不同品牌的骨水泥对不同抗生素释放的影响。方法将骨水泥样品分为4组,每组6个样本:A组,40 g Palacos骨水泥中混入2 g万古霉素; B组,40 g Palacos骨水泥中混入2 g头孢他啶; C组,40 g Copal骨水泥中混入2 g万古霉素;D组,40 g Copal骨水泥中混入2 g头孢他啶。制作成直径(10±1) mm、高(20±1) mm的骨水泥圆柱,每组6个,在体外用磷酸盐缓冲溶液(PBS)浸泡,取4 h、8 h、16 h、24 h、48 h、3 d、4 d、5 d、6 d、7 d、2周、3周、4周、6周的样本,并应用高效液相色谱仪测定药物洗脱浓度。结果在为期6周的洗脱过程中,对于万古霉素的释放,A组Palacos骨水泥前3 d优于C组Copal骨水泥,而5 d到6周时C组Copal骨水泥优于A组Palacos骨水泥;对于头孢他啶的释放,B组Palacos骨水泥在洗脱周期内优于D组Copal骨水泥。结论万古霉素前期释放及头孢他啶释放选择Palacos骨水泥更佳,万古霉素中后期释放选择Copal骨水泥更佳,在临床中需根据已知敏感抗生素添加于适当的骨水泥载体中来发挥其功效。     

老年患者骨水泥型人工髋关节置换前后的凝血功能

背景：由于老年患者自身的高凝倾向,骨水泥型人工髋关节置换后更容易发生深静脉栓塞、弥漫性血管内凝血、肺栓塞、脑栓塞等并发症。 目的：观察老年患者骨水泥型人工髋关节置换前后凝血4项凝血酶原时间、活化部分凝血活酶时间、凝血酶时间和纤维蛋白原的变化。 方法：检测40例人工髋关节置换老年患者骨水泥植入前10 min,植入后30 min、1 h、2 h、3 h 凝血酶原时间、活化部分凝血活酶时间、凝血酶时间和纤维蛋白原各项指标。 结果与结论：与植入前10 min比较,植入后30 min凝血酶原时间明显下降(P < 0.05),纤维蛋白原明显升高(P < 0.05),植入后3 h均恢复到植入前状态(P > 0.05)。活化部分凝血活酶时间、凝血酶时间在骨水泥植入前后变化均不明显(P > 0.05)。结果表明患者在骨水泥植入后短时间内会出现高凝血状态,在植入3 h后基本消除,提示在植入骨水泥后的3 h是监测凝血的重要时间段。     

抗生素骨水泥与人工关节置换后的翻修

背景：抗生素骨水泥是预防和治疗人工关节置换以及翻修后感染的重要方法。 目的：综述抗生素骨水泥的研究进展以及人工关节置换后翻修。 方法：通过计算机检索Pubmed数据库、中国知网数据库、中国生物医学文献数据库、维普期刊全文数据库、万方数据库,时间范围在1978年至2012年,中文检索词“骨水泥”、“抗生素骨水泥”、“感染”、“关节置换”;英文检索词“bone cement”、“antibiotic bone cement”、“infection”、“joint replacement”。 结果与结论：共检索到相关文献335篇。通过阅读标题、摘要以及全文进行初步筛选,最后保留29篇文献进行深入的分析。抗生素骨水泥目前已广泛应用于人工关节置换以及翻修后感染的治疗,可以降低初次关节置换和翻修后感染的风险。适量的抗生素与骨水泥混合后其材料特性和力学性能不会发生改变。不同抗生素在骨水泥中的释放率也存在不同,与骨水泥的孔隙率有着密切的关系,在骨水泥中加入能够增加孔隙率的添加剂,可以达到最终增加抗生素释放的目的。     

负载抗菌药物骨水泥的药物释放实验研究

目的揭示负载抗菌药物骨水泥的药物释放浓度、持续时间、药物残留程度及低于最小有效抑菌浓度的释放时间,为合理应用抗菌药物提供理论依据。方法通过对负载盐酸万古霉素和亚胺培南西司他丁钠的骨水泥进行体外洗提实验,采用高效液相色谱法检测分析两种负载抗菌药物的骨水泥的药物释放浓度、释放持续时间和药物残留程度。结果 (1)负载抗菌药物的骨水泥第一天药物释放量最大,后逐渐持平,且释放时间较长,释放浓度较低;(2)截止到第7周盐酸万古霉素、亚胺培南西司他丁释放量分别只占总负载量的15%、25%;(3)盐酸万古霉素第1周后释放浓度低于最小有效抑菌浓度,亚胺培南西司他丁钠第7周后释放浓度低于最小有效抑菌浓度。结论载抗菌药物骨水泥存在长时间药物残留现象,是导致持续低于最小有效抑菌浓度的主要原因。此种现象不但对细菌起不到抑菌作用,而且是诱导细菌耐药性的危险因素。     

膝关节置换中应用骨水泥和止血带对凝血功能的影响

背景：有研究表明膝关节置换中骨水泥固定假体时骨水泥对患者的血液动力学及凝血功能的影响较大。 目的：观察膝关节置换中骨水泥和止血带对患者凝血功能的影响。 方法：采用随机对照研究方法,将骨性关节行单侧膝关节置换患者40例随机分成2组,置换时分别应用止血带和不用止血带。通过比较两组患者血浆凝血酶原时间、活化的部分凝血活酶时间、凝血酶时间、纤维蛋白原及血浆D-二聚体水平的变化,来观察膝关节置换中骨水泥和止血带对置换中凝血功能的影响。 结果与结论：两组患者在骨水泥置入后60,120 min,血浆凝血酶原时间值缩短(P < 0.05),纤维蛋白原和D-二聚体在注入骨水泥后增多(P < 0.05),其中止血带组的变化更为明显,两组患者在180 min时基本恢复正常,活化的部分凝血活酶时间及凝血酶时间在骨水泥注入前后均无明显变化,另外,所监测的凝血功能相关指标(血浆凝血酶原时间、活化部分凝血酶原时间、凝血酶时间、纤维蛋白原及D-二聚体的数值在注入骨水泥前后均在正常范围内。相比非止血带组,止血带组血浆凝血酶原时间缩短、纤维蛋白原及D-二聚体含量增多(P < 0.05)。说明膝关节置换中骨水泥应用后可以使单侧膝关节置换患者的凝血功能处于高凝状态,止血带可加重患者的高凝状态。     

药物预防全髋关节置换后继发假体周围骨溶解的5年随机对照评价

背景：全髋关节置换后出现轻微的骨溶解,如果能找到理想的药物治疗,不但可减轻痛苦,还可节省医疗费用。 目的：观察阿仑膦酸钠和阿法骨化醇联合应用预防全髋关节置换后假体周围骨溶解的效果。 方法：75例股骨颈骨折患者行骨水泥型人工髋关节置换后随机分为3组,治疗组给予阿仑膦酸钠和阿法骨化醇口服联合治疗、对照组给予复方氨基酸螯合钙胶囊口服治疗,空白组正常饮食。随访1,3,5年,检测假体周围骨密度值变化、髋关节功能评分,5年后进行影像学评价。 结果与结论：髋关节置换后3,5年治疗组骨密度值高于对照组和空白组(P < 0.05),置换后5年治疗组骨溶解率低于对照组和空白组(P < 0.05)。结果显示阿仑膦酸钠和阿法骨化醇联合应用,在预防髋关节假体置换后继发骨溶解发生的过程中起到了一定的积极作用。     

负载抗菌药物的骨水泥的药物释放实验研究

目的 揭示负载抗菌药物的骨水泥的药物释放浓度、持续时间、药物残留程度及低于最小有效抑菌浓度的释放时间,为合理应用抗菌药物提供理论依据。方法 通过对负载盐酸万古霉素和亚胺培南西司他丁钠的骨水泥进行体外洗提实验,采用高效液相色谱法检测分析两种负载抗菌药物的骨水泥的药物释放浓度、释放持续时间和药物残留程度。结果 ①负载抗菌药物的骨水泥第一天药物释放量最大,后逐渐持平,且释放时间较长,释放浓度较低;②截止到第7周盐酸万古霉素、亚胺培南西司他丁释放量分别只占总负载量的15%、25%;③盐酸万古霉素第1周后释放浓度低于最小有效抑菌浓度,亚胺培南西司他丁钠第7周后释放浓度低于最小有效抑菌浓度。结论 载抗菌药物骨水泥存在长时间药物残留现象,是导致持续低于最小有效抑菌浓度的主要原因。此种现象不但对细菌起不到抑菌作用,而且是诱导细菌耐药性的危险因素。     

Gentamicin-loaded bone cement with clindamycin or fusidic acid added: biofilm formation and antibiotic release

The formation of staphylococcal biofilms on experimental bone cements, loaded with 0.5 or 1.0 g of active gentamicin and an additional equivalent amount of gentamicin, clindamycin, or fusidic acid was investigated. The biofilms were formed in a modified Robbins device over a 3-day time span and the influence of the additional antibiotics was quantified by expressing the number of colony forming units relative to the corresponding bone cement containing only gentamicin. Combinations of gentamicin with either fusidic acid or clindamycin reduced growth of clinical isolates of both gentamicin-sensitive Staphylococcus aureus and gentamicin-resistant coagulase-negative staphylococci to approximately 28%. To determine whether adding a second antibiotic has influence on the gentamicin release, cement blocks were placed in phosphate buffer and aliquots were taken at designated sampling intervals. The influence of the additional antibiotics was quantified by expressing the percentage released of the total amount of antibiotic incorporated in the different bone cements. After 3 days, all bone cements had released similar percentages of gentamicin, whereas more clindamycin and fusidic acid were released after doubling their concentration in the bone cements. In conclusion, bone cements loaded with combinations of gentamicin and clindamycin or fusidic acid are more effective in preventing biofilm formation than bone cements with gentamicin as a single drug. In addition, the presence of clindamycin or fusidic acid in gentamicin-loaded bone cement has no influence on the total gentamicin release.     

In vitro evaluation of antibiotic release from and bacteria growth inhibition by antibiotic-loaded acrylic bone cement spacers

The antibiotic release from and the bacteria growth inhibition by antibiotic-loaded acrylic bone cement hip spacers were studied. The cement used was Palacos R, and it was loaded with either one antibiotic powder (gentamicin, vancomycin, teicoplanin, or synercid) [monoantibiotic case] or two antibiotic powders (gentamicin + vancomycin or gentamicin + teicoplanin) [biantibiotic case] and then tested against Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecalis, and methicillin-resistant Staphylococcus aureus (MRSA). Antibiotic elution and bacteria growth were measured every 24 h simultaneously by fluorescence polarization immunoassay and photometrically, respectively. The gentamicin + vancomycin combination achieved the longest growth inhibition on S. epidermidis and MRSA (mean of 20 and 14 days, respectively). Gentamicin + teicoplanin-loaded spacers were capable of inhibiting growth on E. faecalis and S. aureus for the longest period (11 and 16 days, respectively). The highest concentrations of gentamicin and vancomycin could be assayed during the first 4 days. Teicoplanin concentrations could be detected only during the first 72 h, synercid was not detected at all, possibly because of the limitation of the detection technique used. A greater percentage of the gentamicin was released than of the vancomycin. The aminoglycosid-glycopeptid combination showed a synergistic effect on the release of gentamicin, but not on vancomycin or teicoplanin. Biantibiotic-impregnated hip spacers proved to be superior to monoantibiotic ones. Because of important differences between the conditions used for the present tests and the in vivo environment, any recommendation with regard to the use of monoantibiotic- and biantibiotic-loaded acrylic bone cement spacers must await the results of further investigations.     

The influence of ultrasound on the release of gentamicin from antibiotic-loaded acrylic beads and bone cements

Gentamicin-loaded acrylic beads are loosely placed in infected bone cavities, whereas gentamicin-loaded acrylic bone cement is used as a mechanical filler in bone to anchor prosthetic components. Both drug delivery systems are used to decrease infection rates by gentamicin release. The objective of this study is to investigate the effects of pulsed ultrasound on gentamicin release from both materials. Gentamicin release from gentamicin-loaded beads (Septopal) and from three commercially-available brands of gentamicin-loaded bone cement (CMW 1, Palacos R-G, and Palamed G) was measured after 18 h of exposure in PBS to an ultrasonic field of 46.5 kHz in a 1:3 duty cycle with an average acoustic intensity of 167 mW/cm(2). Samples not exposed to ultrasound were used as controls. Pulsed ultrasound significantly enhanced gentamicin release from gentamicin-loaded beads, whereas gentamicin release from the gentamicin-loaded bone cements was not significantly enhanced. Mercury intrusion porosimetry revealed an increased distribution of pores between 0.1 and 0.01 microm in beads after gentamicin release, while in bone cements no increase in the number of pores was found. Increased gentamicin release in beads due to ultrasound may be explained by micro-streaming in a porous structure, whereas the absence of changes in pore structure after gentamicin release in bone cement is concurrent with the lack of an enhanced release of the antibiotic by ultrasound. As an effective treatment of infections requires high local concentrations of antibiotic, increased gentamicin release due to ultrasound may be of clinical significance, especially since ultrasound has been demonstrated to increase bacterial killing by antibiotics.     

Antimicrobial properties and elution kinetics of linezolid-loaded hip spacers in vitro

Bacterial adhesion to and -persistence on antibiotic-loaded bone cement is an increasing problem. New antibiotics with good antimicrobial and pharmacokinetic properties (e.g. linezolid) may be the solution to this problem; however, few data concerning linezolid-loaded acrylic cement are currently available. Ten gentamicin-linezolid-loaded hip spacers (1 g gentamicin/2.4 g linezolid/80 g PMMA; five spacers including a metallic endoskeleton, five with no metallic components) were tested in vitro against a strain of methicillin-resistant Staphylococcus aureus with regard to antibiotic release and bacteria growth inhibition. Daily, the antibiotic elution was determined by high liquid performance chromatography (linezolid) and fluorescence polarization immunoassay (gentamicin), the bacteria growth inhibition photometrically at 546 nm. All spacers demonstrated growth inhibition for 8 days. Peak average concentrations were reached for both agents on day 1 (gentamicin-35.10 mug/mL [24.10-52.52], linezolid-36.28 mug/mL [22.87-71.76]). After 8 days, 0.97% [0.93-1.05%] of the initial amount of linezolid and 3.13% [2.85-3.31%] of gentamicin were meanly released from spacers containing a metallic endoskeleton. In those containing of simple cement these values were 1.22% [0.91-1.59%] and 2.67% [2.12-2.73%], respectively. Linezolid demonstrated acceptable elution kinetics from bone cement; however, further experimental research and animal studies should clarify any possible side effect of linezolid-loaded cement media before definitive use in the clinical practice.     

Gentamicin release from two-solution and powder-liquid poly(methyl methacrylate)-based bone cements by using novel pH method

The release of gentamicin as a function of time was measured for Palacos and two-solution bone cements by using a novel pH technique. The pH of an aqueous solution of gentamicin is a function of the gentamicin concentration and it decreases linearly over concentrations of 0.0-0.1 wt %. Therefore, a new, direct, and inexpensive in vitro technique was developed based on continuous readings of the pH in phosphate-buffered saline (PBS) at 37 degrees C to determine the release kinetics of gentamicin from poly(methyl methacrylate) (PMMA)-based bone cement. In addition, this method was used to compare the release profiles of Palacos R-40 bone cement with a two-solution bone cement developed in our laboratory and loaded with two different concentrations of gentamicin sulfate. Finally, the pH-based method was used to track the elution of gentamicin in both mixed and static conditions to determine the effect of mixing on the diffusion of gentamicin out of the cement. It was found that Palacos R-40 released 4.95 +/- 0.22 wt % of its gentamicin after 24 h in PBS solution. This data compares favorably with previously reported values of gentamicin elution from Palacos R-40, which ranged from 3 to 8 wt % of the total amount of incorporated gentamicin, depending on the size and the surface area of the samples. The results show that Palacos samples released 4.84 +/- 0.27 mg after 24 h, a two-solution cement loaded with an equivalent concentration of gentamicin sulfate released 3.81 +/- 0.52 mg, and two-solution cement loaded with twice the concentration of Palacos released 5.53 +/- 0.26 mg of gentamicin. A higher percentage of release was recorded from Palacos than from the two-solution bone cement, and the effect of PBS mixing conditions on the release kinetics was only significant in the early stages of release and not at 24 h. It was concluded that monitoring the pH is an effective technique to measure gentamicin release from PMMA-based bone cements in PBS solution.     

The effect of the antimicrobial peptide, Dhvar-5, on gentamicin release from a polymethyl methacrylate bone cement

The objective of this study was to investigate the release mechanism and kinetics of the antimicrobial peptide, Dhvar-5, both alone and in combination with gentamicin, from a standard commercial polymethyl methacrylate (PMMA) bone cement. Different amounts of Dhvar-5 were mixed with the bone cement powders of Osteopal and the gentamicin-containing Osteopal G bone cement and their release kinetics from the polymerized cement were investigated. Additionally, the internal structure of the bone cements were analysed by scanning electron microscopy (SEM) of the fracture surfaces. Secondly, porosity was investigated with the mercury intrusion method and related to the observed release profiles. In order to obtain an insight into the mechanical characteristics of the bone cement mixtures, the compressive strength of Osteopal and Osteopal G with Dhvar-5 was also investigated. The total Dhvar-5 release reached 96% in the 100 mg Dhvar-5/g Osteopal cement, whereas total gentamicin release from Osteopal G reached only 18%. Total gentamicin release increased significantly to 67% with the addition of 50mg Dhvar-5/g, but the Dhvar-5 release was not influenced. SEM showed an increase of dissolved gentamicin crystals with the addition of Dhvar-5. The mercury intrusion results suggested an increase of small pores (< 0.1 microm) with the addition of Dhvar-5. Compressive strength of Osteopal was reduced by the addition of Dhvar-5 and gentamicin, but still remained above the limit prescribed by the ISO standard for clinical bone cements. We therefore conclude that the antimicrobial peptide, Dhvar-5, was released in high amounts from PMMA bone cement. When used together with gentamicin sulphate, Dhvar-5 made the gentamicin crystals accessible for the release medium presumably through increased micro-porosity (< 0.1 microm) resulting in a fourfold increase of gentamicin release.     

In vitro elution characteristics of antibiotic laden BoneSource™, hydroxyapatite bone cement

A calcium phosphate – hydroxyapatite (HA) bone cement was loaded with varying concentrations of tobramycin and vancomycin and the elution properties of these antibiotics were evaluated. Nine groups of antibiotic loaded cement cylinders (N?=?6 in each group) were prepared and placed in saline for 28?days. Elution rates of tobramycin and vancomycin from the HA cement were evaluated at high, medium, and low doses of incorporated antibiotic. Tobramycin elution rates did not vary according to dose (0.36, 0.18, and 0.09g). Vancomycin elution rates were also not significantly affected by dose (0.1?, 0.05?, and 0.025?g). The combination of tobramycin and vancomycin increased the elution rate of vancomycin for the medium and low dose of tobramycin. The dose of tobramycin did not affect its elution rate from the cement in the combined groups. Importantly, the concentration of antibiotic eluent stayed above the minimum inhibitory concentration for the entire 28?days for all groups except the medium and low dose of vancomycin alone. Overall, elution rates of both tobramycin and vancomycin in the calcium phosphate-HA cement were comparable to those from polymethylmethacryltate beads in vitro.     

Staphylococcus aureus biofilm formation on different gentamicin-loaded polymethylmethacrylate bone cements

In this in vitro study, the formation of a Staphylococcus aureus biofilm on six gentamicin-loaded bone cements (CMW1, CMW3, CMW Endurance, CMW2000, Palacos, and Palamed) was determined in a modified Robbins device over a 3 days time span and related with previously (Van de Belt et al., Biomaterials 21 (2000) 1981) measured kinetics of antibiotic release by these cement brands. The influence of gentamicin release on biofilm formation was quantified by expressing the number of colony-forming units on gentamicin-loaded cement relative to the number of viable organisms on unloaded cement of the same brand. Biofilms formed on all gentamicin-loaded cements, despite the release of antibiotics, followed a consistent pattern in time with a maximum number of colony-forming units per unit cement area found between 24 and 30 h after inoculation. None of the gentamicin-loaded cements showed a reduction in biofilm formation relative to unloaded cements within 6 h after inoculation, whereas only gentamicin-loaded CMW1 and Palacos reduced biofilm formation 24 h after inoculation. Alternatively, CMW Endurance, CMW2000, and Palamed did not exhibit any initial reductions in biofilm formation, but effects started after 72, 48, and 72 h, respectively. Biofilm reduction by gentamicin-loaded CMW3 lasted the longest from 24 to 72 h. Interestingly, each cement seemed to have a different "window-of-effectiveness" with regard to reduction in biofilm formation that did not relate with the gentamicin-release kinetics. Summarising, this study demonstrates that although gentamicin loading of bone cements yields reductions in biofilm formation, S. aureus is able to grow on gentamicin-loaded bone cements.     

Controlled release of gentamicin from calcium phosphate-poly(lactic acid-co-glycolic acid) composite bone cement

Modification of a self setting bone cement with biodegradable microspheres to achieve controlled local release of antibiotics without compromising mechanical properties was investigated. Different biodegradable microsphere batches were prepared from poly(lactic-co-glycolic acid) (PLGA) using a spray-drying technique to encapsulate gentamicin crobefate varying PLGA composition and drug loading. Microsphere properties such as surface morphology, particle size and antibiotic drug release profiles were characterized. Microspheres were mixed with an apatitic calcium phosphate bone cement to generate an antibiotic drug delivery system for treatment of bone defects. All batches of cement/microsphere composites showed an unchanged compressive strength of 60 MPa and no increase in setting time. Antibiotic release increased with increasing drug loading of the microspheres up to 30% (w/w). Drug burst of gentamicin crobefate in the microspheres was abolished in cement/microsphere composites yielding nearly zero order release profiles. Modification of calcium phosphate cements using biodegradable microspheres proved to be an efficient drug delivery system allowing a broad range of 10-30% drug loading with uncompromised mechanical properties.