利福平/聚乳酸-聚羟基乙酸缓释微球的制备及特性

背景：虽然国内外有很多制备利福平/聚乳酸-聚羟基乙酸共聚物(poly lactic acid-glycolic acid copolymer,PLGA)微球的报道,但这些微球粒径多在10 μm左右,不适合与磷酸钙骨水泥复合制备成具有良好降解性的抗结核修复材料。 目的：制备大粒径利福平/PLGA缓释微球,观察其理化特性和体外缓释特性。 方法：以PLGA为载体,将利福平分散于PLGA的有机溶剂中,采用复乳溶剂挥发法制备利福平/ PLGA缓释微球。光镜和扫描电镜下观察微球的形态特征,测定微球平均直径和跨距,高效液相色谱法测定载药量和包封率,以溶出法和高效液相色谱法观察其体外释药特性,并拟合药物体外释放曲线建立曲线方程。 结果与结论：利福平/PLGA微球电镜观察呈圆球形,分散性好,粘连少,粒径分布集中,平均粒径(80.0±9.4) μm。载药量、包封率分别为(33.18±1.36)%,(54.79±1.13)%。体外缓释试验显示突释期内微球释放度为(14.66±0.18)%,前3 d累计释放度(18.09±0.45)%,到42 d体外累积释放度达到(92.17±1.23)%。提示利福平/PLGA微球具有良好的缓释效果,是一种较为理想的抗结核药物的载体材料和释放系统;PLGA是良好的药物缓释载体,可以用来制备载药缓释微球。     

阿托伐他汀钙缓释微球制备方法的优化北大核心

背景:近年来研究发现,他汀类药物在调节骨代谢、修复骨细微结构、抑制炎症、促进细胞增殖、修复血管内皮、调节信号通路传导等多方面具有显著效果。目的:对载阿托伐他汀钙缓释微球的制作参数进行优化,以期制备出载药量大、形态规则的缓释微球。方法:采用去溶剂法制备载阿托伐他汀钙的牛血清白蛋白缓释微球,筛选出影响去溶剂过程的主要影响因素,包括血清白蛋白溶液质量浓度(40,70,100 g/L)及p H值(7,8,9)、阿托伐他汀钙的用量(200,300,400μg)、乙醇添加速度(0.2,0.5,1 m L/min),通过正交实验筛选出最佳包封率的制备条件。在最佳组合工艺参数下制备载阿托伐他汀钙的牛血清白蛋白缓释微球,置于PBS中进行体外缓释性能测试。结果与结论:(1)最佳的制备工艺参数是:牛血清白蛋白溶液质量浓度为100 g/L、p H值为7,阿托伐他汀钙用量为400μg,乙醇添加速度为0.2 m L/min;(2)在此参数下制备的微球形态规则,表面光滑,微球直径(425.0±13.8) nm,药物包封率高达85.70%,体外释放时间可持续48h以上,累积释放量达到73%,具有较为良好的缓释效果;(3)实验成功制备了负载阿托伐他汀钙的牛血清白蛋白缓释微球,此药物缓释微球具有较高载药量及稳定性,并可以实现的药物缓释。     

喷雾干燥法制备眼用壳聚糖/明胶复合微球**

背景：普通滴眼液由于泪液冲刷与鼻泪管吸收等因素,在眼表停留时间短,生物利用度低。 目的：以壳聚糖、明胶为载体材料,左氧氟沙星为模型药物,制备应用于眼表的缓控释微球并考察其理化性质与体外释放。 方法：采用喷雾干燥法制备左氧氟沙星壳聚糖/明胶微球,通过扫描电镜观察微球的表面形态,激光粒度仪测量微球粒径分布与zeta电位,高效液相色谱法检测微球的载药率与包封率,动态透析法研究微球体外药物释放情况。 结果与结论：所得微球形态良好,粒径分布窄,平均粒径为(1 267.4±115.3) nm,zeta电位为+(32.19±0.85) mV,载药量为(18.31±0.22)%,包封率为(91.53±1.12)%。载药微球体外释放符合一级释药方程Ln(1-Q)=-0.699 1t-0.086 4,r2=0.945 1。说明壳聚糖/明胶载药微球对左氧氟沙星具有缓释作用。实验采用喷雾干燥法成功制备了粒径及分布适宜、释放周期较理想、药物稳定性好的载左氧氟沙星壳聚糖明胶缓释微球。      

植入型表阿霉素缓释药膜的制备及体内抑瘤活性

制备用于实体肿瘤局部治疗的植入型表阿霉素缓释药膜.采用复乳.溶剂挥发法制备聚乳酸载表阿霉素缓释微球,用交联复合法制备含载药微球的植入型胶原药膜;用扫描、透射电镜、共聚焦及粒度仪等考察微球和药膜的形貌、结构、粒径及体外释放;用H22肝癌荷瘤动物模型评价其体内抑瘤效果.结果:载药微球粒径分布均匀,外观圆整,平均粒径为5.8μm;微球的载药量4.39%,包裹率为37.2%;10h内载药微球在模拟体液中的累积释放率为35%;腹腔注射载药微球与瘤体局部植入胶原药膜对H22肝癌均有明显的抑瘤效果;微球注射与药膜植入两种不同给药方式对H22肝癌抑瘤效果也存在显著性差异(P<0.05).植入型载表阿霉素缓释胶原膜具有良好的药物局部缓释特性,在肿瘤的术后局部治疗方面具有良好的临床应用前景.     

聚乙二醇对利福平-聚乳酸-羟基乙酸聚合物缓释微球性能的影响

背景：聚乳酸-羟基乙酸共聚物微球具有良好的生物相容性,是优良的药物缓释载体,但缓释微球的突释问题严重影响了其临床应用。 目的：观察聚乙二醇对利福平-聚乳酸-羟基乙酸聚合物缓释微球特征、载药率、包封率、体外释放规律及突释的影响。 方法：以高分子材料聚乳酸-羟基乙酸共聚物作为载体,采用复乳化-溶剂挥发法制备聚乙二醇-利福平-聚乳酸-羟基乙酸聚合物微球(实验组)和利福平-聚乳酸-羟基乙酸聚合物微球(对照组)。扫描电子显微镜观察两组聚合物缓释微球特征,高效液相色谱法检测两组微球在不同时段模拟体液中的利福平药物浓度及累计释放量,计算两组微球的载药量、包封率。 结果与结论：与对照组比较,实验组微球表面光滑、粒径减小、分散良好,包封率和载药量明显提高。实验组微球3 h内药物释放量最大,1 d左右药物释放趋于平稳稳定状态,1 d药物累计释放量小于20%;对照组微球3 h内药物释放量最大,约为实验组的1.5倍,1 d左右药物释放也趋于平稳状态。表明聚乙二醇可改善利福平-聚乳酸-羟基乙酸聚合物缓释微球的成球率,减小其粒径,增加其载药量和包封率,控制其突释现象。 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

固载去甲万古霉素缓释微球疝补片的制备与表征

应用疝修补术治疗腹壁疝在临床上得到广泛运用,不足之处是患者易受细菌感染.介绍高效固载缓释抗菌药物疝补材料的制备方法及其效果.利用复乳-溶剂挥发法,制备盐酸去甲万古霉素聚乳酸-羟基乙酸共聚物微球(NV-PLGA-MP);以乙烯-醋酸乙烯共聚物(EVA)为支撑剂,将该微球固载至聚丙烯(PP)补片,得到固载有盐酸去甲万古霉素聚乳酸-羟基乙酸共聚物微球的补片(NV-PLGA-MP-PP).采用HPLC法,测定NV含量以及NV-PLGA-MP和NV-PLGA-MP-PP体外药物释放过程.用扫描电镜(SEM)图像进行形貌观测,结果表明,制备的微球表面光滑,NV-PLGA-MP-PP表面平整,载药量高;在实验时间范围内,NV-PLGA-MP释放NV达4 d,NV-PLGA-MP-PP释放NV可持续28 d以上,具有明显的缓释等优点.NV-PLGA-MP-PP载药量高,缓释时间长,符合理想的抗感染疝补片材料的性能要求.     

5-氟尿嘧啶缓释剂制备及体外释药性能比较*

背景：5-氟尿嘧啶-聚乳酸-乙醇酸共聚物缓释微球在青光眼滤过术后抑制滤过泡的瘢痕化具有潜在应用价值,但微球制备程序复杂,微球载药量一般较低,且药物突释现象明显。 目的：比较乳化溶剂挥发法制备的5-氟尿嘧啶-聚乳酸-乙醇酸共聚物微球和喷雾成膜法制备的5-氟尿嘧啶-聚乳酸-乙醇酸共聚物缓释膜两种缓释剂的形态、载药量、体外释放规律,以探讨获得缓释效果较佳的5-氟尿嘧啶缓释剂制备方法。 方法：以聚乳酸-乙醇酸共聚物为载体,采用乳化溶剂挥发法制备5-氟尿嘧啶-聚乳酸-乙醇酸共聚物微球;用喷雾成膜法制备5-氟尿嘧啶-聚乳酸-乙醇酸共聚物缓释膜。 结果与结论：用乳化溶剂挥发法制备的微球外观圆整,粒径为(4 447.4±359.8) nm,载药量(8.67±0.37)%,包封率为(86.68± 1.92)%;用喷雾成膜法制备的缓释膜表面光滑平整,质量为(13.76±0.26) mg ,直径为6 mm ,厚度为(0.24±0.005) mm,载药量(23.76±0.37)%,包封率为(95.04±1.36)%。缓释剂制备过程未影响5-氟尿嘧啶的药物性能。微球体外释放突释明显,缓释膜的体外释放平稳持久,释放曲线符合Higuchi方程。结果表明缓释膜制备方法更简单易行,且能明显提高缓释剂的载药量,降低突释现象,同时延长药物的缓释时间。 关键词：聚乳酸-聚乙醇酸;5-氟尿嘧啶;微球;缓释膜;体外释放 doi:10.3969/j.issn.1673-8225.2012.08.022     

PVA/HA复合栓塞微球的制备与理化性能研究

目的制备聚乙烯醇(PVA)/羟基磷灰石(HA)复合栓塞微球, 并对其理化性能进行研究。方法将PVA与HA的混合溶液作为分散相、含有失水山梨糖醇脂肪酸酯的液体石蜡作为连续相, 以戊二醛为交联剂采用反相悬浮化学交联法, 制备PVA/HA复合栓塞微球。采用光学显微镜和扫描电镜对PVA/HA复合栓塞的外观形貌、粒径分布以及微观形貌进行观察, 采用傅里叶红外光谱对PVA/HA复合栓塞微球的化学结构进行表征, 并对PVA/HA复合栓塞微球的弹性以及载药和释药等性能进行测试。结果 PVA/HA复合栓塞微球为内部多孔状圆形小球, 粒径分布为50～300 μm, 弹性性能为(13.6±0.145)kPa, 为PVA微球的2.28倍, 载药量达(76.80±1.22)mg/g, 包封率为(38.4±12.7)%, 7 d内最高累积释放率为(7.37±0.101)%, 最高累积释药量为(256.2±9.8)μg。结论 PVA/HA复合栓塞微球具有良好的机械性能和载药释药性能, 为其作为医疗器械提供了重要参考依据。     

骨形态发生蛋白2/聚乳酸缓释微球的制备及表征

背景:聚乳酸具有良好的生物相容性,是优良的药物缓释载体。目的:制备重组人骨形态发生蛋白2/聚乳酸缓释微球,考察其理化特性。方法:采用复乳溶剂挥发法制备重组人骨形态发生蛋白2/聚乳酸缓释微球,进行扫描电镜、激光粒度、Zeta电位、溶胀性能检测及采用ELISA试剂盒检测包封率、载药率及体外释药率。结果与结论:扫描电镜见重组人骨形态发生蛋白2/聚乳酸缓释微球微球近似圆形,形态较规则,分散性较好,表面光滑。激光粒度分析重组人骨形态发生蛋白2/聚乳酸缓释微球微平均粒径839.6 nm,Zeta电位(-32.93±3.74)mV,微球溶胀系数1.157±0.059,包封率及载药率分别为(88.943±2.878)%,(0.026±0.001)%;微球在第1天释药约10.199%,随后释药较恒定,至第19天累计释药率为54.643%。说明制备出的重组人骨形态发生蛋白2/聚乳酸缓释微球的粒径达到中华人民共和国药典第10版二部关于亚微球的定义标准及包封率不低于80%的要求,并且在体外具有很好的缓释功能。     

全反式维甲酸-聚酸酐长效缓释剂研制及其可行性

背景：如何提高全反式维甲酸疗效、稳定性和降低毒副作用是临床治疗所面临的最大问题。近年来用可生物降解的聚合物为材料,通过乳化包囊等分散技术将药物制备成微粒分散体系,用作缓释、控释注射剂的研究日益增多。 目的：研制全反式维甲酸-聚酸酐长效缓释微球肿瘤治疗剂,观察其体内外全反式维甲酸经时缓释变化规律。 方法：采用乳剂-扩散溶剂挥发法制备全反式维甲酸-聚酸酐长效缓释微球肿瘤治疗剂,扫描电镜检测微球外观及微球粒径,高效液相色谱法检测微球载药量、包封率及体内外释药量。 结果与结论：所制微球治疗剂光滑圆整,大小均一,平均粒径(154.42±26.76) nm,载药率(16.5±1.45)%,包封率(87.84±4.79)%;体外释放实验证明该微球治疗剂可持续释放全反式维甲酸约50 d,将其肌肉注射到大耳白兔体内,可稳定缓释全反式维甲酸近45 d。结果表明该微球治疗剂载药量及包封率均较高,体内外释药平稳并且具有明显的长效缓释作用。     

MBG/PLGA composite microspheres with prolonged drug release

Mesoporous bioactive glass (MBG) and composite microspheres with MBG particles embedded in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) matrix have been prepared and used to load gentamicin (GS). The in vitro drug release experiments from both MBG and composite microspheres were conducted in distilled water and phosphate buffered saline (PBS) solution at 37 degrees C for more than 30 days. In both water and PBS, GS release from the MBG was very fast with about 60 wt % of the loaded drug released in the first 24 h, and more than 80 wt % released in two days. MBG/PLGA composite microspheres showed an initial release of about 33 wt % in the first day, and 48 wt % in 2 days, and a subsequent sustained release lasting for more than 4 weeks in PBS. MBG/PLGA composite microspheres may be used as an alternative drug release system, especially as a bone void filler for bone repair due to their combined advantages of sustained release of antibiotics and apatite-forming ability.     

Preparation and characterization of biodegradable chitosan/hydroxyapatite nanocomposite rods via in situ hybridization: a potential material as internal fixation of bone fracture

A transparent and slight yellow chitosan (CS)/hydroxyapatite (HA) nanocomposite with high performed, potential application as internal fixation of bone fracture was prepared by a novel and simple in situ hybridization. The method solves the problem of the nano-sized particle aggregation in polymer matrix. XRD, TEM and SEM were used to determine component and morphology of the composite. Results indicated that nano-HA particles were dispersed well in CS matrix, which can also be proved by the transparent appearance of composite rod, and that the structure of composite is assembled by CS molecule in the order of layer-by-layer. The mechanical properties of the composite were evaluated by using bending strength and modulus, and compared with some other bone replacement materials such as PMMA and bone cement. The initial mechanical properties of bending strength and modulus of composite are 86 MPa and 3.4 GPa, respectively, which is double or triple times stronger than that of PMMA and bone cement. It was found that the bending strength and modulus of CS/HA with ratio of 100/5 (wt/wt) is slightly higher than that of pure CS rod. The addition of HA can also reduce the ratio of water absorption of composite, which postponed the retention of mechanical properties of CS/HA composite under moisture condition. The phenomenon can be predicted with the fit exponential function according the data measured.     

Characteristics of hydroxyapatite coated titanium porous coatings on Ti-6Al-4V substrates by plasma sprayed method

A porous metal coating applied to solid substrate implants has been shown, in vivo, to anchor implants by bone ingrowth. Calcium phosphate ceramics, in particular hydroxyapatite [Ca(10)(PO(4))(6)(OH)(2), HA], are bioactive ceramics, which are known to be biocompatible and osteoconductive, and these ceramics deposited on to porous-coated devices may enhance bone ingrowth and implant fixation. In this study, bi-feedstock of the titanium powder and composite (Na(2)CO(3)/HA) powder were simultaneously deposited on a Ti-6Al-4V substrate by a plasma sprayed method. At high temperature of plasma torch, the solid state of Na(2)CO(3) would decompose to release CO(2) gas and then eject the molten Ti powder to induce the interconnected pores in the coatings. After cleaning and soaking in deionized water, the residual Na(2)CO(3) in the coating would dissolve to form the open pores, and the HA would exist at the surface of pores in the inner coatings. By varying the particle size of the composite powder, the porosity of porous coating could be varied from 25.0 to 34.0%, and the average pore size of the porous coating could be varied to range between 158.5 and 202.0 microm. Using a standard adhesive test (ASTM C-633), the bonding strength of the coating is between 27.3 and 38.2 MPa. By SEM, the HA was observed at the surface of inner pore in the porous coating. These results suggest that the method exhibits the potential to manufacture the bioactive ceramics on to porous-coated specimen to achieve bone ingrowth fixation for biomedical applications.     

New concept of 3D printed bone clip (polylactic acid/hydroxyapatite/silk composite) for internal fixation of bone fractures

Abstract

Open reduction with internal fixation is commonly used for the treatment of bone fractures. However, postoperative infection associated with internal fixation devices (intramedullary nails, plates, and screws) remains a significant complication, and it is technically difficult to fix multiple fragmented bony fractures using internal fixation devices. In addition, drilling in the bone to install devices can lead to secondary fracture, bone necrosis associated with postoperative infection. In this study, we developed bone clip type internal fixation device using three- dimensional (3D) printing technology. Standard 3D model of the bone clip was generated based on computed tomography (CT) scan of the femur in the rat. Polylacticacid (PLA), hydroxyapatite (HA), and silk were used for bone clip material. The purpose of this study was to characterize 3D printed PLA, PLA/HA, and PLA/HA/Silk composite bone clip and evaluate the feasibility of these bone clips as an internal fixation device. Based on the results, PLA/HA/Silk composite bone clip showed similar mechanical property, and superior biocompatibility compared to other types of the bone clip. PLA/HA/Silk composite bone clip demonstrated excellent alignment of the bony segments across the femur fracture site with well-positioned bone clip in an animal study. Our 3D printed bone clips have several advantages: (1) relatively noninvasive (drilling in the bone is not necessary), (2) patient-specific design (3) mechanically stable device, and (4) it provides high biocompatibility. Therefore, we suggest that our 3D printed PLA/HA/Silk composite bone clip is a possible internal fixation device.     

Development and in vitro characterisation of novel bioresorbable and bioactive composite materials based on polylactide foams and Bioglass for tissue engineering applications

Bioactive and bioresorbable composite materials were fabricated using macroporous poly(DL-lactide) (PDLLA) foams coated with and impregnated by bioactive glass (Bioglass) particles. Stable and homogeneous Bioglass coatings on the surface of PDLLA foams as well as infiltration of Bioglass particles throughout the porous network were achieved using a slurry-dipping technique in conjunction with pre-treatment of the foams in ethanol. The quality of the bioactive glass coatings was reproducible in terms of thickness and microstructure. Additionally, electrophoretic deposition was investigated as an alternative method for the fabrication of PDLLA foam/Bioglass composite materials. In vitro studies in simulated body fluid (SBF) were performed to study the formation of hydroxyapatite (HA) on the surface of PDLLA/Bioglass composites. SEM analysis showed that the HA layer thickness rapidly increased with increasing time in SBF. The high bioactivity of the PDLLA foam/Bioglass composites indicates the potential of the materials for use as bioactive, resorbable scaffolds in bone tissue engineering.     

Silica sol-gel for the controlled release of antibiotics. I. Synthesis, characterization, and in vitro release

Room temperature processed silica sol-gel (xerogel) was investigated as a novel controlled release carrier of antibiotics (vancomycin). Xerogel characteristics, in vitro release properties, and bactericidal efficacy of the released antibiotic were determined. The xerogel/vancomycin composite showed a long-term sustained release (up to 6 weeks). In addition, bactericidal efficacy of released vancomycin was retained. The kinetics of release and the amount released were dose dependent. The initial, first-order release was followed by a near-zero-order release. The time to transition from the first- to zero-order release increased with vancomycin load (from 2 to 3 weeks with load increase from 2.2 to 11.1 mg/g). Regardless of the load, about 70% of the original vancomycin content was released by the transitional point, and the cumulative release after 6 weeks of immersion was about 90%. This study, combined with other reports documenting biocompatibility and controlled resorbability of the xerogel/drug composite in vivo, suggests that silica xerogel is a promising controlled release material for the treatment of bone infections.     

Histomorphometric study on high-strength hydroxyapatite/poly(L-lactide) composite rods for internal fixation of bone fractures

The purpose of this study was to investigate the bone-implant interface of high-strength hydroxyapatite (HA)/poly(L-lactide) (PLLA) composite rods. As reinforcing particles, two types of HA particles-calcined HA (c-HA) and uncalcined HA (u-HA)-were applied to allow comparison of their suitability as bioactive fillers. Four types of composites (c-HA30, c-HA40, u-HA30, and u-HA40), which contained 30 or 40% by weight of each HA particle, were used. Unfilled PLLA rods were used as controls. A hole was drilled in the distal femora of 50 rabbits, and a composite or unfilled PLLA rod was implanted in a press-fit manner. Two, 4, 8, and 25 weeks after implantation, the samples were examined histologically by light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). An image analyzer was used for histomorphometric analysis of the bone-implant interface. An affinity index was calculated for each material; this was the length of bone directly apposed to the rods expressed as a percentage of the total length of the rod surface. In all the composites, histologic examination showed new bone formation at 2 weeks after implantation. The bone gradually grew along the composite surface. SEM showed direct bone contact with the composites without intervening fibrous tissue. During follow-up, the affinity indices of all the composite rods were significantly higher than those of the unfilled PLLA rods (p < 0.01; two-way ANOVA). The maximum affinity index (41%) was attained at 4 weeks in c-HA40 rods. In contrast, little bone contact was seen in unfilled PLLA rods. The only significant difference in affinity indices among the composites was that c-HA40 had a higher affinity index than u-HA40 (p < 0.05 at 4 weeks). No disintegration of rods or polymer debris, which could elicit inflammatory tissue reactions, was observed even at 25 weeks. Our results indicate that osteoconductive bone formation on composites could enhance the stability between bone and implant in fracture repair.     

Composite surgical sutures with bioactive glass coating

A processing method was developed to coat polyglactin 910 (Vicryl) sutures with bioactive glass powder (45S5 Bioglass). High reproducibility and homogeneity of the coating in terms of microstructure and thickness along the suture length were achieved. Bioglass-coated sutures exhibited a high level of chemical reactivity in simulated body fluid (SBF), indicating their bioactive behavior. This was evident by the prompt formation of hydroxyapatite (HA) crystals on the surface after only 7 days of immersion in SBF. These crystals grew to form a thick HA layer (15 microm thickness) after 3 weeks in SBF. The tensile strength of the sutures was tested before and after immersion in SBF in order to assess the effect of the bioactive glass coating on suture degradation. The tensile strength of composite sutures was lower than that of as-received Vicryl sutures, 385 and 467 MPa, respectively. However, after 28 days of immersion in SBF the residual tensile strengths of coated and uncoated sutures were similar (83 and 88 MPa, respectively), indicating no negative effect of the HA layer formation on the suture strength. The effect of bioactive glass coating on the polymer degradation is discussed. The developed bioactive sutures represent interesting materials for applications in wound healing, fabrication of fibrous three-dimensional scaffolds for tissue engineering, and reinforcement elements for calcium-phosphate temporary implants.     

Strontium in the bone-implant interface

Total hip replacement surgery is being performed on an increasingly large part of the population and at increasingly younger age. Because we live and stay physically active longer, and since hip replacement surgery has become quite successful, the treatment is being offered to progressively more patients. Unfortunately, about 17% of hip replacement surgeries currently involve revisions. Consequently, the longevity of both the primary and revision implant is an issue and warrants further investigation. Implants undergoing early instability or even subsidence correlate with an increased risk of aseptic loosening, subsequently requiring revision. Thus, the goal is early fixation by osseointegration of the implant. For revision implants, this is an even greater challenge since an allograft is often needed during surgery to obtain immediate stability of the implant. Bone grafts are rapidly resorbed. Thus, instability of the prosthesis may develop before new bone formation is well established and can mechanically secure the prosthesis. Strontium is a dual action drug; being both bone anabolic and anti-catabolic. In the form of strontiumranelate, it is used in the treatment of osteoporosis. Strontium may potentially improve the early osseointegration and fixation of implants. This dissertation consists of three studies investigating the effect of strontium at the bone-implant interface. The questions were firstly, what is the optimal delivery method for strontium to the interface, and secondly, can strontium exercise its dual action at the interface? The studies were performed in a cementless, experimental gap model in canine. The effects of strontium were evaluated by histomorphometrical analysis of the osseointegration and mechanical push-out test of implant fixation. Different stereological methods were used for the histomorphometrical analysis of each study. The methods used were reviewed critically and found valid. Study I compared a 5% strontium-substituted hydroxyapatite (HA) coating with an HA coating after 4 weeks and 12 weeks observation time. We examined whether fixation of the implant was improved by the strontium substitution. It was found that fixation of the implant was not improved by the strontium substituted HA coating at any of the two time points. Study II compared a 5% strontium-doped HA bone graft extender with an HA bone graft extender. The bone graft extender was mixed with allograft and impacted around a titanium implant. The objective of this study was to determine whether strontium doping of the bone graft extender could protect the allograft from fast resorption and increase gap healing, leading to the improved fixation of the implant. We found that the strontium doping increased gap healing and protected the allograft, however, results of the mechanical test were inconclusive. The reason might have been that the increased gap healing had not yet reached the implant during the 4 weeks observation time, so ongrowth onto the implant was not improved. Study III investigated the effects of bioactive glass coating with a 0%, 10% or 50% strontium-substitution versus HA coating of grit-blasted titanium alloy implants. The goal was to determine whether fixation of the implant would be improved by the bioactive glass coating, and then further improved by the strontium-substitution of the coating in a dose-dependent manner. Unfortunately, the bioactive glass coating failed, presumably due to aluminum contamination originating from the grit-blasting powder. The HA coated implants were superior in all parameters of osseointegration and the mechanical fixation of the implants. These studies show the importance of performing further experimental investigation. Even when investigating a known agent for use in a new application. Strontium delivered as doping of an HA bone graft extender showed potential as a dual acting agent in the interface. However, delivery methods of strontium to the bone-implant interface clearly need further investigation.     

钛合金表面新型生物玻璃/羟基磷灰石涂层的体内动物实验

目的为促进钛合金植入体与骨的结合,在其表面制备了生物玻璃/羟基磷灰石复合涂层,并植入兔子股骨内进行动物试验,采用等离子喷涂羟基磷灰石涂层和未涂层的Ti6Al4V合金作为对照。方法种植到期的植入体取出后进行组织学切片,采用品红-苦味酸染色后进行组织学观察,采用SEM高倍观察种植体与骨的结合界面,并对骨接触率和凹槽内骨长入量进行了统计分析和比较。结果三种植入体都具有良好的生物相容性。Ti6Al4V合金与骨之间是一种形态固定,而生物玻璃/羟基磷灰石涂层、等离子喷涂羟基磷灰石涂层可与骨形成骨键合。生物玻璃/羟基磷灰石涂层在植入期间与基体没有脱落,同时其与骨的接触率和凹槽内骨长入量要明显高于其余两个植入体,显示出促进骨生长的作用。结论由于具有良好的生物相容性和促进新骨生长的能力,生物玻璃/羟基磷灰石涂层可加快植入体与骨的愈合速度,在骨替代修复方面显示出优势和广阔的应用前景。