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。     

硫酸钙/庆大霉素、硫酸钙/聚乳酸/庆大霉素释药系统的制备与特性分析

目的构建新型骨植入型抗生素释放系统,硫酸钙／庆大霉素、硫酸钙／聚乳酸／庆大霉素释药系统,探讨抗生素释放系统的制备可行性。方法以自行研制的硫酸钙或硫酸钙与聚乳酸的复合物作为抗生素载体,构建抗生素释放系统,对其进行电镜扫描,晶体衍射分析和体外降解实验以分析其构成特点、理化特性和降解特点。结果所构建的抗生素释药系统主要成分为二水硫酸钙,具有初始的生物力学抗压缩强度,具有一定的孔隙率,硫酸钙／聚乳酸／庆大霉素中,聚乳酸对硫酸钙形成包裹。体外可降解,硫酸钙／聚乳酸／庆大霉素降解时间长于硫酸钙／庆大霉素。结论以硫酸钙和硫酸钙聚乳酸复合物作为载体构建抗生素释放系统能够满足药物释放和骨内植入的要求,具有制备的可行性。     

戊二醛交联对壳聚糖／羟基磷灰石-庆大霉素缓释材料性能的影响CSCD

背景:交联是骨组织工程材料改性的一种常用方法,但目前仍缺乏交联剂对载药人工骨材料性能影响的相关研究与报道。目的:研究戊二醛交联对壳聚糖/羟基磷灰石-庆大霉素载药人工骨材料力学性能、降解性能及体外药物缓释行为的影响。方法:分别制备壳聚糖质量分数为10%,20%,30%的壳聚糖/羟基磷灰石-庆大霉素载药人工骨材料与戊二醛交联壳聚糖/羟基磷灰石-庆大霉素载药人工骨材料,检测各组材料的机械强度、吸水率、降解率及体外药物释放行为。结果与结论:壳聚糖含量为10%,20%,30%壳聚糖/羟基磷灰石-庆大霉素的抗压强度分别为(10.16±1.17),(28.40±0.64),(23.28±1.30)MPa,经戊二醛交联后材料的抗压强度分别增大至(36.30±1.20),(51.60±2.08),(36.90±3.22)MPa。壳聚糖含量为10%,20%,30%壳聚糖/羟基磷灰石-庆大霉素交联后的吸水率与降解率均低于交联前。在体外缓释的第1天,30%壳聚糖/羟基磷灰石-庆大霉素的药物释放量为42.2%,材料经戊二醛交联处理后药物释放量降至33.6%,在随后的9 d,交联壳聚糖/羟基磷灰石-庆大霉素的总释放量均低于壳聚糖/羟基磷灰石-庆大霉素。表明戊二醛交联赋予了材料更好的生物稳定性,减缓了材料降解速率,显著改善了药物突释现象。     

戊二醛交联对壳聚糖/羟基磷灰石-庆大霉素缓释材料性能的影响

背景：交联是骨组织工程材料改性的一种常用方法,但目前仍缺乏交联剂对载药人工骨材料性能影响的相关研究与报道。 目的：研究戊二醛交联对壳聚糖/羟基磷灰石-庆大霉素载药人工骨材料力学性能、降解性能及体外药物缓释行为的影响。 方法：分别制备壳聚糖质量分数为10%,20%,30%的壳聚糖/羟基磷灰石-庆大霉素载药人工骨材料与戊二醛交联壳聚糖/羟基磷灰石-庆大霉素载药人工骨材料,检测各组材料的机械强度、吸水率、降解率及体外药物释放行为。 结果与结论：壳聚糖含量为10%,20%,30%壳聚糖/羟基磷灰石-庆大霉素的抗压强度分别为(10.16±1.17),(28.40±0.64),(23.28±1.30) MPa,经戊二醛交联后材料的抗压强度分别增大至(36.30±1.20),(51.60±2.08),(36.90±3.22) MPa。壳聚糖含量为10%,20%,30%壳聚糖/羟基磷灰石-庆大霉素交联后的吸水率与降解率均低于交联前。在体外缓释的第1天,30%壳聚糖/羟基磷灰石-庆大霉素的药物释放量为42.2%,材料经戊二醛交联处理后药物释放量降至33.6%,在随后的9 d,交联壳聚糖/羟基磷灰石-庆大霉素的总释放量均低于壳聚糖/羟基磷灰石-庆大霉素。表明戊二醛交联赋予了材料更好的生物稳定性,减缓了材料降解速率,显著改善了药物突释现象。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：     

新型α-半水硫酸钙/双相生物陶瓷人工骨修复兔桡骨骨缺损的X射线评估

背景:α-半水硫酸钙和双相生物陶瓷作为骨修复材料已在临床广泛应用,但都存在一定的缺点。目的:观察α-半水硫酸钙/双相生物陶瓷人工骨用于修复兔桡骨缺损的效果。方法:建立18只成年新西兰大白兔任一单侧桡骨缺损模型,随机分为3组,分别于骨缺损处植入α-半水硫酸钙材料、α-半水硫酸钙/双相生物陶瓷材料与双相生物陶瓷材料,植入后第4,8,12周时取材,对3组进行大体观察及X射线观察。结果与结论:1大体观察:植入第12周,α-半水硫酸钙/双相生物陶瓷组骨缺损空腔完全修复,桡骨形状基本恢复到术前形态;α-半水硫酸钙组明显缺损凹陷,双相生物陶瓷组仍可见少量材料填充覆盖。2X射线观察:α-半水硫酸钙组材料吸收过快,材料降解快于新骨生成,可见骨缺损;α-半水硫酸钙/双相生物陶瓷组骨缺损已愈合,皮质骨塑形良好,骨髓腔完全再通;双相生物陶瓷组仍可见材料影,受未降解材料影响骨缺损未能修复。表明新型α-半水硫酸钙/双相生物陶瓷骨修复材料能明显促进兔桡骨骨缺损的修复,修复效果优于与单独α-半水硫酸钙材料及双相生物陶瓷材料。     

医用硫酸钙人工骨与同种异体骨修复良性骨肿瘤骨缺损的对比分析

背景：探讨医用硫酸钙人工骨可替代同种异体骨作为骨缺损的修复材料的可行性。 目的：观察医用硫酸钙人工骨材料治疗良性骨肿瘤骨缺损的临床疗效。 方法：纳入应用医用硫酸钙人工骨材料于临床修复良性骨肿瘤刮除术后骨缺损病例31例和同种异体骨材料修复病例36例。观察植入材料后4,8,12周摄X射线片植骨吸收情况及植骨材料降解率。 结果与结论：全部病例均获随访3个月以上。两组病例在随访期间植骨材料降解率差异无显著性意义。良性骨肿瘤植骨区无复发。患者植入材料后3个月X射线片示骨缺损部位有新骨生成。结果表明医用硫酸钙人工骨材料临床疗效和同种异体骨接近。     

乳酸-乙醇酸共聚物载药复合纤维制备及其释药行为研究

乳酸-乙醇酸共聚物(PLGA)复合纤维具有良好的生物相容性和生物可降解性,且降解速率可由相对分子质量和共聚物组成来调控.采用同轴静电纺丝法制备以PLGA为壳层材料、聚乙烯基吡咯烷酮(PVP)为内芯材料的复合纤维,研究两种模型药物(5-氟尿嘧啶和硝苯地平)在同轴复合纤维载体中的药物释放行为,并用扫描、透射电镜观察复合纤维的形貌与结构,用紫外分光光度计测量载药量和累积释放率.实验结果表明,通过改变芯、壳纺丝液浓度、PLGA相对分子质量以及共聚物中LA和GA的组成比,可制得具有芯-壳结构且直径大小不同的复合纤维.采用相同电纺丝条件,可以将不同药物以相同载药量包覆于复合纤维中,但药物的释放行为不相同.     

rhBMP-2/聚乳酸与聚乙醇酸共聚物载药微球的制备及成骨活性研究

目的制备一种具有良好降解性和成骨活性可注射的rhBMP-2载体材料。方法采用复乳-溶剂蒸发技术制备携载rhBMP-2的聚乳酸与聚乙醇酸共聚物P(LGA)微球。测定材料的制备参数及其特性,包括材料的形貌、载药率、释药速度,并将载药微球植入鼠股部肌袋,通过X线、组织学评价载体材料的异位成骨能力。结果载药微球粒径为(253±64)μm,载药率0.52%±0.14%,载药微球rhBMP-2体外释放24h时为15.2%±0.8%,随后呈持续缓慢释放,28d时总计达48.6%±5.3%。载药微球植入鼠股部肌袋4周,材料周围有明显的骨形成。结论载有rhBMP-2的PLGA微球具有良好的缓释效果和生物活性,是一种较为理想的生长因子载体材料和释放系统。     

盐酸多柔比星缓释植入剂体外释药与体外降解的研究

以聚（乳酸-羟基乙酸）共聚物（PLGA）为载体制备盐酸多柔比星缓释植入剂,测定植入剂的释放度和PLGA失重率,结果表明PLGA体外降解曲线呈＂S＂形,起初的迟缓期后降解速率加快,5周时失重率达80%。植入剂表现出趋于零级的药物释放模式（r=0.9880）,在0~25 d日均释放度达3.26%,35 d时累积释放度达90%以上。植入剂可持续释药1个月,释药速率主要取决于PLGA降解速率,通过调节PLGA降解速率可以很好地控制药物的释放度。     

不同浓度载万古霉素半水硫酸钙/丝素微球复合人工骨材料的制备及性能研究

本文以丝素蛋白为载体,以万古霉素(VCM)为药物模型,采用水-油相溶解扩散方法制备了不同浓度的丝素微球(SFM),并进一步构建了载VCM半水硫酸钙(CSH)/SFM复合人工骨材料。实验中用扫描电子显微镜(SEM)观察材料的表面形态,用傅里叶变换红外吸收光谱(FTIR)研究材料的构象,用抑菌圈实验验证材料的抑菌性能,用紫外/可见分光光度计检测材料的药物释放性能,用万能试验机测定样品的抗压性能。结果表明,随着丝素浓度从20、40mg/mL增加到60mg/mL,丝素构象及抑菌性没有显著改变,而SFM粒径增加,药物释放速率减慢;同时在CSH中复合SFM后,随着SFM丝素浓度增加,复合人工骨材料药物释放速率逐渐减小,压缩断裂功逐渐增加。上述结果表明,本研究在一定程度上改进了CSH存在的脆性大、作为药物载体前期释放快的缺点,有望在临床感染性骨缺损的治疗中取得更好的应用成效。     

医用硫酸钙与磷酸钙在创伤性骨缺损中应用的疗效观察

目的观察人工合成医用硫酸钙和磷酸钙在骨创伤中，作为骨替代物的临床疗效。方法对50例创伤骨折并存在骨缺损者，治疗除采用内固定（钢针、钢板）和外固定（石膏、外固定架）外，结合使用医用硫酸钙组24例，使用医用磷酸钙组26例。结果所有使用填充人工骨的病例，骨折均如期愈合，平均愈合时间11周（8～16周），使用硫酸钙者未出现任何异常反应和并发症，使用磷酸钙者有2例浅表渗出，经换药愈合。平均随访时间24周（16～50周），硫酸钙组平均吸收时间较磷酸钙组短约30周。结论医用硫酸钙和磷酸钙人工骨均可作为骨替代物应用，在辅助固定下具有安全，方便，副作用小以及填充效果确实，骨折愈合良好等优点。硫酸钙骨粉固化后较磷酸钙坚固，具有较强支撑作用。在内或外固定确实的情况下，二者均不失为治疗骨缺损的最佳选择。     

骨髓炎治疗用缓释制剂的制备及体外抑菌活性研究

骨髓炎的定点缓释给药治疗是重要的生物医学问题,关键是要制备高效的缓释药棒。我们采用热熔法,以聚(二聚酸(十四烷二酸)共聚物[P(DA-TA),WDA:WTA=50:50]为药物缓释材料,硫酸庆大霉素为模型药物,制备了硫酸庆大霉素-聚酸酐缓释药棒,以期最终用于骨髓炎的定点缓释给药治疗。初步的制剂稳定性研究表明,在室温干燥条件下,该缓释药棒具有良好的制剂稳定性。体外释药结果表明,37℃时,该缓释药棒在蒸馏水中、0．9％生理盐水中和0．1 mol／L pH7．4 PBS中具有明显缓释作用,其体外释药动力学均符合一级动力学方程和Peppas方程。抑菌活性实验表明,该缓释药棒对骨髓炎常见致病菌:金黄色葡萄球菌及大肠杆菌有长达60 d的抑制作用。该类硫酸庆大霉素-聚酸酐缓释药棒具有良好的制剂稳定性和长达60 d的抑菌活性,可望用于骨髓炎治疗领域。     

Release of gentamicin from bone regenerative materials: an in vitro study

Antibiotic loading of bone regenerative materials is a promising way to protect augmentation procedures from infection during the resorption phase of bone substitutes. Especially in the early stage of implantation, it should protect the grafted site against microbiological pathogens. The present study reports the release kinetics of gentamicin after loading from two synthetic bone filling materials. The first, BONITmatrix, is a biphasic calcium phosphate silica composite obtained by the sol-gel route consisting of 13% silicon dioxide (w/w) and calcium phosphates (hydroxyapatite/beta-tricalcium phosphate 60/40 w/w). The second, Synthacer, is a sintered hydroxyapatite ceramic. Gentamicin was loaded by dipping and by vacuum coating. Release kinetics of the loaded Gentamicin was investigated by fluorescence polarization immunoassay and by staphylococcus aureus assay. By dipping, loading failed for Synthacer, and it was 12.7 mg gentamicin per gram bone substitute for BONITmatrix. By vacuum coating, loading was 11.3 mg gentamicin per gram bone substitute for Synthacer and 7.4 mg gentamicin per gram bone substitute for BONITmatrix. Distinct release kinetics were measured. For Synthacer, a high initial release was followed by a lower protracted release level up to 28 days. For BONITmatrix release was continuous over the investigated 70-day period. The present data suggest that the porosity properties at the nano- and microscopic levels, or the composition are responsible for antibiotic loading and subsequent release.     

骨形态发生蛋白2/注射式硫酸钙缓释载体的生物相容性

背景：目前硫酸钙主要被作为抗生素载体和成骨因子载体。 目的：观察骨形态发生蛋白2/注射式硫酸钙缓释系统的体外缓释效果及与种子细胞的生物相容性。 方法：制备骨形态发生蛋白2/注射式硫酸钙缓释系统,检测其体外释放性能。将SD大鼠骨髓间充质干细胞经体外诱导培养、扩增后,种植于骨形态发生蛋白2/注射式硫酸钙缓释载体和单纯的注射式硫酸钙支架上行体外培养。 结果与结论：骨形态发生蛋白2/注射式硫酸钙缓释支架具有缓释骨形态发生蛋白2的效果,持续时间可达31 d。骨形态发生蛋白2/注射式硫酸钙缓释支架与大鼠骨髓间充质干细胞具有优良的生物相容性,并且相同时间点支架上的细胞黏附率、细胞数量及细胞碱性磷酸酶活性均明显高于注射式硫酸钙支架;扫描电镜发现两组材料上均有细胞生长,骨形态发生蛋白2/注射式硫酸钙缓释支架上的细胞在支架表面和孔隙内生长良好,细胞突起接触融合,细胞密集区域可见细胞外基质形成,大量细胞包绕在材料表面;注射式硫酸钙支架上的细胞黏附数量较少,生长情况不及骨形态发生蛋白2/注射式硫酸钙缓释支架上的细胞。     

硫酸钙/脱钙骨基质颗粒在颈椎椎体间融合中的应用

目的观察应用硫酸钙/脱钙骨基质颗粒作为植骨替代材料促进颈椎椎体间融合的效果。方法对35例患者﹙59个节段﹚行颈椎前路间隙减压植骨融合钛板固定术,椎体间植骨采用填充硫酸钙/脱钙骨基质颗粒的聚醚醚酮﹙PEEK﹚融合器。其中男19例,女16例,年龄32~65岁,平均53.2±12.5岁。其中神经根型颈椎病12例,脊髓型颈椎病15例,混合型颈椎病8例。术后观察JOA评分、颈椎曲度、椎体间融合情况。结果 35例均获随访,随访时间24个月。JOA评分术前为7.7±2.1,随访终止时为14.2±2.9﹙<0.01﹚,恢复率为69.9%。术后无钛板、螺钉断裂或松动,无融合器移位现象发生。所有融合节段均融合。结论颈椎前路减压融合术中使用填充硫酸钙/脱钙骨基质颗粒的PEEK椎体间融合器能够获得满意的椎体间融合。     

Changing the release kinetics of gentamicin from poly(D,L-lactide) implant coatings using only one polymer

Creating orthopedic implants that locally deliver drugs is an appealing approach to induce bone regeneration and prevent or treat infections. In this study, titanium K-wires were coated with poly(D,L-lactide) (PDLLA) solutions with different polymer/solvent/drug ratios to modify the release kinetics of the antibiotic gentamicin. The concentrations of PDLLA ranged from one-fold (100 mg/1.5 mL solvent, 1X) to four-fold (400 mg/1.5 mL solvent, 4X), where the higher concentrations led to the thickening of the drug-loaded coatings and an increase of total coating mass. Coated wires were incubated in PBS buffer at 37 °C for up to 32 weeks, and the elution kinetics were analyzed at several time points. Different release profiles were observed: I) a burst release within the first hours for the coatings made out of lower concentrations of PDLLA with higher amounts of gentamicin and II) a sustained release of up to 14 weeks for the different coatings with higher polymer amounts with lower concentrations of gentamicin. Moreover, the amounts of remaining gentamicin on the wires after elution were dependent on the coating composition. Nearly complete gentamicin was released from the 1X PDLLA coatings and approximately one-third with respect to initial gentamicin remained in the 4X coatings. Based on these results, we garnered a better understanding of the parameters that influenced release kinetics in this simple system and described how to realize different release patterns by using only one polymer. Using this knowledge, tailored coated implants that can improve infection prophylaxis or stimulate bone healing may be designed.     

Fabrication of calcium sulfate/PLLA composite for bone repair

The bone-repairing composite material CS/PLLA was fabricated by mixing poly-L-lactic acid (PLLA) and calcium sulfate hemihydrate (CSH). The structure of the composite was analyzed with Infrared spectroscope, X-ray diffraction, and scanning electron microscope. The results indicated that the crystal pattern of calcium sulfate was affected by the addition of PLLA. PLLA part impacted the development of calcium sulfate dihydrate (CSD) crystal by slowing the conversion from CSH to CSD, so the composites are actually composed of CSH, CSD, and PLLA. The absorbing test in vitro showed that CS/PLLA composite absorbed more slowly than pure CS, suggesting the addition of PLLA can adjust the absorption rate of CS to meet different requirements. The pH value changes of the media had similar trends for different composites during the absorbing test of CS/PLLA samples in aqueous medium, which was connected to the absorption of calcium sulfate. The absorption of calcium sulfate in a certain time left a porous PLLA scaffold that will enable cells to further grow in. The surface of CS/PLLA pellets was inoculated with human osteoblasts, and the primary results showed that the osteoblasts could attach and spread on the surface, which will stimulate our desire for further study.     

硫酸钙人工骨修复骨缺损的研究进展

硫酸钙（CS）材料由于其具有生物相容性好、生物可吸收降解性高、制备成本相对低廉、原材料来源丰富等特点,常用于大段骨缺损修复的治疗。然而,其材料存在着降解速度快、骨诱导活性差等问题。因此硫酸钙材料与不同材料的复合,使其相关性能得到改进与加强成为了目前研究的热点,近年来研究人员通过将硫酸钙与不同的材料相结合,负载各种抗生素、药剂、生长因子等无机、有机分子,制备出新型复合硫酸钙材料,并经体外细胞实验和体内动物实验探究评价新型材料的机械和生物性能,为进一步硫酸钙人工骨材料的研究和开发提供了理论与实践支持。本文将通过对近年来以硫酸钙材料为载体的新型复合材料在骨缺损修复方面的研究进展进行综述总结,以期为后续的研究提供参考。     

Gentamicin-loaded calcium carbonate materials: comparison of two drug-loading modes

Synthetic aragonite-based porous materials were drug loaded with gentamicin sulphate, an antibiotic active on Staphylococcus aureus responsible for osteomyelitis. Drug loading was accomplished by two different ways: by integration of gentamicin in material during processing or by soaking material into gentamicin solutions. We first investigated the influence of drug loading on compressive strength of materials. Results indicate that soaked materials presented the same compressive strength than unloaded materials with the same porosity. By contrast, the integration of gentamicin during processing increased significantly the compressive strength of materials. The materials drug content before elution was a least 10 times higher when gentamicin was integrated during processing comparatively to soaked materials. The study of in vitro gentamicin release showed that for materials with gentamicin integrated during material processing, high concentrations of gentamicin were released up to 8 or 12 days, against 4 days for soaked materials. The transport coefficients calculation, for the first step of release, indicated that the rate of release was higher for materials with integrated gentamicin because of the higher gentamicin content. The porosity rate influenced the rate of release for materials positively with gentamicin integrated during processing contrary to soaked materials for which a higher porosity rate allowed a deeper penetration of gentamicin during drug loading and then a slightly slower release. Results indicate that aragonite-based material with gentamicin integrated during material processing may be used either as resorbable device for release of high concentrations of gentamicin or as biomaterial for combined therapy: bone substitution and prevention or treatment of osteomyelitis.