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：     

载羟基喜树碱聚乳酸-羟基乙酸微球的制备及相关性能研究

目的制备一种载羟基喜树碱的聚乳酸-羟基乙酸(PLGA)缓释微球,并考察其相关性能。方法采用乳化-溶剂挥发法制备羟基喜树碱PLGA微球,用扫描电子显微镜观察载药微球表面形态,测定平均粒径及跨距,高效液相色谱检测包封率、载药率及体外释放情况,改良寇氏法计算小鼠半数致死量。结果制备的载药PLGA微球呈圆球形,表面光滑,无粘连,平均粒径30.8μm,跨距0.9,包封率为85.5%、载药率4.28%,在体外28 d累积释放药物81.4%。羟基喜树碱小鼠静脉注射的半数致死量为18.4 mg/kg,肌内注射半数致死量为71.3 mg/kg,而羟基喜树碱PLGA微球肌内注射的半数致死量为138.5 mg/kg。结论乳化-溶剂挥发法制备的羟基喜树碱PLGA微球粒径适宜,包封率、载药率高,缓释效果好,毒性低,具有潜在的临床应用价值。     

注射用雌二醇聚乳酸羟基乙酸缓释微球生物相容性研究

目的：以整体动物为研究对象，考察注射用雌二醇聚乳酸羟基乙酸缓释微球动物体内的生物降解和生物相容性。方法：肌注给药，显微镜观察组织切片，研究空白PLGA微球及载雌二醇PLGA微球的生物降解和相容性。结果：28d内，微球从规则球形降解为不规则微小颗粒，组织学观察空白微球和载雌二醇微球均未见病理改变。结论：注射用雌二醇聚乳酸羟基乙酸缓释微球具有良好的生物降解和相容性。     

复合壳聚糖纳米微球聚乳酸-羟基乙酸/纳米羟基磷灰石缓释载体系统对蛋白的缓释作用

背景：聚乳酸-羟基乙酸支架材料具有良好的生物相容性、无毒、可以良好的塑性,并具有一定的强度和韧性。但其降解产物为酸性,会影响局部pH值变化,不利组织生长。 目的：制备能够良好缓释蛋白类药物的复合支架。 方法：以牛血清蛋白为模型药物,以离子凝胶法制备壳聚糖微球。将微球与纳米羟基磷灰石和聚乳酸-羟基乙酸按一定比例混合,以冰粒子为致孔剂,采用粒子沥虑-冷冻干燥复合工艺制备CMs/nHA/PLGA复合缓释支架。利用扫描电镜、透射电镜、压泵仪和力学性能测试仪检测复合支架的形态和性能,并考察其在体外对蛋白类药物释放的规律。 结果与结论：制备的壳聚糖纳米微球形态良好,呈规则球形或类球形,粒径分布在220~770 nm,以380~650 nm为多。微球对药物的载药量为39.2%,包封率为68.3%,两者均与牛血清蛋白的初始量相关,载药量随牛血清蛋白初始量的增加而增加,包封率则反之。复合支架呈白色多孔状,孔径为125~355 mm,孔与孔之间联通良好,孔隙率达83.4%,压缩强度为1.4~ 2.1 MPa,10周降解率为28.6%。PLGA/nHA支架对牛血清蛋白的2 d累积释放量为85%,而壳聚糖和CMs/nHA/PLGA复合支架对牛血清蛋白的9 d累积释放量分别是为48.9%和35.7%。提示制作的壳聚糖纳米微球和CMs/nHA/PLGA支架材料对牛血清蛋白有良好的缓释作用,复合支架材料形态好,强度和降解速率合适。     

聚乳酸-羟基乙酸共聚物-壳聚糖单向缓释膜制剂的研究

目的研制一种可以携带药物单向作用患处的膜型缓释制剂,避免对周围正常组织产生不良影响。方法昆明小鼠30只,鼠龄6周,雌性,体质量20 g左右。利用聚乳酸-羟基乙酸共聚物(PLGA)和壳聚糖分别制作外层膜和释放膜,通过交联层将2层结合,利用单向释放实验、蛋白释放、淫羊藿苷释放(测定其光密度值)确定膜的单向缓释放性。分别取不同释放时期的膜做扫描电子显微镜观察,确定其在不同释放时期膜微观结构的变化。利用降解率确定膜的物理性质,通过细胞实验和动物实验[苏木精-伊红(HE)染色],了解材料的生物相容性和载药后对治疗的有效性。结果通过释放实验、载药实验,证明单向膜可以包载不同溶解性质(水溶性、脂溶性)的药物,具有单向缓释作用。在释药过程中膜微观结构有明显变化,15 d后降解率达到96%左右。生物相容性实验和HE染色实验证明单向膜具有良好的生物相容性。细胞实验证明包载淫羊藿苷的膜可以使骨髓间充质干细胞产生一定量的碱性磷酸酶,发生分化。结论通过以上实验,确定单向膜具有良好的生物相容性、单向释放性和缓释性,载药后有一定疗效。     

盐酸万古霉素@聚乳酸-羟基乙酸共聚物-壳聚糖-透明质酸复合缓释微球的制备及体外评价北大核心

背景:局部抗生素缓释系统可解决全身应用抗生素时引发的全毒性反应与短期局部注射抗生素半衰期短的问题。目的:制备盐酸万古霉素@聚乳酸-羟基乙酸共聚物-壳聚糖-透明质酸[vaneomyeinhydroehlorid@poly(lactic acid glycolic acid)-chitosanhyaluronic acid,VA@PLGA-CS-HA]复合缓释微球,并对其性能进行评价。方法:采用乳液法制备VA@PLGA-CS-HA复合缓释微球与未载药PLGA-CS-HA复合微球,其中载药微球中万古霉素的质量浓度分别为25,50,100 g/L,检测载药微球的载药量、包封率与体外缓释性能。将3种载药微球分别与金黄色葡萄球菌菌液共培养,相应时间点内检测抑菌率。将4种微球浸提液分别与MC3T3-E1细胞和MG-63细胞共培养,培养1,3,7 d后采用CCK-8法检测细胞毒性。结果与结论:(1)含盐酸万古霉素25,50,100 g/L载药微球的包封率分别为(79.70±5.11)%,(86.41±3.91)%,(63.18±1.96)%,载药量分别为(3.98±0.26)%,(8.64±0.39)%,(12.63±0.39)%;50 g/L载药微球的包封率高于100 g/L载药微球(P<0.05),100 g/L载药微球的载药量高于其他两组(P <0.05);(2)3种载药微球在24 h内均无明显的突释,其中50 g/L载药微球不同时间点的药物释放率快于其他两组,100 g/L载药微球不同时间点的药物释放量高于其他两组,并且3组在56 d时释放的药物质量浓度均高于盐酸万古霉素最小抗菌浓度;(3)3种载药微球均能在一定时间内有效杀死金黄色葡萄球菌,在第14-28天期间3种微球的相对菌落率低于3%,说明3种载药微球能持续而有效杀灭金黄色葡萄球菌;(4)含盐酸万古霉素25,50 g/L载药微球对MC3T3-E1细胞和MG-63细胞无明显的细胞毒性,100 g/L载药微球具有一定的细胞毒性;(5)结果表明,VA@PLGA-CS-HA微球具有良好的缓释性能、抗菌能力与生物组织相容性。     

左氧氟沙星聚乳酸-羟基乙酸共聚物纳米微球的制备及性能分析北大核心

背景:普通剂型的左氧氟沙星在体内代谢快,半衰期短,纳米微球为解决这一问题提供了新的途径。目的:制备一种能够减少给药次数,维持平稳有效的血药浓度且能复合在组织工程支架材料上的左氧氟沙星聚乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]纳米微球。方法:采用乳化溶剂挥发法制备不同条件下的左氧氟沙星纳米微球。(1)取24只新西兰大白兔随机分为3组研究左氧氟沙星纳米微球的体内药代动力学特性,普通剂型组通过耳缘静脉注射普通剂型的左氧氟沙星注射液20 mg/kg,未载药纳米微球组接受等剂量的未载药纳米微球,载药纳米微球组接受等剂量的左氧氟沙星纳米微球,每组8只。于定点时间测定静脉血中左氧氟沙星含量;(2)取45只新西兰大白兔建立尿路感染模型,随机分为3组,空白对照组每日经耳缘静脉注入生理盐水;传统剂型组注入普通剂型的左氧氟沙星(20 mg/kg);纳米微球组注入相应等剂量的左氧氟沙星纳米微球。于不同时间点行尿细菌培养,检测尿白细胞、血白细胞和中性粒细胞数;9 d后行膀胱组织学检测评估左氧氟沙星纳米微球抗菌能力。结果与结论:(1)体内药代动力学特性:与传统剂型相比,最优条件下的左氧氟沙星PLGA纳米微球可以明显减少血药浓度的波动和给药频率;(2)抗菌性能评估:在每日用药的传统剂型组和仅一次给药的纳米微球组,兔感染症状逐步得到控制,在第9天时已基本治愈;此外,在相同时间点纳米微球组兔治愈数量基本高于传统剂型组,虽然只有在用药后的第5天两组之间差异有显著性意义;(3)结果表明:左氧氟沙星PLGA纳米微球抗感染能力强,缓释性能佳,能明显减少给药频次及延长作用时间,在治疗泌尿系统感染方面具有良好的临床和组织工程尿道应用前景。     

构建聚乳酸-羟基乙酸电纺丝-壳聚糖电喷微球牙周仿生膜

文题释义： 离子交联法制备壳聚糖微球：离子交联法利用酸性环境下壳聚糖呈阳离子性,向壳聚糖溶液中边搅拌边滴加三聚磷酸钠,带负电的磷酸根离子与壳聚糖分子链上带正电荷的氨基通过静电吸附,从而形成微球。 牙周膜：是连接牙齿和牙槽骨之间具有方向性的结缔组织,宽度为0.15-0.38 mm,其内含具有一定方向性胶原纤维束,其一端埋入牙骨质,另一端伸入牙槽骨内,具有固定牙根和缓解咀嚼时所产生压力的作用,又称牙周关节;牙周膜能形成牙槽骨及牙骨质,被破坏后能重建。由此可见,牙周膜不是普通的纤维结缔组织,它具有方向性、附着点、可再生牙周组织(牙骨质、牙周膜、牙槽骨)。 背景：当牙齿脱离牙槽窝后,牙周膜断裂,残留在脱位牙根表面的牙周膜由三维变成二维,丧失了支架膜的作用,导致脱位牙再植后根骨粘连。如何研发一种能黏附牙根表面具有一定厚度及强度的三维缓释支架材料,是脱位牙牙周膜再生成功的关键之一。 目的：构建可黏附脱位牙根表面的缓释生长因子的三维仿生膜。 方法：采用静电纺丝技术制备聚乳酸-羟基乙酸电纺膜,研究电纺溶剂二氯甲烷与二甲基甲酰胺混合溶液、六氟异丙醇、三氯甲烷对电纺膜的影响,筛选最佳的电纺溶剂。采用电喷技术与离子交联法制备壳聚糖微球,研究壳聚糖相对分子质量(5万、10万)与质量浓度(10,20 g/L)、接受液三聚磷酸钠浓度(2%,5%,10%)、电压(14,28 kV)对壳聚糖微球的影响,筛选最佳的参数。构建含基质细胞衍生因子1壳聚糖微球(最优参数设计),检测其体外释放基质细胞衍生因子1α的速率。首先将聚乳酸-羟基乙酸电纺膜裹在牙齿根表面,然后在其表面滴加壳聚糖微球,在其外层裹一层薄薄的聚乳酸-羟基乙酸电纺膜,从而形成聚乳酸-羟基乙酸-壳聚糖微球-聚乳酸-羟基乙酸膜。 结果与结论：①利用电纺溶剂六氟异丙醇制备的聚乳酸-羟基乙酸电纺膜平均直径最小、空隙率最大;②当壳聚糖相对分子质量为5万、质量浓度为20 g/L时,微球的大小基本一致,平均直径366.6 μm,单分散性好、饱满、稳定;28 kV电压下形成的壳聚糖微球更符合脱位牙仿生膜的要求;利用5%三聚磷酸钠制备的壳聚糖微球表面微观结构孔径居中,最有利于临床牙周膜再生;壳聚糖微球可持续释放基质细胞衍生因子1α 1个月左右;③实验创建了一种黏附牙齿表面的具有缓释效能的聚乳酸-羟基乙酸-壳聚糖微球-聚乳酸-羟基乙酸三维仿生膜并筛选出构建此仿生膜的最佳参数,可在此模型基础上进一步研究组织工程手段对脱位牙再植的效果及机制。 ORCID: 0000-0003-3957-3423(封小霞) 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     

转化生长因子β3/聚乳酸-羟基乙酸微球对干细胞的调控

文题释义：转化生长因子β3：是转化生长因子β超家族成员,在胚胎软骨形成的多个时期都是必不可少的软骨组织形成的关键调节因子,可以促进间充质干细胞迁移并诱导其向软骨组织分化与成熟,促进软骨缺损的愈合。 聚乳酸-羟基乙酸微球：属于食品药品监督管理局(Food and Drug Administration,FDA)批准的可生物降解聚合物,具有可控的降解性和良好的生物相容性,被广泛应用于医药领域。由于其生物可降解性,聚乳酸-羟基乙酸微球微球被广泛应用于小分子药物、蛋白质和其他大分子药物的可控持续释放。 背景：转化生长因子β3/聚乳酸-羟基乙酸缓释微球系统可使药物在作用部位维持有效药物浓度,提高生长因子的利用率。 目的：优化转化生长因子β3/聚乳酸-羟基乙酸缓释微球制备工艺,探究其对脂肪间充质干细胞增殖和迁移的影响。 方法：采用乳化-溶剂挥发法制备转化生长因子β3/聚乳酸-羟基乙酸缓释微球,并对微球的形态、粒径大小、药物空间分布、包封率、载药量和缓释性能进行表征。将转化生长因子β3/聚乳酸-羟基乙酸缓释微球溶解于PBS中,于相应的时间点检测上清液中转化生长因子β3浓度,对应时间点扫描电镜观察微球形态。将脂肪间充质干细胞分6组培养,分别加入培养基(阴性对照)、含转化生长因子β3的培养基、含空白聚乳酸-羟基乙酸微球的培养基、含10,100,1 000 g/L转化生长因子β3/聚乳酸-羟基乙酸微球的培养基,于对应的时间点CCK-8法检测增殖。将脂肪间充质干细胞分别与培养基(阴性对照)、含转化生长因子β3的培养基、含聚乳酸-羟基乙酸微球的培养基、含10,100,1 000 g/L转化生长因子β3/聚乳酸-羟基乙酸微球的培养基以非接触方式共培养24 h,检测细胞迁移数量。结果与结论：①转化生长因子β3/聚乳酸-羟基乙酸微球呈球形,表面光滑,无粘连,粒径均匀分布,微球直径2-50 μm,微球内的蛋白药物分布均匀,具有较高的包封率与载药量;②缓释微球具有良好的降解性能,体外可于6个月后完全降解;同时具有良好的缓释性能,体外可缓慢释放转化生长因子β3长达45 d;③空白微球及含转化生长因子β3的缓释微球对脂肪间充质干细胞增殖无影响;④空白微球对脂肪间充质干细胞的迁移无影响,转化生长因子β3及含转化生长因子β3的缓释微球可促进脂肪间充质干细胞的迁移,不同质量浓度缓释微球间的促进效果无差异;⑤结果表明,转化生长因子β3/聚乳酸-羟基乙酸缓释微球可在不影响脂肪间充质干细胞增殖的情况下促进其迁移。 ORCID: 0000-0002-2267-4589(杨振) 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     

骨碎补总黄酮/聚乳酸-羟基乙酸微囊的制备

背景：微囊是目前靶向治疗给药体系的主要方向之一,其大小为数微米到数百微米,可用于口服、注射、动脉给药及局部靶器官治疗等多种治疗途径。目的：制备骨碎补总黄酮/聚乳酸-羟基乙酸共聚物微囊,并对微囊制备条件进行优化。方法：采用乳化溶剂挥发法制备骨碎补总黄酮/聚乳酸-羟基乙酸共聚物微囊,单因素分析聚乳酸-羟基乙酸共聚物质量浓度(60,100,140,180 g/L)、搅拌速度(50,1 000,2 000,4 000 r/min)、初乳乳化时间(2,4,6,8 min)及水油比(1∶5、1∶10、1∶15、1∶20)对微囊大体形态、粒径分布宽度与微囊中总黄酮包封率的影响,筛选出微囊粒径较小、分散均匀、包封率较高的骨碎补总黄酮/聚乳酸-羟基乙酸共聚物微囊。结果与结论：确定最佳工艺参数为：140 g/L 聚乳酸-羟基乙酸共聚物溶液,匀浆机2 000 r/min搅拌速度,初乳乳化时间6 min,水油比为1∶15。优化工艺下所制备的微囊分布均匀,平均粒径为(789.8±712.3) nm,粒径分布宽度较窄,基本小于5 μm;扫描电镜下观察所见微囊呈圆形,边缘较规则;微囊平均包封率为47.72%。  中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

乳酸-羟基乙酸共聚物缓控释微球的制备及突释成因与影响因素

背景：乳酸-羟基乙酸共聚物是一种生物可降解高分子材料,以乳酸-羟基乙酸共聚物为原料制备的载药微球和纳米粒既可提高药物的稳定性,又能实现缓释、控释和靶向释放。 目的：分析乳酸-羟基乙酸共聚物缓控释微球的制备方法以及突释的成因、影响因素和改进方法。 方法：应用计算机检索1990/2010中国期刊全文数据库和PubMed数据库与乳酸-羟基乙酸共聚物缓控释微球的制备及突释联系紧密的文章。 结果与结论：目前乳酸-羟基乙酸共聚物缓释微球制备方法主要有单凝聚法、乳化-固化法、喷雾干燥法。造成其突释的原因首先是药物分子和聚合物分子之间的相互作用太弱,导致药物很容易从微球进入释放递质中,其次是在微球释放初期,药物从微球中的孔洞和缝隙中释放出来导致突释。影响突释程度的具体因素有乳酸-羟基乙酸共聚物的相对分子质量、浓度、微球载药量、主药理化性质、微球制备方法及制备参数等。虽然国内外对突释机制以及控制突释措施的研究都还处于初步阶段,通过对各影响因素加以适当优化与控制,可在一定程度上减少微球的突释率,突释问题应该能够得到解决和控制。     

Development of biodegradable poly(propylene fumarate)/poly(lactic-co-glycolic acid) blend microspheres. I. Preparation and characterization

We developed poly(propylene fumarate)/poly(lactic-co-glycolic acid) (PPF/PLGA) blend microspheres and investigated the effects of various processing parameters on the characteristics of these microspheres. The advantage of these blend microspheres is that the carbon-carbon double bonds along the PPF backbone could be used for their immobilization in a PPF scaffold. Microspheres containing the model drug Texas red dextran were fabricated using a double emulsion-solvent extraction technique. The effects of the following six processing parameters on the microsphere characteristics were investigated: PPF/PLGA ratio, polymer viscosity, vortex speed during emulsification, amount of internal aqueous phase, use of poly(vinyl alcohol) (PVA) in the internal aqueous phase, and PVA concentration in the external aqueous phase. Our results showed that the microsphere surface morphology was affected most by the viscosity of the polymer solution. Microspheres fabricated with a kinematic viscosity of 39 centistokes had a smooth, nonporous surface. In most microsphere formulations, the model drug was dispersed uniformly in the polymer matrix. For all fabricated formulations, the average microsphere diameter ranged between 19.0 and 76.9 microm. The external PVA concentration and vortex speed had most effect on the size distribution. Entrapment efficiencies varied from 60 to 98% and were most affected by the amount of internal aqueous phase, vortex speed, and polymer viscosity. Overall, we demonstrated the ability to fabricate PPF/PLGA blend microspheres with similar surface morphology, entrapment efficiency, and size distribution as conventional PLGA microspheres.     

Immune responses in mice of beta-galactosidase adsorbed or encapsulated in poly(lactic acid) and poly(lactic-co-glycolic acid) microspheres

The immune response induced in mice by beta-galactosidase (beta-gal) adsorbed or encapsulated on poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) microspheres was investigated. The encapsulated protein elicited higher antibody response than the protein adsorbed on the microspheres in the case of the PLA microspheres. However, the encapsulated protein elicited weaker antibody response than the adsorbed protein in the case of the PLGA (50:50) microspheres, probably because, in this case, the encapsulation process adversely affected protein immunogenicity. In the case of adsorbed beta-gal, higher antibody response was obtained with the PLA microspheres than with the PLGA (50:50) microspheres. This may be related to the lower rate of beta-gal desorption from the PLA microspheres. Based on the immunoglobulin G1/immunoglobulin G2a ratios and the stimulation indices for interferon-gamma and interleukin-4, beta-gal encapsulated or adsorbed on PLA microspheres induced a Th(1)-biased immune response whereas beta-gal encapsulated or adsorbed on PLGA (50:50) microspheres induced a Th(2)-biased immune response. The results obtained indicate that more potent immune responses are obtained when the protein is encapsulated than adsorbed on the microspheres, providing that the encapsulation process does not adversely affect protein immunogenicity. Also, the type of polymer used to prepare the microspheres, but not the method of protein association with the microspheres, may affect the type of immune response.     

The release profiles and bioactivity of parathyroid hormone from poly(lactic-co-glycolic acid) microspheres

Poly(lactic-co-glycolic acid) (PLGA) microspheres containing bovine serum albumin (BSA) or human parathyroid hormone (PTH)(1-34) were prepared using a double emulsion method with high encapsulation efficiency and controlled particle sizes. The microspheres were characterized with regard to their surface morphology, size, protein loading, degradation and release kinetics, and in vitro and in vivo assessments of biological activity of released PTH. PLGA5050 microspheres degraded rapidly after a 3-week lag time and were degraded completely within 4 months. In vitro BSA release kinetics from PLGA5050 microspheres were characterized by a burst effect followed by a slow release phase within 1-7 weeks and a second burst release at 8 weeks, which was consistent with the degradation study. The PTH incorporated PLGA5050 microspheres released detectable PTH in the initial 24h, and the released PTH was biologically active as evidenced by the stimulated release of cAMP from ROS 17/2.8 osteosarcoma cells as well as increased serum calcium levels when injected subcutaneously into mice. Both in vitro and in vivo assays demonstrated that the bioactivity of PTH was maintained largely during the fabrication of PLGA microspheres and upon release. These studies illustrate the feasibility of achieving local delivery of PTH to induce a biologically active response in bone by a microsphere encapsulation technique.     

Apatite-coated poly(lactic-co-glycolic acid) microspheres as an injectable scaffold for bone tissue engineering

Biodegradable polymer/ceramic composite scaffold could overcome limitations of biodegradable polymers or ceramics for bone regeneration. Injectable scaffold has raised great interest for bone regeneration in vivo, since it allows one for easy filling of irregularly shaped bone defects and implantation of osteogenic cells through minimally invasive surgical procedures The purpose of this study was to determine whether apatite-coated poly(lactic-co-glycolic acid) (PLGA) microspheres could be used as an injectable scaffold to regenerate bone in vivo. Apatite-coated PLGA microspheres were fabricated by incubating PLGA microspheres in simulated body fluid. The apatite that coated the PLGA microsphere surfaces was similar to apatite in natural bone, as demonstrated by scanning electron microscopy, X-ray diffraction spectra, energy-dispersive spectroscopy, and Fourier transformed-infrared spectroscopy analyses. Rat osteoblasts were mixed with apatite-coated PLGA microspheres and injected immediately into subcutaneous sites of athymic mice. Osteoblast transplantation with plain PLGA microspheres served as a control. Histological analysis of the implants at 6 weeks with hematoxylin and eosin staining, Masson's trichrome staining, and von Kossa staining revealed much better regeneration of bone in the apatite-coated PLGA microsphere group than the plain PLGA microsphere group. The new bone formation area and the calcium content of the implants were significantly higher in the apatite-coated PLGA microsphere group than in the plain PLGA microsphere group. This study demonstrates the feasibility of using apatite-coated PLGA microspheres as an injectable scaffold for in vivo bone tissue engineering. This scaffold may be useful for bone regeneration through minimally invasive surgical procedures in orthopedic applications.     

Preparation and characterization of poly(acrylamide-co-acrylic acid)

A series of samples of the acrylamide/acrylic acid system with various compositions was prepared by copolymerization as well as saponification, and some new results on the kinetics of both processes are given. The products were characterized by osmometry, viscometry, GPC, DTA, and elemental analysis. The results led to the conclusion that copolymerisation and saponification lead to copolymers of identical sequential distribution of the monomeric units. It was found that the intrinsic viscosity as well as the slope factor k_H · [η]² —measured in 0,5 m NaBr solution—show a maximum at intermediate comonomer composition. This finding can be interpreted by chain stiffening due to intramolecular segmental interaction.     

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。     

载荷角质细胞生长因子聚乳酸-羟基乙酸共聚物纳米缓释微球在组织工程皮肤构建中的应用

背景：聚乳酸-羟基乙酸共聚物具有良好的生物相容性和可降解性性。 目的：制备载荷角质细胞生长因子聚乳酸-羟基乙酸共聚物控释载药系统用于组织工程皮肤。 方法：采用乳化-溶剂挥发法、冷冻干燥法制备载有角质细胞生长因子的聚乳酸-羟基乙酸共聚物纳米微球,并构建组织工程皮肤。扫描电镜、倒置显微镜、纳米粒度分析仪、紫外分光及ELISA法对微球评价其特性。 结果与结论：纳米微球载药量为(14.05±0.56)%,包封率为(59.86±2.38)%,角质细胞生长因子活性保留率(78.26±5.63)%,体外释放30 d的累积释药率达75%以上,微球形态规则圆润。微球形态规整,在脱细胞真皮表面分布均匀,与其联接良好。毛囊干细胞群在荷载聚乳酸-羟基乙酸共聚物纳米微囊脱细胞真皮上生长活跃,细胞形态良好,并呈克隆团生长。说明实验用组织工程材料制备工艺合理,材料相容性好,可用于构建新型组织工程皮肤。