CIEPQPF, Chemical Engineering Department, FCTUC, University of Coimbra, Rua Sílvio Lima, Pólo II-Pinhal de Marrocos, 3030-790 Coimbra, Portugal.
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782-Santiago de Compostela, Spain; Instituto de Ortopedia y Banco de Tejidos Musculoesqueléticos, Universidad de Santiago de Compostela, 15782-Santiago de Compostela, Spain.
Int J Pharm. 2015 Feb 1;479(1):11-22. doi: 10.1016/j.ijpharm.2014.12.041. Epub 2014 Dec 23.
Homogeneous poly(ε-caprolactone) (PCL) and poloxamines (PLXs) porous blends were prepared using a supercritical carbon dioxide-assisted foaming/mixing (SFM) approach aiming to obtain cytocompatible implantable materials presenting tunable morphologies, bioerosion rates, bioactive molecules release and osteogenic features. Pure PCL, pure PLXs (T908 and T1107 varieties) and three distinct PCL:PLX 75:25, 50:50, 25:75% w/w blends, with and without the osteogenic and angiogenic bioactive molecule simvastatin were processed at constant pressure of 20 MPa and temperature of 40 °C or 43 °C, for T1107 and T908, respectively. Obtained porous blends were characterized applying a wide range of techniques and in vitro methods. Calorimetric analysis showed that hydrophilic T908 and T1107 PLXs are miscible with PCL for all tested compositions. Prepared PCL:PLX porous blends rapidly lost mass when immersed into phosphate buffer pH 7.4 due to PLXs dissolution and then went through slow and almost constant erosion rates for the subsequent weeks due to PCL slow hydrolytic degradation, which explains the rapid initial release of simvastatin and its subsequent sustained release for longer periods of time. PCL and PCL:PLX 75:25% w/w porous blends, containing or not simvastatin, showed a high cytocompatibility with SAOS-2 cells. In addition, prepared biomaterials promoted mesenchymal stem cells proliferation and their differentiation into osteoblasts. Overall, obtained results showed novel possibilities of addressing local treatment of small bone defects/fractures using highly porous PCL:PLX homogeneous blends.
均相聚己内酯(PCL)和聚氧乙烯醚(PLXs)多孔共混物是采用超临界二氧化碳辅助发泡/混合(SFM)方法制备的,目的是获得具有可调节形态、生物侵蚀率、生物活性分子释放和成骨特性的细胞相容性可植入材料。纯 PCL、纯 PLX(T908 和 T1107 品种)和三种不同的 PCL:PLX 75:25、50:50、25:75% w/w 共混物,有和没有成骨和血管生成生物活性分子辛伐他汀,在 20 MPa 的恒定压力和 40°C 或 43°C 的温度下进行处理,分别用于 T1107 和 T908。采用多种技术和体外方法对获得的多孔共混物进行了表征。量热分析表明,亲水 T908 和 T1107 PLX 与 PCL 完全混溶,适用于所有测试的配方。制备的 PCL:PLX 多孔共混物在浸入 pH 7.4 的磷酸盐缓冲液中时,由于 PLX 溶解,其质量迅速损失,然后由于 PCL 缓慢水解降解,其随后的几周内经历缓慢且几乎恒定的侵蚀速率,这解释了辛伐他汀的快速初始释放及其随后更长时间的持续释放。含有或不含有辛伐他汀的 PCL 和 PCL:PLX 75:25% w/w 多孔共混物具有较高的细胞相容性。此外,制备的生物材料促进间充质干细胞增殖,并将其分化为成骨细胞。总体而言,研究结果表明,使用高度多孔的 PCL:PLX 均相共混物局部治疗小骨缺损/骨折具有新的可能性。