Bracaglia Laura G, Messina Michael, Vantucci Casey, Baker Hannah B, Pandit Abhay, Fisher John P
Fischell Department of Bioengineering, University of Maryland, College Park, Maryland 20742, United States.
Centre for Research in Medical Devices (CÚRAM), National University of Ireland Galway, Galway, Ireland.
ACS Biomater Sci Eng. 2017 Jul 10;3(7):1350-1358. doi: 10.1021/acsbiomaterials.6b00460. Epub 2016 Nov 15.
Hybrid biomaterials, combining naturally derived and synthetic materials, offer a tissue engineering platform that can provide initial mechanical support from a synthetic biomaterial, as well as a viable, bioactive substrate to support native cell infiltration and remodeling. The goal of this work was to develop a directional delivery system for bioactive molecules that can be coupled with a hybrid biomaterial. It was hypothesized that by using poly(propylene fumarate) as a scaffold to encapsulate PLGA microparticles, a tunable and directional release would be achieved from the intact scaffold into the bioactive substrate, pericardium. Release will occur as poly(lactic--glycolic acid) microparticles degrade hydrolytically into biocompatible molecules, leaving the PPF scaffold unchanged within the release time frame and able to mechanically support the pericardium substrate through remodeling. This study evaluated the degradation and strength of the composite polymer layer, and determined the release of encapsulated factors to occur over 8 days, while the bulk polymer remained intact with near 100% of its original mass. Next, this study demonstrated sustained bioactive molecule release into cell culture, causing significant changes to cellular metabolic activity. In particular, delivering vascular endothelial growth factor from the composite material to endothelial cells increased metabolic activity over the same cells with unloaded composite material. Additionally, delivering tumor necrosis factor α from the composite material to L929 cells significantly reduced metabolic activity compared to the same cells with unloaded composite material ( < 0.05). Finally, directional release into a bioactive substrate was confirmed with localized immunostaining of the encapsulated factor.
将天然衍生材料与合成材料相结合的混合生物材料提供了一个组织工程平台，该平台可以从合成生物材料提供初始机械支持，以及提供一个可行的、具有生物活性的底物来支持天然细胞浸润和重塑。这项工作的目标是开发一种可与混合生物材料偶联的生物活性分子定向递送系统。据推测，通过使用聚富马酸丙二醇酯作为支架来封装聚乳酸-乙醇酸共聚物微粒，可以实现从完整支架向生物活性底物心包的可调定向释放。随着聚乳酸-乙醇酸共聚物微粒水解降解为生物相容性分子，释放将会发生，在释放时间范围内聚富马酸丙二醇酯支架保持不变，并能够通过重塑为心包底物提供机械支持。本研究评估了复合聚合物层的降解和强度，并确定封装因子在8天内释放，而聚合物主体保持完整，其原始质量接近100%。接下来，本研究证明了生物活性分子持续释放到细胞培养物中，导致细胞代谢活性发生显著变化。特别是，将复合材料中的血管内皮生长因子递送至内皮细胞，与未负载复合材料的相同细胞相比，代谢活性增加。此外，与未负载复合材料的相同细胞相比，将复合材料中的肿瘤坏死因子α递送至L929细胞显著降低了代谢活性（P<0.05）。最后，通过对封装因子进行局部免疫染色证实了向生物活性底物的定向释放。
