Discipline of Biomedical Engineering, College of Engineering and Informatics, (NUI Galway), Galway, H91 HX31, Ireland.
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Adv Healthc Mater. 2019 Aug;8(16):e1900228. doi: 10.1002/adhm.201900228. Epub 2019 Jul 19.
Delivery of therapeutic-laden biomaterials to the epicardial surface of the heart presents a promising method of treating a variety of diseased conditions by offering targeted, localized release with limited systemic recirculation and enhanced myocardial tissue uptake. A vast range of biomaterials and therapeutic agents using this approach been investigated. However, the fundamental factors that govern transport of the drug molecules from the biomaterials to the tissue are not well understood. Here, the transport of a drug analog from a biomaterial reservoir to the epicardial surface is characterized using experimental techniques and microscale modeling. Using the experimentally determined parameters, a multiscale model of transport is developed. The model is then used to study the effect of important design parameters such as loading conditions, biomaterial geometry, and orientation relative to the cardiac fibers on drug delivery to the myocardium. The simulations highlight the significance of the cardiac fiber anisotropy as a crucial factor in governing drug distribution on the epicardial surface and limiting factor for penetration into the myocardium. The multiscale model can be useful for rapid iteration of different device concepts and for determination of designs for epicardial drug delivery that may be optimal and most promising for the ultimate therapeutic goal.
将治疗性生物材料递送到心脏的心外膜表面是一种很有前途的治疗方法，可以通过靶向、局部释放来治疗各种疾病，同时限制全身再循环和增强心肌组织摄取。已经研究了许多使用这种方法的生物材料和治疗剂。然而，控制药物分子从生物材料向组织输送的基本因素还不是很清楚。在这里，使用实验技术和微尺度模型来描述药物类似物从生物材料储库到心外膜表面的输送。使用实验确定的参数，开发了一种多尺度传输模型。然后，该模型用于研究重要设计参数（如加载条件、生物材料几何形状以及相对于心脏纤维的取向）对药物向心肌输送的影响。模拟结果强调了心脏纤维各向异性作为控制心外膜表面药物分布的关键因素和限制药物进入心肌的重要因素的重要性。该多尺度模型可用于快速迭代不同的设备概念，并确定心外膜药物输送的设计，这些设计可能是最终治疗目标的最佳和最有前途的。
