Abstract：
Implantable medical devices that can facilitate therapy transport to localized sites are being developed for a number of diverse applications, including the treatment of diseases such as diabetes and cancer, and tissue regeneration after myocardial infraction. These implants can take the form of an encapsulation device which encases therapy in the form of drugs, proteins, cells, and bioactive agents, in semi-permeable membranes. Such implants have shown some success but the nature of these devices pose a barrier to the diffusion of vital factors, which is further exacerbated upon implantation due to the foreign body response (FBR). The FBR results in the formation of a dense hypo-permeable fibrous capsule around devices and is a leading cause of failure in many implantable technologies. One potential method for overcoming this diffusion barrier and enhancing therapy transport from the device is to incorporate local fluid flow. In this work, we used experimentally informed inputs to characterize the change in the fibrous capsule over time and quantified how this impacts therapy release from a device using computational methods. Insulin was used as a representative therapy as encapsulation devices for Type 1 diabetes are among the most-well characterised. We then explored how local fluid flow may be used to counteract these diffusion barriers, as well as how a more practical pulsatile flow regimen could be implemented to achieve similar results to continuous fluid flow. The generated model is a versatile tool toward informing future device design through its ability to capture the expected decrease in insulin release over time resulting from the FBR and investigate potential methods to overcome these effects.
摘要：
植入式医疗设备，可以促进治疗运输到局部地点正在开发的许多不同的应用，包括治疗糖尿病和癌症等疾病，和心肌梗塞后的组织再生。这些植入物可以采取封装装置的形式，以药物的形式封装治疗，蛋白质，细胞,和生物活性剂，在半透膜中。这种植入物已经显示出一些成功，但是这些设备的性质对重要因素的扩散构成了障碍，由于异物反应（FBR），在植入后进一步加剧。FBR导致在装置周围形成致密的低渗透性纤维胶囊,并且是许多可植入技术中失败的主要原因。用于克服该扩散屏障并增强来自装置的治疗输送的一种潜在方法是结合局部流体流。在这项工作中,我们使用实验信息输入来表征纤维囊随时间的变化，并使用计算方法量化这如何影响设备的治疗释放。胰岛素被用作代表性疗法，因为1型糖尿病的包封装置是表征最充分的。然后，我们探索了如何使用局部流体流动来抵消这些扩散障碍，以及如何实施更实用的脉动流方案以实现与连续流体流动类似的结果。所生成的模型是用于通过其捕获由FBR导致的胰岛素释放随时间的预期减少的能力来通知未来设备设计的通用工具,并研究克服这些影响的潜在方法。
