Biomedical Engineering, School of Engineering, College of Science and Engineering, University of Galway, Galway, Ireland.
Flow Cytometry Core Facility, University of Galway, Galway, Ireland.
Acta Biomater. 2024 Jan 1;173:80-92. doi: 10.1016/j.actbio.2023.11.017. Epub 2023 Nov 14.
The foreign body response (FBR) to implanted materials culminates in the deposition of a hypo-permeable, collagen rich fibrotic capsule by myofibroblast cells at the implant site. The fibrotic capsule can be deleterious to the function of some medical implants as it can isolate the implant from the host environment. Modulation of fibrotic capsule formation has been achieved using intermittent actuation of drug delivery implants, however the mechanisms underlying this response are not well understood. Here, we use analytical, computational, and in vitro models to understand the response of human myofibroblasts (WPMY-1 stromal cell line) to intermittent actuation using soft robotics and investigate how actuation can alter the secretion of collagen and pro/anti-inflammatory cytokines by these cells. Our findings suggest that there is a mechanical loading threshold that can modulate the fibrotic behaviour of myofibroblasts, by reducing the secretion of soluble collagen, transforming growth factor beta-1 and interleukin 1-beta, and upregulating the anti-inflammatory interleukin-10. By improving our understanding of how cells involved in the FBR respond to mechanical actuation, we can harness this technology to improve functional outcomes for a wide range of implanted medical device applications including drug delivery and cell encapsulation platforms. STATEMENT OF SIGNIFICANCE: A major barrier to the successful clinical translation of many implantable medical devices is the foreign body response (FBR) and resultant deposition of a hypo-permeable fibrotic capsule (FC) around the implant. Perturbation of the implant site using intermittent actuation (IA) of soft-robotic implants has previously been shown to modulate the FBR and reduce FC thickness. However, the mechanisms of action underlying this response were largely unknown. Here, we investigate how IA can alter the activity of myofibroblast cells, and ultimately suggest that there is a mechanical loading threshold within which their fibrotic behaviour can be modulated. These findings can be harnessed to improve functional outcomes for a wide range of medical implants, particularly drug delivery and cell encapsulation devices.
异物反应（FBR）导致植入材料在植入部位被肌成纤维细胞沉积一层低渗透性、富含胶原蛋白的纤维囊。纤维囊会对一些医疗植入物的功能产生有害影响，因为它会将植入物与宿主环境隔离。通过间歇性驱动药物输送植入物已经实现了纤维囊形成的调制，但是这种反应的机制还没有很好地理解。在这里，我们使用分析、计算和体外模型来理解使用软机器人对人肌成纤维细胞（WPMY-1 基质细胞系）进行间歇性驱动的反应，并研究驱动如何改变这些细胞分泌胶原蛋白和促炎/抗炎细胞因子。我们的研究结果表明，存在一个机械加载阈值，可以通过减少可溶性胶原蛋白、转化生长因子-β 1 和白细胞介素 1-β 的分泌，以及上调抗炎白细胞介素-10，来调节肌成纤维细胞的纤维状行为。通过提高我们对参与 FBR 的细胞如何对机械驱动做出反应的理解，我们可以利用这项技术来改善广泛的植入式医疗设备应用的功能结果，包括药物输送和细胞封装平台。
许多可植入医疗设备成功临床转化的主要障碍是异物反应（FBR）和由此在植入物周围形成低渗透性纤维囊（FC）。以前已经证明，使用软机器人植入物的间歇性驱动（IA）来干扰植入部位可以调节 FBR 并减少 FC 厚度。然而，这种反应的作用机制在很大程度上是未知的。在这里，我们研究了 IA 如何改变肌成纤维细胞的活性，并最终表明在机械负载阈值内可以调节其纤维状行为。这些发现可以被利用来改善广泛的医疗植入物的功能结果，特别是药物输送和细胞封装设备。
