Degrees of macrophage-facilitated healing in aneurysm occlusion devices

IF 3.2 4区 医学 Q2 ENGINEERING, BIOMEDICAL
Del A. Donehoo, Claudia A. Collier, Sabrina N. VandenHeuvel, Sanjana Roy, Spencer C. Solberg, Shreya A. Raghavan
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引用次数: 0

Abstract

Insufficient healing of aneurysms following treatment with vascular occlusion devices put patients at severe risk of fatal rupture. Therefore, promoting healing and not just occlusion is vital to enhance aneurysm healing. Following occlusion device implantation, healing is primarily orchestrated by macrophage immune cells, ending with fibroblasts depositing collagen to stabilize the aneurysm neck and dome, preventing rupture. Several modified occlusion devices are available currently on-market. Previous in vivo work demonstrated that modifications of occlusion devices with a shape memory polymer foam had enhanced aneurysm healing outcomes. To better understand cellular response to occlusion devices and improve aneurysm occlusion device design variables, we developed an in vitro assay to isolate prominent interactions between devices and key healing players: macrophages and fibroblasts. We used THP-1 monocyte derived macrophages and human dermal fibroblasts in our cell culture models. Macrophages were allowed device contact with on-market competitor aneurysm occlusion devices for up to 96 h, to allow for any spontaneous device-driven macrophage activation. Macrophage secreted factors were captured in the culture media, in response to device-specific activation. Fibroblasts were then exposed to device-conditioned macrophage media (with secreted factors alone), to determine if there were any device-induced changes in collagen secretion. Our in vitro studies were designed to test the direct effect of devices on macrophage activation, and the indirect effect of devices on collagen secretion by fibroblasts to promote aneurysm healing and stabilization. Over 96 h, macrophages displayed significant migration toward and interaction with all tested devices. As compared to other devices, shape memory polymer foams (SMM, Shape Memory Medical) induced significant changes in gene expression indicating a shift toward an anti-inflammatory pro-healing M2-like phenotype. Similarly, macrophages in contact with SMM devices secreted more vascular endothelial growth factor (VEGF) compared with other devices. Macrophage conditioned media from SMM-contacted macrophages actively promoted fibroblast secretion of collagen, comparable to amounts observed with exogenous stimulation via VEGF supplementation. Our data indicate that SMM devices may promote good aneurysm healing outcomes, because collagen production is an essential step to ultimately stabilize an aneurysm.

动脉瘤闭塞装置中巨噬细胞促进愈合的程度
使用血管闭塞装置治疗后,动脉瘤的愈合不足会使患者面临致命破裂的严重风险。因此,促进愈合而不仅仅是闭塞对于提高动脉瘤愈合至关重要。植入闭塞装置后,愈合主要由巨噬细胞免疫细胞协调,最后由成纤维细胞沉积胶原蛋白,以稳定动脉瘤颈和穹顶,防止破裂。目前市场上有几种改良的闭塞装置。之前的体内研究表明,使用形状记忆聚合物泡沫对闭塞装置进行改良可提高动脉瘤愈合效果。为了更好地了解细胞对闭塞装置的反应并改进动脉瘤闭塞装置的设计变量,我们开发了一种体外试验来分离装置与关键愈合参与者(巨噬细胞和成纤维细胞)之间的突出相互作用。我们在细胞培养模型中使用了 THP-1 单核细胞衍生巨噬细胞和人类真皮成纤维细胞。允许巨噬细胞与市场上同类动脉瘤闭塞器械接触长达 96 小时,以允许任何由器械驱动的巨噬细胞自发活化。在培养基中捕获巨噬细胞分泌的因子,以应对特定装置的激活。然后将成纤维细胞暴露于设备调节过的巨噬细胞培养基(仅含有分泌因子)中,以确定胶原蛋白分泌是否有任何设备诱导的变化。我们的体外研究旨在测试设备对巨噬细胞活化的直接影响,以及设备对成纤维细胞分泌胶原蛋白以促进动脉瘤愈合和稳定的间接影响。在 96 小时内,巨噬细胞向所有测试装置迁移并与之相互作用。与其他装置相比,形状记忆聚合物泡沫(SMM,Shape Memory Medical)诱导的基因表达发生了显著变化,表明巨噬细胞向抗炎促进愈合的 M2 类表型转变。同样,与其他设备相比,接触 SMM 设备的巨噬细胞分泌更多的血管内皮生长因子(VEGF)。来自与 SMM 接触的巨噬细胞的条件培养基能积极促进成纤维细胞分泌胶原蛋白,与通过补充血管内皮生长因子观察到的外源性刺激量相当。我们的数据表明,SMM 装置可促进动脉瘤的良好愈合,因为胶原蛋白的产生是最终稳定动脉瘤的重要步骤。
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来源期刊
CiteScore
7.50
自引率
2.90%
发文量
199
审稿时长
12 months
期刊介绍: Journal of Biomedical Materials Research – Part B: Applied Biomaterials is a highly interdisciplinary peer-reviewed journal serving the needs of biomaterials professionals who design, develop, produce and apply biomaterials and medical devices. It has the common focus of biomaterials applied to the human body and covers all disciplines where medical devices are used. Papers are published on biomaterials related to medical device development and manufacture, degradation in the body, nano- and biomimetic- biomaterials interactions, mechanics of biomaterials, implant retrieval and analysis, tissue-biomaterial surface interactions, wound healing, infection, drug delivery, standards and regulation of devices, animal and pre-clinical studies of biomaterials and medical devices, and tissue-biopolymer-material combination products. Manuscripts are published in one of six formats: • original research reports • short research and development reports • scientific reviews • current concepts articles • special reports • editorials Journal of Biomedical Materials Research – Part B: Applied Biomaterials is an official journal of the Society for Biomaterials, Japanese Society for Biomaterials, the Australasian Society for Biomaterials, and the Korean Society for Biomaterials. Manuscripts from all countries are invited but must be in English. Authors are not required to be members of the affiliated Societies, but members of these societies are encouraged to submit their work to the journal for consideration.
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