Electrospun Scaffold Micro-Architecture Induces an Activated Transcriptional Phenotype within Tendon Fibroblasts.
Electrospun Scaffold Micro-Architecture Induces an Activated Transcriptional Phenotype within Tendon Fibroblasts.
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DOI：
10.3389/fbioe.2021.795748
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发表时间：
2021
影响因子：
5.7
通讯作者：
Snelling SJ
中科院分区：
文献类型：
--
作者：
Baldwin MJ;Mimpen JY;Cribbs AP;Stace E;Philpott M;Dakin SG;Carr AJ;Snelling SJ
手术修复肩袖肌腱撕裂的生物材料增强旨在改善传统修复的高失败率（约40%）。通过提供微尺度的地形线索可以改变细胞表型的生物材料目前正在开发中。我们的目的是系统地评估地形结构对健康和患病肌腱成纤维细胞表型的影响。静电纺丝聚对二氧环己酮支架的纤维直径范围从300至4000 nm，在一个高度对齐或随机配置，生产。在具有高度对齐的纤维的支架上培养7天的健康肌腱成纤维细胞表现出独特的细长形态，而在随机配置的纤维上培养的成纤维细胞表现出扁平和扩散的形态。用批量RNA-seq评估支架微结构对健康和患病肌腱成纤维细胞的转录组的影响。健康（n = 3）和患病的肌腱细胞（n = 3）表现出类似的转录反应的建筑变体。基因集富集分析显示，大直径（≥2000 nm）对齐的支架诱导参与细胞复制的基因上调和定义炎症反应和细胞粘附的基因下调。同样，PDPN和CD 248，炎症或“活化”成纤维细胞的标志物，在具有大（≥2000 nm）纤维直径的对齐支架上培养健康和患病成纤维细胞期间下调。总之，支架结构类似于无序的III型胶原，通常存在于伤口愈合的早期阶段，导致肌腱成纤维细胞活化。相反，支架模仿对齐的直径胶原蛋白I原纤维，在组织重塑过程中，没有激活肌腱来源的成纤维细胞。这对肩袖修复加固过程中使用的支架设计有影响。
Biomaterial augmentation of surgically repaired rotator cuff tendon tears aims to improve the high failure rates (∼40%) of traditional repairs. Biomaterials that can alter cellular phenotypes through the provision of microscale topographical cues are now under development. We aimed to systematically evaluate the effect of topographic architecture on the cellular phenotype of fibroblasts from healthy and diseased tendons. Electrospun polydioxanone scaffolds with fiber diameters ranging from 300 to 4000 nm, in either a highly aligned or random configuration, were produced. Healthy tendon fibroblasts cultured for 7 days on scaffolds with highly aligned fibers demonstrated a distinctive elongated morphology, whilst those cultured on randomly configured fibers demonstrated a flattened and spread morphology. The effect of scaffold micro-architecture on the transcriptome of both healthy and diseased tendon fibroblasts was assessed with bulk RNA-seq. Both healthy (n = 3) and diseased tendon cells (n = 3) demonstrated a similar transcriptional response to architectural variants. Gene set enrichment analysis revealed that large diameter (≥2000 nm) aligned scaffolds induced an upregulation of genes involved in cellular replication and a downregulation of genes defining inflammatory responses and cell adhesion. Similarly, PDPN and CD248, markers of inflammatory or “activated” fibroblasts, were downregulated during culture of both healthy and diseased fibroblasts on aligned scaffolds with large (≥2000 nm) fiber diameters. In conclusion scaffold architectures resembling that of disordered type III collagen, typically present during the earlier phases of wound healing, resulted in tendon fibroblast activation. Conversely, scaffolds mimicking aligned diameter collagen I fibrils, present during tissue remodelling, did not activate tendon derived fibroblasts. This has implications for the design of scaffolds used during rotator cuff repair augmentation.
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