Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.
Ministry of Education & Key Disciplines Laboratory of Novel Micro-Nano Devices and System Technology, Chongqing University, Chongqing 400044, China.
ACS Nano. 2022 Jul 26;16(7):10163-10178. doi: 10.1021/acsnano.1c11016. Epub 2022 May 26.
Excessive extracellular matrix deposition drives fibroblasts into a state of high mechanical stress, exacerbating pathological fibrosis and hypertrophic scar formation, leading to tissue dysfunction. This study reports a minimally invasive and convenient approach to obtaining scarless tissue using a silk fibroin microneedle patch (SF MNs). We found that by tuning the MN size and density only, the biocompatible MNs significantly decreased the scar elevation index in the rabbit ear hypertrophic scar model and increased ultimate tensile strength close to regular skin. To advance our understanding of this recent approach, we built a fibroblast-populated collagen lattice system and finite element model to study MN-mediated cellular behavior of fibroblasts. We found that the MNs reduced the fibroblasts generated contraction and mechanical stress, as indicated by decreased expression of the mechanical sensitive gene ANKRD1. Specifically, SF MNs attenuated the integrin-FAK signaling and consequently down-regulated the expression of TGF-β1, α-SMA, collagen I, and fibronectin. It resulted in a low-stress microenvironment that helps to reduce scar formation significantly. Microneedles' physical intervention the mechanotherapeutic strategy is promising for scar-free wound healing.
细胞外基质过度沉积会使成纤维细胞处于高机械应力状态，加剧病理性纤维化和肥厚性瘢痕形成，导致组织功能障碍。本研究报道了一种使用丝素蛋白微针贴片（SF MNs）获得无瘢痕组织的微创便捷方法。我们发现，通过仅调整 MN 的大小和密度，这些生物相容性 MN 可显著降低兔耳肥厚性瘢痕模型中的瘢痕隆起指数，并使极限拉伸强度接近正常皮肤。为了深入了解这一新方法，我们构建了成纤维细胞填充胶原格子系统和有限元模型来研究 MN 介导的成纤维细胞行为。我们发现 MN 减少了成纤维细胞产生的收缩和机械应力，这表现为机械敏感基因 ANKRD1 的表达降低。具体而言，SF MNs 减弱了整合素-FAK 信号通路，从而下调 TGF-β1、α-SMA、胶原 I 和纤维连接蛋白的表达。这导致了一个低应力的微环境，有助于显著减少瘢痕形成。微针的物理干预——力学治疗策略有望实现无瘢痕的伤口愈合。
