Background and objectives

Microneedling therapy is a widely used technique in dermatology. However, little is known about the underlying molecular effects of this therapy on extracellular matrix remodeling, wound healing, and inflammation. The aim of this study was to examine morphological and molecular changes caused by microneedling treatment in a standardized in vitro full-thickness 3D model of human skin.

Materials and methods

A microneedling device was used to treat full-thickness 3D skin models. Specimens were harvested at specified time points and qRT-PCR and microarray studies were performed. Frozen sections were examined histologically.

Results

Microneedling treatment caused morphological changes in the skin model resulting in an almost complete recovery of the epidermis five days after treatment. Microarray analysis identified an upregulation of genes that are associated with tissue remodeling and wound healing (e.g. COL3A1, COL8A1, TIMP3), epithelial proliferation and differentiation (KRT13, IGF1), immune cell recruitment (CCL11), and a member of the heat shock protein family (HSPB6). On the other hand, we detected a downregulation of pro-inflammatory cytokines (e.g. IL1α, IL1β, IL24, IL36γ, IL36RN), and antimicrobial peptides (e.g. S100A7A, DEFB4). These data were confirmed by independent RT-PCR analyses.

Conclusion

We present for the first time the direct molecular effects of microneedling therapy on epidermal keratinocytes and dermal fibroblasts using a standardized 3D skin model. Treatment resulted in histological alterations and changed the expression of various genes related to epidermal differentiation, inflammation, and dermal remodeling. This data suggests that skin microneedling plays a role in dermal remodeling, increases epidermal differentiation, and might also have a direct effect on collagen synthesis. These findings may increase our understanding of the molecular mechanisms of human skin repair induced by microneedling therapy and will allow comparisons with competing applications, such as ablative laser therapies.

中文翻译：

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人类三维皮肤模型中微针治疗的全面分子表征

背景和目标

微针疗法是皮肤病学中广泛使用的技术。但是，对于这种疗法对细胞外基质重塑，伤口愈合和炎症的潜在分子作用知之甚少。这项研究的目的是在人皮肤的标准体外全厚度3D模型中检查微针处理引起的形态和分子变化。

材料和方法

使用微针设备治疗全层3D皮肤模型。在指定的时间点收集标本，并进行qRT-PCR和微阵列研究。对冷冻切片进行组织学检查。

结果

微针治疗导致皮肤模型的形态变化，导致治疗后五天表皮几乎完全恢复。微阵列分析确定了与组织重塑和伤口愈合相关的基因（例如，COL3A1，COL8A1，TIMP3），上皮细胞的增殖和分化（KRT13，IGF1），免疫细胞募集（CCL11）和热休克蛋白的成员相关的基因上调家族（HSPB6）。在另一方面，我们发现促炎性细胞因子的下调（例如IL1α，IL1β，IL24，IL36γ，IL36RN）和抗菌肽（例如S100A7A，DEFB4）。这些数据通过独立的RT-PCR分析得到证实。

结论

我们首次使用标准的3D皮肤模型首次提出了微针疗法对表皮角质形成细胞和皮肤成纤维细胞的直接分子作用。治疗导致组织学改变，并改变了与表皮分化，炎症和皮肤重塑有关的各种基因的表达。该数据表明皮肤微针在真皮重塑中起作用，增加表皮分化，并且也可能对胶原蛋白合成有直接影响。这些发现可能会加深我们对由微针疗法引起的人类皮肤修复的分子机制的了解，并将使之与竞争性应用（例如烧蚀激光疗法）进行比较。