聚(甲基丙烯酸甲酯)(PMMA)被认为是用于制造可穿戴皮肤传感器(诸如健身带和微流体装置)的有吸引力的基底材料。尽管它广泛使用,炎症和过敏反应已归因于使用这种材料。因此,本研究的主要目的是使用NIH3T3成纤维细胞和重建人表皮(RhE)的体外模型,全面了解PMMA在非细胞毒性浓度下引发的潜在生物学效应.假设不降低细胞活力的浓度足以激活皮肤中炎症过程的途径。这项研究包括细胞毒性,细胞代谢,细胞因子定量,组织病理学,和基因表达分析。NIH3T3细胞系用作筛选与具有不同分子量(MWs)的PMMA浓度相关的细胞毒性水平的测试平台(即,MW~5,000和~15,000g/mol)。较低分子量的PMMA具有5.7mg/cm2的半最大抑制浓度(IC50)值,表明更大的有害影响比更高的MW(IC50=14.0mg/cm2)。MW~15,000g/mol的非细胞毒性浓度为3.0mg/cm2,MW~5,000g/mol的非细胞毒性浓度为0.9mg/cm2)诱导NIH3T3细胞负代谢变化。在暴露于PMMA的热和光降解降解后产生的降解副产物后,细胞活力严重降低至7%。非细胞毒性浓度的PMMA仍然诱导促炎细胞因子的过度表达,趋化因子,和生长因子(IL1B,CXCL10,CCL5,IL1R1,IL7,IL17A,VEGFA,FGF2,IFNG,IL15)在RhE模型上。PMMA处理的RhE的组织病理学和基因表达分析也支持炎症反应。表明组织损伤和基因过表达。结果表明,PMMA的非细胞毒性浓度(对于MW〜15,000g/mol为3.0至5.6mg/cm2,对于MW〜5,000g/mol为0.9至2.1mg/cm2)足以负向改变NIH3T3细胞代谢并激活炎症事件在RhE皮肤中。
Poly(methyl methacrylate) (PMMA) is considered an attractive substrate material for fabricating wearable skin sensors such as fitness bands and microfluidic devices. Despite its widespread use, inflammatory and allergic responses have been attributed to the use of this material. Therefore, the main objective of this study was to obtain a comprehensive understanding of potential biological effects triggered by PMMA at non-cytotoxic concentrations using in vitro models of NIH3T3 fibroblasts and reconstructed human epidermis (RhE). It was hypothesized that concentrations that do not reduce cell viability are sufficient to activate pathways of inflammatory processes in the skin. The study included cytotoxicity, cell metabolism, cytokine quantification, histopathological, and gene expression analyses. The NIH3T3 cell line was used as a testbed for screening cell toxicity levels associated with the concentration of PMMA with different molecular weights (MWs) (i.e., MW ~5,000 and ~15,000 g/mol). The lower MW of PMMA had a half-maximal inhibitory concentration (IC50 ) value of 5.7 mg/cm2 , indicating greater detrimental effects than the higher MW (IC50 = 14.0 mg/cm2 ). Non-cytotoxic concentrations of 3.0 mg/cm2 for MW ~15,000 g/mol and 0.9 mg/cm2 for MW ~5,000 g/mol) induced negative metabolic changes in NIH3T3 cells. Cell viability was severely reduced to 7% after the exposure to degradation by-products generated after thermal and photodegradation degradation of PMMA. PMMA at non-cytotoxic concentrations still induced overexpression of pro-inflammatory cytokines, chemokines, and growth factors (IL1B, CXCL10, CCL5, IL1R1, IL7, IL17A, VEGFA, FGF2, IFNG, IL15) on the RhE model. The inflammatory response was also supported by histopathological and gene expression analyses of PMMA-treated RhE, indicating tissue damage and gene overexpression. Results suggested that non-cytotoxic concentrations of PMMA (3.0 to 5.6 mg/cm2 for MW ~15,000 g/mol and 0.9 to 2.1 mg/cm2 for MW ~5,000 g/mol) were sufficient to negatively alter NIH3T3 cells metabolism and activate inflammatory events in the RhE skin.