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The Photoinitiator Lithium Phenyl (2,4,6-Trimethylbenzoyl) Phosphinate with Exposure to 405 nm Light Is Cytotoxic to Mammalian Cells but Not Mutagenic in Bacterial Reverse Mutation Assays
Polymers ( IF 4.7 ) Pub Date : 2020-07-03 , DOI: 10.3390/polym12071489
Alexander K. Nguyen , Peter L. Goering , Rosalie K. Elespuru , Srilekha Sarkar Das , Roger J. Narayan

Lithium phenyl (2,4,6-trimethylbenzoyl) phosphinate (LAP) is a free radical photo-initiator used to initiate free radical chain polymerization upon light exposure, and is combined with gelatin methacryloyl (GelMA) to produce a photopolymer used in bioprinting. The free radicals produced under bioprinting conditions are potentially cytotoxic and mutagenic. Since these photo-generated free radicals are highly-reactive but short-lived, toxicity assessments should be conducted with light exposure. In this study, photorheology determined that 10 min exposure to 9.6 mW/cm2 405 nm light from an LED light source fully crosslinked 10 wt % GelMA with >3.4 mmol/L LAP, conditions that were used for subsequent cytotoxicity and mutagenicity assessments. These conditions were cytotoxic to M-1 mouse kidney collecting duct cells, a cell type susceptible to lithium toxicity. Exposure to ≤17 mmol/L (0.5 wt %) LAP without light was not cytotoxic; however, concurrent exposure to ≥3.4 mmol/L LAP and light was cytotoxic. No condition of LAP and/or light exposure evaluated was mutagenic in bacterial reverse mutation assays using S. typhimurium strains TA98, TA100 and E. coli WP2 uvrA. These data indicate that the combination of LAP and free radicals generated from photo-excited LAP is cytotoxic, but mutagenicity was not observed in bacteria under typical bioprinting conditions.

中文翻译:

暴露在405 nm光下的光引发剂苯基磷酸(2,4,6-三甲基苯甲酰基)磷酸锂对哺乳动物细胞具有细胞毒性,但在细菌反向突变测定中却没有致突变性。

亚苯基苯基(2,4,6-三甲基苯甲酰基)次膦酸锂(LAP)是一种自由基光引发剂,用于在曝光后引发自由基链聚合反应,并与明胶甲基丙烯酰基(GelMA)结合使用以生产用于生物打印的光敏聚合物。在生物印刷条件下产生的自由基可能具有细胞毒性和诱变性。由于这些光生自由基具有高反应活性,但寿命短,因此应在光照下进行毒性评估。在这项研究中,光流变学确定,在来自LED光源的9.6 mW / cm2 405 nm光下曝光10分钟,可使10 wt%GelMA与> 3.4 mmol / L LAP完全交联,这些条件可用于随后的细胞毒性和诱变性评估。这些条件对M-1小鼠肾脏收集导管细胞具有细胞毒性,易受锂中毒的细胞类型。暴露于≤17mmol / L(0.5 wt%)LAP且无光照,无细胞毒性。但是,同时暴露于≥3.4mmol / L LAP和光照下具有细胞毒性。在使用鼠伤寒沙门氏菌菌株TA98,TA100和大肠杆菌WP2 uvrA进行的细菌反向突变测定中,未评估LAP和/或光照条件是否诱变。这些数据表明,LAP和光激发的LAP产生的自由基的组合具有细胞毒性,但是在典型的生物印刷条件下,细菌中未观察到致突变性。大肠杆菌WP2 uvrA。这些数据表明,LAP和光激发的LAP产生的自由基的组合具有细胞毒性,但是在典型的生物印刷条件下,细菌中未观察到致突变性。大肠杆菌WP2 uvrA。这些数据表明,LAP和光激发的LAP产生的自由基的组合具有细胞毒性,但是在典型的生物印刷条件下,细菌中未观察到致突变性。
更新日期:2020-07-03
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