Quantitative determination of residual 1,4-dioxane in three-dimensional printed bone scaffold

Li, Ling; Long, Jing; Li, Long; Cao, Huijuan; Tang, Tingting; Xi, Xinghua; Qin, Ling; Lai, Yuxiao; Wang, Xinluan

In the process of scaffold fabrication, 1,4-dioxane was optimised as a necessary solvent used for dissolving PLGA due to its low melting point, liposolubility and highly volatile nature. However, with two oxygen atoms, 1,4-dioxane has been shown to be carcinogenic to animals and humans [21e24] . Furthermore, 1,4-dioxane may also be toxic to liver, lungs, kidneys, and the central nervous system [25] . 1,4-dioxane was defined as a Class 2 solvent associated with less severe toxicity, which should be limited to below 380 ppm according to international regulations, such as Chinese Pharmacopoeia [26] , International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use [27] , and United States Pharmacopoeia [28] . Therefore, it is mandatory to test residual 1,4-dioxane for PLGA/TCP scaffolds and this testing is also necessary for registration and quality control of novel scaffolds.