A Novel GelMA-OrnMA Electrically Conductive Bioink for Developing Engineered Neural Tissues
Mahmoud A. Sakr, Kartikeya DixitiD, Kinam HyuniD, Sumi SiddiquaiD, Su Ryon ShiniD, Hitendra KumariD, Keekyoung KimiD
Abstract
Electrical conductivity is a crucial requirement of matrices for developing engineered neural tissues. A conductive matrix not only supports cell growth but also provides potential to stimulate the cells. However, electrically conductive matrices often require inclusion of synthetic polymers, nanomaterials and large number of ionic species. While enhancing electrical conductivity, often properties like transparency, mechanical stiffness and biocompatibility are compromised which can render the resulting matrices partially suitable for neural tissue engineering. Further, the byproducts of matrix degradation can have unforeseen influences. Therefore, electrically active matrices are required which provide a suitable combination of electrical conductivity, mechanical properties and biocompatibility. In this work, a novel biomaterial is described which results in optically transparent, electrically conductive and highly biocompatible matrices along with ability to match the native neural tissue stiffness. Using gelatin methacryloyl (GelMA) as base hydrogel, we covalently incorporated zwitterionic functional groups to obtain a composite matrix. The zwitterion moieties were derived from Ornithine by synthesizing ornithine methacryloyl (OrnMA) and blending with GelMA inks. Through systematic characterization we demonstrated the suitability of GelMA-OrnMA hydrogels in providing mechanical stiffness matching the native neural tissues, supporting proliferation of human astrocytes in 3D culture and electrical conductivity in the range required for electrically active cell types like astrocytes. Owing to their electrical conductivity, these matrices also influenced the growth of astrocytes which manifested as significant changes in their organization and morphology. These findings suggest that GelMA-OrnMA has immense potential as a bioink for developing engineered neural tissues.
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