3D-printed, biomimetic, conductive MXene-microfiber composite scaffolds enhance the axonal growth-promoting characteristics of electrical stimulation

Abstract

AbstractThe application of externally applied electrical stimulation can regulate electrical signalling in neural tissues and has the potential to promote repair of tissue following neurotrauma. Conductive biomaterials can enhance the pro-reparative effects of electrical stimulation by channelling and directing its delivery. Ti3C2Txtitanium carbide nanosheets, known as MXenes, are a class of highly conductive (>107S/m) 2D nanomaterials that hold great promise for neural tissue engineering applications. It was hypothesized that functionalizing 3D-printed microfiber scaffolds with MXene nanosheets would produce conductive tissue engineering scaffolds whose tunable electroconductive properties could be adapted to promote axonal growth of seeded neurons in response to extrinsic electrical signals. Melt-electrowriting was used to 3D print polycaprolactone microfiber architectures of varying fiber densities which were coated with a Ti3C2TxMXene ink resulted in highly conductive composite microfiber scaffolds. The electrical conductivity of these microfibrous architectures could be varied in a controlled manner from approximately 0.081 ±0.053 S/m to 18.87 ±2.94 S/m - depending on the microfiber density and layering of MXene ink coatings. The MXene microfiber architectures were filled with a macroporous neurotrophic hyaluronic acid-collagen type- IV/fibronectin biomaterial, designed to mimic the structure and composition of neural tissues and provide an optimal substrate for axonal growth. The application of continuous electrical stimulation (200 mV/mm, 12 Hz) to neurons seeded on the fiber-reinforced biomimetic scaffolds enhanced axonal growth in a manner dependent on the conductive microfiber architecture. These results indicate that optimization of 3D printed conductive microarchitectures can enhance the axonal growth-promoting characteristics of electrical stimulation in a manner dependent on the distribution of conductive material with a tissue engineering scaffold. These biomimetic conductive scaffolds represent a novel approach to the delivery of therapeutic electrical stimulation for neurotrauma repair.