3D-Printing of Electroconductive MXene-Based Micro-Meshes in a Biomimetic Hyaluronic Acid-Based Scaffold Directs and Enhances Electrical Stimulation for Neural Repair Applications.

No effective treatments are currently available for central nervous system neurotrauma although recent advances in electrical stimulation suggest some promise in neural tissue repair. It is hypothesized that structured integration of an electroconductive biomaterial into a tissue engineering scaffold can enhance electroactive signaling for neural regeneration. Electroconductive 2D Ti(3)C(2)T(x) MXene nanosheets are synthesized from MAX-phase powder, demonstrating excellent biocompatibility with neurons, astrocytes and microglia. To achieve spatially-controlled distribution of these MXenes, melt-electrowriting is used to 3D-print highly-organized PCL micro-meshes with varying fiber spacings (low-, medium-, and high-density), which are functionalized with MXenes to provide highly-tunable electroconductive properties (0.081 ± 0.053-18.87 ± 2.94 S/m). Embedding these electroconductive micro-meshes within a neurotrophic, immunomodulatory hyaluronic acid-based extracellular matrix (ECM) produced a soft, growth-supportive MXene-ECM composite scaffold. Electrical stimulation of neurons seeded on these scaffolds promoted neurite outgrowth, influenced by fiber spacing in the micro-mesh. In a multicellular model of cell behavior, neurospheres stimulated for 7 days on high-density MXene-ECM scaffolds exhibited significantly increased axonal extension and neuronal differentiation, compared to low-density scaffolds and MXene-free controls. The results demonstrate that spatial-organization of electroconductive materials in a neurotrophic scaffold can enhance repair-critical responses to electrical stimulation and that these biomimetic MXene-ECM scaffolds offer a promising new approach to neurotrauma repair.