Biomimetic 3D Hydrogels with Aligned Topography for Neural Tissue Engineering

Spinal cord trauma leads to the destruction of the highly organized cytoarchitecture that carries information along the axis of the spinal column. Currently, there are no clinically accepted strategies that can help regenerate severed axons after spinal cord injury (SCI). Hydrogels are soft biomaterials with high water content that are widely used as scaffolds to interface with the central nervous system (CNS). Here, we examine a simple and reproducible method that results in consistently aligned fibrils within 3D matrices using thermally gelling biomimetic polymers. A collagen type I (Col)-based thermally gelling hydrogel system was used in combination with two other native extracellular matrix proteins: laminin I (LN) and hyaluronic acid (HA). Gelling kinetics for all gel types (Col, Col LN, Col HA) showed that at 37 °C, all three hydrogels formed gels consistently. A method of aspiration and ejection was used to produce Col-based hydrogels containing aligned fibrils. In vitro, embryonic spinal cord neurons survived and produced processes aligned to collagen fibrils. Next, we implanted either non-aligned or aligned hydrogels after a bilateral dorsal hemisection of the thoracic spinal cord at T7/T8. Pan neuronal antibody-positive fibrils were found within all implants; aligned hydrogels supported neurite growth along the parallel direction of the implanted hydrogels. Combined, our in vitro and in vivo data indicate that thermally gelling biomimetic hydrogels can produce aligned matrices through a method of aspiration and ejection, and this presents a novel platform for regenerative therapies for the CNS.