Macroporous hydrogels derived from aqueous dynamic phase separation

Abstract

A method to generate injectable macroporous hydrogels based on partitioning of polyethylene glycol (PEG) and high viscous polysaccharides is presented. Step growth polymerization of PEG was used to initiate a phase separation and the formation of a connected macroporous network with tunable dimensions. The possibilities and physical properties of this new category of materials were examined, and then applied to address some challenges in neural engineering. First, non-degradable macroporous gels were shown to support rapid neurite extension from encapsulated dorsal root ganglia (DRGs) with unprecedented long-term stability. Then, dissociated primary rat cortical neurons could be encapsulated with >95% viability, and extended neurites at the fast rate of ≈100 μm/day and formed synapses, resulting in functional, highly viable and long-term stable 3D neural networks in the synthetic extracellular matrix (ECM). Adhesion cues were found unnecessary provided the gels have optimal physical properties. Normal electrophysiological properties were confirmed on 3D cultured mouse hippocampal neurons. Finally, the macroporous gels supported axonal growth in a rat sciatic nerve injury model when used as a conduit filling. The combination of injectability, tunable pore size, stability, connectivity, transparency, cytocompatibility and biocompatibility, makes this new class of materials attractive for a wide range of applications.