Liquid crystalline collagen assemblies as substrates for directed alignment of human Schwann cells

Collagen is a key component of the extracellular matrix (ECM) and well-oriented domains of collagen are important for mimicking the local cell environment in vitro. While there has been significant attention directed towards the alignment of collagen, formation of large-scale oriented domains remains a key challenge. Type I collagen self-assembles to form liquid crystalline (LC) mesophases in acidic conditions at concentrations above 100 mg mL^-1. The LC mesophase provides an efficient platform for large-scale alignment and patterning of collagen coated substrates. However, there still exist challenges related to solubilizing and processing of collagen at such high concentrations in order to replicate the native ECM. In this contribution, we report on centimeter-scale alignment in collagen-coated glass substrates using solutions that are well below the LC-forming concentrations. Importantly, we are also able to extend this method to macroscopic 3-D LC-collagen hydrogels with programmed anisotropy within them to create a mimic of the native ECM. We show that the orientation and aspect ratio of human Schwann cells are strongly coupled with the alignment of the collagen substrate/hydrogel. We use a simple model to estimate the critical magnetic field strength needed for a given concentration of collagen to permit macroscopic alignment-enabling guidance for future studies on alignment of collagen at high concentrations.