Biomaterials cover and are an integral part of tissue engineering and regenerative medicine fields. They are crucial to mimic endogenous tissue responses and help to eliminate high research costs and ethical concerns that come with 2D systems and animal models. In this study, we present a co-culturing system wherein neuroblastoma (SH-SY5Y) and oligodendrocyte (MO3.13) cell lines grow within both a caprolactone-based 3D elastomer and liquid crystal elastomer (LCE) scaffolding. We also demonstrate that LCE scaffolds promote maturation and differentiation of both cell lines alone, and in co-culturing fashion as they provide a suitable 3D in vitro environment to study myelination. Additionally, we validate that these scaffolds are suitable for primary cell growth and proliferation using neurons, oligodendrocyte progenitor cells (OPCs) and astrocytes. Our data suggest that responsive LCE scaffolds can effectively impact cellular function, differentiation, and myelination of co-cultured cell lines, allowing the mimicry of a more endogenous environment and providing support for long term studies to manipulate cellular crosstalk.