Micropatterned shape-memory polymer substrate containing hydrogen bonds creates a long-term dynamic microenvironment for regulating nerve-cell fate

Peripheral nerve injuries (PNIs) caused by mechanical contusion are frequently encountered in clinical practice, using nerve guidance conduits (NGCs) is now a promising therapy. An NGC creates a microenvironment for cell growth and differentiation, thus understanding physical and biochemical cues that can affect nerve-cell fate is a prerequisite for rationally designing NGCs. However, most of the previous works were focused on some static cues, the dynamic nature of the nerve microenvironment has not yet been well captured. Herein, we develop a micropatterned shape-memory polymer as a programmable substrate for providing a dynamic cue for nerve-cell growth. The shape-memory properties enable temporal programming of the substrate, and a dynamic microenvironment is created during standard cell culturing at 37 °C. Unlike most of the biomedical shape-memory polymers that recover rapidly at 37 °C, the proposed substrate shows a slow recovery process lasting 3-4 days and creates a long-term dynamic microenvironment. Results demonstrate that the vertically programmed substrates provide the most suitable dynamic microenvironment for PC12 cells as both the differentiation and maturity are promoted. Overall, this work provides a strategy for creating a long-term dynamic microenvironment for regulating nerve-cell fate and will inspire the rational design of NGCs for the treatment of PNIs.