Unique Chirality Selection in Neural Cells for D‐Matrix Enabling Specific Manipulation of Cell Behaviors

Manipulating neural cell behaviors is a critical issue to various therapies for neurological diseases and damages, where matrix chirality has long been overlooked despite the proven adhesion and proliferation improvement of multiple non-neural cells by L-matrixes. Here, it is reported that the D-matrix chirality specifically enhances cell density, viability, proliferation, and survival in four different types of neural cells, contrasting its inhibition in non-neural cells. This universal impact on neural cells is defined as "chirality selection for D-matrix" and is achieved through the activation of JNK and p38/MAPK signaling pathways by the cellular tension relaxation resulting from the weak interaction between D-matrix and cytoskeleton proteins, particularly actin. Also, D-matrix promotes sciatic nerve repair effectively, both with or without non-neural stem cell implantation, by improving the population, function, and myelination of autologous Schwann cells. D-matrix chirality, as a simple, safe, and effective microenvironment cue to specifically and universally manipulate neural cell behaviors, holds extensive application potential in addressing neurological issues such as nerve regeneration, neurodegenerative disease treatment, neural tumor targeting, and neurodevelopment.