(150j) Engineering Nanofiber Scaffolds with Biomimetic Cues for Differentiation of Neural Crest-like Stem Cells to Schwann Cells

Our laboratory-derived neural crest stem cell (NCSC)-like cells from the interfollicular epidermis of the neonatal and adult skin tissues. These keratinocyte (KC)-derived Neural Crest (NC)-like cells (KC-NC) could differentiate into functional neurons, schwann cells, melanocytes, and smooth muscle cells in vitro. Schwann cells play a crucial role in the peripheral nervous system (PNS) by myelinating neuronal axons and facilitating electrical current propagation. Schwann cells can regenerate the PNS by removing myelin debris and differentiating into myelinating schwann cells following a nerve injury caused by trauma or medical conditions, such as diabetes and tumor-related surgeries. However, this process is often inefficient and requires intervention. Thus, there is a dire need for efficient and scalable approaches to obtain large numbers of functional schwann cells for PNI cell therapy.

Here, we present an innovative design concept for developing anisotropically aligned scaffolds with chemically immobilized biological cues to promote differentiation of the KC-NC towards the schwann cell. Specifically, we designed electrospun nanofibers and examined the effect of several bioactive cues in guiding KC-NC differentiation into schwann cells. The KC-NCs attached to nanofibers and adopted a spindle-like morphology, similar to the native extracellular matrix (ECM) microarchitecture of the peripheral nerves. Immobilization of biological cues, especially soluble Neuregulin1 (NRG1) promoted the differentiation of KC-NC into the schwann cell lineage. This study suggests that poly-ε-caprolactone (PCL) nanofibers decorated with topographical and cell-instructive cues may be a potential platform for enhancing KC-NC differentiation toward schwann cells.