Function Follows Form: Oriented Substrate Nanotopography Overrides Neurite-Repulsive Schwann Cell-Astrocyte Barrier Formation in an In Vitro Model of Glial Scarring

Schwann cell (SC) transplantation represents a promisingtherapeuticapproach for traumatic spinal cord injury but is frustrated by barrierformation, preventing cell migration, and axonal regeneration at theinterface between grafted SCs and reactive resident astrocytes (ACs).Although regenerating axons successfully extend into SC grafts, onlya few cross the SC-AC interface to re-enter lesioned neuropil.To date, research has focused on identifying and modifying the molecularmechanisms underlying such scarring cell-cell interactions,while the influence of substrate topography remains largely unexplored.Using a recently modified cell confrontation assay to model SC-ACbarrier formation in vitro, highly oriented poly(& epsilon;-caprolactone)nanofibers were observed to reduce AC reactivity, induce extensiveoriented intermingling between SCs and ACs, and ultimately enablesubstantial neurite outgrowth from the SC compartment into the ACterritory. It is anticipated that these findings will have importantimplications for the future design of biomaterial-based scaffoldsfor nervous tissue repair.

Automated summary

Schwann cell transplantation is hindered by barrier formation between grafted cells and reactive astrocytes, limiting axonal regeneration. A cell confrontation assay revealed that oriented poly(& epsilon;-caprolactone) nanofibers reduced astrocyte reactivity and facilitated intermingling between Schwann cells and astrocytes, promoting neurite outgrowth. These findings have important implications for the design of biomaterial-based scaffolds for nervous tissue repair.