Nerve Growth Factor-Laden Anisotropic Silk Nanofiber Hydrogels to Regulate Neuronal/Astroglial Differentiation for Scarless Spinal Cord Repair

ACS Appl Mater Interfaces. 2022 Jan 26;14(3):3701-3715. doi: 10.1021/acsami.1c19229. Epub 2022 Jan 10.

Abstract

Scarless spinal cord regeneration remains a challenge due to the complicated microenvironment at lesion sites. In this study, the nerve growth factor (NGF) was immobilized in silk protein nanofiber hydrogels with hierarchical anisotropic microstructures to fabricate bioactive systems that provide multiple physical and biological cues to address spinal cord injury (SCI). The NGF maintained bioactivity inside the hydrogels and regulated the neuronal/astroglial differentiation of neural stem cells. The aligned microstructures facilitated the migration and orientation of cells, which further stimulated angiogenesis and neuron extensions both in vitro and in vivo. In a severe rat long-span hemisection SCI model, these hydrogel matrices reduced scar formation and achieved the scarless repair of the spinal cord and effective recovery of motor functions. Histological analysis confirmed the directional regenerated neuronal tissues, with a similar morphology to that of the normal spinal cord. The in vitro and in vivo results showed promising utility for these NGF-laden silk hydrogels for spinal cord regeneration while also demonstrating the feasibility of cell-free bioactive matrices with multiple cues to regulate endogenous cell responses.

Keywords: anisotropic hydrogels; nerve growth factor; scarless regeneration; silk; spinal cord injury.

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / pathology
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology*
  • Cell Differentiation / drug effects
  • Hydrogels / chemistry
  • Hydrogels / pharmacology*
  • Materials Testing
  • Nanofibers / chemistry*
  • Nerve Growth Factor / chemistry*
  • Neurons / drug effects
  • Neurons / pathology
  • PC12 Cells
  • Rats
  • Silk / chemistry*
  • Spinal Cord Injuries / drug therapy
  • Spinal Cord Injuries / pathology
  • Spinal Cord Regeneration / drug effects*
  • Tissue Scaffolds / chemistry

Substances

  • Biocompatible Materials
  • Hydrogels
  • Ngf protein, rat
  • Silk
  • Nerve Growth Factor