Nerve Guide Conduits Integrated with Fisetin-Loaded Chitosan Hydrogels for Reducing Oxidative Stress, Inflammation, and Nerve Regeneration

Macromol Biosci. 2024 May;24(5):e2300476. doi: 10.1002/mabi.202300476. Epub 2024 Feb 7.

Abstract

Peripheral nerve injuries (PNI) represent a prevalent and severe category of damage resulting from traumatic incidents. Predominantly, the deficiency in nerve regeneration can be ascribed to enduring inflammatory reactions, hence imposing substantial clinical implications for patients. Fisetin, a flavonoid derived from plants, is naturally present in an array of vegetables and fruits, including strawberries, apples, onions, and cucumbers. It exhibits immunomodulatory properties through the reduction of inflammation and oxidative stress. In the present research, a nerve defect is addressed for the first time utilizing a scaffold primed for controlled fisetin release. In this regard, fisetin-loaded chitosan hydrogels are incorporated into the lumen of polycaprolactone (PCL) nerve guide conduits (NGCs). The hydrogel maintained a steady release of an appropriate fisetin dosage. The study outcomes indicated that the fisetin/chitosan/polycaprolactone (FIS/CS/PCL) NGCs amplified Schwann cell proliferation and neural expression, curtailed oxidative stress, alleviated inflammation, and improved functions, electrophysiological properties, and morphology. This pioneering scaffold has the potential to contribute significantly to the field of neuroengineering.

Keywords: chitosan; drug sustained release; electrospinning; fisetin; nerve conduits; nerve injury; peripheral nerve regenerations.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Chitosan* / chemistry
  • Chitosan* / pharmacology
  • Flavonoids / chemistry
  • Flavonoids / pharmacology
  • Flavonols* / pharmacology
  • Guided Tissue Regeneration / methods
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Inflammation* / drug therapy
  • Inflammation* / pathology
  • Nerve Regeneration* / drug effects
  • Oxidative Stress* / drug effects
  • Peripheral Nerve Injuries / drug therapy
  • Peripheral Nerve Injuries / pathology
  • Peripheral Nerve Injuries / therapy
  • Polyesters* / chemistry
  • Polyesters* / pharmacology
  • Rats
  • Schwann Cells / drug effects
  • Schwann Cells / metabolism
  • Tissue Scaffolds / chemistry