Sustained Release of Nitric Oxide-Mediated Angiogenesis and Nerve Repair by Mussel-Inspired Adaptable Microreservoirs for Brain Traumatic Injury Therapy

Adv Healthc Mater. 2024 Oct;13(25):e2302315. doi: 10.1002/adhm.202302315. Epub 2023 Sep 26.

Abstract

Traumatic brain injury (TBI) triggers inflammatory response and glial scarring, thus substantially hindering brain tissue repair. This process is exacerbated by the accumulation of activated immunocytes at the injury site, which contributes to scar formation and impedes tissue repair. In this study, a mussel-inspired nitric oxide-release microreservoir (MINOR) that combines the features of reactive oxygen species (ROS) scavengers and sustained NO release to promote angiogenesis and neurogenesis is developed for TBI therapy. The injectable MINOR fabricated using a microfluidic device exhibits excellent monodispersity and gel-like self-healing properties, thus allowing the maintenance of its structural integrity and functionality upon injection. Furthermore, polydopamine in the MINOR enhances cell adhesion, significantly reduces ROS levels, and suppresses inflammation. Moreover, a nitric oxide (NO) donor embedded into the MINOR enables the sustained release of NO, thus facilitating angiogenesis and mitigating inflammatory responses. By harnessing these synergistic effects, the biocompatible MINOR demonstrates remarkable efficacy in enhancing recovery in mice. These findings benefit future therapeutic interventions for patients with TBI.

Keywords: angiogenesis; nerve repair; nitrogen oxide; particle scaffold; polydopamine.

MeSH terms

  • Angiogenesis
  • Animals
  • Bivalvia* / chemistry
  • Brain Injuries, Traumatic* / drug therapy
  • Brain Injuries, Traumatic* / metabolism
  • Brain Injuries, Traumatic* / pathology
  • Brain Injuries, Traumatic* / therapy
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / pharmacology
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Indoles / chemistry
  • Indoles / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic* / drug effects
  • Nerve Regeneration / drug effects
  • Nitric Oxide* / metabolism
  • Polymers / chemistry
  • Polymers / pharmacology
  • Reactive Oxygen Species / metabolism

Substances

  • Nitric Oxide
  • Delayed-Action Preparations
  • polydopamine
  • Reactive Oxygen Species
  • Polymers
  • Indoles