Reactive Oxygen Species-Scavenging Scaffold with Rapamycin for Treatment of Intervertebral Disk Degeneration

Adv Healthc Mater. 2020 Feb;9(3):e1901186. doi: 10.1002/adhm.201901186. Epub 2019 Dec 10.

Abstract

The chronic inflammatory microenvironment is characterized by the elevated level of reactive oxygen species (ROS). Here, it is hypothesized that developing an ROS-scavenging scaffold loaded with rapamycin (Rapa@Gel) may offer a new strategy for modulating the local inflammatory microenvironment to improve intervertebral disk tissue regeneration. The therapeutic scaffold consisting of ROS-degradable hydrogel can be injected into the injured degeneration site of intervertebral disk (IVD) and can release therapeutics in a programmed manner. The ROS scavenged by scaffold reduces the inflammatory responses. It is found that when rats are treated with Rapa@Gel, this results in an increase in the percentage of M2-like macrophages and a decrease in M1-like macrophages in the inflammatory environment, respectively. Regeneration of IVD is achieved by Rapa@Gel local treatment, due to the increased M2 macrophages and reduced inflammation. This strategy may be extended to the treatment of many other inflammatory diseases.

Keywords: ROS response; drug delivery; inflammation; intervertebral disk degeneration; rapamycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / administration & dosage*
  • Biocompatible Materials / chemistry*
  • Biocompatible Materials / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Drug Delivery Systems
  • Hydrogels
  • Intervertebral Disc Degeneration / drug therapy*
  • Intervertebral Disc Degeneration / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RAW 264.7 Cells
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism*
  • Sirolimus / administration & dosage*
  • Sirolimus / pharmacokinetics
  • Sirolimus / pharmacology

Substances

  • Biocompatible Materials
  • Cytokines
  • Hydrogels
  • Reactive Oxygen Species
  • Sirolimus