Injectable Alginate-Based Hydrogels Encapsulating Engineered Endothelial Extracellular Vesicles for the Treatment of Critical Limb Ischemia

Biomacromolecules. 2024 Oct 14;25(10):6656-6665. doi: 10.1021/acs.biomac.4c00845. Epub 2024 Sep 12.

Abstract

Critical limb ischemia (CLI) is a peripheral arterial disease resulting from chronic inflammation of vascular systems. Recent studies have shown that inhibiting macrophage inflammation has the potential to treat CLI, and extracellular vesicles (EVs) from endothelial cells can inhibit macrophage activation. However, the limited cell-targeting capabilities and rapid clearance of EVs from the injection site limit the in vivo application of the EVs. Here, we modified endothelial EVs with platelet membranes (pM/EVs) to boost the inhibition effects on macrophage inflammation and developed an injectable alginate-based collagen composite (ACC) hydrogel for localized delivery of pM/EVs (pM/EVs@ACC) for CLI treatment. We found that pM/EVs can effectively inhibit macrophage inflammation in vitro. Furthermore, pM/EVs@ACC treatment significantly promotes the recovery of limb functions, restoring the feet' blood supply and relieving inflammation. Our findings provide compelling evidence that the pM/EVs@ACC injectable system mediating delivery of pM/EVs is a promising strategy for CLI treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates* / chemistry
  • Animals
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Extracellular Vesicles* / chemistry
  • Extracellular Vesicles* / metabolism
  • Hindlimb / blood supply
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Inflammation
  • Ischemia* / pathology
  • Ischemia* / therapy
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RAW 264.7 Cells

Substances

  • Alginates
  • Hydrogels