Enhanced diabetic wound healing using platelet-derived extracellular vesicles and reduced graphene oxide in polymer-coordinated hydrogels

J Nanobiotechnology. 2023 Sep 4;21(1):318. doi: 10.1186/s12951-023-02068-x.

Abstract

Impaired wound healing is a significant complication of diabetes. Platelet-derived extracellular vesicles (pEVs), rich in growth factors and cytokines, show promise as a powerful biotherapy to modulate cellular proliferation, angiogenesis, immunomodulation, and inflammation. For practical home-based wound therapy, however, pEVs should be incorporated into wound bandages with careful attention to delivery strategies. In this work, a gelatin-alginate hydrogel (GelAlg) loaded with reduced graphene oxide (rGO) was fabricated, and its potential as a diabetic wound dressing was investigated. The GelAlg@rGO-pEV gel exhibited excellent mechanical stability and biocompatibility in vitro, with promising macrophage polarization and reactive oxygen species (ROS)-scavenging capability. In vitro cell migration experiments were complemented by in vivo investigations using a streptozotocin-induced diabetic rat wound model. When exposed to near-infrared light at 2 W cm- 2, the GelAlg@rGO-pEV hydrogel effectively decreased the expression of inflammatory biomarkers, regulated immune response, promoted angiogenesis, and enhanced diabetic wound healing. Interestingly, the GelAlg@rGO-pEV hydrogel also increased the expression of heat shock proteins involved in cellular protective pathways. These findings suggest that the engineered GelAlg@rGO-pEV hydrogel has the potential to serve as a wound dressing that can modulate immune responses, inflammation, angiogenesis, and follicle regeneration in diabetic wounds, potentially leading to accelerated healing of chronic wounds.

Keywords: Antiinflammation; Hydrogel; Platelet extracellular vesicles (pEVs); Reduced graphene oxide; Wound healing.

MeSH terms

  • Animals
  • Blood Platelets* / chemistry
  • Cell Line
  • Cell Survival
  • Diabetes Complications* / drug therapy
  • Extracellular Vesicles* / chemistry
  • Humans
  • Hydrogels / chemistry
  • Mice
  • Oxidation-Reduction
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Wound Healing*

Substances

  • graphene oxide
  • Reactive Oxygen Species
  • Hydrogels