Gold nanoclusters on a silk fibroin scaffold accelerate fibroblast proliferation and improve burn recovery in a mouse burn model

Abstract

Delayed wound healing in skin burn injuries is common owing to inhibition of proliferation caused by excessive inflammation, necrosis, autophagy, and oxidative stress. Gold nanoclusters modified with lipoic acid (AuNCs) exhibited antioxidant and anti-inflammatory effects in a murine burn healing model. However, the impact of the AuNCs on dermal cell proliferation and granulation tissue formation remains unclear. We therefore examined their effects on dermal cell proliferation, the cell cycle, and the signaling pathways involved. AuNCs were combined with a silk fibroin scaffold and tested in a mouse burn model and human dermal fibroblasts in vitro. Combined with the silk fibroin scaffold, 50 nmol/L of AuNCs activated fibroblast differentiation, collagen deposition, and angiogenesis, increasing granulation-tissue formation, reducing tissue necrosis and systemic inflammatory response, and improving wound healing in the model. The AuNCs increased PI3K/Akt signaling pathway phosphorylation in human dermal fibroblasts, upregulating protein expression of cyclin A, B, and CDK1, which participate in the G2/M cell cycle phase, ultimately promoting fibroblast proliferation. These findings support the beneficial effects of AuNCs on burn wound healing. We suggested that AuNCs on a silk fibroin scaffold or other vector is a potential clinical strategy for burn wound treatment.