Curcumin-Loaded Nanofibrous Matrix Accelerates Fibroblast Cell Proliferation and Enhances Wound Healing via GSK3-β Inhibition

Wound healing is a multifaceted biological process influenced by both intrinsic and extrinsic factors. The ability of Wnt signaling to activate cell proliferation appears to serve a central role in wound healing. Therefore, the direct activation of Wnt or inhibition of the Wnt antagonist could be an ideal approach for the stimulation of wound healing. This study aimed to investigate the underlying mechanism of small molecule-loaded nanofibrous matrix in inducing wound healing. Herein, a naturally derived small molecule, curcumin, was used to inhibit the GSK3-β, which is considered a negative regulator of the Wnt/β-catenin signaling pathway. The docking results demonstrated that curcumin makes a complex with GSK3-β at seven specific sites, thereby inhibiting its activity. Moreover, the stabilization of β-catenin appeared to be increased with the treatment of curcumin. Next, curcumin was incorporated in poly ε-caprolactone nanofibrous matrices for controlled–sustained drug release to induce cell function. Curcumin-loaded nanofibrous matrix not only enhanced fibroblast cell proliferation, but also induced the expression of the fibroblast growth factor (FGF) in vitro. Moreover, the in vivo results showed that these nanofibrous mats significantly induced wound closure in 12 mm critical-sized defect. Collectively, these results suggest that the developed nanofibrous matrix promotes impaired wound healing by modulating cell proliferation and enhancing FGF expression that promotes wound closure.