Polyphenol-driven facile assembly of a nanosized acid fibroblast growth factor-containing coacervate accelerates the healing of diabetic wounds

Diabetic wounds are challenging to heal due to complex pathogenic abnormalities. Routine treatment with acid fibroblast growth factor (aFGF) is widely used for diabetic wounds but hardly offers a satisfy-ing outcome due to its instability. Despite the emergence of various nanoparticle-based protein delivery approaches, it remains challenging to engineer a versatile delivery system capable of enhancing protein stability without the need for complex preparation. Herein, a polyphenol-driven facile assembly of nano -sized coacervates (AE-NPs) composed of aFGF and Epigallocatechin-3-gallate (EGCG) was constructed and applied in the healing of diabetic wounds. First, the binding patterns of EGCG and aFGF were predicted by molecular docking analysis. Then, the characterizations demonstrated that AE-NPs displayed higher stability in hostile conditions than free aFGF by enhancing the binding activity of aFGF to cell surface re-ceptors. Meanwhile, the AE-NPs also had a powerful ability to scavenge reactive oxygen species (ROS) and promote angiogenesis, which significantly accelerated full-thickness excisional wound healing in diabetic mice. Besides, the AE-NPs suppressed the early scar formation by improving collagen remodeling and the mechanism was associated with the TGF-beta/Smad signaling pathway. Conclusively, AE-NPs might be a potential and facile strategy for stabilizing protein drugs and achieving the scar-free healing of diabetic wounds.

Automated summary

A polyphenol-driven assembly of nano-sized coacervates (AE-NPs) composed of Epigallocatechin-3-gallate (EGCG) and acid fibroblast growth factor (aFGF) was successfully constructed for the healing of diabetic wounds. The AE-NPs exhibited higher stability under hostile conditions and showed the ability to scavenge reactive oxygen species (ROS) and promote angiogenesis. This resulted in accelerated wound healing and suppressed scar formation in diabetic mice.