Bioactive fish-derived collagen peptides enhance cutaneous repair by reprogramming the wound microenvironment toward antioxidant, anti-inflammatory and pro-remodeling status

Chronic wounds are marked by persistent inflammation that disrupts normal tissue repair. Growing attention is being directed toward dietary supplements as non-pharmacological strategies to support wound healing. This study evaluated the therapeutic potential of a specific formulation of bioactive fish-derived collagen peptides, Naticol®, in promoting cutaneous repair. The results demonstrated that oral supplementation with Naticol® accelerated excisional wound closure in type 2 diabetic mice by restoring essential histological features of healthy skin and enhancing collagen production. This effect is achieved through the establishment of an antioxidant and anti-inflammatory wound microenvironment, the enhancement of scavenger-dependent efferocytosis, and the modulation of MMP9/TIMP1 ratio in favor of tissue remodeling. Notably, Naticol® drove transcriptional reprogramming of human dermal fibroblasts and monocytes toward antioxidant, anti-inflammatory, and pro-repair phenotypes. In human keratinocytes, Naticol® increased migratory capacity, further contributing to tissue regeneration. Consistent with in vivo findings, Naticol® treatment improved wound healing in human skin explants by reinforcing an antioxidant, anti-inflammatory, and pro-reparative microenvironment. These results highlight Naticol®, a fish-derived bioactive collagen peptide preparation, as a promising functional food component, providing an innovative complementary approach for the management of chronic wounds.