Type III collagen-enriched scaffolds modulate skin wound healing

The major dermal component of adult skin, type I collagen (Col I), has been widely used in skin substitutes to improve wound healing. Modulating the wound microenvironment remains challenging. Fetal skin heals with limited scarring and contains higher levels of type III collagen (Col III), which decline with aging, suggesting a role in wound healing. To investigate the potential benefit of Col III in wound healing, porous crosslinked sponges with different Col I/III ratios mimicking three developmental stages were created. Atelocollagen enriched in Col III was successfully obtained from human placenta. Upon combining Col III enriched atelocollagen with Col I collagen fibrils in Col I + III scaffolds, a higher Col III content altered pore morphology and reduced scaffold stiffness. In vitro, Col III-containing scaffolds downregulated TGFB3 in human dermal fibroblasts. M0 macrophages cultured on these scaffolds exhibited surface marker profiles suggesting a shift toward a pro-healing M2-like phenotype. In a rat full-thickness wound model, the presence of the Col III preparation led to a reduced wound deformation, an epidermal thickness better resembling native skin, and faster scaffold degradation after 28 days than Col I alone. These findings highlight the potential of the human Col III enriched placental extract as a skin substitute component to regulate wound healing in acute wound treatment, with possible future applications in clinical settings.