A study found that mixing the copper peptide GHK-Cu with low‑molecular‑weight hyaluronic acid (HA) in a 1:9 ratio dramatically boosts the skin's production of collagen IV, a key protein that supports the skin's structural layer, showing a 25‑fold increase in cell cultures and a doubling in real skin tissue.

GHK-Cu and HA are two commonly used skin care ingredients, both of which were reported to enhance collagen synthesis. This work aims to investigate their co-effect on collagen regulation. In cell experiments, human dermal fibroblasts were treated by a series of GHK-Cu and HA combinations, and the expressions of collagen I, IV, and VII were measured by qRT-PCR. The best formula screened out from cell experiments were further studied by ex-vivo skin model, and the content of collagen IV was quantified by immunofluorescence method. The combination GHK-Cu and HA was found to promote the generation of collagen I, IV, and VII. Especially, they form a synergy on collagen IV. At the ratio of 1:9, GHK-Cu and LMW HA deliver the strongest effect to elevate collagen IV synthesis by 25.4 times in cell test and 2.03 times in ex-vivo skin test. The co-effect of GHK-Cu and HA was revealed. Their synergy brings an insight to anti-aging technology: choosing proper molecular weight of HA and managing its ratio with GHK-Cu could enhance DEJ health via stimulating collagen IV synthesis.