RPEP-00080 · 1988GHK-Cu stimulated collagen synthesis in fibroblast cell cultures. The effect began at concentrations between 10 picomolar (10^-12 M) and 100 picomolar (10^-11 M), an extraordinarily low threshold.
The stimulation maximized at 1 nanomolar (10^-9 M). Above this concentration, the effect plateaued.
The collagen increase was independent of cell number changes. GHK-Cu was not simply making more cells; it was making existing cells produce more collagen.
A GHK tripeptide sequence (glycine-histidine-lysine) exists naturally within the alpha 2(I) chain of type I collagen. The authors proposed that when wounds break down collagen, proteases could release GHK fragments. These fragments would then bind copper and stimulate new collagen production at the wound site, creating a self-healing feedback loop.
Maquart, F X; Pickart, L; Laurent, M; Gillery, P; Monboisse, J C; Borel, J P · In Vitro
RPEP-00254 · 1992GHK-Cu induced dose-dependent increases in both secreted and cell-associated glycosaminoglycan synthesis by normal human fibroblasts.
Wegrowski, Y; Maquart, F X; Borel, J P · In Vitro
RPEP-00269 · 1993GHK-Cu significantly stimulated connective tissue accumulation and collagen synthesis in rat wounds in vivo, confirming its wound-healing potential first observed in cell culture.
Maquart, F X; Bellon, G; Chaqour, B; Wegrowski, J; Patt, L M; Trachy, R E; Monboisse, J C; Chastang, F; Birembaut, P; Gillery, P · Animal Study
RPEP-00316 · 1995GHK-Cu increased wound collagen (hydroxyproline), protein, DNA, and amine oxidase activity in guinea pig skin wounds, with effects requiring the peptide component, not just copper.
Buffoni, F; Pino, R; Dal Pozzo, A · Animal Study
RPEP-01007 · 2005GHK peptide incorporated into a biotinylated collagenous wound dressing accelerated rat dermal wound healing: faster wound closure, enhanced granulation tissue formation, improved collagen deposition, and better overall histological healing scores versus scaffold alone.
Arul, V; Gopinath, D; Gomathi, K; Jayakumar, R · Animal Study
RPEP-01165 · 2006Topical copper tripeptide complex (GHK-Cu) significantly accelerated healing after CO2 laser resurfacing in a double-blind, vehicle-controlled RCT, with faster re-epithelialization and improved skin quality — clinical validation of GHK-Cu for post-procedure skin recovery.
Miller, Timothy R; Wagner, Jon D; Baack, Bret R; Eisbach, Karl J · RCT
RPEP-01385 · 2008GHK-Cu and other peptide-copper complexes demonstrated measurable skin penetration and bioactive copper delivery to dermal layers, validating the bioavailability of topical copper peptide formulations for skin anti-aging and wound healing applications.
Mazurowska, Lena; Mojski, Miroslaw · In Vitro
RPEP-01402 · 2008GHK-Cu comprehensively reviewed: stimulates collagen/glycosaminoglycan synthesis, wound healing, hair growth, and reprograms gene expression (1,584 genes) toward tissue repair and anti-aging — the most versatile copper-binding tripeptide in regenerative medicine.
Pickart, Loren · Review
RPEP-02868 · 2016GHK-Cu (glycyl-histidyl-lysine copper) is surprisingly stable in water and at pH 4.5–7.4 buffers, remaining intact for at least two weeks even at 60°C. However, it breaks down under basic (alkaline) and oxidative conditions through hydrolytic cleavage, with histidine identified as one of three degradation products.
The peptide is highly water-loving (hydrophilic), with log D values between -2.38 and -2.49, which explains why it struggles to penetrate skin on its own. It was compatible with Span 60-based niosomes (a type of delivery vesicle) but degraded in the presence of negatively charged lipids like dicetyl phosphate. These findings provide a practical roadmap for formulating GHK-Cu into effective topical products.
Badenhorst, Travis; Svirskis, Darren; Wu, Zimei · Laboratory
RPEP-04979 · 2020GHK-Cu inhibited pulmonary fibrosis by reducing TNF-α/IL-6, collagen deposition, and EMT progression through suppression of TGFβ1/Smad2/3 signaling and NF-κB, with Nrf2 pathway activation.
Ma, Wen-Hui; Li, Meng; Ma, Hai-Feng; Li, Wei; Liu, Li; Yin, Yan; Zhou, Xiao-Ming; Hou, Gang · Animal
RPEP-09497 · 2024Rigid-flexible liposome nanocarriers protected GHK-Cu from enzymatic degradation and enabled sustained release, countering skin cell aging through Nrf2, SIRT1, and COX-2/PGE2 pathway modulation.
Wang, Yan; Lin, Jialiang; Yu, Zihao; Cheng, Jinbo; Cheng, Jianhua; Cui, Weikang · In Vitro