GHK-Cu Peptide

Research

GHK-Cu in skin research

GHK-Cu skin research: three randomised topical trials, permeation through excised human skin, and fibroblast and keratinocyte studies.

By the GHK-Cu Peptide editorial team · Last reviewed · Editorial review: pending

Short answer

GHK-Cu skin research covers three randomised topical trials with mixed results [Bishop 1992] [Mulder 1994] [Miller 2006], permeation experiments on excised human skin that measured copper rather than intact peptide [Hostynek 2010], and fibroblast and keratinocyte studies. A 2025 review found the clinical evidence for cosmetic GHK-Cu use surprisingly thin [Mortazavi 2025].

Randomised human trials (topical)

  • 1992, venous leg ulcers, 86 evaluable: the 0.4% copper tripeptide cream did not differ from placebo; silver sulfadiazine did better than both [Bishop 1992].
  • 1994, neuropathic plantar ulcers: greater median closure with the gel than with vehicle, when started immediately after debridement [Mulder 1994].
  • 2006, after CO₂ laser resurfacing, 13 completers: no objective difference in redness, wrinkles or skin quality; patient satisfaction differed [Miller 2006].

A randomised, quadruple-masked phase 2 trial of a topical GHK-Cu gel against vehicle in standardised skin wounds was recruiting at our last check [NCT07437586].

Getting through the skin

GHK and GHK-Cu are very hydrophilic, which limits passage through the outer skin layer. In flow-through cells with human skin, copper applied as the tripeptide crossed dermatomed skin with a permeability coefficient of 2.43 × 10⁻⁴ cm/h [Hostynek 2010]; a second report by the same group gives the same coefficient with a different retained-copper value[Hostynek 2011]. In a liposome-membrane model, the peptide and its 1:1 and 2:1 copper complexes all crossed, faster at higher pH [Mazurowska 2007]. Microneedle[Li 2015] and laser [Lee 2022] pre-treatment increased permeation in vitro, and a 2026 systematic review found microneedle delivery untested in an adequately powered human trial [Najafi 2026].

Formulation research

Liposomes of about 100 nm encapsulated 20–32% of the GHK-Cu offered in one study [Dymek 2023], and a 2026 method tracked the stability of liposomal GHK-Cu inside emulsion and serum bases[Ogórek 2026]. These are formulation measurements; they do not show an effect on skin.

Skin-cell studies

Copper-free GHK increased keratinocyte proliferation and changed basal-cell markers in engineered skin [Choi 2012]; GHK-Cu shortened population-doubling time of normal and previously irradiated dermal fibroblasts in serum-free culture [Pollard 2005]. In a keratinocyte irritation model, GHK-Cu was not cytotoxic at the tested concentrations [Li 2016].

All skin records

Primary GHK-Cu skin research records
StudyModel and routeWhat was measuredLimitationsGrade
Mazurowska 2007
Talanta
Laboratory analytical methods · Skin research · Copper binding
ChemistryNo organism
Flynn diffusion cell with a liposome model membrane
GHK-Cu (copper complex)
The study identified the copper complexes present at different pH by ESI-MS and measured permeability coefficients through a model stratum corneum membrane that increased with pH.Artificial membrane, not skin.Evidence grade D
Wang 2017
Wound Repair Regen
Collagen and extracellular matrix · Skin research
Animaltopical
HUVEC cultures; mouse scald model
GHK-Cu (copper complex)
The study measured a 33.1% higher endothelial-cell proliferation rate with GHK-Cu liposomes and compared CD31 and Ki67 staining and healing time in mice treated with liposomal versus free GHK-Cu.Mice; liposomal formulation; abstract truncated in PubMed.Evidence grade C
Parker 2013
Otolaryngol Head Neck Surg
Collagen and extracellular matrix · Skin research
Animaltopical
Irradiated rat dorsal skin flaps
GHK-Cu (copper complex) · n = 23 (13 test, 10 control)
The study measured ischaemic flap area, caveolin-1 and VEGF staining; mean ischaemic area was 5.0 cm² with GHK-Cu gel and 3.8 cm² with the control ointment.Rats; the measured ischaemic area was larger in the GHK-Cu group.Evidence grade C
Cangul 2006
Vet Dermatol
Collagen and extracellular matrix · Skin research
Animaltopical
New Zealand rabbits, full-thickness dorsal wounds
GHK-Cu (copper complex) · n = 18
The study measured unhealed wound area and contraction on days 7, 14 and 21; the copper-complex group had smaller unhealed areas than the untreated group at each time point.Rabbits; small groups.Evidence grade C
Canapp 2003
Vet Surg
Collagen and extracellular matrix · Skin research
Animaltopical
Rat full-thickness wounds in an ischaemic skin flap
GHK-Cu (copper complex) · n = 24
The study measured wound area daily for 13 days and TNF-α, MMP-2 and MMP-9 in biopsies; wound area decreased in the gel group but not the vehicle group compared with no treatment.Rats; abstract truncated in PubMed.Evidence grade C
Buffoni 1995
Arch Int Pharmacodyn Ther
Collagen and extracellular matrix · Skin research
Animaltopical
Guinea-pig dorsal skin wounds; cultured fibroblasts
GHK-Cu (copper complex)
The study measured hydroxyproline, protein, DNA and amine-oxidase activity and observed slower skin reorganisation and delayed fibroblast activation with the copper-peptide complexes.Guinea pigs; findings run opposite to several other animal reports.Evidence grade C
Jiang 2023
J Cosmet Dermatol
Collagen and extracellular matrix · Skin research
Ex vivoCell culture
Human dermal fibroblasts; ex vivo skin
Multi-ingredient product
The study measured collagen I, IV and VII expression across GHK-Cu and hyaluronic acid ratios and reported collagen IV increases of 25.4-fold in cells and 2.03-fold in ex vivo skin at a 1:9 ratio.Combination with hyaluronic acid; mRNA in cells and staining in excised skin.Evidence grade D
Lee 2022
Pharmaceutics
Skin research
Ex vivotopical
Pig and mouse skin in Franz diffusion cells
GHK-Cu (copper complex)
The study found that all tested laser modalities increased skin permeation of the peptides in vitro, with non-ablative lasers disrupting the stratum corneum ultrastructure.Animal skin; delivery outcome only.Evidence grade D
Li 2015
Pharm Res
Skin research · Safety and tolerability data
Ex vivotopical
Two in vitro skin models; cell and pig models for safety
GHK-Cu (copper complex)
The study found that microneedle depth depended on application force and measured 134 ± 12 nmol of peptide and 705 ± 84 nmol of copper permeating through microneedle-treated skin in 9 hours.Delivery study; does not measure any skin outcome in people.Evidence grade D
Hostynek 2011
Inflamm Res
Skin research · Laboratory analytical methods
Ex vivotopical
Human skin layers in flow-through diffusion cells
GHK-Cu (copper complex)
The study reported the same permeability coefficient (2.43 ± 0.51 × 10⁻⁴ cm/h) and 136.2 µg/cm² copper permeated, with 97 µg/cm² retained in dermatomed skin.Near-duplicate of the 2010 report by the same group with a different retained-copper figure; measures copper, not intact peptide.Evidence grade D
Hostynek 2010
Inflamm Res
Skin research · Laboratory analytical methods
Ex vivotopical
Human skin layers in flow-through diffusion cells
GHK-Cu (copper complex)
The study measured a permeability coefficient through dermatomed skin of 2.43 ± 0.51 × 10⁻⁴ cm/h, with 136.2 µg/cm² copper permeated over 48 h and 82 µg/cm² retained.Measures copper, not intact peptide; infinite-dose conditions; excised skin.Evidence grade D
Mazurowska 2008
J Cosmet Sci
Skin research
Ex vivotopical
Skin barrier models
GHK-Cu (copper complex)
The study measured penetration of copper complexes of GHK and of glutathione through the stratum corneum in vitro.Abstract truncated in PubMed; in vitro barrier model.Evidence grade D
Patel 2025
Cureus
Skin research
Humantopical
Women with acne scars
Multi-ingredient product · n = Not reported in the abstract
The study assessed visible scar change on the Manchester Scar Scale by a dermatologist with a multi-ingredient gel.No control group; four actives in one gel, so no attribution to the copper peptide.Evidence grade B
Patel 2024
Cureus
Hair research · Skin research
Humantopical
Adults with mild-to-moderate scalp flaking
Multi-ingredient product · n = Not reported in the abstract
The study measured adherent scalp flaking, scalp hydration, hair density and hair thickness over 15 days of a two-product regimen.No control group; 15 days; two products and several actives, so no attribution to the copper peptide.Evidence grade B
Byun 2016
J Cosmet Laser Ther
Skin research · Collagen and extracellular matrix
Humantopical
One adult, periocular skin
Multi-ingredient product · n = 1
The case report described photographs and biopsy staining (collagen, fibrillin-1, procollagen type 1) from treated and untreated areas in one person.One person; five active ingredients plus a device; cannot attribute any finding to GHK-Cu.Evidence grade B
Trookman 2009
J Clin Aesthet Dermatol
Skin research
Humantopical
Women 22–40 with mild-to-moderate lip dryness
Multi-ingredient product · n = 32
The study measured visual grading, corneometry, lip caliper dimensions and self-assessment over four weeks of a multi-ingredient lip product.No control group; palmitoyl-GHK is one of many ingredients and not GHK-Cu, so no effect can be attributed to it.Evidence grade B
Miller 2006
Arch Facial Plast Surg
Skin research
Humantopical
Adults after circumoral CO₂ laser resurfacing
GHK-Cu (copper complex) · n = 13 completed
The trial found no significant difference in resolution of post-laser redness, wrinkles or overall skin quality on objective and blinded assessment; only patient-reported satisfaction differed (P = .04).13 completers; primary objective measures were null.Evidence grade A
Mulder 1994
Wound Repair Regen
Skin research · Collagen and extracellular matrix
Humantopical
Adults with neuropathic plantar ulcers
GHK-Cu (copper complex) · n = Not reported in the abstract
The trial reported median plantar-ulcer area closure of 98.5% with the gel vs 60.8% with vehicle (p < 0.05), a larger difference in ulcers over 100 mm², and fewer ulcer infections (7% vs 34%).Sample size not given in the abstract; one 1994 topical gel; the authors note the effect depended on starting immediately after debridement. No independent replication is indexed.Evidence grade A
Bishop 1992
J Vasc Surg
Skin research · Collagen and extracellular matrix
Humantopical
Adults with venous leg ulcers
GHK-Cu (copper complex) · n = 86 evaluable
The trial measured ulcer size: silver sulfadiazine reduced it more than the copper tripeptide cream or placebo, and there was no difference between the copper tripeptide cream and placebo.Single trial of one 1992 topical formulation; the comparison with placebo was null.Evidence grade A
Ye 2026
Curr Issues Mol Biol
Collagen and extracellular matrix · Skin research
In vitroCell culture
Dermal fibroblasts
Multi-ingredient product
The study measured elastin expression and secretion by dermal fibroblasts exposed to copper tripeptide-1, alongside two other ingredients tested for elastase and scaffold-gene effects.Cell culture; combination study.Evidence grade D
Hur 2020
J Pept Sci
Skin research · Collagen and extracellular matrix
In vitroCell culture
Cell cultures and skin delivery models
Derivative or conjugate
The study compared GHK with a tetra-arginine conjugate and found faster cellular penetration and higher in vitro collagen biosynthesis with the conjugate.Conjugate differs from GHK-Cu; the authors attribute part of the effect to the arginine tail itself.Evidence grade D
Li 2016
Sci Rep
Skin research · Safety and tolerability data
In vitroCell culture
Human keratinocyte model
GHK-Cu (copper complex)
The study compared irritation potential at the same concentrations and found GHK-Cu not cytotoxic and without significant change in the irritation markers measured, while the copper salts differed.Keratinocyte culture model; not a human patch test; tested concentrations are those of the paper.Evidence grade D
Gruchlik 2014
Acta Pol Pharm
Skin research
In vitroCell culture
Normal human dermal fibroblasts
GHK-Cu (copper complex)
The study measured IGF-2-dependent TGF-β1 secretion by dermal fibroblasts exposed to 1 nM GHK, GHK-Cu or copper chloride.Abstract truncated in PubMed; single cell type.Evidence grade D
Choi 2012
J Pept Sci
Skin research
In vitroCell culture
Normal human keratinocytes; skin-equivalent models
GHK without copper
The study measured keratinocyte proliferation and staining for integrins α6 and β1, p63 and PCNA in skin equivalents cultured with copper-free GHK.Cultured cells and engineered tissue.Evidence grade D
Gruchlik 2012
Acta Pol Pharm
Skin research
In vitroCell culture
Normal human dermal fibroblasts (NHDF)
GHK-Cu (copper complex)
The study measured TNF-α-dependent IL-6 secretion and reported decreases with GHK, GGH, copper chloride and their copper complexes.Single cell type; copper chloride alone also changed the readout.Evidence grade D
Pollard 2005
Arch Facial Plast Surg
Skin research
In vitroCell culture
Primary human dermal fibroblasts, normal and previously irradiated, serum-free
GHK-Cu (copper complex)
The study measured faster population-doubling times in normal and irradiated fibroblasts exposed to GHK-Cu than in untreated controls, and their bFGF, TGF-β1 and VEGF output.Cultured cells from surgical specimens.Evidence grade D
McCormack 2001
Arch Facial Plast Surg
Skin research
In vitroCell culture
Primary human facial dermal fibroblasts (normal and keloid-derived), serum-free
GHK-Cu (copper complex)
The study measured fibroblast viability and secretion of basic FGF and TGF-β1 after copper tripeptide or tretinoin exposure.Primary cell lines from surgical samples; abstract truncated in PubMed.Evidence grade D

Frequently asked questions

Does GHK-Cu penetrate the skin?

In flow-through cells with excised human skin, copper applied as the tripeptide crossed dermatomed skin with a permeability coefficient of about 2.4 × 10⁻⁴ cm/h. The measurement was of copper, not of the intact peptide. Microneedle and laser pre-treatment increased permeation in vitro.

What has GHK-Cu serum research shown?

No randomised trial of a GHK-Cu serum on its own is indexed. Serum studies in PubMed are open-label tests of multi-ingredient products, and formulation work has focused on liposomes and on stability in cosmetic bases.

References

  1. Bishop JB, Phillips LG, Mustoe TA et al. (1992). A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers. J Vasc Surg. PubMed 1495150 · doi:10.1067/mva.1992.37086[Human, grade A]
  2. Mulder GD, Patt LM, Sanders L et al. (1994). Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper. Wound Repair Regen. PubMed 17147644 · doi:10.1046/j.1524-475X.1994.20406.x[Human, grade A]
  3. Miller TR, Wagner JD, Baack BR et al. (2006). Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin. Arch Facial Plast Surg. PubMed 16847171 · doi:10.1001/archfaci.8.4.252[Human, grade A]
  4. Hostynek JJ, Dreher F, Maibach HI (2010). Human skin retention and penetration of a copper tripeptide in vitro as function of skin layer towards anti-inflammatory therapy. Inflamm Res. PubMed 20703511 · doi:10.1007/s00011-010-0214-4[Ex vivo, grade D]
  5. Hostynek JJ, Dreher F, Maibach HI (2011). Human skin penetration of a copper tripeptide in vitro as a function of skin layer. Inflamm Res. PubMed 20721598 · doi:10.1007/s00011-010-0238-9[Ex vivo, grade D]
  6. Mazurowska L, Mojski M (2007). ESI-MS study of the mechanism of glycyl-l-histidyl-l-lysine-Cu(II) complex transport through model membrane of stratum corneum. Talanta. PubMed 19071668 · doi:10.1016/j.talanta.2006.11.034[Chemistry, grade D]
  7. Li H, Low YS, Chong HP et al. (2015). Microneedle-Mediated Delivery of Copper Peptide Through Skin. Pharm Res. PubMed 25690343 · doi:10.1007/s11095-015-1652-z[Ex vivo, grade D]
  8. Lee WR, Hsiao CY, Chang ZY et al. (2022). Cutaneous Delivery of Cosmeceutical Peptides Enhanced by Picosecond- and Nanosecond-Domain Nd:YAG Lasers with Quick Recovery of the Skin Barrier Function: Comparison with Microsecond-Domain Ablative Lasers. Pharmaceutics. PubMed 35214181 · doi:10.3390/pharmaceutics14020450[Ex vivo, grade D]
  9. Choi HR, Kang YA, Ryoo SJ et al. (2012). Stem cell recovering effect of copper-free GHK in skin. J Pept Sci. PubMed 23019153 · doi:10.1002/psc.2455[In vitro, grade D]
  10. Pollard JD, Quan S, Kang T et al. (2005). Effects of copper tripeptide on the growth and expression of growth factors by normal and irradiated fibroblasts. Arch Facial Plast Surg. PubMed 15655171 · doi:10.1001/archfaci.7.1.27[In vitro, grade D]
  11. Li H, Toh PZ, Tan JY et al. (2016). Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain Copper Compounds. Sci Rep. PubMed 27892491 · doi:10.1038/srep37664[In vitro, grade D]
  12. Mortazavi SM, Mohammadi Vadoud SA, Moghimi HR (2025). Topically applied GHK as an anti-wrinkle peptide: Advantages, problems and prospective. Bioimpacts. PubMed 39963574 · doi:10.34172/bi.30071[Review, grade R]
  13. Najafi N, Maatouk H, Vardanyan KG et al. (2026). A Systematic Review of the Mechanisms and Therapeutic Applications of GHK-Cu (Glycyl-L-Histidyl-L-Lysine-Copper Complex) in Topical Microneedle Delivery: A Case for Expanded Clinical Trials. Arch Intern Med Res. PubMed 42787770 · doi:10.26502/aimr.0255[Review, grade R]
  14. Dymek M, Olechowska K, Hąc-Wydro K et al. (2023). Liposomes as Carriers of GHK-Cu Tripeptide for Cosmetic Application. Pharmaceutics. PubMed 37896245 · doi:10.3390/pharmaceutics15102485[Chemistry, grade D]
  15. Ogórek K, Mierzwa M, Drozd M et al. (2026). Characterization of copper tripeptide-loaded lipid carriers and their stability in complex cosmetic matrices. J Chromatogr A. PubMed 42887096 · doi:10.1016/j.chroma.2026.467540[Chemistry, grade D]
  16. ClinicalTrials.gov (2026-02-02). Topical GHK-Cu Gel for Acute Skin Wound Healing (NCT07437586). Source[retrieved 2026-11-11]