Research

GHK-Cu in collagen and extracellular matrix research

Fibroblast, wound-chamber and skin-flap experiments measuring collagen, glycosaminoglycans and matrix metalloproteinases with GHK-Cu.

By the GHK-Cu Peptide editorial team · Last reviewed November 11, 2026 · Editorial review: pending

Short answer

GHK-Cu collagen research is mostly fibroblast cultures and animal wound models. Collagen synthesis in fibroblasts rose with GHK-Cu and peaked at 10⁻⁹ M [Maquart 1988], and rat wound chambers injected with GHK-Cu accumulated more collagen and glycosaminoglycans than saline controls [Maquart 1993]. Collagen has not been an outcome of a controlled human study.

Cell studies

Collagen synthesis by fibroblasts began rising at 10⁻¹²–10⁻¹¹ M and was maximal at 10⁻⁹ M, independent of cell number [Maquart 1988].
Glycosaminoglycan synthesis was biphasic, maximal at 10⁻⁹–10⁻⁸ M and back to control at higher concentrations [Wegrowski 1992].
MMP-2 and its inhibitors TIMP-1 and TIMP-2 increased; copper ions alone reproduced the MMP-2 effect and GHK alone did not [Siméon 2000].
Collagen IV expression rose with GHK-Cu combined with hyaluronic acid in fibroblasts and excised skin [Jiang 2023]; elastin expression was measured with copper tripeptide-1 in a combination study [Ye 2026].
GHK-Cu coatings increased the attachment of osteoblastic cells without changing spreading [Godet 1995].

Animal studies

In rat wound chambers, GHK-Cu injected directly into the implanted chamber increased dry weight, collagen and glycosaminoglycans [Maquart 1993] [Siméon 2000] and changed MMP-2 and MMP-9 profiles [Siméon 1999]. Topical gels reduced wound area in rats [Canapp 2003] and rabbits [Cangul 2006], and liposomal GHK-Cu was compared with free GHK-Cu in a mouse scald model [Wang 2017]. Not every result points the same way: a guinea-pig study observed slower skin reorganisation [Buffoni 1995], and an irradiated rat-flap study measured a larger ischaemic area with the GHK-Cu gel than with the control ointment [Parker 2013].

Related: mechanism of action · skin research.

All collagen and matrix records

Primary GHK-Cu collagen and extracellular matrix records
Study	Model and route	What was measured	Limitations	Grade
Maquart 1988 FEBS Lett Collagen and extracellular matrix	In vitroCell culture Fibroblast cultures GHK-Cu (copper complex)	The study measured collagen synthesis in fibroblast cultures that rose from 10⁻¹²–10⁻¹¹ M GHK-Cu and peaked at 10⁻⁹ M, independent of cell number.	Cultured cells; the wound-site liberation hypothesis is the authors’ suggestion.	Evidence grade D
Wegrowski 1992 Life Sci Collagen and extracellular matrix	In vitroCell culture Normal human fibroblast cultures GHK-Cu (copper complex)	The study measured a biphasic increase in glycosaminoglycan synthesis, maximal at 10⁻⁹–10⁻⁸ M and returning to control at higher concentrations, mainly dermatan sulfate and heparan sulfate.	Cultured cells.	Evidence grade D
Maquart 1993 J Clin Invest Collagen and extracellular matrix	Animalwound chamber Rat wound-chamber model (mesh chamber implanted under the skin) GHK-Cu (copper complex)	The study measured concentration-dependent increases in dry weight and connective-tissue components (collagen, DNA, glycosaminoglycans) in GHK-Cu-injected wound chambers compared with saline.	Rats; material delivered directly into an implanted chamber, which is not a route of administration to a person.	Evidence grade C
Pesáková 1995 Biomaterials Collagen and extracellular matrix	In vitroCell culture Chick embryo chondrocytes on three supports GHK-Cu (copper complex)	The study measured chondrocyte proliferation and synthesis of collagen types I, II and III with the copper-tripeptide supplement on plastic and collagen supports.	Avian cells; biomaterials context; abstract truncated in PubMed.	Evidence grade D
Godet 1995 Cell Mol Biol (Noisy-le-grand) Collagen and extracellular matrix	In vitroCell culture Rat calvaria cells, human trabecular osteoblasts, human marrow stromal cells GHK-Cu (copper complex)	The study found that GHK-Cu and GHK coatings (10⁻¹⁰–10⁻⁸ M) did not change cell spreading but increased the attachment of rat and human osteoblastic cells.	Cultured cells on coated surfaces.	Evidence grade D
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
Siméon 1999 J Invest Dermatol Collagen and extracellular matrix	Animalwound chamber Rat wound-chamber model GHK-Cu (copper complex)	The study measured matrix metalloproteinase expression and activation in wound fluid; GHK-Cu did not alter interstitial collagenase activity and changed MMP-2 and MMP-9 profiles.	Rats; chamber delivery; abstract truncated in PubMed.	Evidence grade C
Siméon 2000 Life Sci Collagen and extracellular matrix	In vitroCell culture Dermal fibroblast cultures GHK-Cu (copper complex)	The study measured higher MMP-2, TIMP-1 and TIMP-2 secretion with GHK-Cu; copper ions reproduced the MMP-2 effect and GHK alone did not.	Cultured cells; the copper-only result complicates attribution to the complex.	Evidence grade D
Siméon 2000 J Invest Dermatol Collagen and extracellular matrix	Animalwound chamber Rat wound-chamber model and rat dermal fibroblasts GHK-Cu (copper complex)	The study measured increased wound-tissue dry weight, protein, type I collagen and glycosaminoglycans with repeated GHK-Cu injections, with greater chondroitin and dermatan sulfate accumulation.	Rats; chamber delivery.	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
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
Huang 2007 Photomed Laser Surg Collagen and extracellular matrix	In vitroCell culture Human fibroblast line HS68 GHK-Cu (copper complex)	The study measured fibroblast viability, procollagen type I C-peptide and bFGF with LED light alone or combined with Cu-GHK.	Cell line; combined with a light treatment; abstract truncated in PubMed.	Evidence grade D
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
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
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
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
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

Frequently asked questions

Does GHK-Cu increase collagen?

In fibroblast cultures, collagen synthesis rose with GHK-Cu and peaked at 10⁻⁹ M, and in rat wound chambers collagen content increased with injected GHK-Cu. Collagen has not been measured as an outcome in a controlled human study.

Is there a GHK sequence in collagen?

Yes. The 1988 fibroblast study noted a GHK triplet in the α2(I) chain of type I collagen and suggested the tripeptide might be released at wound sites. That release is the authors’ hypothesis.

References

Maquart FX, Pickart L, Laurent M et al. (1988). Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. FEBS Lett. PubMed 3169264 · doi:10.1016/0014-5793(88)80509-x[In vitro, grade D]
Wegrowski Y, Maquart FX, Borel JP (1992). Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. Life Sci. PubMed 1522753 · doi:10.1016/0024-3205(92)90504-i[In vitro, grade D]
Maquart FX, Bellon G, Chaqour B et al. (1993). In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds. J Clin Invest. PubMed 8227353 · doi:10.1172/JCI116842[Animal, grade C]
Siméon A, Monier F, Emonard H et al. (1999). Expression and activation of matrix metalloproteinases in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. J Invest Dermatol. PubMed 10383745 · doi:10.1046/j.1523-1747.1999.00606.x[Animal, grade C]
Siméon A, Wegrowski Y, Bontemps Y et al. (2000). Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+). J Invest Dermatol. PubMed 11121126 · doi:10.1046/j.1523-1747.2000.00166.x[Animal, grade C]
Siméon A, Emonard H, Hornebeck W et al. (2000). The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures. Life Sci. PubMed 11045606 · doi:10.1016/s0024-3205(00)00803-1[In vitro, grade D]
Godet D, Marie PJ (1995). Effects of the tripeptide glycyl-L-histidyl-L-lysine copper complex on osteoblastic cell spreading, attachment and phenotype. Cell Mol Biol (Noisy-le-grand). PubMed 8747089[In vitro, grade D]
Jiang F, Wu Y, Liu Z et al. (2023). Synergy of GHK-Cu and hyaluronic acid on collagen IV upregulation via fibroblast and ex-vivo skin tests. J Cosmet Dermatol. PubMed 37062921 · doi:10.1111/jocd.15763[Ex vivo, grade D]
Ye S, Kang S, Jeong ET et al. (2026). Multi-Target Restoration of Dermal Elastic Fibers Through Elastin Upregulation, Elastase Suppression, and Scaffold Reinforcement. Curr Issues Mol Biol. PubMed 42193036 · doi:10.3390/cimb48050431[In vitro, grade D]
Parker NP, Ardeshirpour F, Schmechel SC et al. (2013). Effects of topical copper tripeptide complex on wound healing in an irradiated rat model. Otolaryngol Head Neck Surg. PubMed 23744835 · doi:10.1177/0194599813492644[Animal, grade C]
Canapp SO, Farese JP, Schultz GS et al. (2003). The effect of topical tripeptide-copper complex on healing of ischemic open wounds. Vet Surg. PubMed 14648529 · doi:10.1111/j.1532-950x.2003.00515.x[Animal, grade C]
Cangul IT, Gul NY, Topal A et al. (2006). Evaluation of the effects of topical tripeptide-copper complex and zinc oxide on open-wound healing in rabbits. Vet Dermatol. PubMed 17083573 · doi:10.1111/j.1365-3164.2006.00551.x[Animal, grade C]
Buffoni F, Pino R, Dal Pozzo A (1995). Effect of tripeptide-copper complexes on the process of skin wound healing and on cultured fibroblasts. Arch Int Pharmacodyn Ther. PubMed 8836453[Animal, grade C]
Wang X, Liu B, Xu Q et al. (2017). GHK-Cu-liposomes accelerate scald wound healing in mice by promoting cell proliferation and angiogenesis. Wound Repair Regen. PubMed 28370978 · doi:10.1111/wrr.12520[Animal, grade C]
Byun SY, Chae JB, Na JI et al. (2016). Significant improvement in crow's feet after treatment with Jet-M and a mixed solution of copper-GHK, oligo-hyaluronic acid, rhodiolar extract, tranexamic acid, and β-glucan (GHR formulation). J Cosmet Laser Ther. PubMed 27064823 · doi:10.3109/14764172.2016.1157367[Human, grade B]