The human tri-peptide GHK and tissue remodeling

J Biomater Sci Polym Ed. 2008;19(8):969-88. doi: 10.1163/156856208784909435.


Tissue remodeling follows the initial phase of wound healing and stops inflammatory and scar-forming processes, then restores the normal tissue morphology. The human peptide Gly-(L-His)-(L-Lys) or GHK, has a copper 2+ (Cu(2+)) affinity similar to the copper transport site on albumin and forms GHK-Cu, a complex with Cu(2+). These two molecules activate a plethora of remodeling related processes: (1) chemoattraction of repair cells such as macrophages, mast cells, capillary cells; (2) anti-inflammatory actions (suppression of free radicals, thromboxane formation, release of oxidizing iron, transforming growth factor beta-1, tumor necrosis factor alpha and protein glycation while increasing superoxide dismutase, vessel vasodilation, blocking ultraviolet damage to skin keratinocytes and improving fibroblast recovery after X-ray treatments); (3) increases protein synthesis of collagen, elastin, metalloproteinases, anti-proteases, vascular endothelial growth factor, fibroblast growth factor 2, nerve growth factor, neutrotropins 3 and 4, and erythropoietin; (4) increases the proliferation of fibroblasts and keratinocytes; nerve outgrowth, angiogenesis, and hair follicle size. GHK-Cu stimulates wound healing in numerous models and in humans. Controlled studies on aged skin demonstrated that it tightens skin, improves elasticity and firmness, reduces fine lines, wrinkles, photodamage and hyperpigmentation. GHK-Cu also improves hair transplant success, protects hepatic tissue from tetrachloromethane poisoning, blocks stomach ulcer development, and heals intestinal ulcers and bone tissue. These results are beginning to define the complex biochemical processes that regulate tissue remodeling.

Publication types

  • Review

MeSH terms

  • Albumins / chemistry
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Binding Sites
  • Copper / chemistry
  • Fibroblasts / metabolism
  • Glycine / chemistry*
  • Histidine / chemistry*
  • Humans
  • Inflammation
  • Keratinocytes / cytology
  • Lysine / chemistry*
  • Peptides / chemistry
  • Tissue Engineering / methods*
  • Wound Healing


  • Albumins
  • Anti-Inflammatory Agents
  • Peptides
  • Histidine
  • Copper
  • Lysine
  • Glycine