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<p>Glycyl-L-histidyl-L-lysine–copper (GHK-Cu), an endogenous tripeptide–metal complex, has attracted increasing interest due to its multifaceted biological roles in tissue repair, anti-inflammatory regulation, extracellular matrix remodeling, and redox homeostasis. In recent years, GHK-Cu has evolved from a dermatological bioactive ingredient into a representative model system linking coordination chemistry, peptide bioactivity, and biomanufacturing engineering. This review provides a comprehensive synthesis of the molecular mechanisms, production strategies, quality-control frameworks, and emerging applications of GHK-Cu in advanced biomaterials and delivery systems. Particular emphasis is placed on the key technologies enabling the transition from chemical synthesis to scalable biomanufacturing, including tandem-repeat expression, high-cell-density fermentation, inclusion-body-assisted purification, and Cu(II) complex stabilization. Analytical approaches for structural verification and impurity profiling, as well as global regulatory classifications and formulation-stability considerations, are also summarized. Remaining challenges in clinical translation, production standardization, and large-scale quality assurance are highlighted. This work aims to provide a systematic and forward-looking framework to support the industrial and biomedical deployment of copper–peptide therapeutics.</p> Graphical abstract <p></p>

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GHK-Cu as a multifunctional copper peptide: synthesis routes, process engineering and emerging applications

  • 期刊论文

  • 发表日期：

    2026年3月17日

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  • Wanbo Lu,
  • Sanjiang Kang,
  • Shasha Liu,
  • Yuying Wang,
  • Hongbin Wang

摘要

Glycyl-L-histidyl-L-lysine–copper (GHK-Cu), an endogenous tripeptide–metal complex, has attracted increasing interest due to its multifaceted biological roles in tissue repair, anti-inflammatory regulation, extracellular matrix remodeling, and redox homeostasis. In recent years, GHK-Cu has evolved from a dermatological bioactive ingredient into a representative model system linking coordination chemistry, peptide bioactivity, and biomanufacturing engineering. This review provides a comprehensive synthesis of the molecular mechanisms, production strategies, quality-control frameworks, and emerging applications of GHK-Cu in advanced biomaterials and delivery systems. Particular emphasis is placed on the key technologies enabling the transition from chemical synthesis to scalable biomanufacturing, including tandem-repeat expression, high-cell-density fermentation, inclusion-body-assisted purification, and Cu(II) complex stabilization. Analytical approaches for structural verification and impurity profiling, as well as global regulatory classifications and formulation-stability considerations, are also summarized. Remaining challenges in clinical translation, production standardization, and large-scale quality assurance are highlighted. This work aims to provide a systematic and forward-looking framework to support the industrial and biomedical deployment of copper–peptide therapeutics.

Graphical abstract