GHK-Cu IN REGENERATIVE MEDICINE: MOLECULAR MECHANISMS, CLINICAL APPLICATIONS AND THERAPEUTIC PERSPECTIVES IN A META-ANALYSISTÍTULO

Abstract

Objective: To systematize the scientific evidence on the copper tripeptide complex GHK-Cu (glycyl-L-histidyl-L-lysine-Cu2+) in regenerative medicine, analyzing its molecular mechanisms, current clinical applications, and future therapeutic perspectives. Methods: A systematic review with meta-analysis was conducted following the PRISMA 2020 guidelines. The search was conducted in the PubMed/MEDLINE, Scopus, Web of Science, Cochrane Library, and EMBASE databases until February 2025. Randomized clinical trials, controlled studies, in vitro/in vivo preclinical research, and gene profiling studies that evaluated the efficacy of GHK-Cu in regenerative processes were included. Methodological accuracy was assessed using the PEDro and Newcastle-Ottawa scales. Statistical analysis employed a random-effects model with standardized mean difference (SMD) calculation and a 95% confidence interval. Results: Twenty-two studies were included (14 clinical and 8 preclinical) totaling 1,124 participants. The meta-analysis demonstrated significant efficacy in tissue regeneration (SMD = 0.89; 95% CI: 0.62-1.16; p<0.001), reduction of inflammation (SMD = -0.76; 95% CI: -1.02 to -0.50; p<0.001), and modulation of regenerative gene expression (SMD = 1.34; 95% CI: 0.98-1.70; p<0.001). GHK-Cu modulated approximately 4,000 genes, suppressed 70% of metastasis genes in colorectal cancer, and restored the function of irradiated fibroblasts. Clinical studies have demonstrated a 70% increase in collagen synthesis, a 55.8% reduction in wrinkle volume, and a 25% improvement in post-dermatological procedure healing. Conclusion: GHK-Cu emerges as a master regulatory molecule in regenerative medicine, with well-established epigenetic mechanisms, a favorable safety profile, and promising applications in dermatology, oncology, orthopedics, and aesthetic medicine.