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Hydrogels for Osteochondral
Tissue Engineering
Journal of Biomedical

(March 2020)
Anti-Wrinkle Activity
& Transdermal Delivery
of GHK Peptide
Journal of Peptide Science
(March 2020)
Pulsed Glow Discharge
to GHK-Cu Determination
International Journal
of Mass Spectrometry

(March 2020)
Protective Effects of GHK-Cu
in Pulmonary Fibrosis
Life Sciences
(January 2020)
Anti-Wrinkle Benefits
of GHK-Cu Stimulating
Skin Basement Membrane
International Journal of Molecular Sciences
(January 2020)
Structural Analysis
Molecular Dynamics of
Skin Protective
TriPeptide GHK
Journal of Molecular Structure
(January 2020)
In Vitro / In Vivo Studies
pH-sensitive GHK-Cu in
Superabsorbent Polymer
GHK Enhances
Stem Cells Osteogenesis
Acta Biomaterialia
Antibacterial GHK-Cu
Nanoparticles for
Wound Healing
Particle & Particle (2019)
Effect of GHK-Cu
on Stem Cells and
Relevant Genes
OBM Geriatrics
GHK Alleviates
Neuronal Apoptosis Due
to Brain Hemorrhage
Frontiers in Neuroscience
Endogenous Antioxidant
International Journal of Pathophysiology and Pharmacology (2018)
Regenerative and
Protective Actions of
GHK-Cu Peptide
International Journal of
Molecular Sciences
Skin Regenerative and
Anti-Cancer Actions
of Copper Peptides
GHK-Cu Accelerates
Scald Wound Healing
Promoting Angiogenesis
Wound Repair and

GHK Peptide Inhibits
Pulmonary Fibrosis
by Suppressing TGF-β1
Frontiers in Pharmacology
Skin Cancer Therapy
with Copper Peptides
The Effect of Human
Peptide GHK Relevant to
Nervous System Function
and Cognitive Decline
Brain Sciences (2017)
Effects of Tripeptide
GHK in Pain-Induced
Aggressive Behavior
Bulletin of Experimental
Biology & Medicine
GHK-Cu Elicits
In Vitro Alterations
in Extracellular Matrix
Am Journal of Respiratory
and Critical Care Medicine

Selected Biomarkers &
Copper Compounds
Scientific Reports

GHK-Cu on Collagen,
Elastin, and Facial Wrinkles
Journal of Aging Science
Tri-Peptide GHK-Cu
and Acute Lung Injury

Effect of GHK Peptide
on Pain Sensitivity
Experimental Pharmacology

New Data of the
Cosmeceutical and
TriPeptide GHK
SOFW Journal
GHK Peptide as a
Natural Modulator of
Multiple Cellular Pathways
in Skin Regeneration
BioMed Research (2015)
Resetting Skin Genome
Back to Health
Naturally with GHK
Textbook of Aging Skin
GHK-Cu May Prevent
Oxidative Stress in Skin
by Regulating Copper and
Modifying Expression of
Numerous Antioxidant Genes Cosmetics (2015)
GHK Increases
TGF-β1 in
Human Fibroblasts

Acta Poloniae

The Human Skin Remodeling Peptide Induces Anti-Cancer
Expression and DNA Repair Analytical Oncology
Resetting the
Human Genome to Health
BioMed Research
Enhanced Tropic Factor Secretion of Mesenchymal
Stem Cells with GHK
Acta Biomater
Anxiolytic (Anti-Anxiety)
Effects of GHK Peptide
Bulletin of Experimental
Biology & Medicine
Lung Destruction and
its Reversal by GHK
Genome Medicine
TriPeptide GHK Induces
Programmed Cell Death
of Neuroblastoma
Journal of Biotechnology
Stem Cell
Recovering Effect
of GHK in Skin
Peptide Science
Skin Penetration of
Copper Tripeptide in Vitro
Journal of International
Inflammation Research
Possible Therapeutics
for Colorectal Cancer
Journal of Clinical and
Experimental Metastasis
Methods of Controlling
Differentiation and
Proliferation of Stem Cells
Effects of
Copper Tripeptide
on Irradiated Fibroblasts
American Medical Association
Avoid Buying Fake Copper Peptides Dangerous














International Symposium on LIGAMENTS AND TENDONS XIII

Friday, 18 October 2013 Italy, Tuscany, Arezzo

INTRA-ARTICULAR INJECTION OF TRIPEPTIDE COPPER COMPLEX GHK-CU (II) IMPROVED GRAFT HEALING IN ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION Sai-Chuen Fu,Yau-Chuk Cheuk, Wai-Hang Cheng, Shu-Hang Yung, Christer G Rolf, Kai-Ming Chan 1 1 Department of Orthopaedics and Traumatology, Faculty of Medicine, Faculty of Medicine, The Chinese University of Hong Kong. Department of Orthopaedic Surgery, Huddinge University Hospital, CLINTEC, Karolinska Institutet, Stockholm, Sweden

Anterior cruciate ligament reconstruction (ACLR) is the standard treatment to restore knee function. However, the biological healing of the graft is often slow and poor healing can lead to ACLR failure and excessive knee laxity. If this process can be further enhanced, it will reduce the time of maturation of the graft, and hence earlier returns to full activities and sports. In the present study, the possibilities of biological augmentation of graft healing in ACLR were investigated. Recent findings show that bioactive small molecules such as matrikines may also take part in tissue remodeling. Matrikines are small peptides liberated by partial proteolysis of extracellular matrix macromolecules, which are able to regulate cell activities. Among different classes of matrikines, Glycyl-Histidyl- Lysine (GHK) tripeptide and its copper (II) chelated form (GHK-Cu) exhibit profound involvements in the tissue remodeling processes. GHK have been extensively used in the cosmetic industry for skin tissue remodeling for years with its high safety profile in humans. GHK-Cu can simultaneously activate the in vivo synthesis of matrix components, and the in vivo production of degradative enzymes and the inhibitors. GHK-Cu can promote bone healing and promote implant attachment to bony tissues. It can also act as chemoattractant for repair cells and induce wound angiogenesis. It is possible that GHK-Cu can promote graft healing in ACLR.

The animal experiments in this study were approved by the Animal Experimentation Ethics Committee in authors’ institution (Ref. no.: 11/054/GRF and 460611). The procedures of ACLR were performed on the right knee according to our previous study. Seventy-two male Sprague Dawley rats (12 weeks old, 400-450g) were used. Intra-articular injection (50μl per injection) of saline or GHK-Cu solution (0.3 or 3 mg/ml) was performed weekly from 2nd week to 5th week post operation. At 6 or 12 weeks post- operation, the rats were euthanized to harvest knee specimens for static anterior-posterior (AP) knee laxity test and graft pull-out test (n=8). Histological scoring on H&E stained sections was performed (n=4) with polarization microscopy. A 2-way ANOVA was used to analyze the effect of time and treatment on the outcome measures. Statistical significance was accepted at α=0.05 RESULTS At 6 weeks post operation, rats treated with 0.3 or 3 mg/ml GHK-Cu resulted in a significantly smaller side-to-side difference in AP-knee laxity as compared to saline group, but no difference in AP laxity was detected at 12 weeks post operation (p=0.531) (Figure 1). There was no significant difference in pull-out strength of the graft complex between GHK-Cu groups and saline group at 6 and 12 weeks post operation (p=0.301, 0.834), however, the stiffness of the graft complex was significantly higher in 0.3 mg/ml GHK-Cu as compared to saline group at 6 weeks post operation (p=0.007). All grafts failed at mid-substance during the pull-out test. Histological examination showed that graft incorporation and bone healing inside tunnels was significantly better in the GHK-Cu treated groups. Graft degeneration as shown by decreased collagen birefringence was less severe in the 0.3 mg/ml GHK-Cu group as compared to saline group, but significantly increased cell recruitment to graft mid-substance in 3 mg/ml GHK-Cu group also rendered poor graft integrity (Figure 2).

Our study suggests that GHK-Cu may improve graft healing in ACLR. GHK-Cu may improve tissue remodeling in graft mid- substance and graft tunnel interface, but extensive tissue remodeling may not be beneficial as shown in 3 mg/ml GHK-Cu group. Further studies are necessary to investigate the underlying mechanisms for the observed effects of GHK-Cu. As restoration of A-P knee laxity after ACLR was improved at earlier time point, biological enhancement in graft healing by GHK-Cu may imply earlier return to normal activity after operation. However, as the pull-out strength was not improved, high demand activities may not be warranted safe. There are still plenty of rooms for biological augmentation of graft healing in ACLR.

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