Tripeptide-copper complex GHK-Cu (II) transiently improved healing outcome in a rat model of ACL reconstruction.
After anterior cruciate ligament reconstruction (ACLR), the biological healing of the graft is a rate-limiting step which can contribute to graft failure. The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(II) (GHK-Cu) is a well-known activator of tissue remodeling. We investigated whether GHK-Cu can improve graft healing following ACLR. Seventy-two rats underwent unilateral ACLR were randomized to saline, 0.3 or 3 mg/ml GHK-Cu groups (n = 24). Post-operational intra-articular injections were given from week 2, once a week, for 4 weeks. Gait analysis was performed pre-injury and at harvesting time. At 6 or 12 weeks post-operation, knee specimens were harvested for knee laxity test, graft pull-out test, and histology. At 6 weeks post-ACLR, GHK-Cu groups resulted in a smaller side-to-side difference in knee laxity as compared to the saline group (p = 0.009), but there was no significant difference at 12 weeks post-operation. The graft complex in the 0.3 mg/ml GHK-Cu group had higher stiffness than saline group at 6 weeks post-operation (p = 0.026), but there was no significant difference in ultimate load, gait parameters, and histological scores among treatment groups. All grafts failed mid-substance during pull-out test. Intra-articular supplementation with a bioactive small molecule GHK-Cu improved graft healing following ACLR in rat, but the beneficial effects could not last as treatment discontinued.
Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.|Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Sai-Chuen
SC
Fu
Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.|Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Yau-Chuk
YC
Cheuk
Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.|Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Wai-Yin Vivien
WY
Chiu
Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.|Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Shu-Hang
SH
Yung
Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.|Division of Orthopedics and Biotechnology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Christer G
CG
Rolf
Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.|Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Kai-Ming
KM
Chan
D000818:Animals; D059549:Anterior Cruciate Ligament Reconstruction; D005684:Gait / Q000187:drug effects; D007270:Injections, Intra-Articular; D007593:Joint Instability / Q000517:prevention & control; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D019737:Transplants / Q000187:drug effects* / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects*
D009842:Oligopeptides; C020905:glycyl-histidyl-lysine
anterior cruciate ligament reconstruction; biological modulation; graft remodeling; rat; tripeptide copper complex