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Tripeptide–copper complex GHK‐Cu (II) transiently improved healing outcome in a rat model of ACL reconstruction
Author(s) -
Fu SaiChuen,
Cheuk YauChuk,
Chiu WaiYin Vivien,
Yung ShuHang,
Rolf Christer G.,
Chan KaiMing
Publication year - 2015
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.22831
Subject(s) - medicine , saline , anterior cruciate ligament reconstruction , anterior cruciate ligament , surgery , urology
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. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1024–1033, 2015.