Tripeptide-copper complex GHK-Cu (II) transiently improved healing outcome in a rat model of ACL reconstruction
Open accessAbstract
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.
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GHK-Cu enhances osteoblastic cell attachment.
“Moreover, GHK-Cu promotes bone healing and enhances osteoblastic cell attachment, potentially through the increase in collagen synthesis [14–15].”
From The potential of GHK as an anti-aging peptide (2020) · cites this paper as [15]
The paper’s introductory passage says GHK-Cu can enhance attachment of an implant to bone, and its References list a study on osteoblastic cell attachment. The paper does not itself state or test that GHK-Cu enhances osteoblastic cell attachment; its own ACL-reconstruction results concern graft and bone-tunnel healing. (LLM, conf=0.83)
Experimental — accuracy not yet measuredGHK-Cu promotes bone healing.
“Moreover, GHK-Cu promotes bone healing and enhances osteoblastic cell attachment, potentially through the increase in collagen synthesis [14–15].”
From The potential of GHK as an anti-aging peptide (2020) · cites this paper as [15]
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The potential of GHK as an anti-aging peptide
Department of Comparative Medicine, S. O. M., Dou, Y., Lee, A., Zhu, L., Morton, J., & Ladiges, W. (2020) · Aging Pathobiology and Therapeutics · doi:10.31491/apt.2020.03.014 · Cited by 33 · see citing works
“3 mg/ml GHK-Cu enhances some of the healing outcomes in a rat model of anterior cruciate ligament reconstruction (ACLR), and the treatment of GHK-Cu encapsulated in liposome significantly fasten burn wound healing in mice with scald wound [7, 16].”
BackgroundLocal and Systemic Peptide Therapies for Soft Tissue Regeneration: A Narrative Review
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- Authors
- Fu, S., Cheuk, Y., Chiu, W. V., Yung, S., Rolf, C. G., & Chan, K.
- Affiliations
- Chinese University of Hong Kong (HK)
- Department of Orthopaedics and Traumatology Faculty of Medicine, The Chinese University of Hong Kong Hong Kong SAR China
- Corresponding author
- Chan, Kai‐Ming
- Venue
- Journal of Orthopaedic Research
- Publisher
- Wiley
- Published
- 2015-04-10
- Volume
- 33
- Issue
- 7
- Pages
- 1024-1033
- ISSN
- 0736-0266 (ISSN-L)
- 1554-527X
- OpenAlex
- W1912900577
- Cited by
- 25
- References
- 29
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 5 · 2020: 5 · 2017: 3 · 2016: 1 · 2015: 1
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Orthopaedic Research® (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Research Grants Council of the Hong Kong SAR (CUHK 460611)
- Topics
- Health Sciences › Medicine › Surgery › Knee injuries and reconstruction techniques
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Tendon Structure and Treatment
- Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
- Keywords
- GHK-Cu, anterior cruciate ligament reconstruction, graft healing, graft failure, tissue remodeling, intra-articular injection, knee laxity, graft stiffness, rat model
- MeSH terms
- Animals, Gait, Injections, Intra-Articular, Joint Instability, Male, Oligopeptides, Random Allocation, Wound Healing, Rats, Sprague-Dawley, Transplants, Anterior Cruciate Ligament Reconstruction
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