---
title: "In vivo stimulation of connective tissue accumulation by the…"
description: "GHK-Cu stimulates the accumulation of connective tissue components like collagen and glycosaminoglycans in rat wounds."
url: "https://magellanlongevity.com/study/d8227353.md"
canonical: "https://magellanlongevity.com/study/d8227353.html"
html: "https://magellanlongevity.com/study/d8227353.html"
type: "study"
study_key: "d8227353"
journal: "J Clin Invest"
year: 1993
pmid: "8227353"
doi: "10.1172/JCI116842"
citations: 1
updated: 2026-09-02
author: "Gabriel Radu, DO"
author_credentials: "Physiatrist (PM&R). NY medical license 275110. NPI 1376861765."
publisher: "Magellan Longevity"
content_format: "markdown"
---

# In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex GHK-Cu in rat wounds

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## Citation

| Field | Value |
| --- | --- |
| Journal | J Clin Invest |
| Year | 1993 |
| PMID | [8227353](https://pubmed.ncbi.nlm.nih.gov/8227353/) |
| DOI | [10.1172/JCI116842](https://doi.org/10.1172/JCI116842) |
| Study key | d8227353 |

## Takeaway

GHK-Cu stimulates the accumulation of connective tissue components like collagen and glycosaminoglycans in rat wounds.

## The question

Does the tripeptide-copper complex GHK-Cu stimulate connective tissue accumulation in rat wounds in vivo?

## Hypothesis

GHK-Cu, previously identified as a growth factor and potential activator of wound repair in vitro, will increase extracellular matrix accumulation in vivo.

## Methods

Stainless steel wire mesh cylinders were subcutaneously implanted into the backs of rats. Rats were divided into groups receiving sequential injections of either saline (control) or various concentrations of GHK-Cu into the wound chambers. After the experiment, wound chambers were collected and analyzed for dry weight, total proteins, collagen, DNA, elastin, glycosaminoglycans, and specific mRNAs for collagens and TGF beta. A control tripeptide, L-glutamyl-L-histidyl-L-proline, was also tested.

## Results

GHK-Cu injections resulted in a concentration-dependent increase in dry weight, DNA, total protein, collagen, and glycosaminoglycan content within the wound chambers. Collagen synthesis was twice that of noncollagen proteins. Increases were observed in type I and type III collagen mRNAs, but not in TGF beta mRNAs. An increase in the relative amount of dermatan sulfate was also found. The control tripeptide had no significant effect.

## Conclusion

GHK-Cu effectively increases extracellular matrix accumulation in wounds in vivo.

## Limitations

The study was conducted in rats using a specific wound chamber model, which may not directly translate to human wound healing processes.

## Verbatim from the abstract

> GHK-Cu increases extracellular matrix accumulation in wounds through stimulation of collagen synthesis

## Collagen Synthesis vs. Noncollagen Protein Synthesis with GHK-Cu

| Measure | Relative Stimulation |
| --- | --- |
| Noncollagen Proteins | 1 |
| Collagen | 2 |

*The stimulation of collagen synthesis was twice that of noncollagen proteins in GHK-Cu-injected wound chambers.*

## Where this study is used on Magellan

This paper is one of the citations behind the evidence grade on the pages below. Grades are assigned from the published research and are independent of affiliate commissions.

| Compound or device | Evidence grade | Graded pages |
| --- | --- | --- |
| Copper Tripeptide (GHK-Cu) Serum | Preliminary | [Copper Tripeptide (GHK-Cu) Serum](https://magellanlongevity.com/p/186.md) |

## Reference

1. **In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex GHK-Cu in rat wounds**
   J Clin Invest 1993 · [PMID 8227353](https://pubmed.ncbi.nlm.nih.gov/8227353/) · [DOI 10.1172/JCI116842](https://doi.org/10.1172/JCI116842)

   > GHK-Cu increases extracellular matrix accumulation in wounds through stimulation of collagen synthesis

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## Related on Magellan Longevity

- [Copper Tripeptide (GHK-Cu) Serum](https://magellanlongevity.com/p/186.md) — product graded on this and related evidence
- [The human tri-peptide GHK and tissue remodeling.](https://magellanlongevity.com/study/s186.md)
- [Longevity research map](https://magellanlongevity.com/longevity-research-map.html)
- [Evidence-based longevity supplements](https://magellanlongevity.com/longevity-supplements.md)

## Scope and disclosures

Educational information, not medical advice. Nothing here is intended to diagnose, treat, cure, or prevent any disease. Talk to your physician before starting any supplement or device, especially if you are pregnant, nursing, or taking medication.

Editorial firewall: evidence grades are assigned from the published research and are independent of any affiliate commission. As an Amazon Associate, Magellan Longevity earns from qualifying purchases.

Reviewed for accuracy by a board-certified physician (DO).
