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Updated: Jul 16, 2026
Assessment of Acute Wound Healing using the Dorsal Subcutaneous Polyvinyl Alcohol Sponge Implantation and Excisional Tail Skin Wound Models.
Published on: March 25, 2020
Sirolimus impairs wound healing
Michael Schäffer1, Robert Schier, Markus Napirei
1Department of Surgery, Chirurgische Universitätsklinik, Knappschaftskrankenhaus Bochum-Langendreer, In der Schornau 23-25, 44892 Bochum-Langendreer, Germany. michael.schaeffer@kk-bochum.de
Background And Aims:
Clinically, the immunosuppressive drug sirolimus, used in organ transplantation, appears to impair wound healing. Little is known about the mechanisms of action. We investigated the effect of sirolimus on wound healing, and we analyzed the expression of stimulating mediators of angiogenesis (VEGF, vascular endothelial growth factor) and collagen synthesis (nitric oxide) in wounds.
Materials And Methods:
Groups of ten rats underwent dorsal skin incision, and polyvinyl alcohol sponges were implanted subcutaneously. Beginning at the day of wounding, rats were treated with 0.5, 2.0, or 5.0 mg sirolimus/kg/day. Animals were killed 10 days later to determine wound breaking strength and reparative collagen deposition. Expression of VEGF and nitric oxide was studied in wounds.
Results:
Splenic lymphocyte proliferative activity was significantly decreased by sirolimus (p < 0.05). Sirolimus levels in wound fluid were found to be approximately two- to fivefold higher than blood levels (p < 0.01). Sirolimus (2.0 and 5.0 mg kg(-1) day(-1)) reduced wound breaking strength (p < 0.01) and wound collagen deposition (p < 0.05). This was paralleled by decreased expression of VEGF and nitric oxide in wounds.
Conclusion:
Experimentally, our data show that sirolimus impairs wound healing, and this is reflected by diminished expression of VEGF and nitric oxide in the wound.
Insights
Sirolimus, an immunosuppressive drug, impairs wound healing by reducing collagen and vascular endothelial growth factor (VEGF) and nitric oxide expression in wounds.
Area of Science:
- Immunology
- Wound Healing Research
- Pharmacology
Background:
- Sirolimus is an immunosuppressive drug commonly used in organ transplantation.
- Clinical observations suggest sirolimus may negatively impact wound healing.
- The precise mechanisms by which sirolimus affects wound repair are not well understood.
Purpose of the Study:
- To investigate the effects of sirolimus on wound healing in a preclinical model.
- To analyze the expression of key mediators involved in angiogenesis and collagen synthesis, specifically vascular endothelial growth factor (VEGF) and nitric oxide, in response to sirolimus treatment.
Main Methods:
- Rats received dorsal skin incisions and subcutaneous polyvinyl alcohol sponges.
- Sirolimus was administered at doses of 0.5, 2.0, or 5.0 mg/kg/day.
- Wound breaking strength, collagen deposition, and expression of VEGF and nitric oxide were assessed 10 days post-wounding.
Main Results:
- Sirolimus significantly decreased splenic lymphocyte proliferation.
- Wound fluid sirolimus concentrations were higher than blood levels.
- Higher doses of sirolimus (2.0 and 5.0 mg/kg/day) reduced wound breaking strength and collagen deposition.
- A parallel decrease in VEGF and nitric oxide expression was observed in the wounds.
Conclusions:
- Sirolimus demonstrably impairs wound healing in an experimental setting.
- The impairment of wound healing by sirolimus is associated with reduced expression of VEGF and nitric oxide.
- These findings provide mechanistic insights into the clinical observation of delayed wound healing in patients treated with sirolimus.
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