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Updated: May 9, 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
Effects of systemic pretreatment with CpG oligodeoxynucleotides on skin wound healing in mice
Bettina Hergert1, Eberhard Grambow, Antje Butschkau
1Institute for Experimental Surgery, University of Rostock, Rostock, Germany.
Abstract:
Unmethylated CpG oligodeoxynucleotides (ODN) bind to the Toll-like receptor 9, thus stimulating the immune system. To study the effects of systemic pretreatment with CpG ODN on dermal regeneration, C57BL6/J Tyr mice were treated with CpG or control ODN 6 days prior to implantation of a dorsal skinfold chamber and skin wounding. Wound epithelialization was analyzed by planimetric microscopy. On day 18, wound tissues were taken for (immuno)histochemical staining. CpG ODN increased epithelialization compared with control ODN treatment. Histological analysis revealed reduced capillary density, reduced wound cellularity, and reduced numbers of infiltrating leukocytes, as well as reduced F4/80-positive macrophages, but increased numbers of RELM-α-positive M2 macrophages after CpG ODN treatment, reflecting a better quality of wound healing on day 18 compared with control ODN treatment. Reverse transcription-polymerase chain reaction analysis of Toll-like receptor 9 showed the receptor expression on both fibroblasts and keratinocytes. Fibroblasts showed an increase of migration upon increasing dosages of CpG and not control ODN, reaching ∼50% of the response of basic fibroblast growth factor-exposed cells. Keratinocytes dose-dependently responded to both CpG and control ODN up to values found in keratinocyte growth factor-exposed cells. In summary, CpG ODN support late tissue-remodeling processes that contribute to resolution of inflammation and solid wounds during skin regeneration.
Insights
Systemic pretreatment with CpG oligodeoxynucleotides (ODN) enhances skin wound healing by promoting epithelialization and improving tissue remodeling. CpG ODN treatment led to better wound quality and reduced inflammation in mice.
Area of Science:
- Immunology
- Dermatology
- Regenerative Medicine
Background:
- Unmethylated CpG oligodeoxynucleotides (ODN) activate Toll-like receptor 9 (TLR9), stimulating immune responses.
- Dermal wound healing involves complex processes including inflammation, proliferation, and remodeling.
- Modulating immune responses may influence the quality and speed of skin regeneration.
Purpose of the Study:
- To investigate the impact of systemic CpG ODN pretreatment on dermal wound healing.
- To assess the effects of CpG ODN on wound epithelialization and tissue remodeling.
- To explore the cellular mechanisms underlying CpG ODN-mediated effects on skin regeneration.
Main Methods:
- C57BL6/J Tyr mice were pretreated with CpG or control ODN before dorsal skinfold chamber implantation and wounding.
- Wound epithelialization was quantified using planimetric microscopy.
- Immunohistochemistry and reverse transcription-polymerase chain reaction were employed to analyze wound tissue composition and receptor expression.
Main Results:
- CpG ODN treatment significantly increased wound epithelialization compared to controls.
- Histological analysis revealed reduced capillary density, cellularity, and leukocyte infiltration, alongside increased M2 macrophages (RELM-α positive) in CpG-treated wounds.
- Fibroblasts showed dose-dependent migration in response to CpG ODN, while keratinocytes responded to both CpG and control ODN.
Conclusions:
- Systemic CpG ODN pretreatment supports late-stage tissue remodeling in skin regeneration.
- CpG ODN promotes resolution of inflammation and improves the quality of solid wound healing.
- TLR9 activation by CpG ODN influences fibroblast and keratinocyte behavior, contributing to enhanced dermal repair.
