OxInflammatory Responses in the Wound Healing Process: A Systematic Review

Area of Science:

• Immunology
• Dermatology
• Molecular Biology

Background:

• Skin wound healing involves complex inflammatory and repair processes.
• Current treatments aim to control inflammation and accelerate skin repair, but challenges remain.
• Understanding the molecular mechanisms of skin wound cure is crucial for developing effective therapies.

Purpose of the Study:

• To investigate the key mechanisms underlying skin wound healing.
• To provide insights for developing novel therapies targeting oxidative inflammation and infection.
• To reduce functional loss and associated costs in wound management.

Main Methods:

• Systematic review adhering to PRISMA guidelines.
• Searches conducted in MEDLINE (PubMed), Scopus, and Web of Science databases.
• Analysis of 23 original studies with bias and quality assessment using SYRCLE tool.

Main Results:

• Early wound healing involves activation of membrane receptors (IFN-δ, TNF-α, toll-like) on phagocytes, particularly macrophages.
• STAT1, IP3, and NF-kβ pathways are upregulated; Ca2+ mobilization correlates with ROS production and NLRP3 inflammasome activation.
• This leads to caspase-1 cleavage, releasing IL-1β and IL-18, and subsequent release of mediators like IL-1, iNOS, TNF-α, and TGF-β, creating a pro-oxidative environment and depleting antioxidant defenses.

Conclusions:

• A positive feedback loop exists between IFN-δ, ROS production, and inflammatory markers, exacerbating oxidative stress and inflammation.
• The NLRP3 inflammasome activation, ROS, and pro-inflammatory cytokines contribute to chronic inflammation and tissue damage.
• Targeting these interconnected pathways offers potential for improved therapeutic strategies in wound healing.