Protease activity as a prognostic factor for wound healing in complex wounds

Area of Science:

• Biomedical Science
• Wound Healing Research
• Protease Biochemistry

Background:

• Complex wounds exhibit disrupted healing mechanisms.
• Persistent protease activity is observed in nonhealing wounds.

Purpose of the Study:

• To determine if protease activity, protease inhibitor activity, or their ratios are independent prognostic factors for complex wound healing.
• To analyze existing literature on proteases and wound healing outcomes.

Main Methods:

• Systematic literature search of MEDLINE, EMBASE, CINAHL, and The Cochrane Library up to March 2019.
• Meta-analysis of longitudinal studies assessing proteases, inhibitors, or their ratios in complex wound healing.
• Data extraction and risk of bias assessment by two independent reviewers.

Main Results:

• Elevated protease activity (SMD: -0.41) and protease: inhibitor ratios (SMD: -0.47) were associated with less healing (low to very low certainty evidence).
• Elevated protease inhibitor activity (SMD: 0.37) was associated with more healing (low certainty evidence).
• MMP-1 may be associated with improved healing, while other proteases may impede it (low/very low certainty evidence).

Conclusions:

• Protease activity and protease: inhibitor ratios may negatively impact complex wound healing.
• Protease inhibitor activity may positively influence healing.
• Further high-quality research is necessary to validate these findings and explore protease-specific effects.