Accelerated Wound Border Closure Using a Microemulsion Containing Non-Inhibitory Recombinant α1-Antitrypsin

Area of Science:

• Biochemistry
• Wound Healing Research
• Immunology

Background:

• Wound healing involves complex inflammatory and anti-inflammatory processes.
• Human alpha1-antitrypsin (hAAT) is a protective glycoprotein with anti-inflammatory properties that also enhances revascularization.
• The role of hAAT in wound healing is unclear due to its protease inhibition activity.

Purpose of the Study:

• To investigate the impact of recombinant wild-type hAAT (hAAT^WT) and protease-inhibition-lacking hAAT (hAAT^CP) on wound healing.
• To determine if hAAT's wound healing benefits are dependent on its protease inhibition function.

Main Methods:

• Epithelial cell gap closure assay to assess cell migration.
• Excisional skin injury model in vivo using a microemulsion for open wounds.
• Analysis of neutrophilic infiltration and gene expression of interleukin-1β and VEGF at 8 hours.

Main Results:

• Both hAAT^WT and hAAT^CP significantly accelerated epithelial gap closure and excisional wound closure, especially at early stages.
• Wounds treated with hAAT forms showed closed borders at 8 hours, unlike untreated wounds.
• hAAT^WT led to compartmentalized neutrophilic infiltration, while hAAT^CP resulted in widespread infiltration, similar to untreated wounds.

Conclusions:

• Human alpha1-antitrypsin (hAAT) enhances epithelial cell migration and improves in vivo wound healing outcomes independently of its protease inhibition activity.
• Both native and modified hAAT facilitate neutrophil infiltration, but only native hAAT organizes them into distinct tissue clusters.
• hAAT treatment modulated inflammatory (reduced IL-1β) and pro-angiogenic (increased VEGF) gene expression during wound healing.