A Virus-Derived Immune Modulating Serpin Accelerates Wound Closure with Improved Collagen Remodeling

Area of Science:

• Wound Healing Research
• Immunomodulation
• Biomaterials Science

Background:

• Early wound healing involves complex processes including inflammation and clotting.
• Existing treatments aim to optimize these stages for better outcomes.
• Serine protease inhibitors (SERPINs) are being explored for their therapeutic potential.

Purpose of the Study:

• To investigate the efficacy of a virus-derived SERPIN, Serp-1, in promoting wound healing.
• To assess Serp-1's impact on inflammation, angiogenesis, and scar formation.
• To evaluate different delivery methods and dosing strategies for Serp-1.

Main Methods:

• A mouse excisional wound model was used to test recombinant Serp-1.
• Serp-1 was administered via direct application or loaded into a chitosan-collagen hydrogel.
• Wound healing, scarring, immune cell dynamics, and angiogenesis were assessed over 15 days.

Main Results:

• Serp-1 significantly accelerated wound healing, an effect blocked by uPAR antibody.
• Repeated low-dose Serp-1 was more effective than single high doses.
• Serp-1 treatment increased M2-polarized macrophages and periwound angiogenesis, improving collagen organization.

Conclusions:

• Serp-1 is a potent immune modulator that accelerates healing and reduces scarring in cutaneous wounds.
• Optimized dosing and hydrogel delivery enhance Serp-1 efficacy.
• Serp-1 represents a promising therapeutic agent targeting thrombolytic proteases for improved wound repair.