Engineered Tandem Thymosin Peptide Promotes Corneal Wound Healing

Area of Science:

• Regenerative Medicine
• Biotechnology
• Ophthalmology

Background:

• Thymosin beta-4 (TB4) promotes corneal wound healing but has limitations.
• Short half-life and high synthesis costs hinder TB4 therapeutic applications.
• TB4 plays roles in cell migration, angiogenesis, and inflammation.

Purpose of the Study:

• To engineer a tandem thymosin beta-4 (tTB4) peptide for enhanced corneal wound repair.
• To improve the therapeutic potential and scalability of TB4-based therapies.
• To overcome limitations of current TB4 treatments.

Main Methods:

• Engineered tTB4 by fusing two TB4 monomers, creating dual G-actin binding domains.
• Assessed tTB4 and TB4 effects on corneal epithelial cell viability and migration in vitro.
• Evaluated corneal wound healing efficacy in a murine alkali-induced injury model in vivo.

Main Results:

• Structural modeling showed tTB4 enhances actin polymerization by binding two G-actin molecules.
• In vitro studies demonstrated increased corneal epithelial cell viability and migration with tTB4 compared to TB4.
• In vivo experiments revealed tTB4 promoted corneal wound healing and reduced scarring more effectively than TB4.

Conclusions:

• Engineered tTB4 exhibits superior bioactivity and corneal wound-healing efficacy over TB4.
• tTB4 production via bacterial fermentation is more cost-effective and simplified.
• Tandem peptide engineering shows potential for improving regenerative peptide pharmacokinetics and therapeutic performance.