Core-shell fibrous threads loaded with VEGF plasmid polyplexes for sustained, threshold-guided gene delivery

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Gene Delivery

Background:

• Precise vascular endothelial growth factor (VEGF) delivery is critical for angiogenesis in tissue engineering.
• Uncontrolled VEGF can lead to abnormal vascular development.
• Existing methods lack sustained and localized gene delivery capabilities.

Purpose of the Study:

• To develop a scaffold-mediated platform for sustained VEGF gene delivery using aligned core-shell fibrous threads.
• To investigate the release kinetics and biological activity of VEGF-encoding polyplexes within the fibrous scaffolds.
• To evaluate the potential of these scaffolds for localized angiogenic gene therapy.

Main Methods:

• Optimization of polymer/plasmid DNA ratio for polyplexes in human umbilical vein endothelial cells (HUVECs).
• Fabrication of core-shell fibrous scaffolds using modified coaxial electrospinning with gelatin/poly(ε-caprolactone).
• Incorporation of VEGF-encoding polyplexes (bPEI1.8-DA/pVEGF) into the fiber core and subsequent genipin crosslinking.

Main Results:

• Bead-free aligned core-shell fibers with successful polyplex incorporation were fabricated.
• Genipin crosslinking enhanced scaffold stability and mechanical properties.
• The fibrous threads demonstrated sustained polyplex release over 33 days, reducing initial burst release and prolonging VEGF secretion by HUVECs, while supporting cell viability.

Conclusions:

• Aligned core-shell fibrous threads provide sustained plasmid polyplex availability for localized gene delivery.
• The developed scaffolds effectively prolong downstream VEGF secretion, crucial for controlled angiogenesis.
• This platform shows significant promise for angiogenic tissue engineering applications requiring directional fibrous architecture.