Ultrasound-responsive gene-activated matrices for osteogenic gene therapy using matrix-assisted sonoporation

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Gene-activated matrices (GAMs) show promise for tissue regeneration but face challenges in efficacy, spatiotemporal control, and cell availability.
• Clinical translation of GAMs is hindered by limitations in current therapeutic strategies.

Purpose of the Study:

• To develop an advanced ultrasound-responsive GAM capable of inducing osteogenic differentiation via matrix-assisted sonoporation (MAS).
• To evaluate the efficacy of MAS-enhanced GAMs for bone regeneration both in vitro and in vivo.

Main Methods:

• Fabrication of ultrasound-responsive GAMs using fibrin/collagen hybrid matrices with microbubbles, BMP2/7 plasmids, and C2C12 cells.
• Application of ultrasound treatment in vitro and following intramuscular implantation in vivo.
• Assessment of osteogenic differentiation using alkaline phosphatase activity, von Kossa staining, immunohistochemistry, X-ray microcomputed tomography, and histological analysis.

Main Results:

• MAS-stimulated osteogenic differentiation was confirmed in vitro within 7 days post-ultrasound treatment.
• Ectopic osteogenic differentiation and bone structure formation were observed in vivo 30 days post-ultrasound treatment.
• Animals treated with MAS exhibited statistically significant increases in bone volume compared to control groups.

Conclusions:

• The developed ultrasound-responsive GAM with MAS capability offers a novel approach for osteogenic gene-based therapies.
• This technology can facilitate either ex vivo gene transfer followed by implantation or minimally invasive in situ transgene delivery.
• MAS-enhanced GAMs represent a promising strategy for advancing bone regeneration therapies.