A PLG/HAp composite scaffold for lentivirus delivery

Area of Science:

• Biomaterials Science
• Gene Therapy
• Tissue Engineering

Background:

• Gene delivery from tissue engineering scaffolds offers control over the cellular microenvironment.
• Hydroxyapatite (HAp) nanoparticles can bind lentivirus, suggesting potential for scaffold-based gene delivery systems.

Purpose of the Study:

• To investigate the incorporation of HAp nanoparticles into poly(lactide-co-glycolide) (PLG) scaffolds for enhanced lentivirus retention and gene delivery.
• To evaluate the in vitro and in vivo performance of PLG/HAp scaffolds for sustained transgene expression.

Main Methods:

• Fabrication of PLG scaffolds with varying HAp nanoparticle content.
• Loading of lentivirus onto PLG and PLG/HAp scaffolds.
• In vitro assessment of transgene expression levels.
• In vivo implantation of scaffolds and longitudinal monitoring of transgene expression and cell infiltration.

Main Results:

• PLG/HAp scaffolds demonstrated over 10-fold enhanced in vitro transgene expression compared to PLG scaffolds.
• In vivo implantation resulted in sustained transgene expression exceeding 100 days, with enhanced levels and duration in PLG/HAp scaffolds.
• HAp incorporation influenced scaffold porous architecture, impacting gene expression. Macrophages were primarily transduced at day 3, shifting to preferential non-immune cell transduction by day 21 in PLG/HAp scaffolds.

Conclusions:

• PLG/HAp scaffolds effectively retain lentivirus and enhance gene delivery for tissue engineering applications.
• The HAp incorporation not only improves viral retention but also modulates scaffold architecture and cellular infiltration, leading to preferential non-immune cell transduction.
• These findings highlight the potential of HAp-modified PLG scaffolds for advanced regenerative medicine strategies.