Development and Characterization of Adeno-Associated Virus-Loaded Coaxial Electrospun Scaffolds for Potential Viral Vector Delivery.

Gene therapy, which treats genetic diseases by fixing defective genes, has gained significant attention. Viral vectors show great potential for gene delivery but face limitations like poor targeting, uncontrolled release, and risks from high-dose delivery which can lower efficiency and trigger immune responses. Loading viral vectors onto tissue engineered scaffolds presents a promising strategy to address these challenges, but their widespread application remains limited due to concerns regarding viral vector bioactivity, scaffold biocompatibility, and the stability of sustained release. An adeno-associated virus (AAV), recognized for its safety, high efficiency, and low immunogenicity, was employed as a model virus. In this study, we developed an electrospun scaffold (AAV/PCL-PEO@Co-ES) by encapsulating the AAV within core-shell fibers composed of polycaprolactone (PCL) and polyethylene oxide (PEO) via coaxial electrospinning. This configuration ensures viral vector protection while enabling controlled and sustained release. The physicochemical characterization results indicated that the scaffold exhibited excellent mechanical properties (tensile strength: 3.22 ± 0.48 MPa) and wettability (WCA: 67.90 ± 8.45°). In vitro release and cell transduction assays demonstrated that the AAV-loaded scaffold effectively controls viral vector release and transduction. Furthermore, both in vitro and in vivo evaluations demonstrated good biocompatibility and efficient viral vector delivery. These findings highlight the potential of the AAV/PCL-PEO@Co-ES scaffold as a safe and effective platform for sustained gene delivery, offering valuable insights for the future design of clinically relevant viral vector delivery systems.