Zhang Haiguang, Zhou Bing, Dong Wei, Song Yongteng, Hu Qingxi, Zhang Heng, Yu Min, Zhu Guanglang, Sun Yudong, Feng Jiaxuan
Rapid Manufacturing Engineering Center, School of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, China.
National Demonstration Center for Experimental Engineering Training Education, Shanghai University, Shanghai 200444, China.
Polymers (Basel). 2025 May 17;17(10):1381. doi: 10.3390/polym17101381.
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.
基因疗法通过修复缺陷基因来治疗遗传疾病，已受到广泛关注。病毒载体在基因递送方面显示出巨大潜力，但面临着靶向性差、释放不受控制以及高剂量递送带来的风险等局限性，这些风险可能会降低效率并引发免疫反应。将病毒载体加载到组织工程支架上是解决这些挑战的一种有前景的策略，但由于对病毒载体生物活性、支架生物相容性和持续释放稳定性的担忧，其广泛应用仍然有限。腺相关病毒（AAV）因其安全性、高效性和低免疫原性而被用作模型病毒。在本研究中，我们通过同轴静电纺丝将AAV封装在由聚己内酯（PCL）和聚环氧乙烷（PEO）组成的核壳纤维中，开发了一种静电纺丝支架（AAV/PCL-PEO@Co-ES）。这种结构确保了病毒载体的保护，同时实现了可控的持续释放。物理化学表征结果表明，该支架具有优异的力学性能（拉伸强度：3.22±0.48 MPa）和润湿性（水接触角：67.90±8.45°）。体外释放和细胞转导试验表明，负载AAV的支架有效地控制了病毒载体的释放和转导。此外，体外和体内评估均表明该支架具有良好的生物相容性和高效的病毒载体递送能力。这些发现突出了AAV/PCL-PEO@Co-ES支架作为持续基因递送的安全有效平台的潜力，为临床相关病毒载体递送系统的未来设计提供了有价值的见解。
