Therapeutic strategies for flexor tendon healing by nanoparticle-mediated co-delivery of bFGF and VEGFA genes
Therapeutic strategies for flexor tendon healing by nanoparticle-mediated co-delivery of bFGF and VEGFA genes
复制标题
通过纳米颗粒介导的 bFGF 和 VEGFA 基因共同传递实现屈肌腱愈合的治疗策略
DOI：
10.1016/j.colsurfb.2018.01.031
复制
发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Zhou You Lang
中科院分区：
文献类型：
--
作者：
Yang Qian Qian;Shao Yi Xiang;Zhang Lu Zhong;Zhou You Lang
肌腱损伤是肌肉皮肤系统的常见损伤。由于缺乏足够的细胞结构和低生长因子活性，断裂的指屈肌腱的愈合很麻烦，而且过程漫长且无效。 bFGF 和 VEGFA 基因被证明对促进肌腱愈合至关重要。如何持续增强这些基因的表达是一个挑战。在这项研究中，我们开发了一种联合治疗方法，通过引入生长因子基因-病毒载体纳米颗粒来纠正滑膜内肌腱愈合的基本问题。 PLGA 纳米粒子作为载体用于将 bFGF+VEGFA 基因递送到受伤的肌腱组织中。转染后肌腱细胞中bFGF和VEGFA的表达上调。我们将纳米颗粒/bFGF+VEGFA 基因复合物注射到受伤的肌腱中，产生肌腱早期愈合期间所需的足够量的这些因子。治疗后，纳米颗粒/bFGF+VEGFA质粒复合物处理后修复肌腱的极限强度显着增加，联合治疗还可以增强屈肌腱的滑动功能。因此，复合基因治疗与纳米粒子可能是肌腱修复的有效生物学策略。
Tendon injuries are a common injury of musculocutaneous system. Due to the lack of sufficient cellularity and low growth factor activity, healing of disrupted digital flexor tendon is troublesome and the process is lengthy and ineffective. bFGF and VEGFA gene were proved to be responsible and critical for promoting tendon healing. How to continuously enhance expression of these genes is a challenge. In this study, we developed a combination therapeutic approach that corrects the fundamental problem underlying intrasynovial tendon healing with introduction of growth factor genesvianon-viral vector nanoparticle. PLGA nanoparticles as vehicle were used to delivery bFGF+VEGFA genes into injured tendon tissues. The expression of bFGF and VEGFA was upregulated in the tenocytes after transfection. We injected nanoparticle/bFGF+VEGFA gene complexes into injured tendons producing sufficient amounts of these factors required during early tendon healing period. After treatment, the ultimate strength of repaired tendons treated with nanoparticle/bFGF+VEGFA plasmid complexes was significantly increased, and combination therapy could also enhance flexor tendon gliding function. Therefore, combination gene therapyviananoparticles may be an effective biological strategy for tendon repair.