The Hand Surgery Research Center, Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, PR China; Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226001, PR China.
Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226001, PR China.
Colloids Surf B Biointerfaces. 2018 Apr 1;164:165-176. doi: 10.1016/j.colsurfb.2018.01.031. Epub 2018 Jan 31.
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 genes via non-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 therapy via nanoparticles may be an effective biological strategy for tendon repair.
肌腱损伤是肌肉皮系统的常见损伤。由于缺乏足够的细胞性和低生长因子活性，破坏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负责和关键。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，通过非病毒载体纳米颗粒将生长因子基因引入滑膜内肌腱愈合的根本问题，以纠正该问题。PLGA 纳米颗粒作为载体，将 bFGF+VEGFA 基因递送到受伤的肌腱组织中。转染后，成纤维细胞中的 bFGF 和 VEGFA 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，产生早期肌腱愈合期间所需的足够数量的这些因子。治疗后，用纳米颗粒/bFGF+VEGFA 质粒复合物治疗的修复肌腱的最终强度显著增加，联合治疗还可以增强屈肌腱滑动功能。因此，通过纳米颗粒进行联合基因治疗可能是一种有效的肌腱修复的生物学策略。
