Hand Surgery Research Center, Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong 226001, PR China.
Biomaterials. 2013 Nov;34(33):8269-78. doi: 10.1016/j.biomaterials.2013.07.072. Epub 2013 Aug 4.
Treatment of the disrupted digital flexor tendon is troublesome because of the lack of sufficient healing capacity and the formation of adhesions. Sustained gene delivery may be a promising approach of modulating gene expression in enhancing tendon healing and decreasing adhesions. In this study, a microRNA-based RNAi plasmid was used to specifically silence the expression of TGF-β1 gene associated with scar and adhesion formation in the flexor tendons. The miRNA plasmids were complexed with polylactic-co-glycolic acid (PLGA) nanoparticles to form nanoparticle/TGF-β1 miRNA plasmid (nanoparticle/plasmid) complexes. In vitro and in vivo transfection efficiencies experiments against tenocytes revealed that nanoparticle/plasmid complexes have significantly superior transfection efficiency over the lipofectamine/plasmid complexes. The gene and protein expression associated with adhesion of tendon treated with nanoparticle/plasmid complexes were evaluated by real-time PCR and immunoblotting. The grading of adhesions for tendons treated with nanoparticle/plasmid complexes was less severe than that treated with the nanoparticle/mock plasmid complexes. However, the ultimate strength of repaired tendons treated with nanoparticle/plasmid complexes was significantly lower than that of tendons treated with the nanoparticle/mock plasmid complexes.
治疗受损的指屈肌腱很麻烦，因为缺乏足够的愈合能力和形成粘连。持续的基因传递可能是一种有前途的方法，可以调节基因表达，增强肌腱愈合和减少粘连。在这项研究中，一种基于 microRNA 的 RNAi 质粒被用来特异性沉默与瘢痕和粘连形成相关的 TGF-β1 基因在屈肌腱中的表达。miRNA 质粒与聚乳酸-共-羟基乙酸（PLGA）纳米粒复合，形成纳米粒/TGF-β1 miRNA 质粒（纳米粒/质粒）复合物。针对肌腱细胞的体外和体内转染效率实验表明，纳米粒/质粒复合物比脂质体/质粒复合物具有显著更高的转染效率。通过实时 PCR 和免疫印迹评估了纳米粒/质粒复合物处理的肌腱的基因和蛋白表达与粘连相关。用纳米粒/质粒复合物处理的肌腱的粘连分级明显低于用纳米粒/模拟质粒复合物处理的肌腱。然而，用纳米粒/质粒复合物处理的修复肌腱的最终强度明显低于用纳米粒/模拟质粒复合物处理的肌腱。
