Gene-Loaded Nanoparticle-Coated Sutures Provide Effective Gene Delivery to Enhance Tendon Healing

Mol Ther. 2019 Sep 4;27(9):1534-1546. doi: 10.1016/j.ymthe.2019.05.024. Epub 2019 Jun 7.

Abstract

How to accelerate tendon healing remains a clinical challenge. In this study, a suture carrying nanoparticle/pEGFP-basic fibroblast growth factor (bFGF) and pEGFP-vascular endothelial growth factor A (VEGFA) complexes was developed to transfer the growth factor genes into injured tendon tissues to promote healing. Polydopamine-modified sutures can uniformly and tightly absorb nanoparticle/plasmid complexes. After tendon tissues were sutured, the nanoparticle/plasmid complexes still existed on the suture surface. Further, we found that the nanoparticle/plasmid complexes delivered into tendon tissues could diffuse from sutures to tendon tissues and effectively transfect genes into tendon cells, significantly increasing the expression of growth factors in tendon tissues. Finally, biomechanical tests showed that nanoparticle/pEGFP-bFGF and pEGFP-VEGFA complex-coated sutures could significantly increase the ultimate strengths of repaired tendons, especially at 4 weeks after operation. Two kinds of nanoparticle/plasmid complex-coated sutures significantly increased flexor tendon healing strength by 3.7 times for Ethilon and 5.8 times for PDS II, respectively, compared with the corresponding unmodified sutures. In the flexor tendon injury model, at 6 weeks after surgery, compared with the control suture, the nanoparticle/plasmid complex-coated sutures can significantly increase the gliding excursions of the tendon and inhibit the formation of adhesion. These results indicate that this nanoparticle/plasmid complex-coated suture is a promising tool for the treatment of injured tendons.

Keywords: gene delivery; growth factors; nanoparticle; surgical suture; tendon repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival
  • Coated Materials, Biocompatible* / chemistry
  • Disease Models, Animal
  • Drug Liberation
  • Gene Expression
  • Gene Transfer Techniques*
  • Genetic Therapy
  • Kinetics
  • Nanoparticles* / chemistry
  • Nanoparticles* / ultrastructure
  • Plasmids / genetics
  • Sutures*
  • Tendon Injuries / genetics*
  • Tendon Injuries / therapy*
  • Transgenes* / genetics
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing* / genetics

Substances

  • Coated Materials, Biocompatible
  • Vascular Endothelial Growth Factor A