Therapeutic strategies for flexor tendon healing by nanoparticle-mediated co-delivery of bFGF and VEGFA genes

[Display omitted] •bFGF and VEGF genes were complexed with PEI-modified PLGA nanoparticles to form complexes.•Nanoparticle/gene complexes have no apparent cytotoxicity against cultured tenocytes.•The expression of bFGF and VEGF protein was upregulated in the tenocytes transfected with complexes.•Complexes produced sufficient amounts factors required during early tendon healing period after injection into injured tendons.•Complexes significantly enhanced the healing ability and gliding function of repaired tendons. 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.