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Gene-loaded sutures to promote tendon healing

Author: Robyn Bell, 14th October 2019

Injuries to tendons, the tissue that links muscle to bone, are commonly seen in the clinic yet few strategies exist to improve upon slow and largely poor tendon healing standards. Published in the September issue of Molecular Therapy, Zhou et al. from The Nanomedicine Research Laboratory in Nantong China, investigated loading surgical sutures with genes that code for ‘pro-healing’ factors to promote repair of injured tendons.

Previous attempts have injected ‘pro-healing’ factors, known as growth factors, directly into injured tendons with limited success. This approach was restricted by the small volumes that can be injected and the short duration of effect which results from degradation of growth factors within tissue.

For successful repair of tissue and renewal of cells, a sustained and continued source of growth factors is required. A solution is to deliver the genes which provide the instructions for the production of growth factor proteins, prolonging the therapeutic effect compared to delivering protein directly. To overcome barriers of delivery, Zhou et al. were able to coat surgical sutures, used routinely for repair of tendons, with growth factor genes to provide a local and sustained supply to injured tendons during repair.

To create a loaded suture, Zhou et al. first covered the surface of surgical sutures with a sticky protein extracted from mussels, called polydopamine. Secondly the genes coding for basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGFA) were affixed to very small, spherical structures known as nanoparticles, made from a material called polylactic-co-glycolic acid (PLGA). Subsequently the DNA-nanoparticle complexes were applied to the sutures by means of the adhesive polydopamine coating, forming novel sutures loaded with growth factors.

Using animal models of tendon injury, sutures loaded with DNA-nanoparticle complexes were applied during surgery and their healing properties investigated. Significantly enhanced levels of bFGF and VEGFA proteins were detected in the tendon three weeks post-surgery, indicating DNA-nanoparticle complexes were released from sutures and had successfully entered cells for protein production. Tang et al. further investigated the therapeutic effect in two animal models of tendon injury, demonstrating enhanced tendon healing strength and gliding tendon function compared to unmodified sutures at extended time points post-surgery.

In conclusion, Zhou et al. demonstrated a novel method for attachment of DNA-nanoparticles to surgical sutures which effectively promoted healing in animal models of tendon injury without any observed side-effects. Perhaps with further investigation, surgical sutures loaded with growth factor genes could hold promise as a strategy for enhanced healing of injured tendons in the future.

References

Zhou, Y. L., et al. (2019). “Gene-Loaded Nanoparticle-Coated Sutures Provide Effective Gene Delivery to Enhance Tendon Healing.“ Mol Ther 27(9): 1534-1546.