Gene therapy strategies to improve strength and quality of flexor tendon healing

Rupture of the repair and adhesion around a tendon are two major problems after tendon surgery. Novel biological therapies which enhance healing and reduce adhesions are goals of many investigations. Gene therapy offers a new and promising approach to tackle these difficult problems. In the past decade, we sought to develop methods to augment tendon healing and reduce tendon adhesion through gene therapy.

This review discusses the methods and results of adeno-associated viral (AAV) type 2 vector gene therapy to increase tendon healing strength and reduce adhesions in a chicken model. Micro-RNA related gene therapy is also discussed. We also developed a controlled release system, which incorporates nanoparticles to deliver micro-RNAs to regulate tendon healing.

We obtained promising results of enhancement of tendon healing strength in a chicken model using AAV2-mediated gene transfer. AAV2-mediated micro-RNA transfer also limited adhesions around the tendon. Controlled release systems incorporating nanoparticles have ideally delivered genes to the healing tendons and resulted in a moderate (but incomplete) reduction of adhesions. It remains to be determined what the best doses are and what other factors are in play in adhesion formation. These are two targets in our future investigations.