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Titel på arbejdetFlexor tendon adhesions -A mouse model of flexor tendon injury and repair
NavnSys Hasslund Svensson
Afdeling / StedAfd. E/ Aarhus Universitetshospital
UniversitetAarhus Universitet -Klinisk institut
  • Hand Surgery
Abstract / Summary

The flexor tendons of the human hand are prone to injuries due to their superficial anatomical position and the multiple functions of the hand. The repair of flexor tendon injuries is complicated by the formation of fibrotic adhesions, which restrict tendon gliding and flexion of the injured digits. Even a small reduction in digits’ range of motion can be disabling and complicate everyday activities. Despite implementation of modern suture techniques and post-operative motion protocols, the rehabilitation following these injuries is unpredictable. Further improvement and consistency of the outcome following flexor tendon injuries is likely to warrant manipulation of the biological tendon-healing response. For further understanding of the molecular mechanisms contributing to adhesion formation, in vivo screening models are needed. In this thesis I describe the first mouse model of flexor tendon injury and reconstruction. We have developed a functional test of tendon gliding and adhesions, and a subsequent test of tendon healing strength.
Tendon reconstruction by the use of tendon autografts is a common secondary procedure, when primary repair is not possible or has failed. Autografts are limited, however, by availability and donor site morbidity, and an attractive alternative may be tendon allografts. Allografts are moderately studied in flexor tendon reconstruction; but despite their advantages, their use has been limited by concerns of impaired healing capacity and long-term side effects. In our mouse model we have compared live autograft and freeze-dried allograft. We have found that the mechanical advantages of the autograft over the allograft are minimal in our model. Furthermore, we have observed no increase in adhesion formation over that found in autografts, but rather a decrease in adhesions and an increase in digit range of motion.
Growth and differentiation factor 5 (GDF-5) is known to be involved in tendon development, and it has been demonstrated to increase tendon healing strength in several animal models. GDF-5’s effect on tendon adhesions, however, has not previously been investigated. In our experimental model, we have reconstructed flexor tendons by freeze-dried allografts coated with recombinant protein GDF-5 or with viral vectors encoding GDF-5 (rAAV-Gdf5). We have found that the GDF-5-loaded allografts have an anti-fibrotic effect on tendon healing and demonstrate a significantly improved range of motion in the digits. The anti-fibrotic effect seems to be independent of delivery method (protein vs. rAAV).
The mouse model of flexor tendon injury and repair has, despite its limitations, proven to be a valuable screening tool for evaluating the molecular, cellular and biomechanical effects of specific genes and molecules on the tendon-healing process.

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