Can we improve tendon healing in the horse? A multi-angle study of a multi-facet problem

Tendon problems are frequent among horses and humans as both species face athletic challenges. Repetitive exercise often leads to overuse injuries in tendons and the number of reported cases of tendon injuries has increased enormously during the last decades, due to changes in demographics and lifestyle. Of the many existing treatment options none can be classified as sufficiently effective. In this thesis, the subject of tendon injuries is approached from various angles. The first study describes a model for tendinopathy in the equine superficial digital flexor tendon; a tendon which is often injured in horses and is comparable to the human Achilles tendon. For testing the efficacy of different treatments it is crucial to have a well-characterized model which mimics the clinical signs of naturally occurring tendinopathy. This equine model met all the important criteria and therefore has interesting potential for further studies. The second study investigates whether casting of the limb, thereby preventing loading of an injured tendon, would be beneficial. After casting one of two front legs of horses having similar tendon injuries in both front legs lesion propagation was monitored. The lesion in the cast-protected leg remained significantly smaller. This result may influence standing veterinary practice for the treatment of acute tendon injuries in the horse. In the third study the model described above was used to test the efficacy of platelet rich plasma (PRP) a new and popular treatment made directly from the patient’s own blood . . The repair tissue from the PRP-treated tendon had a better structure and better mechanical properties than from its placebo-treated counterpart. The fourth study focuses on genipin, a drug from traditional Chinese medicine, which is a strong cross-linker and hence might improve the quality of the repair tissue. Unfortunately, cell survival was insufficient at effective concentrations. In the fifth study the healing potential of two cell populations, one from the tendon core and one from the sheaths surrounding the tendons (the peritenon) was studied. Peritenon-derived cells showed in vitro a higher reactive potential for healing than cells from the tendon core, but showed also increased propensity to differentiate towards bone cells or myofibroblasts; cells that are associated with permanent scarring. The last study looks in closer detail into the differentiation of tendon cells into myofibroblasts and their subsequent contraction. Differentiation into myofibroblasts was influenced by matrix stiffness and by the tethering of the collagen ligands on the matrix. The different contraction assays also revealed the stimulating effect of transforming growth factor beta 1 on cell contraction. In summary, this thesis addresses then problem of tendon healing from various angles (immobilization, PRP and Genipin) and contributes to the understanding of the etiopathogenesis of defective healing.