The use of growth factors in the management of tendinopathies

Abstract

Tendinopathies present a difficult therapeutic problem for the patient as well as the health care professional because their etiology and management are uncertain [1]. Although many forms of management have been advocated, current treatment strategies are not effective because they do not definitively resolve the disease. Pharmacological management with non-steroidal anti-inflammatory drugs (NSAIDs) or corticosteroids can result in some pain relief but the relief is often temporary. Ideal management should have minimal side effects. The currently used corticosteroids have frequently been associated with side effect is such as depigmentation, poor wound healing and even complete tendon rupture. Finally, the ideal treatment should accomplish its goal in a relatively short period of time with little discomfort or disability to the patient. Surgery can definitively treat tendinopathy. However, the recovery is associated with pain and discomfort, and recovery is often protracted. Many of our current management methods do not fulfill the criteria of ideal treatment, therefore the search for such a treatment continues. Results of many studies suggest a poor or inadequate healing response in tendinopathies. Part of the search for new treatments has been focused on methods to start or stimulate a healing response. This is fundamentally different than the thought behind the use of NSAIDs and corticosteroids. These drugs are aimed at the symptoms that result from the injury or problem rather than the healing response. Symptoms such as pain and swelling can be interpreted as inflammatory aspects of the tendinopathy. Treatment with NSAIDs and corticosteroids can counteract these responses. On the other hand, the inflammatory response can be viewed as the first physiologic step in the healing of a tendon, followed by cell migration into a wound and matrix maturation. However, tendinopathies may not evoke a sufficient inflammatory response to elicit an adequate repair response. Inhibition of inflammation with NSAIDs and corticosteroids will manage some of the symptoms, but may not improve and may even inhibit the eventual healing response. More recent research has been focused on agents that may affect tendinopathies by directly acting on the healing response. Growth factors such as platelet-derived growth factor (PDGF-AA,BB, or AB), insulin-like growth factor (IGFI and II), transforming growth factor beta (TGF-b), epidermal growth factor (EGF), fibroblast growth factors (FGF 1,2) and bone morphogenetic proteins (BMPs) represent a group of substances that can act in such a manner. Growth factors may be produced locally by cells in areas of injury, growth and repair, or may be delivered by blood. Since their discovery, they have been implicated in numerous responses where they modulate cell migration, replication, matrix synthesis, and cell transformation. Exogenous supplementation of these factors in failed healing responses, such as in resistant tendinopathies, may lead to a definitive healing response.