The Future: Rehabilitation, Gene Therapy, Optimization of Healing
Section snippets
Tendon healing
Tendon healing studies have been performed predominantly on transected animal tendons or ruptured human tendons; their relevance to tendinopathic and ruptured human tendons remains unclear. Tendon healing occurs in three overlapping phases. In the initial inflammatory phase, erythrocytes and inflammatory cells, particularly neutrophils, enter the site of injury. In the first 24 hours, monocytes and macrophages predominate, and phagocytosis of necrotic materials occurs. Vasoactive and
Optimization strategies
Current management strategies, such as nonsteroidal anti-inflammatory drugs or corticosteroids, offer symptomatic relief but do not result in definitive disease resolution. Surgery may be appropriate for certain patients, but recovery may be protracted and is associated with pain and discomfort. The ideal management should accomplish its goal in a short period of time with little discomfort or disability to the patient. Novel management methods should aim to stimulate a healing response to
Cytokines and growth factors
The use of growth factors remains largely experimental and has been restricted to in vitro studies and animal models. The clinical use of growth factors for tendon problems has not been reported.
Insulin-like growth factor (IGF) is expressed in avian flexor tendons, and induces tenocyte migration, division, and matrix expression [50], [51], [52]. IGF-I and -II increase collagen synthesis in a dose-dependent manner in animal models, and also increase proteoglycan synthesis [50], [53]. The
Gene therapy
Gene therapy delivers genetic material to cells to alter synthesis and function, and can be achieved by way of viral vectors or liposomes [78], [79]. Several animal studies have investigated the feasibility of gene transfer to tendons. Liposome constructs have been used to deliver β-galactosidase to rat patellar tendons [80]. In vivo and ex vivo adenoviral transduction of the lac Z gene into rabbit patellar tenocytes has been reported. Gene expression lasted for 6 weeks, possibly long enough
Tissue engineering
Mesenchymal stem cells (MSCs) are capable of undergoing differentiation into a variety of specialized mesenchymal tissues, including bone, tendon, cartilage, muscle, ligament, fat, and marrow stroma [92]. In adults, MSCs are prevalent in bone marrow, but also are found in muscle, fat, skin, and around blood vessels [93].
MSCs can be applied directly to the site of injury or can be delivered on a suitable carrier matrix, which functions as a scaffold while tissue repair takes place.
Physical modalities
Several studies evaluated the application of electrical and magnetic fields to tendons. Pulsed magnetic fields with a frequency of 17 Hz resulted in improved collagen fiber alignment in a rat Achilles tendinopathy model [101]. Tenotomized rat Achilles tendons were sutured and treated with low-intensity galvanic current for 15 minutes a day for 2 weeks [102]. Biomechanical analysis revealed an increased force to breakage in the anode-stimulated group compared with controls and the
Adhesion prevention
Trauma is the most important factor that is implicated in adhesion formation [109]. Many attempts have been made to reduce adhesion formation using materials that act as mechanical barriers (eg, polyethylene, silicone) or pharmacologic agents (eg, indomethacin, ibuprofen) however; no simple method is used widely [110], [111], [112], [113].
Hyaluronate, a high molecular weight polysaccharide that is found in synovial fluid around tendon sheaths, decreased adhesion formation in rabbit flexor
Mobilization and mechanical loading
Animal experiments have demonstrated that training results in improved tensile strength, elastic stiffness, weight, and cross-sectional area of tendons [122], [123]. These effects can be explained by an increase in collagen and extracellular matrix synthesis by tenocytes [123]. Little data exist on the effect of exercise on human tendons, although intensively-trained athletes are reported to have thicker Achilles tendons than control subjects [124].
Prolonged immobilization following
Summary
Tendon injuries give rise to significant morbidity, and, at present, only limited scientifically-proven management modalities exist. A better understanding of tendon function and healing will allow specific management strategies to be developed. Many interesting techniques are being pioneered. The optimization strategies that were discussed in this article are at an early stage of development. Although these emerging technologies may develop into substantial clinical management options, their
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