Current Concepts in Tendon Bioengineering
Due to their specific morphologic structure, tendons are the soft tissue with the highest tensile strength, needed to transfer muscle power to the skeletal system. In case of tendon injury, such as traumatic tendon tears, chronic overuse of tendons, or degenerative tendinopathy, function and motion are impaired. However, repaired tendon tissue rarely achieves functionality equal to that of the pre-injured state, whereas final tear resistance may be reduced by up to 30%. The fact that tendons often tear upon an underlying tendinopathy as a precondition, is considered rather rarely for research and treatment of patients with acute tendon injuries. For optimal treatment, enhanced understanding of tendon physiology, degenerative pathology, and healing processes in ruptured tendons is necessary. Due to their similar structure, healing of ligaments is usually compared and subsumed to tendon healing.
For a preferably comprehensive survey, literature was systematically reviewed for English peer-reviewed journals on tendon healing and tendon bioengineering including cytokine modulation, autologous sources of growth factors, biomaterials, gene therapy, and cell-based therapy.
Collagen Recycling: Apart from the classical stages of tendon healing by collagen de novo synthesis via weak collagen type III, a collagen type I recycling process from adjacent tendon tissue has been reported.
Mechanical Load: Tenocytes are able to respond to mechanical stress, which helps to structure the maturing tendon during development or the healing tendon during remodeling. Mechanical load leads to an up-regulation of type III collagen mRNA expression and increased growth factor concentrations inducing cell proliferation, differentiation, and matrix formation in tendon tissue
Cytokine Modulation of Tendon Healing: The expression of a variety of natural growth factors is induced at multiple stages throughout natural tendon healing. Leading to increased cellularity and tissue volume.
Gene Therapy: Short half-life and quick clearance are issues of delivering growth factors to the healing site. For a potential longer and constant growth factor release transfer of genetic material (DNA) to cells has been studied. Thereby the cells incorporate the genetic material and produce the desired growth factors over a substantial period of time. Improved tendon healing was found in animal models for gene transfer of BMP12, PDGF, TGFβ, and VEGF.
Cell-Based Therapy: Stem cells are subject of interest and research aiming for new tendon tissue formation. Improved tendon healing in acute tears or tendinopathy has been described using stem cells in laboratory studies. Though results may be promising, use of these cells is ethically problematic and far away from routine clinical use.
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