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Tendon and Bone Regeneration

Bones represent the supporting structure of the body, whereas the tendons allow our movement by transferring forces from the muscle to the bone. About 20% of all medical consultations are in the musculoskeletal area, of which about 30% are associated with tendon injuries. In addition to bone regeneration, the aim of our research group is to better understand tendon regeneration and thus to develop improved therapies for patients in the future.

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Importance of research on tendon regeneration

Figure 1: Risc factors influence healing after rotator cuff reconstructions. From: Wildemann B, and Klatte F. 2011. Ligaments and Tendons Journal 1:160-167.

Tendon pathologies are a widespread clinical problem and due to rising demands, with increasing sporting activity at older age, its prevalence was highly increasing in the last decades. In the year 2000, 12,077 patients with rotator cuff lesions at the shoulder were treated in hospitals in Germany and the number rises to 52,065 patients in 2017 (numbers taken from Tendon disorders can be of acute or chronic nature as a result of acute injury, recurrent mechanical overload or autoimmune disease. The overlapping problem is the often insufficient tendon regeneration as well as the limited treatment options. For example, in the area of rotator cuff lesions, non-healing or recurrent defects of the tissue occur in up to 80% of cases. These complications as well as the tendon pathologie itself are favored by various risk factors (Figure 1). The high prevalence of tendon diseases together with the limited therapeutic treatment options highlight the need for further research in the field of tendon regeneration.

Chronic tendon pathologies at the shoulder

Figure 2: Differentiation of tenocytes from female donors 65 years of age into the adipogenic, osteogenic and chrondrogenic direction.

Rotator cuff lesions mostly occur due to recurrent mechanical overload of the shoulder, which leads to degenerative processes, finally resulting in the rupture of the tissue. Different demographic and clinically determined risk factors negatively influence tendon regeneration, such as an older age, the female sex as well as the grade of tendon degeneration. We could show that these patient characteristics are associated with inferior cellular biological parameters (reduced cell growth and stem cell potential (see figure 1), which might be a reason for the limited healing potential in these patient groups. As potential therapeutic option we tested the stimulation of tenocytes of different patient groups with growth factors such as Bone Morphogenetic Protein 2 (BMP-2) or BMP-7 as well as growth factor depots such as platelet rich plasma (PRP), which is conducted from whole blood of the patients.

Acute and chronic Achilles tendon pathologies

Figure 3: Fiber of an acute ruptured Achilles tendon after Movat Pentachrome staining.

Next to chronic tendon pathologies, we furthermore aim to understand the development and regeneration of acute tendon pathologies. Therefore, we focus on the comparison of different Achilles tendon pathologies. Acute Achilles tendon ruptures (Fig. 3) mostly affect athletes, in which the demand for an optimal tendon regeneration is of high importance. Also chronic Achilles tendons pathologies occur often and are due to recurrent microtraumata as a result of increasing overload. Especially, the direct comparison of acute and chronic diseases of the Achilles tendon can lead to the identification of overlapping pathomechanisms to better understand possible reasons for inadequate healing. The functional and clinical analysis of the patients within the healing progress, which is performed by our clinical colleagues of the Center for Musculoskeletal Surgery (CMSC), allows us to correlate our biological findings with the functional healing outcome. With this we aim to identify signaling cascades or single factors that might be responsible for an insufficient tendon regeneration.