Tendon and Bone Regeneration

We are an interdisciplinary research group working tightly together with the clinical colleagues. This cooperation gives us the possibility to identify the problems in orthopedic and trauma surgery and to work on new strategies to solve them.

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Tendon

Since 2007 the research group is dealing with different aspects of tendon healing. The aim is to better understand the processes of tendon healing and degenerative changes to perspectively counteract frequent complications such as recurrent defects or the non healing of the tendon tissue.

Tendon Healing and Regeneration

Figure 1: Risc factors influence healing after rotator cuff reconstructions. To date cellbiological parameters influencing the healing are mostly unknown. From: Wildemann B, and Klatte F. 2011. Ligaments and Tendons Journal 1:160-167.
Figure 2: Multipotent differentiation of TLCs from female donors 65 years of age: A,E) Adipogenic differentiated TLCs formed lipid vacuoles. B, C, F, G) For osteogenic differentiation, Alizarin Red S staining was weak, but ALP staining revealed a strong blue color. D, H) Chondrogenic differentiated cell pellets were blue after Alcian Blue staining. Klatte-Schulz F et al., PLoS ONE 8(6): e67209.
Figure 3: Fiber of an acute ruptured Achilles tendon after Movat Pentachrome staining.

A cell bank was generated with tendon cells (tenocytes) from over 100 donors with chronic rotator cuff ruptures. Different demographical and clinical risk factors can negatively affect the tendon healing outcome (Figure 1). Some donor characteristics such as an older age, the female sex, and a higher degenerative status of the tendon could be linked to inferior cell biological properties such as a reduced cell growth and stem cell potential (Figure 2). Theses inferior cell biological characteristics might be the reason for a weaker healing potential in the patient cohort. The effect of the growth factors Bone Morphogenetic Protein 2 (BMP-2) and BMP-7 on Tenocytes was analyzed. These growth factors are clinically approved for the treatment of bone defects and could also positively influence tendon healing. The cell growth and expression and secretion of important proteins such as Collagen I was clearly increased. Additionally, primarily BMP-7 led to an up-regulation of markers for tendon differentiation (Smad 8, Scleraxis), while markers for osteogenic and chondrogenic differentiation were suppressed.

 

Next to the chronic tendon ruptures, the focus of the research group lay since more than 2 years primarily on the analysis of healing processes after acute Achilles tendon ruptures. At different time points at which the surgical reconstruction of the Achilles tendon takes place, tendon biopsies are taken and examined. This enables the insight into the early phase of acute tendon healing. The focus is on the analysis of matrix-degrading enzymes, the Matrix Metalloproteases (MMPs) and their natural inhibitors, the Tissue Inhibitors of Metalloproteases (TIMPs) as well as inflammatory factors and processes. The gained knowledge can perspectively be used to develop new therapeutical approaches to counteract inferior tendon healing.

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