In vivo monitoring of angiogenesis during tendon repair : a novel MRI-based technique in a rat patellar tendon model

Recent in vivo studies were able to show the impairing effect of neoangiogenesis in degenerative tendon diseases. Clinical in vivo monitoring of angiogenesis in injured tendons therefore seems to be crucial for an accurate therapeutic approach. The aim of this study was to develop a novel magnetic resonance imaging (MRI)-based technique for observing angiogenesis during tendon healing in vivo. Tendinopathy was induced by an in situ freezing model of rat patellar tendon and monitored after 7, 14, and 28 days. Animals were randomly divided into an imaging and immunohistochemical group. MRI with a 'blood pool' contrast agent was used to determine neoangiogenesis during tendon healing. MRI was compared to histochemical staining and quantification of blood vessels in injured and native tendons. MRI data revealed a peak in changes in the transverse relaxation rate (Delta R (2)*), which is proportional to relative blood volume, 7 days after surgery and decrease until day 28. Histological microvessel density and vascular endothelial growth factor synthesis were also most evident at day 7 and decreased over time. The current results are demonstrating a time-dependent correlation between microvessel density and Delta R (2)*. Thus, MRI-based evaluation of angiogenesis in the tendon might be a new promising technique for in vivo monitoring of angiogenesis and therapy response in the future

Influence of antiTNF-alpha antibody treatment on fracture healing under chronic inflammation

Background: The overexpression of tumor necrosis factor (TNF)-α leads to systemic as well as local loss of bone and cartilage and is also an important regulator during fracture healing. In this study, we investigate how TNF-α inhibition using a targeted monoclonal antibody affects fracture healing in a TNF-α driven animal model of human rheumatoid arthritis (RA) and elucidate the question whether enduring the anti TNF-α therapy after trauma is beneficial or not. Methods: A standardized femur fracture was applied to wild type and human TNF-α transgenic mice (hTNFtg mice), which develop an RA-like chronic polyarthritis. hTNFtg animals were treated with anti-TNF antibody (Infliximab) during the fracture repair. Untreated animals served as controls. Fracture healing was evaluated after 14 and 28 days of treatment by clinical assessment, biomechanical testing and histomorphometry. Results: High levels of TNF-α influence fracture healing negatively, lead to reduced cartilage and more soft tissue in the callus as well as decreased biomechanical bone stability. Blocking TNF-α in hTNFtg mice lead to similar biomechanical and histomorphometrical properties as in wild type. Conclusions: High levels of TNF-α during chronic inflammation have a negative impact on fracture healing. Our data suggest that TNF-α inhibition by an anti-TNF antibody does not interfere with fracture healing.<br