Study on biomechanics: Novel mechanism uncovered in tissue

The ECM of musculoskeletal tissues plays crucial roles in physiology. Beyond a diversity of biochemical functions, the ECM defines physical cues for cells and serves as a scaffold for them. In living tissues, water is a main component of intra- and extracellular microenvironments, for example 62 percent in tendon. The present publication, which originated from the dissertation of Dr. Matthias Kollert, examines the role of the water-binding properties of the ECM in tendons. It focuses on the modulation of water binding by ion concentration and on the electrostatic properties of charged proteoglycans—macromolecules particularly abundant in connective tissue, cartilage and intervertebral discs—and their influence on elasticity and stress relaxation of the matrix.  

“We modified the ion concentrations of incubation solutions to tune the function of ECM components in fresh tissue samples,” explains Prof. Georg Duda, Director of the Julius Wolff Institute (JWI) at the BIH, who supervised the dissertation together with Prof. Viola Vogel, Einstein BIH Visiting Fellow and Head of the Laboratory of Applied Mechanobiology at ETH Zurich. 

Kollert, first author of the publication, adds: "These simple manipulations caused impressive changes in tissue mechanics. We measured up to a fourfold increase in stiffness, transforming the tissue’s consistency from spongy to hard, and observed significantly faster relaxation times." 

Advanced interpretation of conventional MRI for clinical application

The imaging technique of conventional quantitative MRI largely detects differences in tissue hydration, e.g. water accumulation. This study demonstrates the potential of quantitative MRI to gain more detailed insight into biophysical ECM properties by linking changes in water-binding function of matrix components to changes in mechanical parameters such as stiffness and viscosity. These advances were made possible by collaboration with Dr. Martin Krämer and Prof. Jürgen Reichenbach of the Medical Physics group in Jena and their extensive MRI experiments and meticulous sequence development. In a pilot in vivo MRI study on inflammatory Achilles tendinopathy in collaboration with senior physician Dr. Serafeim Tsitsilonis at Charité – Universitätsmedizin Berlin, the scans showed MRI signal alterations akin to those observed in the modified ex vivo tissue samples. This indicates that the developed MRI protocols for combined T₁ and T₂^* mapping are applicable in clinical settings and may offer a more differentiated non-invasive diagnostic tool to evaluate tissue health in the future. Tsitsilonis emphasizes: “Such methods could help us trauma and orthopaedic surgeons better assess pathological changes in tendons—which would be particularly useful for this tissue, which has long been difficult to image and evaluate objectively.”  

Findings and outlook

By elucidating the interplay between osmotic environment, water-binding properties and mechanical characteristics of the ECM, this work not only deepens the fundamental understanding of ECM physiology, but may also stimulate the development of novel biomaterials and disease-modeling strategies that address pathologies with dysregulated ECM properties. Duda adds: "These insights into tissue properties together with our extensive MRI data pave the way for more advanced diagnostic methods that can better guide therapeutic decisions. Moreover, the implications of our findings extend beyond tendon pathologies to other fields in which inflammation alters tissue properties and water uptake, such as cancer, cardiovascular inflammation, or cachexia—where extracellular-matrix alterations are considered an important marker for tissue healing or disease progression."