Angiogenesis and Immunomechanics

The extracellular matrix (ECM) continuously adapts to the respective requirements and this dynamic process is essential in tissue development, wound healing but also for regular tissue homeostasis. Mechanical boundary conditions (Wolff's law) provide essential stimuli for this dynamic process and the physical properties of the matrix also determine cellular behaviour. Together with the group Cellular Biomechanics & Biomaterials (A. Petersen) we try to decipher the basic principles of tissue remodeling using the dynamic process of scar-free healing of bones as an example. To decipher the interplay of cells and matrix, we use novel probes developed by V. Vogel at ETH Zurich. These probes allow for the first time to observe the mechanical interaction of cells with native and synthetic ECM.

The development of a functional vascular network plays a key role in healing processes. Nevertheless, we know little about the mechanisms of early vascularization during regeneration. Using bone healing as an example, we are trying to decipher the interplay between extrinsic (tissue) mechanics and biomechanics in the forming vessels in the early phase healing. For these processes of early self-organisation at the beginning of healing, energy is necessary, but after rupture of the vessels, this energy cannot be provided by a local blood supply. The early metabolic cascades at the beginning of healing and the self-organisation of vascular structures are the focus of our research.

We were able to show the importance of the early healing phases for the later success of the healing (or the formation of a replacement tissue, a scar). The change from pro-inflammation to anti-inflammation is essential for the successful healing process for bone and muscle regeneration. Together with the group "Bone Healing" (K. Schmidt-Bleek) and "Musculoskeletal Cell Biology" (S. Geissler) we develop local immune modulations to accelerate bone and muscle healing. In a partnership with the group around D. Mooney (Harvard, Wyss Institute) we develop immune cell traps from biomaterials, which, comparable to cell therapies, shift the local immune balance towards a pro-regenerative milieu. With this strategy we want to make local immune therapies available for broader fields of application than currently possible with Car-T Cell therapies.

At the Julius Wolff Institute and in close collaboration with the CSMC of the Orthopaedics and Trauma Surgery Department of the Charité, we have developed strategies to characterise the clinical problem of delayed healing or non-union of bone, muscle or tendon. These approaches allow us to more precisely identify the medical need from both a clinical and basic scientific perspective. It has been shown that, in addition to tissue competence, local and systemic immune competence is of major importance for healing. This results in novel approaches for diagnostics and therapy. To make these advanced diagnostics and advanced therapies available in orthopaedics and trauma surgery, we work closely with national and international partners. We have been able to establish special research bridges with technology-oriented hubs in Boston, Zurich and Oxford.