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    FOR 5177 SP6: Decoding Spinal Dysfunction: Causal Mechanisms of Muscle and Compensatory Adaptations through Functional Animal and Musculoskeletal Modeling
    The aim of the first funding period of FOR 5177 was to systematically investigate the mechanical influences on tissue adaptation and degeneration following surgical interventions to the spine, using a large animal model combined with numerical simulations. Contrary to the widely accepted assumptions from in vitro studies, neither compensatory hypermobility in adjacent segments after fusion nor persistent hypermobility of the operated segment after nucleotomy could be confirmed in vivo. Instead, movement restrictions were observed, indicating spinal stabilization and suggesting effective neuromuscular adaptations. Complementary finite element analyses demonstrated that local changes in mechanical loading can induce targeted osseous adaptations, and that dynamic loading scenarios promote the restoration of segmental stability. Furthermore, activity level was shown to have a significant impact on the dynamic movement patterns of the spine. Using specially developed AI-supported video analysis methods for large animals, we revealed functional relationships between limb function and spinal motion, thus demonstrating the integrative neuromuscular control underlying spinal movement. Building on these insights, the second funding period focuses on the role of muscle function as a central driver of spinal adaptation processes. The core objective is to analyze causal mechanisms by which muscle dysfunction induces functional alterations in spinal mechanics. For this purpose, we employ a functional large animal model that mimics muscular changes observed in chronic low back pain by inducing selective muscle inactivity through targeted neurotomy. An integrative methodological approach combines functional in vivo assessments (including EMG, kinematics, and behavioral analyses), ex vivo structural evaluations, and in silico simulations to investigate the interplay between muscle (in)activity, mechanical loading, structural changes, and pain mechanisms. The central hypothesis posits a self-reinforcing vicious cycle: muscle dysfunction leads to mechanical overload, which triggers a neuroinflammatory response that promotes pain chronification - thereby further exacerbating muscle dysfunction. This project makes a crucial contribution to the overall initiative by systematically elucidating neuromuscular mechanisms in chronic low back pain and establishing a methodological foundation for improved diagnostics.
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    GRK 3144: Multiscale Imaging and Analytics of Interfaces in Musculoskeletal Health
    The interdisciplinary Research Training Group (RTG) program entitled "Multiscale Imaging and Analytics of Interfaces in Musculoskeletal Health" extends beyond traditional assessments of bone quantity and density to investigate the complexities of musculoskeletal integrity. This program seeks to understand the interactions between bones, muscles, tendons, fat, and vessels, including their interfaces. By integrating biomedical and technological insights, the program aims to drive innovation in diagnostics and preventive healthcare. Its research objectives include exploring the muscle-fat-bone axis, the tendon-bone interface, the role of vascularization in skeletal health, advanced imaging techniques, models for tissue interfaces, and the use of posture and motion as health indicators. Graduates will gain proficiency in state-of-the-art imaging, disease modeling, and machine learning techniques focused on interfaces, equipping them for addressing global challenges in medicine and technology. The Qualification Program is designed to train a new generation of interdisciplinary STEM scientists in musculoskeletal research. Spanning three cohorts over nine years, it emphasizes skill development in interdisciplinary project management, research ethics, and foundational musculoskeletal research knowledge. Networking opportunities are facilitated through workshops, industry excursions, and international conferences. The inclusion of a Mercator fellow position and the involvement of physicians promote international collaboration and research profile development. This program prepares students for careers in research, teaching, and industry, with a strong emphasis on ethical conduct, collaborative skills, and independence. Located in Hamburg, the RTG benefits from the Interdisciplinary Competence Center for Interface Research (ICCIR) and operates across five laboratory campuses in Hamburg-Eppendorf, Hamburg-Harburg, and Hamburg’s Science City Bahrenfeld. The University Medical Center Hamburg (UKE) provides an interdisciplinary research environment, laboratory facilities, and high-resolution imaging tools. The Hamburg University of Technology (TUHH) specializes in engineering sciences, with a focus on artificial intelligence, data analysis, and computational modeling. Hereon, a member of the Helmholtz Association, offers large-scale facilities for synchrotron science and bone interface research. Hamburg's strategic positioning, robust research infrastructure, and collaborative culture create an optimal setting for musculoskeletal research. The RTG is committed to promoting diversity and gender equality, providing support and initiatives for female scientists. Our interdisciplinary approach not only strengthens healthcare and technological innovation but also prepares graduates for significant roles in academic and corporate research sectors, benefiting both the local and global research communities.
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    CRC 1444 - Project P10 - Spatiotemporal regulation of sprouting angiogenesis through combined mechanical and geometrical cues
    Die Vaskularisierung ist eng mit der Mineralisierung des Gewebes während der Knochenregeneration verknüpft. Bei gestörter Angiogenese ist die Knochenregeneration eingeschränkt und es entwickelt sich eine verzögerte Heilung oder einees bildet sich eine sogenannte Non-Union bei der ein Knochendefekt vom Körper nicht überbrückt werden kann. Es ist bekannt, dass mechanische Signale die Vaskularisierung und somit den Knochenheilungsprozess beeinflussen. In diesem Projekt wird untersucht, wie die lokale mechanische Dehnung des Gewebes und die Eigenschaften der extrazellulären Matrix (Zusammensetzung, Strukturierung) das Wachstum von Gefäßen beeinflussen. Zu diesem Zweck wird ein in vitro 3D-Knochendefektmodell mit Computersimulationen kombiniert, um die räumliche Verteilung der Dehnung und die resultierende Zellreaktion zu untersuchen. Wir stellen die Hypothese auf, dass mechanische und geometrische Signale in architektonischen Biomaterial-Scaffolds synergetisch kombiniert werden können, um die Re-Vaskularisierung für eine verbesserte Heilung von Knochendefekten zu steuern.
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