In Vitro and In Silico Modeling of Vertebral Endplate Degeneration Mechanisms

Developed within the Disc4All consortium, this thesis investigates the structural,
mechanical, and inflammatory mechanisms driving intervertebral disc
endplate degeneration through complementary in vitro and in silico approaches.
Recognizing the endplate as a heterogeneous structure, this work
distinguishes its three main regions: the non-calcified cartilaginous endplate,
calcified cartilaginous endplate, and bony endplate, highlighting their distinct
contributions to degeneration processes. Imaging-based computational
approaches are employed to characterize bony endplate microarchitecture
and estimate its mechanical properties, while multi-tissue explant models
are used to investigate region-specific responses to inflammatory cytokines.
Additionally, cell-seeded hydrogel models are developed to specifically assess
cartilaginous endplate cell responses to mechanical loading and inflammatory
cytokine stimulation. Furthermore, a computational–experimental workflow
and a custom perfusion bioreactor concept are proposed to establish
a framework for future studies of fluid transport conditions within endplate
tissues and their influence on cellular stress responses. By integrating
structural characterization, computational modeling, and experimental approaches,
this thesis establishes a comprehensive framework linking endplate
regional heterogeneity, biomechanics, and cellular responses. These findings
contribute to the development of more physiologically relevant models for
studying intervertebral disc degeneration and support future investigations
into endplate-driven degeneration mechanisms.