Computational Mechanobiology in Cartilage and Bone Tissue Engineering: From Cell Phenotype to Tissue Structure - Computational Modeling in Tissue Engineering - page 332

theoretical models can help overcome particular experimental hurdles and in
order to illustrate some aspects of structural reorganisation in cell biology.
• Section 3 introduces the concept of testing theories of mechanoregulated tissue
differentiation by performing simulations, where the hypothesis under investi-
gation can be corroborated or rejected by comparing in silico predictions with in
vivo results. The main focus will be on simulations of fracture healing and
osteochondral defect healing. The section is kept brief with a focus on providing
essential historical and conceptual background information. It closes with some
recent work from our lab on differentiation guided by substrate stiffness and
oxygen tension as well as the incorporation of tissue structure into simulations
of tissue regeneration.
• Section 4 is concerned with the application of computational models to tissue
engineering and regeneration approaches involving bioreactors and scaffolds.
The focus here is on understanding how scaffold heterogeneity and architecture
affect mechanical stimuli imposed on cells and the role of modelling in complex
design challenges. We further provide an example of tissue adaptation during
bioreactor culture demonstrating how modelling approaches somewhat akin to
those introduced in Sects. 2 and 3 can be used to determine the role of collagen
remodelling on the mechanical properties of engineered cartilage subjected to
dynamic compression.
• Section 5 finally bridges the gap between the scales by giving a short overview
over multiscale simulations in tissue engineering and regeneration.
2 Single Cell Models and Cell-Substrate Interactions
2.1 Mechanosensing, Cell Rheology and Substrate Effects
When descending to the cellular level the main mechanobiological question relates
to the fundamental aspect of mechanosensing—how does the cell sense, integrate
and translate mechanical signals of different kinds to evoke a biological response.
But cells are not merely passive sensors. Cells actively interact with their envi-
ronment, probe it, sense it and adapt to it. Cytoskeletal components such as actin
filaments and microtubuli undergo continuous polymerisation and depolymerisa-
tion depending on cell activity, attachment and external cues. Hence, an inherent
problem of elucidating cellular properties and behaviours is the living nature of the
cell itself—it interacts with the commonly applied measurement tools such that the
measurement itself alters the cellular properties that are to be measured. For that
reason, intrinsic properties are difficult to obtain by experimental methods alone
and constitutive models that feature the salient aspects of cellular behaviour are
required for a thorough evaluation [ 27 ]. Since the understanding of mechano-
transduction pathways requires knowledge on the mechanics of the cell and its