Multilevel experimental and modelling techniques for bioartificial scaffolds and matrices

Tissue engineering (TE) is the application of principles and methods of engineering and life sciences towards the fundamental understanding of structure–function relationships in normal and pathological mammalian tissues and the development of biological substitutes to restore, maintain or improve tissue function. One key component to TE is using three-dimensional porous scaffolds to guide cells during the regeneration process. These scaffolds are intended to provide cells with an environment that promotes cell attachment, proliferation, and differentiation. After sufficient tissue regeneration using in vitro culturing methods, the scaffold/tissue structure is implanted into the patient, where the scaffold will degrade away, thereby leaving only regenerated tissue; on a different approach, non-cellularised scaffolds are inserted into the patient to elicit in vivo cell recruitment, growth and tissue regeneration. Tissue-engineered scaffolds need to meet both the biological goals of tissue formation and the stresses and loading conditions present in the human body. For this reason, any design approach must ensure that the mechanical properties of the resulting scaffold structure are compatible and optimally match the requirements from the environment, that, respectively, are the cell adhesion transmembrane protein, the cytoskeleton structure, the cell population. The need to design scaffold structures, the need for precision control during their fabrication and for determining the metrological indices and the need to characterise their structural behaviour at different scales have lead to numerous experimental and computational challenges. In particular, there is a need for modelling and test tissue at multiple scales to gain insight into issues such as drug delivery, drug interaction, gene expression and cellular–environment interactions. The analysis of the tissue constructs at different scales includes a macro-scale model where the macro-scale tissue construct is characterised, a multi-cellular model where a sufficiently large multi-cellular representative element volume is selected to represent a microstructure of the tissue construct and a single cell model wherein the microstructures of the cell like the nucleus and the cytoplasm have been incorporated. A multi-scale approach is already being applied to bridge nano- and micro-scales as well as micro- and macro-scales within various research areas in TE. In this chapter, a review of the experimental and modelling techniques used for the evaluation, at different scales, of the mechanical and morphological properties of bioartificial scaffolds and matrices, such as compression testing, nanoindentation, AFM technique, Dynamical Mechanical Analysis (DMA), micro-CT, micro-MR, Asymptotic Homogenisation Theory, Finite Element Analysis (FEA), Rule-of- Mixtures, is proposed