The inter-sample structural variability of regular tissue-engineered scaffolds significantly affects the micromechanical local cell environment

Abstract

One contribution of 11 to a theme issue 'Multiscale modelling in biomechanics: theoretical, computational and translational challenges'. Rapid prototyping techniques have been widely used in tissue engineering to fabricate scaffolds with controlled architecture. Despite the ability of these techniques to fabricate regular structures, the consistency with which these regular structures are produced throughout the scaffold and from one scaffold to another needs to be quantified. Small variations at the pore level can affect the local mechanical stimuli sensed by the cells thereby affecting the final tissue properties. Most studies assume rapid prototyping scaffolds as regular structures without quantifying the local mechanical stimuli at the cell level. In this study, a computational method using a micro-computed tomographybased scaffold geometry was developed to characterize the mechanical stimuli within a real scaffold at the pore level. Five samples from a commercial polycaprolactone scaffold were analysed and computational fluid dynamics analyses were created to compare local velocity and shear stress values at the same scaffold location. The five samples did not replicate the computeraided design (CAD) scaffold and velocity and shear stress values were up to five times higher than the ones calculated in the CAD scaffold. In addition high variability among samples was found: at the same location velocity and shear stress values could be up to two times higher from sample to sample. This study shows that regular scaffolds need to be thoroughly analysed in order to quantify real cell mechanical stimuli so inspection methods should be included as part of the fabrication process.

Mechanical response of 3D Insert® PCL to compression

“…Importantly the extensive mechanical characterisation of those scaffolds show the variability encountered from sample to sample and the importance of controlling and characterising parameters such as pore architecture, temperature and strain rate. Data obtained by this study are currently used for the development of computational models aiming to establish the local distribution of stresses and fluid flow [29] within the structure and give a much clearer representation of forces when 3D porous scaffolds undergo external compression. Table 3 SAMPLE TRIPLICATES SHAPIRO TEST LEVENE S TEST ANOVA T-TEST T-TEST VARYING Architecture by µCT highlight  3D PCL responded linearly to compression for strains between 1 and 2.5%.…”

Numerical accuracy comparison of two boundary conditions commonly used to approximate shear stress distributions in tissue engineering scaffolds cultured under flow perfusion

“…Unfortunately, however, the complex internal structure of the porous scaffolds makes estimation of the required shear stresses via experimental or analytical techniques impractical. Hence, computational fluid dynamics models, based on either idealized pore geometries or actual scaffold images, are commonly utilized.…”

“…The latter is the more realistic approach since it is based on the actual microscopic pore structures, which are typically obtained via a 3D scanning technique such as micro‐computed tomography (μCT). Yet, due to the computationally intensive nature of the scaffold reconstructions resulting from such high‐resolution imaging, researchers are forced to resort to implementing approximations . For example, rectangular “representative volume elements” (RVE) are cut from whole scaffolds and implemented in conjunction with various boundary conditions along the artificially created periphery.…”

“…For example, rectangular “representative volume elements” (RVE) are cut from whole scaffolds and implemented in conjunction with various boundary conditions along the artificially created periphery. Two common types of boundary conditions that are typically implemented for this purpose are the “wall boundary condition” (WBC) and the “periodic boundary condition” (PBC) . In the former case, the RVE is surrounded by solid walls in the non‐flow directions, while the latter is an application of periodicity in all three dimensions.…”

Multiscale modelling in biomechanics

“…Erdemir et al [8] explore the multiscale modelling of articular cartilage from a methodological point of view, considering the resolution of challenges that a large-scale exploration of all regions and all possible loading conditions raises. Campos Marin & Lacroix [9] use a multiscale modelling approach to an interesting tissue engineering problem, emphasizing the translational utility of in silico approaches.…”