The Local Matrix Distribution and the Functional Development of Tissue Engineered Cartilage, a Finite Element Study

Abstract

Abstract-Assessment of the functionality of tissue engineered cartilage constructs is hampered by the lack of correlation between global measurements of extra cellular matrix constituents and the global mechanical properties. Based on patterns of matrix deposition around individual cells, it has been hypothesized previously, that mechanical functionality arises when contact occurs between zones of matrix associated with individual cells. The objective of this study is to determine whether the local distribution of newly synthesized extracellular matrix components contributes to the evolution of the mechanical properties of tissue engineered cartilage constructs. A computational homogenization approach was adopted, based on the concept of a periodic representative volume element. Local transport and immobilization of newly synthesized matrix components were described. Mechanical properties were taken dependent on the local matrix concentration and subsequently the global aggregate modulus and hydraulic permeability were derived. The transport parameters were varied to assess the effect of the evolving matrix distribution during culture. The results indicate that the overall stiffness and permeability are to a large extent insensitive to differences in local matrix distribution. This emphasizes the need for caution in the visual interpretation of tissue functionality from histology and underlines the importance of complementary measurements of the matrix's intrinsic molecular organization.

Mechanically induced structural changes during dynamic compression of engineered cartilaginous constructs can potentially explain increases in bulk mechanical properties

“…Despite equivalence of the bulk biochemical content, DL could lead to different distributions of the ECM proteins and hence affect mechanical properties [47]. However, finite-element studies [50] on the local distribution of ECM in tissueengineered cartilage concluded that the global aggregate modulus and permeability were largely insensitive to the microscopic matrix distribution.…”

Influence of crosslinking on the mechanical behavior of 3D printed alginate scaffolds: Experimental and numerical approaches

“…In a similar study, isotropic linear elastic behavior was reported and 10% strain used to calculate the elastic modulus of scaffolds fabricated as cardiac-mimetic structures; furthermore, 10 to 25% strain was reported as the cardiac-relevant strain range in physiological conditions (Neal et al, 2012). Finally, a finite element study assigned linear elastic elements to a model to predict the mechanical properties of tissue-engineered cartilage constructs (Sengers et al, 2004). Hence, the direct determination of elastic modulus from the linear section of stressstrain curve is appropriate if the possible applications are taken into account.…”

Modeling Morphogenesisin silicoandin vitro: Towards Quantitative, Predictive, Cell-based Modeling

“…Rejniak and Anderson derived a plausible set of rules and conditions, including oriented cell division, differentiation, polarization and apoptosis, by which single cells can develop into well-organized acinar structures. Aiming to get a better control over the mechanical properties of tissue-engineered cartilage, Sengers and coworkers [46,47] computationally assessed extracellular matrix (ECM) deposition by chondrocytes ( Figure 1B,E). In a continuous interaction between cell culture and agent-based computational modeling work, the Epitheliome project (see e.g.…”