Multiscale Modeling of Bone Healing: Toward a Systems Biology Approach

Abstract

Bone is a living part of the body that can, in most situations, heal itself after fracture. However, in some situations, healing may fail. Compromised conditions, such as large bone defects, aging, immuno-deficiency, or genetic disorders, might lead to delayed or non-unions. Treatment strategies for those conditions remain a clinical challenge, emphasizing the need to better understand the mechanisms behind endogenous bone regeneration. Bone healing is a complex process that involves the coordination of multiple events at different length and time scales. Computer models have been able to provide great insights into the interactions occurring within and across the different scales (organ, tissue, cellular, intracellular) using different modeling approaches [partial differential equations (PDEs), agent-based models, and finite element techniques]. In this review, we summarize the latest advances in computer models of bone healing with a focus on multiscale approaches and how they have contributed to understand the emergence of tissue formation patterns as a result of processes taking place at the lower length scales.

Keywords: bone healing; computer modeling; multiscale modeling; systems biology; tissue regeneration.

Figure 1

(A) Histological section (Safranin-O von Kossa staining) of sheep callus stabilized with an external fixator (9 weeks). (B) Map of elastic coefficient (GPa) of the same sample measured by quantitative acoustic scanning microscopy. (C) FEMs of callus region (black square B) under 10% compression showing the influence of callus tissue structure and heterogeneity on the mechanical strains within the healing region. High mechanical strains are induced in regions between the highly organized bone tissue, which cannot be predicted when describing the tissues as continuous and homogeneous materials.

Figure 2

Although computer models of bone healing tend toward a multiscale approach to understand interactions between and within the different length and time scales, computer models at the intracellular level are still lacking.