Part II: A new perspective for modeling the bone remodeling process: Biology, mechanics, and pathologies.

In this paper, we explore the effects of biological (pathological) and mechanical damage on bone tissue within a benchmark model. Using the Finite Element Methodology, we analyze and numerically test the model's components, capabilities, and performance under physiologically and pathologically relevant conditions. Our findings demonstrate the model's effectiveness in simulating bone remodeling processes and self-repair mechanisms for micro-damage induced by biological internal conditions and mechanical external ones within bone tissue. This article is the second part of a series, where the first part presented the mathematical model and the biological and physical significance of the terms used in a simplified benchmark model. It explored the bone remodeling model's application, implementation, and results under physiological conditions.

Tumor growth for remodeling process: A 2D approach.

This paper aims to present a comprehensive framework for coupling tumor-bone remodeling processes in a 2-dimensional geometry. This is achieved by introducing a bio-inspired damage that represents the growing tumor, which subsequently affects the main populations involved in the remodeling process, namely, osteoclasts, osteoblasts, and bone tissue. The model is constructed using a set of differential equations based on the Komarova's and Ayati's models, modified to incorporate the bio-inspired damage that may result in tumor mass formation. Three distinct models were developed. The first two models are based on the Komarova's governing equations, with one demonstrating an osteolytic behavior and the second one an osteoblastic model. The third model is a variation of Ayati's model, where the bio-inspired damage is induced through the paracrine and autocrine parameters, exhibiting an osteolytic behavior. The obtained results are consistent with existing literature, leading us to believe that our in-silico experiments will serve as a cornerstone for paving the way towards targeted interventions and personalized treatment strategies, ultimately improving the quality of life for those affected by these conditions.

A coupled mathematical model between bone remodeling and tumors: a study of different scenarios using Komarova's model.

This paper aims to construct a general framework of coupling tumor-bone remodeling processes in order to produce plausible outcomes of the effects of tumors on the number of osteoclasts, osteoblasts, and the frequency of the bone turnover cycle. In this document, Komarova's model has been extended to include the effect of tumors on the bone remodeling processes. Thus, we explored three alternatives for coupling tumor presence into Komarova's model: first, using a "damage" parameter that depends on the tumor cell concentration. A second model follows the original structure of Komarova, including the tumor presence in those equations powered up to a new parameter, called the paracrine effect of the tumor on osteoclasts and osteoblasts; the last model is replicated from Ayati and collaborators in which the impact of the tumor is included into the paracrine parameters. Through the models, we studied their stability and considered some examples that can reproduce the tumor effects seen in clinic and experimentally. Therefore, this paper has three parts: the exposition of the three models, the results and discussion (where we explore some aspects and examples of the solution of the models), and the conclusion.

Both network architecture and micro cracks effects on lacuno-canalicular liquid flow efficiency within the context of multiphysics approach for bone remodeling.

When physical forces are applied to bone, its mechanical adaptive behaviors change according to the microarchitecture configuration. This leads to changes in biological and physical thresholds in the remodeling cell population, involving sensor cells (osteocytes) interacting with each other and changes in osteocyte shape due to variation in lacunar shape. The resulting alterations in fluid flow leads to changes in the membrane electrical potential and shear stress. Eventual creation of microcracks, may lead in turn to modify cell activity. In contrast, the redundancy in the lacuno canalicular network (LCN) interconnectivity maintains partial flow. Our goal was to investigate the role of fluid flow in LCN by proposing a model of electro-mechanical energy spread through inhomogeneous microarchitectures. We focused on mechano-sensitivity to changes in load-induced flow impacted by neighboring micro cracks and quantifying its critical role in changing, velocity, shear stress and orientation of liquid mass transportation from one cell to another. To enhance the concept of intricacy LCN micro-structure to fluid flow, we provide a new combined effects factor considered as osteocytes sensor efficiency. We customized an influence function for each osteocyte, coupling: in one hand, the spatial distribution within remodeling influence areas, conducting a significant fluid spread, leading hydro-dynamic behavior and impacted further by presence of micro cracks and; in other hand, the fluid electro kinetic behavior. As an attempt to fill the limitations stated by many of the recent studies, we reveal in numerical simulation, some results which cannot be measured in vitro/in vivo studies. Numerical calculations were performed in order to evaluate, among many others, how liquid flow conditions changes between lacunas, how the orientation and the magnitude of the governing flow in LCN can regulate osteocytes efficiency. In addition to be regulated by osteocytes, a direct effects of fluid flow are also acting on osteoblast activity. In summary, this new approach considers mechano-sensitivity in relation to liquid flow dynamic and suggests additional pathway for Osseo integration via osteoblast regulation. However, this novel modeling approach may help improve the mapping and design bone scaffolds and/or selection of scaffold implantation regions.