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Bone is an engineering marvel that achieves a unique combination of stiffness and toughness exceeding that of synthesized materials. In orthopedics, we are currently challenged for the child population that needs a less stiff but a tougher bone substitute than adults. Recent evidence suggests that the relationship between inter-molecular connections that involve the two main bone building blocks, TropoCollagen molecules (TC) and carbonated Hydroxyapatite (cAp), and bone macroscopic mechanical properties, stiffness and toughness, are key to building bone substitute materials for children. The goal of our study is to establish how inter-molecular connections that occur during bone mineralization are related to macroscopic mechanical properties in child bones. Our aim is to link the biological alterations of the TC-cAp self assembly process happening during bone mineralization to the bone macroscopic mechanical properties’ alterations during aging. To do so, we have developed a multiscale mathematical model that includes collagen cross links (TC–TC interface) from experimental studies of bone samples to forecast bone macroscopic mechanical properties. Our results support that the Young’s modulus cannot be a linear parameter if we want to solve our system. In relation to bone substitute material with innovative properties for children, our results propose values of several biological parameters, such as the number of crystals and their size, and collagen crosslink maturity for the desired bone mechanical competence. Our novel mathematical model combines mineralization and macroscopic mechanical behavior of bone and is a step forward in building mechanically customized biomimetic bone grafts that would fit children’s orthopedic needs.


This article was originally published in Materials, available at DOI:10.3390/ma11061045.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 (CC BY 4.0) license (



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