Multi-scale characterization of the spatio-temporal interplay between elemental composition, mineral deposition and remodelling in bone fracture healing

Bone mineralization involves a complex orchestration of physico-chemical responses from the organism. Despite extensive studies, the detailed mechanisms of mineralization remain to be elucidated. This study aims to characterize bone mineralization using an in-vivo long bone fracture healing model in the rat. The spatio-temporal distribution of relevant elements was correlated to the deposition and maturation of hydroxyapatite and the presence of matrix remodeling compounds (MMP-13). Multi-scale measurements indicated that (i) zinc is required for both the initial mineral deposition and resorption processes dur -ing mature mineral remodeling; (ii) Zinc and MMP-13 show similar spatio-temporal trends during early mineralization; (iii) Iron acts locally and in coordination with zinc during mineralization, thus indicat-ing novel evidence of the time-events and inter-play between the elements. These findings improve the understanding of bone mineralization by explaining the link between the different constituents of this process throughout the healing time. Statement of significance Bone mineralization involves a complex orchestration of physico-chemical responses from the organism, the detailed mechanisms of which remain to be elucidated. This study presents a highly novel multi-scale multi-modal investigation of bone mineralization using bone fracture healing as a model system. We present original characterization of tissue mineralization, where we relate the spatio-temporal distribu-tion of important trace elements to a key matrix remodeling compound (MMP-13), the initial deposition and maturation of hydroxyapatite and further remodeling processes. This is the first time that mineral-ization has been probed down to the nanometric level, and where key mineralization components have been investigated to achieve a comprehensive and mechanistic understanding of the underlying mineral-ization processes during bone healing. & COPY; 2023 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Automated summary

This study aims to characterize bone mineralization using an in-vivo long bone fracture healing model in the rat. Multi-scale measurements indicated that zinc is required for both the initial mineral deposition and resorption processes, zinc and MMP-13 show similar spatio-temporal trends during early mineralization, and iron acts locally and in coordination with zinc during mineralization. These findings improve the understanding of bone mineralization.