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. 2021 Jan 18;8:592008. doi: 10.3389/fbioe.2020.592008

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Copyright © 2021 Anastasio, Paniagua, Diamond, Ferlauto and Fernandez-Moure.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Stages of secondary bone healing (endochondral ossification). The stages of fracture healing are partially overlapping. (1) Coagulation and acute inflammatory response—initial stabilization, recruitment of inflammatory cells and cytokines. (2) Repair—(a) Revascularization, soft cartilage callus. Chondroblasts derived from MSCs deposit cartilage, mature to chondrocytes that express VEGF, inducing neovascularization; (b) Hard bony callus—hyperproliferative chondrocytes transdifferentiate to osteoblasts and osteocytes, tissue invaded by osteoblasts; (3) Remodeling—deposition of lamellar bone and restoration of pre-injury anatomic dimensions. This figure was created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by-sa/3.0/legalcode); https://smart.servier.com.