How the Morphology of Osteocytes Contributes to their Mechanotransduction near Microdamage
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How the Morphology of Osteocytes Contributes to their Mechanotransduction near Microdamage Elisa Budyn1,2, Morad Bensidhoum3, Patrick Tauc4, Eric Deprez4 and Herve Petite3 1 Department of Mechanical engineering, LMT Laboratory CNRS UMR 8535, Ecole Normale Superieure Cachan, 61 Avenue du President Wilson, 94230 Cachan, France; 2University of Illinois at Chicago, 842 West Taylor Street, Chicago, IL 60607, USA. 3 Department of Biology, B2OA Laboratory UMR CNRS 7052, University Paris Diderot, Avenue de Verdun, 75010 Paris, France. 4 Department of Biology, LBPA Laboratory CNRS UMR 8113, Ecole Normale Superieure Cachan, 61 Avenue du President Wilson, 94230 Cachan, France. ABSTRACT A dual experimental and numerical top-down approach is applied to investigate the link between osteocyte morphology and mechanical perception of their environment at the progenitor and mature stages. The numerical model is based on explicit tissue morphology discretization to identify bone diffuse damage at the cellular scale. The in vitro experimental model presents a live allograft bone system where a patient progenitor or mature osteocytes were reseeded in fresh human donor cortical bone tissues subjected to mechanical loading. The live systems behaved mechanically as fresh bone and the cells spatially reorganized in vitro as in vivo. The system under mechanical load also showed an adaptation of the calcium membrane transport rate to the expected in vivo mechanical load detected by bone cells at different stages of differentiation. INTRODUCTION With increasing life expectancy, bone pathologies related to massive bone loss occur later in life and carry $5-$10 billion financial burden on the U.S. healthcare system. Human Haversian cortical bone is a complex hierarchical heterogeneous tissue resulting from continuous remodeling. Microdamage are therefore resorbed by osteoclasts cells before tubular lamellar structures called osteons are formed by osteoblast cells laying Type I collagen fibrils mineralized by hydroxyapatite nano-platelet crystals glued together with non-collagen proteins and proteoglycans. Trapped osteoblasts further differentiate into mechano-sensitive osteocytes that are able to sense stimulation produced by microdamage. However bone healing ability declines with long term degeneration during aging, massive trauma or large tissue resections such as tumor removals. To promote bone growth in large defects, autograft bone offers the gold standard repair but is limited by suitable tissue quantities and donor site morbidity. Successful techniques for massive tissue regeneration can be however difficult to produce and often require addition of functional materials. Nonetheless, allograft bone can be stored but does not always perform as well as fresh autograft and the current tissue disinfection procedures such as supercritical carbon dioxide significantly modifies the tissue properties. Yet cleaned and decellularized tissue from a donor represents the ideal matrix for cocultures of the recipient patient cells for fast tissue reinteg
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