A 3D bioreactor model to study osteocyte differentiation and mechanobiology under perfusion and compressive mechanical loading

Abstract: Osteocytes perceive and process mechanical stimuli in the lacuno-canalicular network in bone. As a result, they secrete signaling molecules that mediate bone formation and resorption. To date, few three-dimensional (3D) models exist to study the response of mature osteocytes to biophysical stimuli that mimic fluid shear stress and substrate strain in a mineralized, biomimetic bone-like environment. Here we established a biomimetic 3D bone model by utilizing a state-of-art perfusion bioreactor platform where immortomouse/Dmp1-GFP-derived osteoblastic IDG-SW3 cells were differentiated into mature osteocytes. We evaluated proliferation and differentiation properties of the cells on 3D microporous scaffolds of decellularized bone (dBone), poly(L-lactide-co-trimethylene carbonate) lactide (LTMC), and beta-tricalcium phosphate (β-TCP) under physiological fluid flow conditions over 21 days. Osteocyte viability and proliferation were similar on the scaffolds with equal distribution of IDG-SW3 cells on dBone and LTMC scaffolds. After seven days, the differentiation marker alkaline phosphatase (Alpl), dentin matrix acidic phosphoprotein 1 (Dmp1), and sclerostin (Sost) were significantly upregulated in IDG-SW3 cells (p = 0.05) on LTMC scaffolds under fluid flow conditions at 1.7 ml/min, indicating rapid and efficient maturation into osteocytes. Osteocytes responded by inducing the mechanoresponsive genes FBJ osteosarcoma oncogene (Fos) and prostaglandin-endoperoxide synthase 2 (Ptgs2) under perfusion and dynamic compressive loading at 1 Hz with 5 % strain. Together, we successfully created a 3D biomimetic platform as a robust tool to evaluate osteocyte differentiation and mechanobiology in vitro while recapitulating in vivo mechanical cues such as fluid flow within the lacuno-canalicular network

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Acta biomaterialia. - 184 (2024) , 210-225, ISSN: 1878-7568

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2024
• Creator: Rindt, Wyonna Darleen ; Krug, Melanie ; Yamada, Shuntaro ; Sennefelder, Franziska ; Belz, Louisa ; Cheng, Wen-Hui ; Azeem, Muhammad ; Kuric, Martin ; Evers, Marietheres ; Leich-Zbat, Ellen ; Hartmann, Tanja ; Pereira, Ana ; Herrmann, Marietta ; Hansmann, Jan ; Mussoni, Camilla ; Stahlhut, Philipp ; Ahmad, Taufiq ; Yassin, Mohammed Ahmed ; Mustafa, Kamal ; Ebert-Dümig, Regina ; Jundt, Franziska

Further information

• DOI: 10.1016/j.actbio.2024.06.041
• URN: urn:nbn:de:bsz:25-freidok-2555063
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 14.08.2025, 10:55 AM CEST