Inlet flow rate of perfusion bioreactors affects fluid flow dynamics, but not oxygen concentration in 3D-printed scaffolds for bone tissue engineering: Computational analysis and experimental validation

Hadi Seddiqi; Alireza Saatchi; Ghassem Amoabediny; Marco N Helder; Sonia Abbasi Ravasjani; Mohammadreza Safari Hajat Aghaei; Jianfeng Jin; Behrouz Zandieh-Doulabi; Jenneke Klein-Nulend

doi:10.1016/j.compbiomed.2020.103826

Inlet flow rate of perfusion bioreactors affects fluid flow dynamics, but not oxygen concentration in 3D-printed scaffolds for bone tissue engineering: Computational analysis and experimental validation

Comput Biol Med. 2020 Sep:124:103826. doi: 10.1016/j.compbiomed.2020.103826. Epub 2020 Aug 4.

Authors

Hadi Seddiqi¹, Alireza Saatchi², Ghassem Amoabediny³, Marco N Helder⁴, Sonia Abbasi Ravasjani⁵, Mohammadreza Safari Hajat Aghaei⁶, Jianfeng Jin⁷, Behrouz Zandieh-Doulabi⁸, Jenneke Klein-Nulend⁹

Affiliations

¹ Department of Biomedical Engineering, Research Center for New Technologies in Life Science Engineering, University of Tehran, Tehran, P.O. Box 11365-4563, Iran. Electronic address: seddiqi.hadi@gmail.com.
² Department of Biomedical Engineering, Research Center for New Technologies in Life Science Engineering, University of Tehran, Tehran, P.O. Box 11365-4563, Iran; School of Chemical Engineering, College of Engineering, University of Tehran, P.O. Box 11365-4563, Tehran, Iran. Electronic address: saatchi@ut.ac.ir.
³ Department of Biomedical Engineering, Research Center for New Technologies in Life Science Engineering, University of Tehran, Tehran, P.O. Box 11365-4563, Iran; School of Chemical Engineering, College of Engineering, University of Tehran, P.O. Box 11365-4563, Tehran, Iran; Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands. Electronic address: amoabediny@ut.ac.ir.
⁴ Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands. Electronic address: m.helder@amsterdamumc.nl.
⁵ Department of Biomedical Engineering, Research Center for New Technologies in Life Science Engineering, University of Tehran, Tehran, P.O. Box 11365-4563, Iran. Electronic address: so.abbasi1991@gmail.com.
⁶ Department of Biomedical Engineering, Research Center for New Technologies in Life Science Engineering, University of Tehran, Tehran, P.O. Box 11365-4563, Iran. Electronic address: mrsafari1368@gmail.com.
⁷ Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Gustav Mahlerlaan 3004, 1081 LA, Amsterdam, the Netherlands. Electronic address: j.jin@acta.nl.
⁸ Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Gustav Mahlerlaan 3004, 1081 LA, Amsterdam, the Netherlands. Electronic address: bzandiehdoulabi@acta.nl.
⁹ Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Gustav Mahlerlaan 3004, 1081 LA, Amsterdam, the Netherlands. Electronic address: j.kleinnulend@acta.nl.

PMID: 32798924
DOI: 10.1016/j.compbiomed.2020.103826

Abstract

Fluid flow dynamics and oxygen-concentration in 3D-printed scaffolds within perfusion bioreactors are sensitive to controllable bioreactor parameters such as inlet flow rate. Here we aimed to determine fluid flow dynamics, oxygen-concentration, and cell proliferation and distribution in 3D-printed scaffolds as a result of different inlet flow rates of perfusion bioreactors using experiments and finite element modeling. Pre-osteoblasts were treated with 1 h pulsating fluid flow with low (0.8 Pa; PFF^low) or high peak shear stress (6.5 Pa; PFF^high), and nitric oxide (NO) production was measured to validate shear stress sensitivity. Computational analysis was performed to determine fluid flow between 3D-scaffold-strands at three inlet flow rates (0.02, 0.1, 0.5 ml/min) during 5 days. MC3T3-E1 pre-osteoblast proliferation, matrix production, and oxygen-consumption in response to fluid flow in 3D-printed scaffolds inside a perfusion bioreactor were experimentally assessed. PFF^high more strongly stimulated NO production by pre-osteoblasts than PFF^low. 3D-simulation demonstrated that dependent on inlet flow rate, fluid velocity reached a maximum (50-1200 μm/s) between scaffold-strands, and fluid shear stress (0.5-4 mPa) and wall shear stress (0.5-20 mPa) on scaffold-strands surfaces. At all inlet flow rates, gauge fluid pressure and oxygen-concentration were similar. The simulated cell proliferation and distribution, and oxygen-concentration data were in good agreement with the experimental results. In conclusion, varying a perfusion bioreactor's inlet flow rate locally affects fluid velocity, fluid shear stress, and wall shear stress inside 3D-printed scaffolds, but not gauge fluid pressure, and oxygen-concentration, which seems crucial for optimized bone tissue engineering strategies using bioreactors, scaffolds, and cells.

Keywords: 3D-printed scaffold; Bone tissue engineering; Finite element modeling; Fluid flow dynamics; Osteoblasts; Oxygen; Perfusion bioreactor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bays
Bioreactors*
Perfusion
Printing, Three-Dimensional*
Tissue Engineering*
Tissue Scaffolds*