TY - JOUR
T1 - Inlet flow rate of perfusion bioreactors affects fluid flow dynamics, but not oxygen concentration in 3D-printed scaffolds for bone tissue engineering
T2 - Computational analysis and experimental validation
AU - Seddiqi, H.
AU - Saatchi, A.
AU - Amoabediny, G.
AU - Helder, M.N.
AU - Abbasi Ravasjani, S.
AU - Safari Hajat Aghaei, M.
AU - Jin, J.
AU - Zandieh-Doulabi, B.
AU - Klein-Nulend, J.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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; PFFlow) or high peak shear stress (6.5 Pa; PFFhigh), 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. PFFhigh more strongly stimulated NO production by pre-osteoblasts than PFFlow. 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.
AB - 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; PFFlow) or high peak shear stress (6.5 Pa; PFFhigh), 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. PFFhigh more strongly stimulated NO production by pre-osteoblasts than PFFlow. 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.
KW - 3D-printed scaffold
KW - Bone tissue engineering
KW - Finite element modeling
KW - Fluid flow dynamics
KW - Osteoblasts
KW - Oxygen
KW - Perfusion bioreactor
UR - http://www.scopus.com/inward/record.url?scp=85089278902&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.compbiomed.2020.103826
DO - https://doi.org/10.1016/j.compbiomed.2020.103826
M3 - Article
C2 - 32798924
SN - 0010-4825
VL - 124
JO - Computers in Biology and Medicine
JF - Computers in Biology and Medicine
M1 - 103826
ER -