Alireza Saatchi - School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran.
Ghassem Amoabediny - School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran
Marco N Helder - Department of Oral and Maxillofacial Surgery, VU University Medical Center, Amsterdam Movement Sciences, Amsterdam, The Netherlands
Behrouz Zandieh-Doulabi - Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA) -University of Amsterdam and VU University Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands

Introduction Cell density in scaffolds is a critical bottleneck to create large engineered constructs for large bone defects. Objectives We aimed to assess whether mathematical modelling can be used as a preliminary design tool for engineering channeled scaffolds, and to employ 3D-porous PLGA/β-TCP scaffolds to assess the effect of scaffold channeling on cell proliferation and distribution in static flask bioreactors.Methods Finite element modeling was used to test the effect of channel number (9-18), diameter (0.5-2 mm), and pattern (1 or 2 rows) within scaffold on cell and oxygen distribution after 7 days. MC3T3-E1 osteoblasts were seeded on scaffolds (radius: 1.1 cm; height 1 cm; channel number: 12; channel diameter: 1 mm), and cultured for 21 days to determine cell viability and distribution and ALP activity. Results 3D-simulation demonstrated enhanced oxygen concentration, oxygen distribution, cell density and distribution by increasing channel number, channel diameter, and uniformity of channel distribution. With increased channel number, the oxygen concentration was maximal at day 7. Scaffold channeling increased metabolic activity of the cell/polymer constructs at day 7 (+15%, p=0.24). Metabolic activity of non-channeled cell/polymer constructs was higher compared to channeled counterparts at day 14 and 21 (13%, p=0.39, and 14%, p=0.40 respectively). Conclusion Excellent agreement between model predictions and experimental data suggesting that mathematical modeling might be useful to predict cell proliferation and distribution within a 3D-porous scaffold. Channeling of scaffolds significantly enhanced cell proliferation, spatial distribution, and viability in static flask bioreactors, suggesting this is a promising approach toward creating thick tissue-engineered constructs.

Bone tissue engineering, 3D-porous channeled scaffold, Finite element modeling, Static flask bioreactor, Cell distribution