Detaillierte Beitrags-Information
| Beitragstitel | Assessment of fluid dynamic stimulation effects on cell mineralization in bioprinted scaffolds |
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| Beitragscode | P114 |
| Autoren | |
| Präsentationsform | Poster |
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| Abstract |
Introduction. Regeneration of bone tissue in critical sized defects is still an issue and, in this context, biological substitutes based on scaffolds loaded with osteogenic cells, can be a promising therapeutic approach. However, the development of clinically relevant cellularized constructs is limited by inadequate construct architecture and oxygenation. Bioprinting allows controlled cell positioning, but static culture of bioprinted structures leads to inhomogeneous extracellular matrix formation and insufficient oxygen transport in internal scaffold regions. Our aim is thus to use perfusion bioreactors to enhance homogeneity of mineral deposition by human mesenchymal stem cells (hMSCs) and oxygen transport in bioprinted constructs. Methods. Cylindrical porous scaffolds (d=10mm, h=3mm) were designed with SolidWorks and bioprinted using a hydrogel made of 0.8%(w/v)-alginate and 4.1%(w/v)-gelatin embedding hMSCs at 5Mcells/ml. Bioprinted scaffolds were cultured in osteogenic medium comparing 0.7 and 7 ml/min flow rates to static control. Micro-computed tomography was performed weekly to analyze mineral deposition for up to 42 days. Computational Fluid Dynamic (CFD) simulations were run on scaffolds using COMSOL Multiphysics to evaluate fluid velocity, wall shear stress (WSS) and pressure distributions on scaffold fibers, and oxygen diffusion through the hydrogel. Results. Bone formation was observed in all groups starting from scaffold edges. In internal cylindrical regions (d=5.4mm), bone volume (BV) significantly increased in perfused culture as compared to static. In particular, it ranged from 0.73%±1.04%, 1.49%±0.87%* and 8.24%±8.41% at week 3 to 1.95%±1.49%#, 5.19%±1.68%* and 17.7%±18.51%# at week 6 in static, 0.7ml/min and 7ml/min samples, respectively (P-values *0.03, #0.02). WSS on scaffold fibers were equal to 3.67 and 36.86mPa in 0.7 ml/min and 7ml/min samples, respectively, pressure values were equal to 0.12 and 1.35Pa, respectively, while the entire scaffold was properly oxygenated in both perfused samples, confirming the absence of hypoxic regions. Conclusions. The combination of experimental planning, based on CFD simulations, and dynamic culture, based on perfusion bioreactors, enhanced quantity and homogeneity of minerals deposited by hMSCs and construct oxygenation, compared to static control, and could help the development of adequate cellularized bone substitutes suitable for clinical applications. |