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Beitragstitel Culture of 3D Bioprinted Bone Constructs Requires an Increased Fluid Dynamic Stimulation
Beitragscode P67
  1. Valerio Luca Mainardi Ente Ospdealiero Cantonale EOC Vortragender
  2. Marina Rubert ETH Zurich
  3. Claudia Sabato Ente Ospdealiero Cantonale EOC
  4. Anke de Leeuw ETH Zurich
  5. Chiara Arrigoni Ente Ospedaliero Cantonale EOC
  6. Gabriele Dubini Politecnico di Milano
  7. Christian Candrian Ente Ospdealiero Cantonale EOC
  8. Ralph Müller ETH Zurich
  9. Matteo Moretti Ente Ospdealiero Cantonale EOC
Präsentationsform Poster
  • A08 - Grundlagenforschung
Abstract INTRODUCTION: Regeneration of bone tissue in critical sized defects is still an open issue and, in this context, biological substitutes based on constructs loaded with osteogenic cells can be a promising therapeutic approach [1]. During in vitro culture, flow-induced mechanical stimulation has been shown to favor mineral deposition in scaffolds seeded with cells directly exposed to the fluid flow [2]. However, the effect of fluid dynamic parameters, such as shear stress (SS), within 3D bioprinted constructs, is still unclear. Thus, the aim of this study was to correlate the levels of fluid flow SS and the mineral deposition in 3D bioprinted constructs, evaluating the possible dampening effect of alginate and gelatin-based hydrogels on the embedded cells.
METHODS: Cylindrical porous scaffolds (d = 10 mm, h = 3 mm) 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 5 Mcells/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 simulations were run on scaffolds using COMSOL Multiphysics to evaluate SS, fluid velocity, and pressure distribution on construct fibers.
RESULTS: Bone volume (BV) significantly increased in perfused groups as compared to static control (Fig. 1). It ranged from 0.35±0.28 mm3, 11.90±8.74 mm3 and 25.81±5.02 mm3 at week 3 to 2.28±0.78 mm3, 22.55±2.45 mm3 and 46.05±5.95 mm3 at week 6 in static, 0.7 and 7 ml/min groups, respectively. SS values on construct fibers in the range 10-100 mPa in 7 ml/min samples (52.81%) were twice those in 0.7 ml/min samples (23.41%), showing the same trend of BV. DISCUSSION & CONCLUSIONS: The obtained results suggest that, to increase mineral deposition by hMSCs within in vitro cultured 3D bioprinted constructs, it is necessary to enhance the flow-induced mechanical stimulation within cell-embedded hydrogel structures, as compared to what has been generally reported for the development of bone constructs when employing scaffolds with cells directly exposed to the fluid flow [2].

ACKNOWLEDGEMENTS: This research was partially funded by an IDEA League Student Grant and by the Swiss National Science Foundation through the grant SNF 310030 179167.

REFERENCES: [1] Pina, S. et al. 2019 Materials (Basel); [2] Melke, J. et al. 2018 Eur Cell Mater.