Professor Anayancy Osorio-Madrazo (Freiburg i. Br., DE; Jena, DE; Heilbad Heiligenstadt, DE), Shaghayegh Jahangir (Heilbad Heiligenstadt, DE; Freiburg i. Br., DE), Dr. Fritz Koch (Freiburg i. Br., DE), Dr. Ingo Doench (Heilbad Heiligenstadt, DE), Tuan Anh Tran (Jena, DE; Heilbad Heiligenstadt, DE), Dr. Stefan Zimmermann (Freiburg i. Br., DE), Marilù Casini (Freiburg i. Br., DE), Dr. Rémi Peyronnet (Freiburg i. Br., DE)
Abstract text (incl. figure legends and references)
Introduction: Bioprinting provides the ability to adjust factors like cell distribution in biomaterials; cells, growth factors concentration; matrix resolution, polymers combination as well as achieve processing for good cell viability, coculture, 3D cell growth. The capability to load different cell types is other benefit allowing mimicking cell microenvironments to develop functional tissues.
Objectives: We aim bioprinting cell-laden hydrogels at high cell density, with the highest precision of bioink deposition into hydrogel patterns, by droplet-based bioprinting DBB. We advance the development of functional tissue models in the context of cardiac lesions, allowing for cardiac cell coculture in target microstructures.
Materials & Methods: Flow behavior of inks of alginate at 0.5, 1 and 2%wt and of fibrinogen at 2%wt without and with cells was investigated by rheology. Initially, fibroblast cells were incorporated in bioink at a conc. of 3x10^6 cells/mL. Then, to design cardiac models, 2 types of cells were used: mesenchymal stem cells (BM-hMSC) and immortalized human ventricular fibroblast (HVF) cell line. DBB was performed with a RegenHU 3D bioprinter under minimum pressure 0.05MPa and a valve opening time range: 120-210µs. Cells were fluorescence stained and printed biomaterials were observed at confocal microscope.
Results: By increasing valve opening time the droplet size increased and droplet patterns with dosing distance of 1 mm were achieved, preventing the droplets from merging. The smallest alginate droplets were achieved at conc 0.1 %wt by printing with a microvalve of inner diameter 0.2mm and a valve opening time of 120µs. The highest precision in designing cardiac models was achieved with the pattern closest gap of ca. 250µm between fibrinogen/cardiac cell areas.
Conclusion: Cell-laden hydrogel patterns of target resolution with high precision and at high cell density were developed, allowing co-culture studies in cardiac functional tissue models.