Annabelle Neuhäusler (Darmstadt, DE), Katharina Rogg (Tübingen, DE), Sebastian Schröder (Aachen, DE), Dieter Spiehl (Darmstadt, DE), Dr. Hanna Hartmann (Tübingen, DE), Prof. Dr. Andreas Blaeser (Darmstadt, DE)
Abstract text (incl. figure legends and references)
Introduction: The artificial cultivation of biological tissues and organs has been a research goal in the field of regenerative medicine for many years. To mimic the complex structure of natural tissues, 3D-bioprinting techniques are a promising new field. Despite recent progress, however, supplying cells with oxygen and nutrients in macroscopic tissue precursors remains a challenge.
Objective: The aim of this work is to provide a biomimetic solution for the unmet nutrient supply gap in macroscopic tissues. This is to be achieved by incorporating either electro-spun fibers made of poly-caprolactone (PCL) (diameter 5-10 µm) or wet spun collagen fibers (diameter 5-20 µm) to increase passive diffusion as well as endothelial cell alignment.
Methods: The bioinks comprising an agarose hydrogel with either PCL or collagen fibers, were thoroughly characterized regarding topographical, mechanical, diffusional and swelling properties. 3D-bioprinting was tested via drop-on-demand printing as well as microextrusion printing to achieve in-situ alignment of the printed fibers. Cytocompatibility of the composite bioinks was tested using human umbilical vein endothelial cells (HUVECs).
Results: Rheological measurements showed slight shear thinning properties of all bioinks. Swelling of the bioinks at 37 °C was roughly doubled compared to the hydrogel without PCL fibers. In line with these results, the diffusion rate of PCL-laden hydrogel was increased by 26 %. All bioinks exhibited a significant fiber, when being microextruded. Interestingly, collagen fibers supported guided growth of HUVECs in the aligned direction. All applied fiber types did not show cytotoxic side-effects.
Conclusion: The presented study reveals that the addition of microfibers is an exciting platform technology for the biofabrication of tissue precursors. In combination with the 3D-bioprinting process, the orientation of the fibers also enables the tuning of anisotropic material behavior.