One of the key challenges in the field of blood vessel engineering is the in vitro production of small and large diameter vessels. Considering that a combination of alginate di-aldehyde and gelatin (ADA-GEL) has been successfully applied for different biofabrication approaches, the aim of this study was to exploit ADA-GEL for the fabrication of vessel structures with diameters up to 4 mm. To explore plotting possibilities and to study the swelling behaviour, a library of vessel-like constructs with different diameters made from 2, 3 and 4% (w/v) alginate was created by using various hand-crafted double-needle extrusion systems. Vessel diameters were varied through changes of the double-needle core and outer diameters. A straightforward model for the production of vessel of different diameters from a variety of double-needle systems was established and vessel-constructs with diameters of up to 3.7 mm could be created. It was successfully demonstrated that an artificial vessel, consisting of an outer layer of 7.5% ADA50-GEL50 and an inner core of 3% gelatin, can support the proliferation and migration of an immobilized co-culture containing fibroblast (NHDF) and endothelial (HUVEC) cells. The openness and tightness of the hollow ADA-GEL structures were further confirmed by a dye injection test. Nanoindentation was performed to determine the Young’s modulus of the used materials. Cell vitality was proved after 1, 2 and 3 weeks of incubation. The results showed a nearly twofold increase of viable cells per week. Fluorescent images confirmed cell migration during the whole incubation time.
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This work was supported by the German Research Foundation (DFG) within the collaborative research center TRR225 (project Nr. 326998133) (subprojects A01 and B06). Furthermore, this work was technically supported by Dr. Raminder Singh and PD Dr. Iwona Cicha from the Translational Research Center (TRC) of the University Medical Centre Erlangen. The authors would also like to thank Dr. T. Zehnder for his help with the used hydrogels and Ms. A. Grünewald for cell culturing.
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Ruther, F., Distler, T., Boccaccini, A.R. et al. Biofabrication of vessel-like structures with alginate di-aldehyde—gelatin (ADA-GEL) bioink. J Mater Sci: Mater Med 30, 8 (2019). https://doi.org/10.1007/s10856-018-6205-7