Biofabrication of 3D printed, pre-cross-linked alginate dialdehyde-gelatin (ADA-GEL) scaffolds for the in vivo metastatic Arteriovenous loop tumor model

Evelin Sandor¹Tannaz Karimi¹Rafael Schmid¹Yvonne Kulicke¹Stefanie Heltmann-Meyer¹Carolin Eckert²Sonja K. Schmidt²Jonas Röder²Aldo R. Boccaccini²Raymund E. Horch¹Anja K. Boßerhoff²Annika Kengelbach-Weigand^1*Andreas Arkudas¹

• ¹University Hospital Erlangen, Erlangen, Germany
• ²Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany

Vascularized models mimicking tumor pathophysiology to investigate tumor characteristics are of high interest. The arteriovenous loop (AVL) model is an established methodAn in vivo vascularization strategy to vitalize bioengineered tissue grafts. is the arteriovenous loop (AVL) model, Iin which this model, an artificial vascular axis serves as the only connection between thea living organism and the biomaterials. The objective of this study wasThe current study aimed to establish a three-dimensional (3D) printed, functional scaffold design for the AVL rat rodent model, in which Hhuman melanoma cells, derived from lymph node metastasis, were are embedded in pre-cross-linked alginate dialdehyde-gelatin (ADA-GEL) and implanted in rats (N = 10) for 4 weeks. Bioink scaffolds were 3D printed in two different shapes (n = 5), specially designed specifically for the AVL model's isolation chamber. Before implantation, the swelling behavior of the biofabricates was evaluated analyzed in vitro. The fluid uptake ratio of the hydrogel resulted in size extension, a finding which that is highly relevant for the AVL model's closed system. The biocompatibility of the pre-cross-linked ADA-GEL and the impact of the scaffold-morphology shapes were examined through macroscopic analysis and histological stainings.analyzed macroscopically and by using histological stainings. Biofabricated scaffolds made of pPre-cross-linked ADA-GEL remained stable in vivo and allowed for de novo fibrovascular tissue formation. The hypothesized biocompatibility of the analyzedA good biocompatibility of hydrogel was shownconfirmed. The two different scaffold models shapes resulted exhibited in variations regarding tumor growth and de novo fibrovascular tissue formation capacity. In both groups, metastatic cells were found detected in the lymph nodes of rodents. The present study demonstrated With this study we could show that the AVL model is an excellent in vivo tool for melanoma research, combining biofabrication and vascularization for melanoma research with a high ability to replicate metastasis. special focus on metastasis. At the same we conclude, that adapting the design of the biofabricated implants to the AVL model precisely, depending specifically on the ink used is of major importance.it is highly relevant to precisely adapt the design of biofabricated implants to the AVL model depending on the ink used.