A New Printable Alginate/Hyaluronic Acid/Gelatin Hydrogel Suitable for Biofabrication of In Vitro and In Vivo Metastatic Melanoma Models

Abstract

Two-dimensional (2D) cancer models have been the standard for drug development over the past few years, but they frequently do not resemble in vivo properties adequately. 3D models are superior in many aspects and are, therefore, more similar to human pathophysiology. Over the past years, the emerging field of biofabrication has made significant advances, resulting in even more sophisticated 3D models. With this study, a hydrogel is created for biofabrication that is suitable for mimicking the tumor microenvironment in vitro and is further tested as a new vascularized melanoma model in vivo. The alginate/hyaluronic acid/gelatin bioink shows good shape-fidelity, high cell survival rates, and enables successful cultivation of melanoma cells and adipose-derived stem cells as well as cell differentiation in vitro. In vivo, in the arteriovenous loop model, it proves to be a unique method to study melanoma progression, tumor vascularization, and ultimately and reliably metastases in an isolated and controlled environment. These results show that this 3D model is very application-oriented for molecular research and therapy development.

An Innovative Arteriovenous (AV) Loop Breast Cancer Model Tailored for Cancer Research

“…This model is suited for engineering vascularized tissues in vivo in an isolated and controlled environment, and can be tailored by varying matrices, cells, and other factors [ 8 ]. Moreover, the AV loop model is confirmed to mimic the desired microenvironment more specifically in the chamber than the typical subcutaneous model [ 9 ]. In accordance, recently a new vascularized melanoma model was developed using the AV loop by our group with the aid of a novel printable hydrogel consisting of alginate, hyaluronic acid, and gelatin for mimicking the tumor microenvironment [ 9 ].…”

“…By varying the matrices and cells in the implantation chamber, a spectrum of different tailored tissues to a particular research area can be generated [ 8 ]. In our previous study, we successfully established a melanoma model in alginate/hyaluronic acid/gelatin hydrogel in the AV loop [ 9 ]. However, to the best of our knowledge, the AV loop model has never been employed to generate breast tumors within the isolated chamber.…”

A Guide to Polysaccharide-Based Hydrogel Bioinks for 3D Bioprinting Applications

“…Among the various seaweed-derived polysaccharides, alginic acid (and particularly its salt form, sodium alginate) [ 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ], carrageenan [ 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ], and agarose [ 75 , 76 , 77 , 78 , 79 ] have been widely used as polymeric matrices (either solely or in combination with other polysaccharides or proteins) for the development of hydrogel-based bioinks for 3D bioprinting, as outlined in Table 1 .…”

“…Due to the proven and cumulated knowledge regarding alginate hydrogels bioinks in the latter years, the most important efforts on the development of novel alginate-based bioinks have been essentially centered on creating more sophisticated 3D living scaffolds from alginate that allow the fabrication of both “soft” (skin) [ 57 ] and “hard” (bone and cartilage) [ 55 , 56 ] biomimetic tissue constructs, on engineering vascular structures [ 62 , 65 ] and on the design of disease models [ 58 , 59 ]. On this matter, for instance, Somasekharan et al [ 57 ] reported a bioink based on alginate blended with gelatin and diethylaminoethyl cellulose (DCEL) to produce skin tissue analogues by extrusion bioprinting.…”

“…Specifically, this study aimed at the optimization of the precise printing parameters to maximize cell viability in alginate hydrogels at 2% ( w / v ) for 7 days, creating a tumor model for the testing of novel anti-tumoral drugs [ 59 ]. Following the same premise, Schmid et al developed an alginate bioink with hyaluronic acid and gelatin (0.5% alginate, 0.1% hyaluronic acid, 3% gelatin ( w / v )) loaded with malignant melanoma cells (Mel Im) to produce a melanoma 3D disease model [ 58 ].…”