Viability and Functionality of Neonatal Porcine Islet-like Cell Clusters Bioprinted in Alginate-Based Bioinks

Abstract

The transplantation of pancreatic islets can prevent severe long-term complications in diabetes mellitus type 1 patients. With respect to a shortage of donor organs, the transplantation of xenogeneic islets is highly attractive. To avoid rejection, islets can be encapsulated in immuno-protective hydrogel-macrocapsules, whereby 3D bioprinted structures with macropores allow for a high surface-to-volume ratio and reduced diffusion distances. In the present study, we applied 3D bioprinting to encapsulate the potentially clinically applicable neonatal porcine islet-like cell clusters (NICC) in alginate-methylcellulose. The material was additionally supplemented with bovine serum albumin or the human blood plasma derivatives platelet lysate and fresh frozen plasma. NICC were analysed for viability, proliferation, the presence of hormones, and the release of insulin in reaction to glucose stimulation. Bioprinted NICC are homogeneously distributed, remain morphologically intact, and show a comparable viability and proliferation to control NICC. The number of insulin-positive cells is comparable between the groups and over time. The amount of insulin release increases over time and is released in response to glucose stimulation over 4 weeks. In summary, we show the successful bioprinting of NICC and could demonstrate functionality over the long-term in vitro. Supplementation resulted in a trend for higher viability, but no additional benefit on functionality was observed.

Recent Advances in Alginate-Based Hydrogels for Cell Transplantation Applications

“…It is crucial to consider these parameters to optimize cell viability in the printing process [ 129 ]. Alginate alone and in combination with various polymers has been extensively utilized as a bioink for cell transplantation [ 125 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 ]. For example, while gelatin methacryloyl (GelMA) upon light exposure forms chemically stable hydrogels for cell encapsulation, it was observed that creating uniform and stacked cell-laden fibers using low-concentration GelMA hydrogels can pose challenges for regular printing processes in certain cases [ 141 ].…”

Smart alginate inks for tissue engineering applications

“…2 ) [ 18 , 71 , 72 ]. Most importantly, it can provide a proper niche for cells as it resembles another polysaccharide in the native ECM – hyaluronic acid – moreover it can simultaneously act as a suitable immuno-protective barrier for their delivery into the body [ [73] , [74] , [75] ]. It can simulate a niche that offers specific external conditions for cell attachment, proliferation, differentiation, as well as migration, thereby promoting tissue regeneration.…”

Bioinks for Space Missions: The Influence of Long‐Term Storage of Alginate‐Methylcellulose‐Based Bioinks on Printability as well as Cell Viability and Function

“…[11] During alginate crosslinking and the subsequent cultivation, the methylcellulose is partially released, forming a crosslinked construct of mainly alginate.. [11,12] This versatile ink has been successfully applied for bioprinting of various mammalian cell types such as pancreatic islets of Langerhans and chondrocytes, but also for bioprinting of microalgae. [13][14][15][16][17][18][19] Based on the promising results in these ground-based studies, Alg-MC was the first bioink to be selected by the company OHB for use in space. As part of the ISS mission Cosmic Kiss of the German ESA astronaut Matthias Maurer, it was used as one of two for the mission selected bioinks to generate constructs with the aid of a hand-held printer, which in combination with dermal fibroblasts should later provide rapid assistance in the wound closure of large-area skin injuries.…”

“…[ 11 ] During alginate crosslinking and the subsequent cultivation, the methylcellulose is partially released, forming a crosslinked construct of mainly alginate.. [ 11,12 ] This versatile ink has been successfully applied for bioprinting of various mammalian cell types such as pancreatic islets of Langerhans and chondrocytes, but also for bioprinting of microalgae. [ 13–19 ]…”