bims-orenst 2021-09-05 papers

Issue of 2021–09–05
four papers selected by
Joram Mooiweer, University of Groningen

Biofabrication. 2021 Sep 03.

High resolution stereolithography fabrication of perfusable scaffolds to enable long-term meso-scale hepatic culture for disease modeling.

Pierre Sphabmixay, Micha Sam Brickman Raredon, Alex J-S Wang, Howon Lee, Paula T Hammond, Nicholas Xuanlai Fang, Linda G Griffith.

Microphysiological systems (MPS), comprising human cell cultured in formats that capture features of the 3D microenvironments of native human organs under microperfusion, are promising tools for biomedical research. Here we report the development of a mesoscale physiological system (MePS) enabling the long-term 3D perfused culture of primary human hepatocytes at scales of over 106 cells per MPS. A central feature of the MePS, which employs a commercially-available multiwell bioreactor for perfusion, is a novel scaffold comprising a dense network of nano- and micro-porous polymer channels, designed to provide appropriate convective and diffusive mass transfer of oxygen and other nutrients while maintaining physiological values of shear stress. The scaffold design is realized by a high resolution stereolithography fabrication process employing a novel resin. This new culture system sustains mesoscopic hepatic tissue-like cultures with greater hepatic functionality (assessed by albumin and urea synthesis, and CYP3A4 activity) and lower inflammation markers compared to comparable cultures on the commercial polystyrene scaffold. To illustrate applications to disease modeling, wemodeling, we established a chronicn insulin-resistant phenotype by exposing liver cells to hyperglycemic and hyperinsulinemic media. Future applications of the MePS include the co-culture of hepatocytes with resident immune cells and the integration with multiple organs to model complex liver-associated diseases.

Keywords: Mesoscale; insulin resistance; liver; oxygen; perfusion; projection micro-stereolithography; shear stress

DOI: https://doi.org/10.1088/1758-5090/ac23aa

Stem Cell Reports. 2021 Aug 30. pii: S2213-6711(21)00421-5. [Epub ahead of print]

Engineered 3D vessel-on-chip using hiPSC-derived endothelial- and vascular smooth muscle cells.

Marc Vila Cuenca, Amy Cochrane, Francijna E van den Hil, Antoine A F de Vries, Saskia A J Lesnik Oberstein, Christine L Mummery, Valeria V Orlova.

Crosstalk between endothelial cells (ECs) and pericytes or vascular smooth muscle cells (VSMCs) is essential for the proper functioning of blood vessels. This balance is disrupted in several vascular diseases but there are few experimental models which recapitulate this vascular cell dialogue in humans. Here, we developed a robust multi-cell type 3D vessel-on-chip (VoC) model based entirely on human induced pluripotent stem cells (hiPSCs). Within a fibrin hydrogel microenvironment, the hiPSC-derived vascular cells self-organized to form stable microvascular networks reproducibly, in which the vessels were lumenized and functional, responding as expected to vasoactive stimulation. Vascular organization and intracellular Ca2+ release kinetics in VSMCs could be quantified using automated image analysis based on open-source software CellProfiler and ImageJ on widefield or confocal images, setting the stage for use of the platform to study vascular (patho)physiology and therapy.

Keywords: 3D vessel-on-chip; VoC; functional readouts; hiPSC-ECs; hiPSC-VSMCs; hiPSC-derived endothelial cells; hiPSC-derived vascular smooth muscle cells; microfluidics; organ-on-chip; vessels-on-chip

DOI: https://doi.org/10.1016/j.stemcr.2021.08.003

Adv Mater Technol. 2021 Aug;pii: 2000683. [Epub ahead of print]6(8):

Microfluidic Printing of Tunable Hollow Microfibers for Vascular Tissue Engineering.

Zhuhao Wu, Hongwei Cai, Zheng Ao, Junhua Xu, Samuel Heaps, Feng Guo.

Bioprinting of vascular tissues holds great potential in tissue engineering and regenerative medicine. However, challenges remain in fabricating biocompatible and versatile scaffolds for the rapid engineering of vascular tissues and vascularized organs. Here, we report novel bioink-enabled microfluidic printing of tunable hollow microfibers for the rapid formation of blood vessels. By compositing biomaterials including sodium alginate, gelatin methacrylate (GelMA), and glycidyl-methacrylate silk fibroin (SilkMA), we prepared a novel composite bioink with excellent printability and biocompatibility. This composite bioink can be printed into hollow microfibers with tunable dimensions using a microfluidic co-axial printing. After seeding human umbilical vein endothelial cells (HUVEC) into the hollow chambers via a microfluidic prefusion device, these cells can adhere to, grow, proliferate, and then cover the internal surface of the printed hollow scaffolds to form vessel-like tissue structures within three days. By combining the unique composite bioink, microfluidic printing of vascular scaffolds, and microfluidic cell seeding and culturing, our strategy can fabricate vascular-like tissue structures with high viability and tunable dimension within three days. The presented method may engineer in vitro vasculatures for the broad applications in basic research and translational medicine including in vitro disease models, tissue microcirculation, and tissue transplantation.

Keywords: Bioprinting; Hollow Microfiber; Microfluidics; Tubular tissues; Vascular Tissue Engineering

DOI: https://doi.org/10.1002/admt.202000683

Biofabrication. 2021 Sep 03.

A 3D bioprinted hybrid encapsulation system for delivery of human pluripotent stem cell-derived pancreatic islet-like aggregates.

Dong Gyu Hwang, Yeonggwon Jo, Myungji Kim, Uijung Yong, Seungyeon Cho, Yoo-Mi Choi, Jaewook Kim, Jinah Jang.

Islet transplantation is a promising treatment for Type 1 diabetes. However, treatment failure can result from loss of functional cells associated with cell dispersion, low viability, and severe immune response. To overcome these limitations, various islet encapsulation approaches have been introduced. Among them, macroencapsulation offers the advantages of delivering and retrieving a large volume of islets in one system. In this study, we developed a hybrid encapsulation system composed of a macroporous polymer capsule with stagger-type membrane and assemblable structure, and a nanoporous dECM hydrogel containing pancreatic islet-like aggregates using 3D bioprinting technique. The outer part (macroporous polymer capsule) was designed to have an interconnected porous architecture, which allows insulin-producing β cells encapsulated in the hybrid encapsulation system to maintain their cellular behaviors, including viability, cell proliferation, and insulin-producing function. The inner part (nanoporous dECM hydrogel), composed of the 3D biofabricated pancreatic islet-like aggregates, was simultaneously placed into the macroporous polymer capsule in one step. The developed hybrid encapsulation system exhibited biocompatibility in vitro and in vivo in terms of M1 macrophage polarization. Furthermore, by controlling the printing parameters, we generated islet-like aggregates, improving cell viability and functionality. Moreover, the 3D bioprinted pancreatic islet-like aggregates exhibited structural maturation and functional enhancement associated with intercellular interaction occurring at the β cell edges. In addition, we also investigated the therapeutic potential of a hybrid encapsulation system by integrating human pluripotent stem cell-derived insulin-producing cells, which are promising to overcome the donor shortage problem. In summary, these results demonstrated that the 3D bioprinting approach facilitates the fabrication of a hybrid islet encapsulation system with multiple materials and potentially improves the clinical outcomes by driving structural maturation and functional improvement of cells.

Keywords: 3D bioprinting; cell aggregate; islet encapsulation; tissue-specific bioink; type 1 diabetes

DOI: https://doi.org/10.1088/1758-5090/ac23ac