With improvements in stem cell-derived islet (SC-islet) biomanufacturing protocols and ongoing clinical studies, the need to better understand the limitations and improve the design of cell delivery systems has become clear. Our teams are developing various pre-vascularized devices or engineered tissues either to study the impact of vascular networks on SC‑derived islets in vitro or to improve SC-islet survival and function in vivo (Figure 1).

In one project, we are developing a vascular lattice device that would anastomosed to existing vasculature. The current device is obtained through 3D printing of vascular lattice templates using carbohydrate glass as sacrificial material. The carbohydrate glass lattices are then coated with polyurethane via solvent casting and particulate leaching to obtain a porous membrane after dissolution of the lattice template. An external compartment is obtained in a similar manner. These devices show excellent mechanical properties for use as vascular grafts, including high suture retention strength and burst pressures. The external compartment can be filled with a mixture of SC-islets and an immunoprotective formulation of alginate to combine the advantage of vascularization and immunoprotection. MIN6 clusters immobilized in this system show glucose-responsive insulin secretion under in vitro perfusion. SC-islets can be maintained viable for a week of in vitro culture. We are investigating physiological responses of SC-islets in vitro and adapting device design for implantation into small and large animals.

Another approach is to 3D print sacrificial materials directly into a cell-laden hydrogel support matrix using embedded writing. Compared to more conventional extrusion-based techniques, this approach reduces the printing time. It also enables implementation of a broader range of materials to support 3D culture of SC-islets.

The 3D printing approach leads to versatile platforms in terms of geometry and implementation with a variety of cell types and hydrogels. We envision the application of these strategies to generate models to study the combinatorial effects of oxygenation, endothelial interactions with SC-islets and molecules that can be perfused through the tissue constructs. These vascularized bioartificial tissues can be implemented to study fundamental SC-islet but also developing or adult pancreas biology. The polyurethane devices are also particularly adapted for transplantation applications.