Development of biomimetic tissue engineering scaffolds for cell transplantation

Type 1 diabetes is a chronic disease characterized by lack of insulin due to autoimmune destruction of pancreatic beta cells. Insulin replacement therapy, although suboptimal, is the standard treatment for type 1 diabetes. Cell encapsulation has the potential to provide a more ideal solution for treatment of endocrine disorders, including type 1 diabetes. To pursue this goal, a subcutaneously implantable dual-reservoir encapsulation system called NICHE has recently been developed. This platform integrates in situ prevascularization and the local administration of immunosuppressants, providing a conducive environment for long term endocrine cell transplantation and engraftment. The procedure used to load the pancreatic islets in the vascularized cell reservoir of NICHE consists in a transcutaneous injection through the silicone port of the device. This results in the confinement of the pancreatic islets in the space created by the needle and at the same time causes the destruction of the previously formed blood vessels, leading to cell death and lack of engraftment. For these reasons it was hypothesized that by inducing a more rapid revascularization it would be possible to implant the device loaded with pancreatic islets, allowing for their uniform distribution. Therefore, the aim of this study is to develop a 3D-printable scaffold integrated into the NICHE to promote rapid vascularization within the device. The scaffold structure is made of an alginate/gelatin hydrogel that incorporates mesenchymal stem cells (MSCs), which are well known for their ability to enhance vascularization through endocrine and paracrine activity. The degradation test of the 3D-printed hydrogel showed that, after 6 weeks, the samples retained 60% of their initial weight. In vitro MSCs viability tests were performed to evaluate the feasibility of the printing process and the integrity of the cellular structures within the scaffold. The cells showed good survival within the 3D-printed hydrogel after 48 hours of incubation. Furthermore, there were no significant differences in terms of viability between MSCs incapsulated in the scaffold and the ones simply resuspended in the hydrogel. In conclusion, we can state that the developed printing technique allows to obtain stable constructs with a good cell viability. The next steps of the project involve conducting in vivo experiments to evaluate the vascularization time, islets engraftment and distribution.