Type one diabetes affects 542’000 children per year worldwide and heavily worsens the quality of life of these young patients and their families. In addition to this, diabetes also accounts for substantial costs on national healthcare systems. An emerging treatment for managing unbalanced glucose metabolism in type one diabetes patients is clinical islet transplantation. This procedure has been developed as a less invasive alternative to total pancreas transplantation with the aim of reaching independence from insulin injections in patients. Islet transplantation into the portal vein however has heavy limitations and research has focused on the creation of alternative transplantation site that can overcome these limitations and provide a more favorable environment for islets to reside in. In most cases, devices are used to provide a vehicle for islet transplantation and to contain them in situ. These devices also offer the possibility of providing proteins and growth factors for increasing islet viability and functionality after implantation, to ameliorate revascularization and oxygen supply and in general to recreate the most optimal condition for islet metabolism. In this thesis, several strategies and scaffold design have been investigated for islet transplantation. The performance of the embedded islets has been evaluated in vitro and some critical parameters of the scaffold design have been identified as potential predictors of islet functionality in vitro. The general introduction provides background information about this disease, its complications and the currently available methods for managing hyperglycemia. Chapter 1 develops a model system resembling human islet functionality that will be used as a pseudo-islet substitute in some experimental procedures requiring large amount of islets. In the “hydrogel section”, two strategies involving the use of an hydrogel matrix for islet embedding are investigated. Chapter 2 is focused on the fabrication of a two-layer hydrogel construct with specific functionalization of the two layers to achieve islet embedding and induction of blood vessels ingrowth. Chapter 3 describes the use of a 3D printing device for creating porous hydrogel scaffolds for islet transplantation. In the “polymer section” the approaches described are focused on the use of thermoplastic polymers as main constituents of the scaffold for islet transplantation. In Chapter 4 a porous structure for islet embedding is obtained by salt leaching processing. Chapter 5 describes a scaffold design for the creation of an extra-hepatic islet transplantation site based on the combination of hydrogel core and polymeric outer structure in an hybrid configuration. In Chapter 6 a proof of concept is given for the functionalization of the polymeric surface with a layer-by-layer strategy to induce cell transfection on the scaffold surface. Finally, in the General Discussion overall conclusions about the main findings of this thesis are drawn and future recommendations are given about important parameters to consider in scaffold design.
|Award date||3 Feb 2017|
|Place of Publication||Enschede|
|Publication status||Published - 3 Feb 2017|