Tissue engineering strategies for type 1 diabetes treatment

A.A. van Apeldoorn¹, M. Buitinga¹, J. Hilderink¹, G. Marchioli¹, R. Truckenmuller¹, M.A. Engelse², C.A. van Blitterswijk¹, E.J.P. de Koning², M. Karperien^1
1 MIRA institute of biomedical technology and technical medicine, Tissue Regeneration, Enschede, The Netherlands; ² Clinical Islet Transplantation /Nephrology, Leiden University Medical Centre, Leiden, The Netherlands

Objective: Type I Diabetes is an autoimmune disease, patients suffer from destruction of beta cells residing in the islets of Langerhans. As a result these patient suffer poor glycemic control, which ultimately leads to symptoms such as retinopathy, heart and kidney failure or atherosclerosis. Infusion of Islets of Langerhans from donor pancreata (the so-called Edmonton protocol) into the portal vein is a suitable treatment. However, 60-80% of the transplanted islets die within a few days after transplantation. We are exploring the use of micro-thermo-formed scaffolds as an alternative for islet transplantation extra-hepatically.

Methods: We use embossing techniques to create porous and non-porous microwell patterned films based on 4000PEOT30PBT70 block-copolymers to create a proper microenvironment for islets to protect and preserve their function. The micro-well scaffolds with diameters of ~130 μ m and ~330 μ m were seeded with human, rat and mouse islets to study morphology and insulin secretion after culture.

Results: All islets kept their rounded morphology after several days of culture. Three human donors responded equally to a raise in glucose levels, by insulin secretion (ELISA), when seeded into these scaffolds compared to free islets in culture. In addition, we tested properties of the microwell scaffolds in relation to contact angle (±40 ⁰ ), water uptake (60%) and used AFM to visualize the phase separated domains of the soft and hard blocks within the polymer before and after heat treatment, in order to relate material properties to cell behavior. We used confocal Raman and immune fluorescent microscopy to study the quality of the cultured islets. Comparison of free-floating and scaffold seeded islets showed no difference regarding beta and Alfa cell content and showed that both cell types were not affected in function and morphology by the microwell scaffolds.