Master assignment - Development of bioactive membranes for bioartificial kidney device

Background

The number of patients with end-stage renal disease (ESRD) is progressively increasing and the need for renal replacements therapies is rising. Since transplant options are limited, approximately 70% of patients receive (hemodialysis or peritoneal) dialysis treatment. While dialysis therapy has already prolonged many ESRD patients’ lives, the treatment cannot completely replace renal function. Mortality (15-20% per year) and morbidity of these patients remain high, whereas their quality of life is generally low. Haemodialysis (HD) therapy removes mainly small, unbound substances from the circulation, while leaving large, compartmentalized and protein-bound uremic retention solutes untouched.

The need for improved renal replacement therapies is a stimulance for innovative research for the development of a cell based Bioartificial Kidney Device (BAK). A key requirement for such device is the formation of a “living membrane” consisting of a tight kidney cell monolayer with preserved functional organic ion transporters, on suitable artificial membrane surfaces (Figure 1). Several prototypes of BAKs have been developed over the last decade, but many challenges remain to be overcome before creation of clinically relevant products.

Figure 1 – Living membrane: functional renal cell monolayer on a polymeric coated membrane. Source: Schophuizen et al, Acta Biomater., 2015.

Aim

Bioactive membranes for a BAK will be developed. One side of the membrane will be in contact with blood and/or plasma and therefore should be highly haemocompatible to prevent blood coagulation, whereas the other membrane side should be cytocompatible and bioactive for adhesion of the conditionally immortalized proximal tubule cells (ciPTEC).

Approach

We will co - develop and evaluate different bioactive membranes for their ability to support ciPTEC function. In fact, various bioactive coatings will be applied on specifically selected polymeric membranes, and the transport characteristics of the developed membranes will be evaluated. CiPTEC function will be characterized via microscopy and toxin transport experiments.

Contact

Prof. Dr. Dimitrios Stamatialis, Tel:+31 53 4894675, e-mail: d.stamatialis@utwente.nl

Natalia Chevtchik, Tel: 31 53 4892862, e-mail n.v.chevtchik@utwente.nl