Non-adhesive biopolymer capsules for pancreatic cell implant

Transplantation of encapsulated islets is a promising therapy for patients suffering from type I diabetes. However, cell overgrowth and adhesion on the microcapsules after transplantation strongly limit the lifespan of grafted islets. A new rising strategy consists in preparing capsules with an antifouling coating to prevent non-specific adsorption on its surface. In this context, our project describes the investigation of antifouling films. This project has been led as follow, first a protocol for depositing and evaluating the efficiency of antifouling coating is set up using two commercially available polymers: poly(ethylene glycol) - block - poly(L-lysine) (PEG-b-PLL) used as antifouling layer and poly(L-ornithine) (PLO) as anchoring and barrier layer. The protocol is developed using two systems allowing to broaden the range of possible characterization techniques. Second, new antifouling materials are synthesised and characterized by elemental analysis, Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The synthesised materials obtained are phosphorylcholine derivatives grafted on sodium hyaluronate and on chitosan. Third, the synthesised antifouling polymers are deposited on the surface of flat alginate films and alginate microcapsules using the protocol previously developed with commercial polymers. Fourth, the antifouling property of these new materials is assessed by adsorption tests with model fluorescent proteins on alginate microcapsules and films. The experiments performed demonstrate promising results for PEG-b-PLL as an antifouling layer. On the other hand and despite its stabilizing effect on the microcapsules, it has been learned that PLO promotes strongly protein adsorption even when multiple layers of hyaluronic acid or alginate are coated on the surface of alginate/PLO. Consequently, it has been concluded that more research needs to be carried out to understand the interaction between alginate and PLO in order to find the optimal composition/concentration leading to an optimal PLO barrier. During the synthesis of antifouling materials based on zwitterion molecules, cross-linking problems have occurred leading most of the time to non-soluble products which therefore cannot be further used. Only one product shows enough solubility to be tested on the capsules; the phosphorylcholine derivative grafted onto sodium hyaluronate at 8% grafting degree. After tests on alginate microcapsules and alginate films, it seems that the grafting degree is too low to provide antifouling properties. Finally, the results suggest that finding a new path is requiring to synthesise antifouling materials with zwitterionic moieties, in order to achieve a higher grafting degree while avoiding undesired secondary reactions.