Polymeric microspheres with enhanced stability and biocompatibility for encapsulation of pancreatic islets in diabetes treatment
Name of the supervisor
Ing. Igor Lacík, DrSc.
Faculty of Chemical and Food Technology STU
Insulin therapies in diabetes treatment aim to achieve blood glucose levels that mirror the function of the native pancreas. This is manifested by progress in glucose sensing and insulin delivery, however, the expected glycemic goals are achieved only in a small population of diabetic patients. Current approaches to improve the control of diabetes involve automated insulin delivery and cell therapy. The Ph.D. topic deals with the in-situ preparation of hydrogels based on polysaccharides stabilized by both transient non-covalent and covalent cross-links within its network structure for cell therapy. Resulting hydrogels as implantable polymeric devices should be suitable predominantly for the long-term immunoprotection of transplanted cells. This dual cross-linking strategy will be established to overcome the low mechanical and chemical stability of ionically cross-linked cell-laden hydrogels upon exposure to the in vivo environment. In this Ph.D. thesis, a clickable polysaccharide, having enough ionic-binding sites and biocompatible moieties, will be synthesized by introducing the ionic-binding and click-reacting functional groups on the backbone of modified polysaccharides. The obtained polymers will lead to the formation of hydrogels via combining the bioorthogonal click-non-covalent and click-covalent crosslinks. The host-guest complexation will be selected as a click-non-covalent bond. The click-covalent bond will include “copper- and light free” reactions such as thiol/aza-Michael addition and Diels-Alder cycloaddition. Finally, the physicochemical properties of the achieved hydrogels and their cytocompatibility behavior will be studied by encapsulation of various cell types (e.g. insulin-producing β-cell, native islets) with the potential for the in vivo testing.