Vascularization of Diabetes-reversing Implants: Development of Sustained Release Formulations of Proangiogenic Growth Factors

Abstract

The work described in this thesis was part the European consortium DRIVE (Diabetes-reversing implants with enhanced viability and long-term efficacy), which was funded by European Union’s Horizon 2020 research and innovation program. The aim of the DRIVE consortium was to develop a pancreatic islet transplantation device that functions as an “artificial pancreas” for treating diabetes type 1. One of the major hurdles towards clinical success of such a pancreatic islet transplantation device is the poor islet survival due to insufficient supply of nutrients and oxygen. To tackle this, microspheres that release vascular endothelial growth factor (VEGF) in an appropriate time frame for the induction of blood vessel formation (angiogenesis) are included in the devices that are developed for the DRIVE approach for encapsulation of pancreatic islets. As a result, the device will be vascularized, thereby supplying islets with oxygen and nutrients and removing waste products via the blood circulation. The work in this thesis focused on the development of sustained release formulations of VEGF and other proangiogenic growth factors via mild, protein-friendly encapsulation methods. In this context, endothelial cell based assays were applied for evaluating the bioactivity of released growth factors. Special emphasis was laid on obtaining a target release time frame of four weeks, which has been shown as ideal for stable blood vessel formation in rodent models.