1059-P: Additive Manufactured Macroencapsulation Devices for Islet Cell Replacement Therapy

Abstract

Islet encapsulation devices can induce a Foreign Body Response (FBR) and the formation of a dense avascular fibrotic capsule. This FBR is heightened when the device has a smooth surface as fibrous tissue is unable to adhere, instigating a substantial immunological reaction, islet death and ultimately implant failure. In this study, we examine whether additive manufactured multiscale porous devices promote optimal tissue integration and vascularisation for long-term functional islet encapsulation. Furthermore, we examine the potential for this method to be scaled for functional use in a large diabetic animal model. Silicone devices exhibiting progressively more complex surface architectures (quantity of macro- and micro-pores), were implanted submuscularly in rodents. Upon explant, analysis of fibrous capsule, angiogenic and macrophage response were performed. To determine its potential as an encapsulation device, multiscale porosity devices were used for intra-peritoneal syngeneic islet transplantation in 8 diabetic rats. Circulating blood glucose levels were monitored for 8 weeks. To validate scalability and functionality, devices were implanted submuscularly in an STZ-induced diabetes pig model for 2 weeks before blood glucose levels were measured in response to the infusion of insulin through the device. Degree of tissue integration and vascularity in proximity to the implant was shown to increase 2.5 fold with precisely controlled multiscale device topography. Moreover, encapsulated islets maintain glucose responsiveness and function for 8 weeks. Bioavailability was equal when the same dose of insulin is delivered via the device vs. subcutaneously in diabetic pig model. The use of additive manufactured multiscale porous coatings on macroencapsulation devices can increase tissue integration and vascularity. These findings demonstrate functionality, scalability and could help to resolve the immunological and diffusion limitations of current encapsulation devices. Disclosure R.E. Levey: None. F.B. Coulter: None. S.T. Robinson: None. L. McDonough: None. S. Deotti: None. E.B. Dolan: None. P. Dockery: None. H. Kelly: None. E.D. OCearbhaill: None. G.P. Duffy: None. Funding European Union (645991)