Additive manufactured macroencapsulation devices for islet cell replacement therapy
Ruth E. Levey1, Fergal B. Coulter2, Scott T. Robinson1, Giulio Ghersi3, Peter Dockery1, Eoin D. O'Cearbhaill2, Garry P. Duffy1.
1Anatomy and Regenerative Medicine Institute (REMEDI), College of Medicine, National University of Ireland Galway, Galway, Ireland; 2UCD Centre for Biomedical Engineering, School of Mechanical and Materials Engineering, University College Dublin, Dublin, Ireland; 3Abiel, Università degli Studi di Palermo, Palermo, Italy
Introduction: Islet macroencapsulation devices can induce a Foreign Body Response (FBR) and the formation of a dense avascular fibrotic capsule. This FBR can instigate a substantial immunological reaction, islet death and ultimately implant failure. Previously we developed additive manufactured multiscale porous devices which demonstrated a 2.5-fold increase in tissue vascularity and integration when compared to a non-textured device. In the present study we describe the next step towards clinical implementation of this islet macroencapsulation device by encapsulating syngeneic islets and implanting intra-peritoneally in a diabetic rodent model for up to 8 weeks.
Methods: To achieve these aims, additive manufactured multiscale porous devices containing a hydrogel suspension of VEGF microspheres and 2000 IEQ of syngeneic islets were implanted intra-peritoneally in 8 STZ-induced diabetic rats. Fasting blood glucose levels were monitored every 3/4 days. Following explantation, devices and the associated surrounding tissue were removed and processed for micro-CT, histological, immunohistochemical, and SEM analysis to assess fibrous capsule composition and vascularization.
Summary of Results: Six out of n=8 rats demonstrated an average fasting blood glucose concentration of 100 mg/dL for up to 8 weeks, indicative of successful reversion of diabetes. Post explantation experimentation findings demonstrated successful integration of the device, the development of a highly vascularized network with an abundance of mature permanent vessels in the surrounding tissue.
Conclusion: In conclusion, syngeneic islet encapsulation within additive manufactured multiscale porous devices can facilitate efficacious islets and the maintenance of normoglycemia in diabetic rodents for up to 8 weeks. The device can enable the development of a highly interconnected vascularized network that largely mirrors the natural physiological vascularisation of the native pancreas, providing adequate oxygenation and nutrient supply for active and sustained engraftment.
The DRIVE project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement number 645991.