Many different strategies have been developed through the years to address diabetes care. Among these, the transplant of immunoisolated pancreatic islets could be an effective therapy to treat type-1 diabetes in absence of immunosuppression. Immunoisolation is achieved through the encapsulation of the islets of Langerhans in a biocompatible and permeable polymeric coating that acts as a physical barrier between the islet and the recipient's immune system, without compromising diffusion mechanisms. The Conformal Coating (CC) microencapsulation through a fluid dynamic platform is an innovative technique developed at the Diabetes Research Institute of Miami, allowing for a conformal (i.e. thin and uniform) coating around the islets, thus minimizing capsule thickness (10-30 μm), size and graft volume. The microfluidic device for CC encapsulation exploits a flow-focusing geometry where two immiscible fluids flow coaxially to coat individual islets within a continuous layer of hydrogel. The coating thickness and homogeneity, fundamental for a proper functionality of the islets, are independent of the clusters diameters but depend on the rheological properties and the flow rates of fluid phases and on the chamber geometry. The aim of the present work was to develop a triphasic model of the conformal coating microfluidic process. In particular, the interest was to i) verify the feasibility of reproducing the physical phenomenon leading to islet encapsulation, ii) test the influence of modulating different process parameters on the fluid dynamic output and coating characteristics, and iii) overcome the limits of the previous related computational works while expanding the investigation area. The computational model is based on the Smoothed Particle Hydrodynamics (SPH) method and was implemented at the Laboratory of Computational Biomechanics (LCB) of the Department of Electronics, Information and Bioengineering (DEIB) of Politecnico di Milano in collaboration with the Università degli Studi di Pavia and the Diabetes Research Institute (DRI), University of Miami, Miller School of Medicine. An experimental activity was also performed at the DRI to evaluate the influence of different process parameters on the coating thickness and to investigate the impact of the encapsulation procedure on the cellular biological response.
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Development of an SPH numerical model of a microfluidic device for conformal coating encapsulation of pancreatic islets
CAZZATO, TOMMASO;COLOMBO, FEDERICA
2015/2016
Abstract
Many different strategies have been developed through the years to address diabetes care. Among these, the transplant of immunoisolated pancreatic islets could be an effective therapy to treat type-1 diabetes in absence of immunosuppression. Immunoisolation is achieved through the encapsulation of the islets of Langerhans in a biocompatible and permeable polymeric coating that acts as a physical barrier between the islet and the recipient's immune system, without compromising diffusion mechanisms. The Conformal Coating (CC) microencapsulation through a fluid dynamic platform is an innovative technique developed at the Diabetes Research Institute of Miami, allowing for a conformal (i.e. thin and uniform) coating around the islets, thus minimizing capsule thickness (10-30 μm), size and graft volume. The microfluidic device for CC encapsulation exploits a flow-focusing geometry where two immiscible fluids flow coaxially to coat individual islets within a continuous layer of hydrogel. The coating thickness and homogeneity, fundamental for a proper functionality of the islets, are independent of the clusters diameters but depend on the rheological properties and the flow rates of fluid phases and on the chamber geometry. The aim of the present work was to develop a triphasic model of the conformal coating microfluidic process. In particular, the interest was to i) verify the feasibility of reproducing the physical phenomenon leading to islet encapsulation, ii) test the influence of modulating different process parameters on the fluid dynamic output and coating characteristics, and iii) overcome the limits of the previous related computational works while expanding the investigation area. The computational model is based on the Smoothed Particle Hydrodynamics (SPH) method and was implemented at the Laboratory of Computational Biomechanics (LCB) of the Department of Electronics, Information and Bioengineering (DEIB) of Politecnico di Milano in collaboration with the Università degli Studi di Pavia and the Diabetes Research Institute (DRI), University of Miami, Miller School of Medicine. An experimental activity was also performed at the DRI to evaluate the influence of different process parameters on the coating thickness and to investigate the impact of the encapsulation procedure on the cellular biological response.| File | Dimensione | Formato | |
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https://hdl.handle.net/10589/133408