Briefing - The Kidney Project

Transcription

1 Briefing - Goal 1 - Implantable Artificial Kidney Shuvo Roy, PhD Professor Department of Bioengineering and Therapeutic Sciences Department of Surgery Schools of Pharmacy and Medicine UC San Francisco September 20, 2018 Silicon Organs Update on the Artificial Kidney and Pancreas UCSF Transplant 2018 Disclosure: Silicon Kidney Hemofilter Bioreactor Data 2 Build & Grow Strategy The Renal Filter Unit: the Nephron FILTER BUILD what we cannot GROW Glomerulus Proximal Distal TUBULE GROW what we do not know how to BUILD Loop of Henle Collecting Duct

2 Briefing - Natural Hemofilter Silicon Membrane Characteristics High hydraulic permeability up to 600 ml/hr/mmhg/m 2 High permselectivity over 80% middle-molecule clearance less than 0.1% albumin passage SEM Silicon Membranes No Pumps Improved Clearance Glomerulus: Uniform Slit Pores 5 6 Hemocompatibility Considerations Non-Coated Silicon Coated Silicon The Renal Filter Unit: the Nephron Cell Adhesion (1000X) Platelet 10 μm 10 μm Glomerulus Proximal Distal Platelet activation (CD62) 10 μm 10 μm Minimal cell adhesion and platelet activation with polysbma coatings. Loop of Henle Collecting Duct

3 Briefing - Renal Cell Growth on Silicon Membranes Membrane Immunoisolation Polymer Membrane Ideal Membrane (small pore size dimension & tight pore size distribution) Glucose cytokine Antibody Insulin Bacterium RBC nm DNA Cell nucleus Small enough to pass through membrane Too large to pass through membrane Blue Nucleus Green Boundary Red Cilia 9 10 Membrane Performance Perfusion Flow Bioreactor 80% reduction in cytokine passage 100% passage of glucose and insulin No passage of BSA and antibodies Bioreactor features microchannels for controlled shear stress on cells membrane for cell support and transport pathway basolateral chamber for membrane support and fluid collection

4 Briefing - Shear Effects Current Status Preclincial Testing Water Transport (LL-PCK1) 140 Transport in ul/cm2/day Shear Flow in Dyne/cm2 14 Silicon Nanopore Membranes (SNM) Goal 2 Bioartificial Pancreas Nanopores Precise pore size control Well-defined isolation barrier to host immune system High permeability Implantable form factor & pump-less operation under perfusion pressure Inert material Mechanical and chemically stable Modifiable surface Improved biocompatibility 15 Venous connection Arterial connection Convective flow replenishes nutrients

5 Briefing - Capsule for Ultrafiltration First Study Goals Patency of the capsule/snm Viability of the SNM-encapsulated islets Functionality of the encapsulated islets First Device Experimental Plan 3 days Implantation In vitro: noncirculating (positive control) In vitro: circulating (stayed) In vitro: circulating (travelled) In vivo 500 IEQ mouse islets per each side; total 1000 IEQ Daily glucose challenge: In vitro 300 mg/dl In vivo 40% glucose sol, 0.5 g/kg administered -> 37.5 mg glucose in total Sample point (min): 0, 5, 10, 15, 30, 60, 90 Travelled at the animal facility then brought back Stayed always in lab

6 Briefing - Angiogram Explanted Capsule Post-Explant SNM Islet Viability in vitro non-connecting device in vitro device (stayed) in vitro device (traveled) in vivo device FDA/PI: green live; red dead

7 Briefing - Acknowledgements Ms. Patsy Guglielmo The Wildwood Foundation Patterson-Barclay Memorial Foundation Harry W. and Diana V. Hinds Distinguished Professorship Team