title: Silicon nanopore membrane (SNM) for islet encapsulation and immunoisolation under convective transport.
abstract: Problems associated with islet transplantation for Type 1 Diabetes (T1D) such as shortage of donor cells, use of immunosuppressive drugs remain as major challenges. Immune isolation using encapsulation may circumvent the use of immunosuppressants and prolong the longevity of transplanted islets. The encapsulating membrane must block the passage of host's immune components while providing sufficient exchange of glucose, insulin and other small molecules. We report the development and characterization of a new generation of semipermeable ultrafiltration membrane, the silicon nanopore membrane (SNM), designed with approximately 7 nm-wide slit-pores to provide middle molecule selectivity by limiting passage of pro-inflammatory cytokines. Moreover, the use of convective transport with a pressure differential across the SNM overcomes the mass transfer limitations associated with diffusion through nanometer-scale pores. The SNM exhibited a hydraulic permeability of 130 ml/hr/m(2)/mmHg, which is more than 3 fold greater than existing polymer membranes. Analysis of sieving coefficients revealed 80% reduction in cytokines passage through SNM under convective transport. SNM protected encapsulated islets from infiltrating cytokines and retained islet viability over 6 hours and remained responsive to changes in glucose levels unlike non-encapsulated controls. Together, these data demonstrate the novel membrane exhibiting unprecedented hydraulic permeability and immune-protection for islet transplantation therapy.
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California-San Francisco, San Francisco, CA, 94158, United States.
authors.forename: Shang
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Surgery, University of California-San Francisco, San Francisco, CA, 94143, United States.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Faleo
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California-San Francisco, San Francisco, CA, 94158, United States.
authors.forename: Raymond
authors.initials: R
authors.lastname: Yeung
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California-San Francisco, San Francisco, CA, 94158, United States.
authors.forename: Rishi
authors.initials: R
authors.lastname: Kant
authors.affiliation: Department of Surgery, University of California-San Francisco, San Francisco, CA, 94143, United States.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Posselt
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California-San Francisco, San Francisco, CA, 94158, United States.
authors.forename: Tejal A
authors.initials: TA
authors.lastname: Desai
authors.affiliation: Department of Surgery, University of California-San Francisco, San Francisco, CA, 94143, United States.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California-San Francisco, San Francisco, CA, 94158, United States.
authors.forename: Shuvo
authors.initials: S
authors.lastname: Roy
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation; D008567:Membranes, Artificial; D058608:Nanopores; D036103:Nanotechnology / Q000295:instrumentation*; D010316:Particle Size; D012825:Silicon / Q000737:chemistry*
chemical_list: D008567:Membranes, Artificial; D012825:Silicon