title: A new bioartificial pancreas utilizing amphiphilic membranes for the immunoisolation of porcine islets: a pilot study in the canine.
abstract: We have developed a replaceable bioartificial pancreas to treat diabetes utilizing a unique cocontinous amphiphilic conetwork membrane created for macroencapsulation and immunoisolation of porcine islet cells (PICs). The membrane is assembled from hydrophilic poly(N,N-dimethyl acrylamide) and hydrophobic/oxyphilic polydimethylsiloxane chains cross-linked with hydrophobic/oxyphilic polymethylhydrosiloxane chains. Our hypothesis is that this membrane allows the survival of xenotransplanted PICs in the absence of prevascularization or immunosuppression because of its extraordinarily high-oxygen permeability and small hydrophilic channel dimensions (3-4 nm). The key components are a 5-10 microm thick semipermeable amphiphilic conetwork membrane reinforced with an electrospun nanomat of polydimethylsiloxane-containing polyurethane, and a laser-perforated nitinol scaffold to provide geometric stability. Devices were loaded with PICs and tested for their ability to maintain islet viability without prevascularization, prevent rejection, and reverse hyperglycemia in three pancreatectomized dogs without immunosuppression. Tissue tolerance was good and there was no systemic toxicity. The bioartificial pancreas protected PICs from toxic environments in vitro and in vivo. Islets remained viable for up to 3 weeks without signs of rejection. Neovascularization was observed. Hyperglycemia was not reversed, most likely because of insufficient islet mass. Further studies to determine long-term islet viability and correction of hyperglycemia are warranted.
authors.affiliation: Department of General Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. grundfs@ccf.org
authors.forename: Sharon F
authors.initials: SF
authors.lastname: Grundfest-Broniatowski
authors.forename: Gurkan
authors.initials: G
authors.lastname: Tellioglu
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Rosenthal
authors.forename: Jungmee
authors.initials: J
authors.lastname: Kang
authors.forename: Gabor
authors.initials: G
authors.lastname: Erdodi
authors.forename: Baris
authors.initials: B
authors.lastname: Yalcin
authors.forename: Miko
authors.initials: M
authors.lastname: Cakmak
authors.forename: Judith
authors.initials: J
authors.lastname: Drazba
authors.forename: Ana
authors.initials: A
authors.lastname: Bennett
authors.forename: Lina
authors.initials: L
authors.lastname: Lu
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Kennedy
mesh_terms: D000497:Alloys / Q000737:chemistry; D000818:Animals; D001187:Artificial Organs; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D004285:Dogs; D006943:Hyperglycemia / Q000628:therapy*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000379:methods; D007834:Lasers; D010179:Pancreas / Q000276:immunology / Q000601:surgery*; D010865:Pilot Projects; D011140:Polyurethanes / Q000737:chemistry; D013552:Swine; D014183:Transplantation, Heterologous
chemical_list: D000497:Alloys; D004129:Dimethylpolysiloxanes; D007166:Immunosuppressive Agents; D011140:Polyurethanes; C013616:nitinol; C013830:baysilon