Toward a Bioartificial Pancreas: Diffusion of Insulin and IgG Across Immunoprotective Membranes with Controlled Hydrophilic Channel Diameters

• Published in: Macromolecular bioscience Vol. 10; no. 4; pp. 369 - 377
• Main Authors: Kang, Jungmee, Erdodi, Gabor, Kennedy, Joseph P., Chou, Hongshiue, Lu, Lina, Grundfest-Broniatowski, Sharon
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 08.04.2010; WILEY‐VCH Verlag; Wiley-VCH
• Subjects: Acrylamides - chemistry; Animals; Application fields; Applied sciences; Bioartificial Organs; Biological and medical sciences; biomaterials; Blood Glucose - metabolism; Cell Survival; Diabetes Mellitus, Experimental - therapy; Diffusion; Dimethylpolysiloxanes - chemical synthesis; Dimethylpolysiloxanes - chemistry; Exact sciences and technology; Glucose - pharmacology; Hydrophobic and Hydrophilic Interactions; Immunoglobulin G - metabolism; immunoprotection; Insulin - metabolism; Islets of Langerhans - cytology; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Kinetics; macroencapsulation; Medical sciences; Membranes, Artificial; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Oxygen - metabolism; Pancreas; Permeability; Polymer industry, paints, wood; Polyurethanes - chemistry; Serum Albumin, Bovine - metabolism; Siloxanes - chemistry; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Technology of polymers; Technology. Biomaterials. Equipments; Transport properties; Graft copolymer; IgG; Nanofiber; Acrylamide derivative copolymer; Hydrosilylation; Crosslinked copolymer; Biomaterial; Pancreas; Nitinol; Framework; Release; Amphiphilic polymer; Immunoprotection; Semipermeable membrane; Artificial organ; Diabetes mellitus; Rodentia; Langerhans islet; Experimental study; Insulin; In vivo; Gas permeability; Vertebrata; Mammalia; Mouse; Animal; Preparation; Polyurethane; Methacrylate copolymer; Radical copolymerization; Dimethylsiloxane copolymer; Glycemia
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.200900386

Research continued toward a bioartificial pancreas (BAP). Our BAPs consist of a perforated nitinol scaffold coated with reinforced amphiphilic conetwork membranes and contain live pancreatic islets. The membranes are assemblages of cocontinuous hydrophobic domains and hydrophilic channels whose diameters were varied by the MW of hydrophilic segments between crosslinks (Mc,HI = 32, 44, and 74 kg · mol−1). We studied the diffusion rate of insulin, BSA, and IgG across the membrane of the BAP in the absence of islets. Membranes of Mc,HI = 74 kg · mol−1 showed rapid insulin and BSA transport and negligible IgG diffusion. BAPs containing ≈300 mouse islets showed appropriate response upon glucose challenge in vitro. The BAP implanted into diabetic mice reduced hyperglycemia and maintained islet viability for at least 4 d. A bioartificial pancreas (BAP) was assembled by depositing nanomat‐reinforced immunoprotective amphiphilic conetwork (APCN) membranes onto a laser‐perforated nitinol scaffold and filling it with mouse islets. The figure shows mouse islets recovered from our BAP after four days of implantation into a diabetic mouse. The islets are stained and most of them are viable (viable cells are bright fluorescent green, dead cells are bright fluorescent red).