Jungmee Kang

A new bioartificial pancreas utilizing amphiphilic membranes for the immunoisolation of porcine islets: a pilot study in the canine.

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 μm 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.

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

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 (M(c,HI) = 32, 44, and 74 kg x 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 M(c,HI) = 74 kg x mol(-1) showed rapid insulin and BSA transport and negligible IgG diffusion. BAPs containing approximately 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.