A New Bioartificial Pancreas Utilizing Amphiphilic Membranes for the Immunoisolation of Porcine Islets

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.

Animal Models of Diabetes Mellitus for Islet Transplantation

“…Many groups examined the usefulness of immunosuppressants including cyclosporine using islet allotransplanted dog [108–110] and pig models [111]. Pancreatomized diabetic large animals were also used for studies about bioartificial pancreas (i.e., islet encapsulation technology using high molecular compound to prevent from immune attack) in allo- and xenotransplantation [112–118]. Large pancreatomized animal models for islet transplantation, including pig, dog, and monkey, are considered preclinical models and tend to be selected for evaluating some treatments in the clinical setting.…”

Vascularization and cellular isolation potential of a novel electrospun cell delivery vehicle

“…Of equal importance the viability of transplanted cells depends on a functional microcirculation to provide nutrients and to provide a route for cell specific product release into the circulation. Several strategies have emerged to address these issues including the direct encapsulation of individual cells and polymer based devices to enclose the cells …”

Polyvinylpyrrolidone–polydimethylsiloxane amphiphilic co‐networks: Synthesis, characterization, and perm‐selective behavior

“…Particularly, PDMS has attracted great attention due to its own characteristics, that is, excellent biocompatibility, high elasticity, heat resistance, low surface free energy, biological inertness as well as the highest oxygen permeability among all the polymers, which has been widely associated with other hydrophilic units into block and graft copolymer, so‐called PDMS‐based amphiphilic copolymer that can further crosslink into PDMS‐based APCN . In addition, PDMS‐based APCN exhibits channel type structure to allow rapid diffusion of both water and oxygen, which has potential application in the area of biocatalysis, ophthalmic applications, soft contact lenses, and especially coating material for islet encapsulation . Although one of the most commonly hydrophilic segments used in APCN fabrication is polyethylene glycol (PEG) due to its low biotoxicity and well biocompatibility, the PEG segment is prone to oxidative degradation as indicated from accelerated air/moisture degradation tests, which limits its further practical applications.…”