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

Sharon F. Grundfest-Broniatowski, Gurkan Tellioglu, Kenneth S. Rosenthal, Jungmee Kang, Gabor Erdodi, Baris Yalcin, Miko Cakmak, Judith Drazba, Ana Bennett, Lina Lu, Joseph P. Kennedy

Research output: Contribution to journalArticle

29 Scopus citations

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 /mm thick semipermeable amphiphilic conetwork membrane reinforced with an electro- spun nanomat of polydimethylsiloxane-containing polyure- thane, 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 pan- createctomized 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.

Original languageEnglish (US)
Pages (from-to)400-405
Number of pages6
JournalASAIO Journal
Volume55
Issue number4
DOIs
StatePublished - Jul 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Biomedical Engineering

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    Grundfest-Broniatowski, S. F., Tellioglu, G., Rosenthal, K. S., Kang, J., Erdodi, G., Yalcin, B., Cakmak, M., Drazba, J., Bennett, A., Lu, L., & Kennedy, J. P. (2009). A new bioartificial pancreas utilizing amphiphilic membranes for the immunoisolation of porcine islets a pilot study in the canine. ASAIO Journal, 55(4), 400-405. https://doi.org/10.1097/MAT.0b013e3181a8deba