A Retrievable, Efficacious Polymeric Scaffold for Subcutaneous Transplantation of Rat Pancreatic Islets

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Abstract

Objective:

We aim on developing a polymeric ectopic scaffold in a readily accessible site under the skin.

Summary Background Data:

The liver as transplantation site for pancreatic islets is associated with significant loss of islets. Several extrahepatic sites were tested in experimental animals, but many have practical limitations in the clinical setting and do not have the benefit of easy accessibility.

Methods and Results:

Functional survival of rat islets was tested during 7 days of culture in the presence of poly(D,L-lactide-co-ε-caprolactone) (PDLLCL), poly(ethylene oxide terephthalate)/polybutylene terephthalate (PEOT/PBT) block copolymer, and polysulfone. Tissue responses were studied in vivo after subcutaneous implantation in rats. Culture on PEOT/PBT and polysulfone profoundly disturbed function of islets, and induced severe tissue responses in vivo. Modification of their hydrophilicity did not change the suitability of the polymers. PDLLCL was the only polymer that promoted functional survival of rat islets in vitro and was associated with minor tissue reactions after 28 days. Rat islets were transplanted in the PDLLCL scaffold in a diabetic rat model. Before islet seeding, the scaffold was allowed to engraft for 28 days to allow the tissue response to dampen and to allow blood vessel growth into the device. Islet transplantation into the scaffold resulted in normoglycemia within 3 days and for the duration of the study period of 16 weeks.

Conclusions:

In conclusion, we found that some polymers such as PEOT/PBT and polysulfone interfere with islet function. PDLLCL is a suitable polymer to create an artificial islet transplantation site under the skin and supports islet survival.

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