title: Selection of polymers for application in scaffolds applicable for human pancreatic islet transplantation.
abstract: The liver is currently the site for transplantation of islets in humans. This is not optimal for islets, but alternative sites in humans are not available. Polymeric scaffolds in surgically accessible areas are a solution. As human donors are rare, the polymers should not interfere with functional survival of human-islets. We applied a novel platform to test the adequacy of polymers for application in scaffolds for human-islet transplantation. Viability, functionality, and immune parameters were included to test poly(D,L-lactide-co-ε-caprolactone) (PDLLCL), poly(ethylene oxide terephthalate)/polybutylene terephthalate (PEOT/PBT) block copolymer, and polysulfone. The type of polymer influenced the functional survival of human islets. In islets cultured on PDLLCL the glucagon-producing α-cells and insulin-producing β-cells contained more hormone granules than in islets in contact with PEOT/PBT or polysulfone. This was studied with ultrastructural analysis by electron microscopy (nanotomy) during 7 d of culture. PDLLCL was also associated with statistically significant lower release of double-stranded DNA (dsDNA, a so called danger-associate molecular pattern (DAMP)) from islets on PDLLCL when compared to the other polymers. DAMPs support undesired immune responses. Hydrophilicity of the polymers did not influence dsDNA release. Islets on PDLLCL also showed less cellular outgrowth. These outgrowing cells were mainly fibroblast and some β-cells undergoing epithelial to mesenchymal cell transition. None of the polymers influenced the glucose-stimulated insulin secretion. As PDLLCL was associated with less release of DAMPs, it is a promising candidate for creating a scaffold for human islets. Our study demonstrates that for sensitive, rare cadaveric donor tissue such as pancreatic islets it might be necessary to first select materials that do not influence functionality before proposing the biomaterial for in vivo application. Our presented platform may facilitate this selection of biomaterials.
authors.affiliation: Department of Pathology and Medical Biology, Section of Immunoendocrinology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, EA11, 9700 GZ, Groningen, The Netherlands.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Smink
authors.forename: Bart J
authors.initials: BJ
authors.lastname: de Haan
authors.forename: Genaro A
authors.initials: GA
authors.lastname: Paredes-Juarez
authors.forename: Anouk H G
authors.initials: AH
authors.lastname: Wolters
authors.forename: Jeroen
authors.initials: J
authors.lastname: Kuipers
authors.forename: Ben N G
authors.initials: BN
authors.lastname: Giepmans
authors.forename: Leendert
authors.initials: L
authors.lastname: Schwab
authors.forename: Marten A
authors.initials: MA
authors.lastname: Engelse
authors.forename: Aart A
authors.initials: AA
authors.lastname: van Apeldoorn
authors.forename: Eelco
authors.initials: E
authors.lastname: de Koning
authors.forename: Marijke M
authors.initials: MM
authors.lastname: Faas
authors.forename: Paul
authors.initials: P
authors.lastname: de Vos
mesh_terms: D000328:Adult; D001672:Biocompatible Materials / Q000737:chemistry; D002470:Cell Survival; D004247:DNA / Q000737:chemistry; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005947:Glucose / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008099:Liver; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D010641:Phenotype; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D012997:Solvents; D013450:Sulfones / Q000737:chemistry; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D011108:Polymers; D012997:Solvents; D013450:Sulfones; C017662:polysulfone P 1700; D011092:Polyethylene Glycols; D004247:DNA; D005947:Glucose