Selection of polymers for application in scaffolds applicable for human pancreatic islet transplantation

Alexandra M Smink; Bart J de Haan; Genaro A Paredes-Juarez; Anouk H G Wolters; Jeroen Kuipers; Ben N G Giepmans; Leendert Schwab; Marten A Engelse; Aart A van Apeldoorn; Eelco de Koning; Marijke M Faas; Paul de Vos

doi:10.1088/1748-6041/11/3/035006

Selection of polymers for application in scaffolds applicable for human pancreatic islet transplantation

Alexandra M Smink, Bart J de Haan, Genaro A Paredes-Juarez, Anouk H G Wolters, Jeroen Kuipers, Ben N G Giepmans, Leendert Schwab, Marten A Engelse, Aart A van Apeldoorn, Eelco de Koning, Marijke M Faas, Paul de Vos

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

27 Citations (Scopus)

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.

Original language	English
Pages (from-to)	035006
Journal	Biomedical materials (Bristol, England)
Volume	11
Issue number	3
DOIs	https://doi.org/10.1088/1748-6041/11/3/035006
Publication status	Published - 2016

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Smink, A. M., de Haan, B. J., Paredes-Juarez, G. A., Wolters, A. H. G., Kuipers, J., Giepmans, B. N. G., Schwab, L., Engelse, M. A., van Apeldoorn, A. A., de Koning, E., Faas, M. M., & de Vos, P. (2016). Selection of polymers for application in scaffolds applicable for human pancreatic islet transplantation. Biomedical materials (Bristol, England), 11(3), 035006. https://doi.org/10.1088/1748-6041/11/3/035006

@article{2da0ef46e4ac402f9e12bee4adf6d366,

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.",

author = "Smink, {Alexandra M} and {de Haan}, {Bart J} and Paredes-Juarez, {Genaro A} and Wolters, {Anouk H G} and Jeroen Kuipers and Giepmans, {Ben N G} and Leendert Schwab and Engelse, {Marten A} and {van Apeldoorn}, {Aart A} and {de Koning}, Eelco and Faas, {Marijke M} and {de Vos}, Paul",

year = "2016",

doi = "10.1088/1748-6041/11/3/035006",

language = "English",

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pages = "035006",

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Smink, AM, de Haan, BJ, Paredes-Juarez, GA, Wolters, AHG, Kuipers, J, Giepmans, BNG, Schwab, L, Engelse, MA, van Apeldoorn, AA, de Koning, E, Faas, MM & de Vos, P 2016, 'Selection of polymers for application in scaffolds applicable for human pancreatic islet transplantation', Biomedical materials (Bristol, England), vol. 11, no. 3, pp. 035006. https://doi.org/10.1088/1748-6041/11/3/035006

TY - JOUR

T1 - Selection of polymers for application in scaffolds applicable for human pancreatic islet transplantation

AU - Smink, Alexandra M

AU - de Haan, Bart J

AU - Paredes-Juarez, Genaro A

AU - Wolters, Anouk H G

AU - Kuipers, Jeroen

AU - Giepmans, Ben N G

AU - Schwab, Leendert

AU - Engelse, Marten A

AU - van Apeldoorn, Aart A

AU - de Koning, Eelco

AU - Faas, Marijke M

AU - de Vos, Paul

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

U2 - 10.1088/1748-6041/11/3/035006

DO - 10.1088/1748-6041/11/3/035006

M3 - Article

C2 - 27173149

SN - 1748-6041

VL - 11

SP - 035006

JO - Biomedical materials (Bristol, England)

JF - Biomedical materials (Bristol, England)

IS - 3

ER -

Selection of polymers for application in scaffolds applicable for human pancreatic islet transplantation

Abstract

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