title: Microwell scaffolds for the extrahepatic transplantation of islets of Langerhans.
abstract: Allogeneic islet transplantation into the liver has the potential to restore normoglycemia in patients with type 1 diabetes. However, the suboptimal microenvironment for islets in the liver is likely to be involved in the progressive islet dysfunction that is often observed post-transplantation. This study validates a novel microwell scaffold platform to be used for the extrahepatic transplantation of islet of Langerhans. Scaffolds were fabricated from either a thin polymer film or an electrospun mesh of poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT) block copolymer (composition: 4000PEOT30PBT70) and were imprinted with microwells, ∼400 µm in diameter and ∼350 µm in depth. The water contact angle and water uptake were 39±2° and 52.1±4.0 wt%, respectively. The glucose flux through electrospun scaffolds was three times higher than for thin film scaffolds, indicating enhanced nutrient diffusion. Human islets cultured in microwell scaffolds for seven days showed insulin release and insulin content comparable to those of free-floating control islets. Islet morphology and insulin and glucagon expression were maintained during culture in the microwell scaffolds. Our results indicate that the microwell scaffold platform prevents islet aggregation by confinement of individual islets in separate microwells, preserves the islet's native rounded morphology, and provides a protective environment without impairing islet functionality, making it a promising platform for use in extrahepatic islet transplantation.
authors.affiliation: Department of Developmental BioEngineering, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: Mijke
authors.initials: M
authors.lastname: Buitinga
authors.forename: Roman
authors.initials: R
authors.lastname: Truckenmüller
authors.forename: Marten A
authors.initials: MA
authors.lastname: Engelse
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moroni
authors.forename: Hetty W M
authors.initials: HW
authors.lastname: Ten Hoopen
authors.forename: Clemens A
authors.initials: CA
authors.lastname: van Blitterswijk
authors.forename: Eelco Jp
authors.initials: EJ
authors.lastname: de Koning
authors.forename: Aart A
authors.initials: AA
authors.lastname: van Apeldoorn
authors.forename: Marcel
authors.initials: M
authors.lastname: Karperien
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D004058:Diffusion; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D055616:Microtechnology / Q000379:methods*; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D054457:Tissue Scaffolds / Q000737:chemistry; D014184:Transplantation, Homologous; D017155:Wettability
chemical_list: D011091:Polyesters; C072932:polyethylene oxide-polybutylene terephthalate copolymer; D011092:Polyethylene Glycols; D005947:Glucose