Hybrid Polycaprolactone/Alginate Scaffolds Functionalized with VEGF to Promote de Novo Vessel Formation for the Transplantation of Islets of Langerhans.
Although regarded as a promising treatment for type 1 diabetes, clinical islet transplantation in the portal vein is still hindered by a low transplantation outcome. Alternative transplantation sites have been proposed, but the survival of extra-hepatically transplanted islets of Langerhans critically depends on quick revascularization after engraftment. This study aims at developing a new 3D scaffold platform that can actively boost vascularization and may find an application for extra-hepatic islet transplantation. The construct consists of a 3D ring-shaped polycaprolactone (PCL) scaffold with heparinized surface to electrostatically bind vascular endothelial growth factor (VEGF), surrounding a hydrogel core for islets encapsulation. Heparin immobilization improves the amount of VEGF retained by the construct, up to 3.6 fold, compared to untreated PCL scaffolds. In a chicken chorioallanthoic membrane model, VEGF immobilized on the construct enhances angiogenesis in close proximity and on the surface of the scaffolds. After 7 days, islets encapsulated in the alginate core show functional response to glucose stimuli comparable to free-floating islets. Thus, the developed platform has the potential to support rapid vascularization and islet endocrine function.
Department of Developmental BioEngineering, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, Drienerlolaan 5, 7522 NB, Enschede, The Netherlands.
Giulia
G
Marchioli
Department of Tissue Regeneration, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, Drienerlolaan 5, 7522 NB, Enschede, The Netherlands.
Andrea Di
AD
Luca
Department of Nephrology and Department of Endocrinology, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, The Netherlands.
Eelco
E
de Koning
Department of Nephrology and Department of Endocrinology, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, The Netherlands.
Marten
M
Engelse
Department of Tissue Regeneration, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, Drienerlolaan 5, 7522 NB, Enschede, The Netherlands.|Department of Complex Tissue Regeneration, MERLN Institute for Technology Inspired Regenerative Medicine, Maastricht University, Universiteitssingel 40, 6229, ER, Maastricht, The Netherlands.
Clemens A
CA
Van Blitterswijk
Department of Developmental BioEngineering, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, Drienerlolaan 5, 7522 NB, Enschede, The Netherlands.
Marcel
M
Karperien
Department of Developmental BioEngineering, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, Drienerlolaan 5, 7522 NB, Enschede, The Netherlands.
Aart A
AA
Van Apeldoorn
Department of Tissue Regeneration, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, Drienerlolaan 5, 7522 NB, Enschede, The Netherlands.|Department of Complex Tissue Regeneration, MERLN Institute for Technology Inspired Regenerative Medicine, Maastricht University, Universiteitssingel 40, 6229, ER, Maastricht, The Netherlands.
Lorenzo
L
Moroni
D000464:Alginates / Q000737:chemistry*; D000818:Animals; D002642:Chick Embryo; D020723:Glucuronic Acid / Q000737:chemistry; D006493:Heparin / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007515:Islets of Langerhans / Q000098:blood supply / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011091:Polyesters / Q000737:chemistry*; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000494:pharmacology
D000464:Alginates; D006603:Hexuronic Acids; D011091:Polyesters; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C016240:polycaprolactone; D020723:Glucuronic Acid; D006493:Heparin
additive manufacturing; alginate; islets of Langerhans; polycaprolactone; vascularization