TY - JOUR
T1 - Hybrid Polycaprolactone/Alginate Scaffolds Functionalized with VEGF to Promote de Novo Vessel Formation for the Transplantation of Islets of Langerhans
AU - Marchioli, Giulia
AU - Luca, Andrea Di
AU - de Koning, Eelco
AU - Engelse, Marten
AU - Van Blitterswijk, Clemens A
AU - Karperien, Marcel
AU - Van Apeldoorn, Aart A
AU - Moroni, Lorenzo
N1 - © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2016/7
Y1 - 2016/7
N2 - 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.
AB - 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.
U2 - 10.1002/adhm.201600058
DO - 10.1002/adhm.201600058
M3 - Article
C2 - 27113576
SN - 2192-2640
VL - 5
SP - 1606
EP - 1616
JO - Advanced healthcare materials
JF - Advanced healthcare materials
IS - 13
ER -