Hybrid Polycaprolactone/Alginate Scaffolds Functionalized with VEGF to Promote de Novo Vessel Formation for the Transplantation of Islets of Langerhans

• Published in: Advanced healthcare materials 2016-07, Vol.5 (13), p.1606-1616
• Main Authors: Marchioli, Giulia, Luca, Andrea Di, de Koning, Eelco, Engelse, Marten, Van Blitterswijk, Clemens A., Karperien, Marcel, Van Apeldoorn, Aart A., Moroni, Lorenzo
• Format: Article
• Language: English
• Subjects: additive manufacturing; alginate; Alginates; Alginates - chemistry; Animals; Blood vessels; Chick Embryo; Construction; Encapsulation; Glucuronic Acid - chemistry; Heparin - chemistry; Hexuronic Acids - chemistry; Humans; islets of Langerhans; Islets of Langerhans - blood supply; Islets of Langerhans - metabolism; Islets of Langerhans Transplantation; Neovascularization, Physiologic - drug effects; Polycaprolactone; Polyesters - chemistry; Proximity; Scaffolds; Tissue Scaffolds - chemistry; Transplantation; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - chemistry; Vascular Endothelial Growth Factor A - pharmacology; vascularization
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.201600058

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. A hybrid scaffold for embedding the islets of Langerhans to achieve enhanced revascularization upon transplantation is presented. Islets are secured in the central alginate core, while the outer polycaprolactone ring is functionalized with vascular endothelial growth factor. These constructs provide protection for islets and facilitate blood vessel ingrowth in proximity to the embedded tissue.