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

Adv Healthc Mater. 2016 Jul;5(13):1606-16. doi: 10.1002/adhm.201600058. Epub 2016 Apr 26.

Abstract

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.

Keywords: additive manufacturing; alginate; islets of Langerhans; polycaprolactone; vascularization.

MeSH terms

  • Alginates / chemistry*
  • Animals
  • Chick Embryo
  • Glucuronic Acid / chemistry
  • Heparin / chemistry
  • Hexuronic Acids / chemistry
  • Humans
  • Islets of Langerhans Transplantation*
  • Islets of Langerhans* / blood supply
  • Islets of Langerhans* / metabolism
  • Neovascularization, Physiologic / drug effects*
  • Polyesters / chemistry*
  • Tissue Scaffolds / chemistry*
  • Vascular Endothelial Growth Factor A* / chemistry
  • Vascular Endothelial Growth Factor A* / pharmacology

Substances

  • Alginates
  • Hexuronic Acids
  • Polyesters
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • polycaprolactone
  • Glucuronic Acid
  • Heparin