Engineered VEGF-releasing PEG-MAL hydrogel for pancreatic islet vascularization

Drug Deliv Transl Res. 2015 Apr;5(2):125-36. doi: 10.1007/s13346-013-0142-2.

Abstract

Biofunctionalized polyethylene glycol maleimide (PEG-MAL) hydrogels were engineered as a platform to deliver pancreatic islets to the small bowel mesentery and promote graft vascularization. VEGF, a potent stimulator of angiogenesis, was incorporated into the hydrogel to be released in an on-demand manner through enzymatic degradation. PEG-MAL hydrogel enabled extended in vivo release of VEGF. Isolated rat islets encapsulated in PEG-MAL hydrogels remained viable in culture and secreted insulin. Islets encapsulated in PEG-MAL matrix and transplanted to the small bowel mesentery of healthy rats grafted to the host tissue and revascularized by 4 weeks. Addition of VEGF release to the PEG-MAL matrix greatly augmented the vascularization response. These results establish PEG-MAL engineered matrices as a vascular-inductive cell delivery vehicle and warrant their further investigation as islet transplantation vehicles in diabetic animal models.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alginates / chemistry
  • Animals
  • Collagen / chemistry
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Hydrogels / administration & dosage*
  • Hydrogels / chemistry
  • Intestine, Small / blood supply
  • Intestine, Small / drug effects
  • Intestine, Small / physiology
  • Islets of Langerhans / blood supply
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / physiology
  • Islets of Langerhans Transplantation
  • Male
  • Maleimides / chemistry*
  • Mesentery / drug effects
  • Mesentery / physiology
  • Neovascularization, Physiologic / drug effects
  • Polyethylene Glycols / chemistry*
  • Rats, Inbred Lew
  • Vascular Endothelial Growth Factor A / administration & dosage*
  • Vascular Endothelial Growth Factor A / chemistry

Substances

  • Alginates
  • Hexuronic Acids
  • Hydrogels
  • Maleimides
  • Vascular Endothelial Growth Factor A
  • maleimide
  • Polyethylene Glycols
  • Glucuronic Acid
  • Collagen