Heparin desulfation modulates VEGF release and angiogenesis in diabetic wounds

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

While vascular endothelial growth factor (VEGF) has been shown to be one of the key players in wound healing by promoting angiogenesis current clinical applications of this growth factor to the wound environment are poorly controlled and not sustainable. Hydrogels made of sulfated glycosaminoglycans (GAG) allow for the sustained release of growth factors since GAGs engage in electrostatic complexation of biomolecules. In here, we explore a set of hydrogels formed of selectively desulfated heparin derivatives and star-shaped poly(ethylene glycol)with respect to VEGF binding and release and anticoagulant activity. As a proof of concept, supportive effects on migration and tube formation of human umbilical vein endothelial cellswere studied in vitro and the promotion of wound healing was followed in genetically diabetic (db/db) mice. Our data demonstrate that the release of VEGF from the hydrogels is modulated in dependence on the GAG sulfation pattern. Hydrogels with lowsulfate content (11% of initial heparin) were found to be superior in efficacy of VEGF administration, lowanticoagulant activity and promotion of angiogenesis.

Details

Original languageEnglish
Pages (from-to)79-88
Number of pages10
JournalJournal of controlled release
Volume220
Publication statusPublished - 28 Dec 2015
Peer-reviewedYes

External IDs

PubMed 26478015
ORCID /0000-0003-0189-3448/work/161890448

Keywords

ASJC Scopus subject areas

Keywords

  • Angiogenesis, Glycosaminoglycans, Growth factors, Heparin, Hydrogels, VEGF