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Anti‐angiogenic potential of VEGF blocker dendron loaded on to gellan gum hydrogels for tissue engineering applications
Author(s) -
Perugini Valeria,
Guildford Anna L.,
SilvaCorreia Joana,
Oliveira Joaquim M.,
Meikle Steven T.,
Reis Rui L.,
Santin Matteo
Publication year - 2018
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.2340
Subject(s) - aptamer , self healing hydrogels , angiogenesis , chemistry , chorioallantoic membrane , in vivo , dendrimer , gellan gum , vascular endothelial growth factor , biophysics , in vitro , microbiology and biotechnology , biochemistry , vegf receptors , cancer research , biology , polymer chemistry , food science
Damage of non‐vascularised tissues such as cartilage and cornea can result in healing processes accompanied by a non‐physiological angiogenesis. Peptidic aptamers have recently been reported to block the vascular endothelial growth factor (VEGF). However, the therapeutic applications of these aptamers are limited due to their short half‐life in vivo . In this work, an enhanced stability and bioavailability of a known VEGF blocker aptamer sequence (WHLPFKC) was pursued through its tethering of molecular scaffolds based on hyperbranched peptides, the poly(ɛ‐lysine) dendrons, bearing three branching generations. The proposed design allowed simultaneous and orderly‐spaced exposure of 16 aptamers per dendrimer to the surrounding biological microenvironent, as well as a relatively hydrophobic core based on di‐phenylalanine aiming to promote an hydrophobic interaction with the hydrophobic moieties of ionically crosslinked methacrylated gellan gum (iGG‐MA) hydrogels. The VEGF blocker dendrons were entrapped in iGG‐MA hydrogels, and their capacity to prevent endothelial cell sprouting was assessed qualitatively and quantitatively using 3D in vitro models and the in vivo chick chorioallantoic membrane assay. The data demonstrate that at nanoscale concentrations, the dendronised structures were able to enhance control of the biological actvity of WHLPFKC at the material/tissue interface and hence the anti‐angiogenic capacity of iGG‐MA hydrogels not only preventing blood vessel invasion, but also inducing their regression at the tissue/iGG‐MA interface. The in ovo study confirmed that iGG‐MA functionalised with the dendron VEGF blockers do inhibit angiogenesis by controlling both size and ramifications of blood vessels in the proximity of the implanted gel surface. Copyright © 2016 John Wiley & Sons, Ltd.