The regeneration of cartilage in the intervertebral disc nucleus pulposus
and joints is impaired by the formation of fibrocartilage that is
caused by the invasion of the tissue by blood vessels. Peptides have
been identified by phage display technique which are able to bind
VEGF thus inhibiting angiogenesis. The present works focusses on the
synthesis of poly(epsilon-lysine) dendrons of three branching generations
in which the molecular root of the dendron bears a di-phenylalanine
sequence to promote hydrophobic interactions with material
surfaces and the uppermost molecular branches are functionalised with
the amino acid sequenceWHLPFKC that is known to block VEGF. These
biofunctionalised dendrons were entrapped in methacrylated Gellan
Gum (GG-MA) hydrogels and tested for their ability to inhibit endothelial
cell sprouting by both a 3D in vitro cell models and an in ovo
model. The results show that when GG-MA is functionalised with the
dendronised VEGF blockers, a regression of angiogenesis takes place
around the hydrogel boundary. The in ovo study supports these findings
as the GG-MA functionalised with the dendronised VEGF blockers
did not elicit any acute inflammatory response, and decrease the number
of converging macroscopic blood vessels as compared to positive
controls. Moreover, the hydrogels prevented the infiltration of blood
vessels, after 4 days of implantation.Fundação para a Ciência e TecnologiaEU 7th Framework ProgrammeMICINNJunta de Castilla y LeónCIBER-BBNFundo Social EuropeuPrograma Operacional Potencial Human