Functionalisation of Methacrylated Gellan Gum Hydrogels by Anti-Angiogenic Dendrons

The regeneration of cartilage in the intervertebral disc nucleus pulpo- sus 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 genera- tions in which the molecular root of the dendron bears a di-phenylala- nine sequence to promote hydrophobic interactions with material surfaces and the uppermost molecular branches are functionalised with the amino acid sequence WHLPFKC 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 endothe- lial 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 find- ings as the GG-MA functionalised with the dendronised VEGF blockers did not elicit any acute inflammatory response, and decrease the num- ber of converging macroscopic blood vessels as compared to positive controls. Moreover, the hydrogels prevented the infiltration of blood vessels, after 4 days of implantation.
Acknowledgements: This work was supported by the EC FP7 Project Disc Regeneration, n. NMP3-LA-2008-21390