Control of angiogenesis

Coronary artery disease and stroke are leading causes of mortality in Europe, resulting in a loss of function of the affected tissue. The challenge is to restore the myocardium tissue functionality using growth-factors mimicking peptides to stimulate the development of pre-existing blood vessels and enhance tissue regeneration.

In this research, poly (ɛ-lysine) dendrons of different branching generations (Gx) have been used as protein scaffold to present, at their uppermost branching generation, the Angiopoietin-1 (Ang-1), the VEGF or the PDGF-BB peptide analogue. The resulting dendritic angiogenic peptides have been designed specifically to target myocardial ischemic tissue starting from a root [di-phenilalanine (FF) ] capable of interacting with the tissue ECM and ending with specific angiogenic bioactive aminoacid sequences that potentially induce a precise biological response on targeting cells.

The angiogenic potential of dendritic angiogenic peptides has been evaluate in a 2D in vitro model where the molecules have been spiked on HUVECs resulting in an endothelial sprouting behaviour provoked by dendritic angiogenic peptides used as “ free drugs”.

Successively, dendritic angiogenic peptides have been used as grafting molecules onto collagen type I fashioned as injectable biomaterials (beads) or patches (scaffold) in order to test the potential of the novel synthesised molecules in inducing angiogenesis in vitro when embedded in a biomaterial.

From the obtained results, it becomes obvious how dendritic angiogenic peptides have a role in inducing angiogenesis when they are presented to cells and tissue in a specific manner.

Indeed, the present study for the first time unveils a novel biomaterial approach to stimulate angiogenesis through nano-structured biomaterials and emphasise the need for a finely spaced presentation of the relevant peptide sequence to obtain established endothelial sprouting.