The potential of collagen scaffolds for promoting angiogenesis/arteriogenesis was
studied in vivo by implantation on healthy or cryoinjured left ventricles of rats
up to 60 days post-injury. Blood vessels content and extra-vascular cell infiltration
were evaluated within the collagen scaffold, the cryoinjured areas, and the "border
zones" of the myocardium facing the cryoinjured zones. The collagen cardiac patches
were almost completely absorbed in 60 days and became populated by new arterioles
and capillaries in both intact and cryoinjured heart (arterioles in cryoinjured vs.
intact zones were about 2,3-fold higher; capillaries in cryoinjured vs. intact zones
were 1.7-fold higher). Collagen cardiac patches exerted a "trophic" effect on the
organizing granulation tissue that emerged from the wound-healing process, increasing
vessel density of 2.7-fold for arterioles and 4-fold for capillaries. Interstitial
cells in collagen cardiac patches rarely (<1%) expressed cardiogenic stem cells markers
such as Sca-1- or MDR1, whereas markers of neural crest cells GFAP(+)/nestin(+) cells
ranged from 3/30% to 30/70% in collagen cardiac patches placed on intact vs. cryoinjured
heart, respectively. Myofibroblasts and cardiomyocytes (CM) were absent but macrophages
populated the collagen scaffolds even after 60 days from implantation. Western blotting
of collagen cardiac patches after implantation on intact/cryoinjured hearts confirmed
that markers of endothelial and smooth muscle cells, but not of CM, were expressed.
The porous collagen scaffold was able to elicit a powerful angiogenetic and arteriogenetic
response in the intact and cryoinjured hearts, representing an ideal tool for therapeutic
angio-arteriogenesis and a potentially useful substrate for stem cell seeding.