Effects of recipient age, heparin release and allogeneic bone marrow-derived stromal cells on vascular graft remodeling.

Small-caliber vascular grafts are used in a wide range of clinical conditions. However, there remains a substantial unfulfilled need for readily-available, synthetic vascular grafts with high long-term patency rate. To fulfill the translational goal for bioengineered vascular grafts, important considerations for the pre-clinical evaluation include the graft design, cell incorporation and selection of an animal model. To assess the three factors, we used vascular grafts consisting of core/shell-structured microfibers of polycaprolactone/gelatin with a thin polycaprolactone overlay. The respective influences of the heparin release mode, animal age, and allogeneic bone marrow-derived stromal cells (MSCs) seeded in the lumen on the graft remodeling were assessed after four-and-half-month implantation on an interposition graft of abdominal aorta model. Except two rats dying from graft-unrelated issues, all other rats (18 out of 20) showed good graft patency upon explantation. The cell phenotype, matrix content and structure in the neotissues around the graft, as well as the flow perfusion through the graft were examined. More grafts in the aged rats showed local narrowing and flow incongruence than the other grafts in young adult rats. Compared to acellular grafts, cellular grafts showed efficient recruitment of vascular cells to form more organized structures with elastin in the vascular wall. Endothelialization and α-smooth muscle actin-positive cells were shown in all four types of vascular grafts. This study revealed the significant effects of MSC and recipient age but not heparin release pattern on graft remodeling. STATEMENT OF SIGNIFICANCE: The vascular graft is a mainstream of surgical intervention to treat vascular diseases. Currently, vascular grafts, particularly small-diameter ones, still show high failure rates. This study has evaluated the respective impacts of heparin release pattern, allogeneic bone marrow-derived stromal cell seeding, and recipient age on the long-term remodeling of vascular grafts. There is a dearth of literature which considers the recipient age as an influencing factor for vascular grafting. However, adults particularly elderly constitute the majority of vascular graft recipients in the "real" clinical environment. While juvenile animals were widely used for graft evaluations, this study involved adult animals. The study outcomes provided important implications regarding graft designs and evaluation approaches.