Development of a pre-vascularized 3D scaffold-hydrogel composite graft using an arterio-venous loop for tissue engineering applications

Abstract

Hyaluronic acid (HA) and fibrin glue (FG) are effective hydrogels for tissue engineering applications as they support tissue in-growth, retain growth factors, and release them slowly with time. The scaffolds, in combination with a hydrogel, effectuate a successful graft. However, the survival of a graft entirely depends upon a functional vascular supply. Therefore, hydrogels must support the in-growing vasculature. To study and compare the vascular patterns, HA and FG hydrogel-containing PLDLLA-TCP-PCL scaffolds were implanted in the groin of male Lewis rats and supplied with a micro-surgically prepared arterio-venous (A-V) loop. The rats were perfused with a vascular contrast media after 4 and 8 weeks and sacrificed for further analysis. The specimens were scanned with micro-CT to find the vascular growth patterns. Corrosion casting of blood vessels followed by SEM demonstrated a high vascular density near the parent blood vessels. Histologically, HA and FG implanted animal groups showed significant angiogenetic activity, especially within the pores of the scaffold. However, formation of new blood vessels was more conspicuously observed at 4 weeks in FG than HA implants. Furthermore, by 8 weeks, the number and pattern of blood vessels were comparable between them. At this time, HA was still present indicating its slow degradation. The finding was confirmed by histomorphometric analysis. This experimental study demonstrates that HA containing composite scaffold systems permit stabile in-growth of blood vessels due to sustained degradation over 8 weeks. HA is a potential matrix for a tissue engineered composite graft.