The Effect of Side-Specific Coating with SDF1α and Fibronectin on the In Vivo Cellularization and Degeneration of Rat Aortic Decellularized Implants

Objectives: The improvement of biocompatibility and durability of vascular implants is an ongoing demand for cardiovascular surgery. Previously, a combined coating with fibronectin and stromal cell-derived factor 1α (SDF1α) has been shown to accelerate the in vivo cellularization of synthetic vascular grafts and to reduce the calcification of biological pulmonary root grafts. In this study, we evaluate the effect of side-specific coating with SDF1α and fibronectin on the in vivo cellularization and degeneration of decellularized grafts in vivo in the systemic circulation.

Methods: Donor aortic arch vascular grafts were decellularized with a combination of different detergents. Site-specific coating with SDF1α (luminal graft surface) and fibronectin (adventitial surface) were performed. SDF1a coated/ uncoated grafts were implanted infrarenally in rats (n = 5 each group). At 2 and 8 weeks, grafts were explanted for histology and immunohistology. Explanted grafts were divided into four regions: ascending aorta (region A1), proximal aortic arch (region A2), distal aortic arch (region B1), and descending aorta (region B2).

Results: Intima endothelialization was accelerated with luminal SDF1α coating at 2 weeks (92.4 ± 2.95% vs. 61.1 ± 6.51%, p < 0.0001; SDF1α vs. control). At 8 weeks, SDF1α coating inhibited neo-intimal hyperplasia, resulting in a significantly decreased intima-to-media ratio (0.62 ± 0.15 vs. 1.35 ± 0.26, p < 0.05; SDF1α vs. control) and thickness of intima (37.7 ± 1.00 µm vs. 85.0 ± 15.1 µm, p < 0.05; SDF1α vs. control). Furthermore, media calcification decreased significantly in the SDF1α group as compared with the control group at 8 weeks (area of calcification in region A2, 1092 ± 517.2 µm² vs. 11814 ± 1883 µm², p = 0.0006, in region B1, 14127 ± 7467 µm² versus 97836 ± 29152 µm², p < 0.05; SDF1α vs. control). No intima or media calcification in anastomotic regions (A1, B2) in group SDF1α was found at 8 weeks. Inflammatory cell markers (CD3 and CD68) proved negative at all time points.

Conclusion: Our findings indicate that luminal coating of SDF1α promotes early in vivo autologous intima recellularization and attenuates neo-intima hyperplasia as well as late mineralization of grafts. These data suggest the luminal coating of SDF1α as a promising tool for long durability of the engineered vascular graft.

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