Well-organized neointima of large-pore poly(l-lactic acid) vascular graft coated with poly(l-lactic-co-ε-caprolactone) prevents calcific deposition compared to small-pore electrospun poly(l-lactic acid) graft in a mouse aortic implantation model

Abstract

Objective: Tissue engineering techniques have emerged that allow bioresorbable grafts to be implanted that restore function and transform into biologically active arteries. However, these implants are susceptible to calcification during the remodeling process. The objective of this study was to evaluate the role of pore size of bioabsorbable grafts in the development of calcification. Methods: Two types of grafts were prepared: a large-pore graft constructed of poly(l-lactic acid) (PLA) fibers coated with poly(l-lactide-co-ε-caprolactone) (PLCL) (PLA–PLCL), and a small-pore graft made of electrospun PLA nanofibers (PLA-nano). Twenty-eight PLA–PLCL grafts and twenty-five PLA-nano grafts were implanted as infra-renal aortic interposition conduits in 8-week-old female SCID/Bg mice, and followed for 12 months after implantation. Results: Large-pore PLA–PLCL grafts induced a well-organized neointima after 12 months, and Alizarin Red S staining showed neointimal calcification only in the thin neointima of small-pore PLA-nano grafts. At 12 months, macrophage infiltration, evaluated by F4/80 staining, was observed in the thin neointima of the PLA-nano graft, and there were few vascular smooth muscle cells (VSMCs) in this layer. On the other hand, the neointima of the PLA–PLCL graft was composed of abundant VSMCs, and a lower density of macrophages (F4/80 positive cells, PLA–PLCL; 68.1 ± 41.4/mm2 vs PLA-nano; 188.3 ± 41.9/mm2, p = 0.007). The VSMCs of PLA–PLCL graft expressed transcription factors of both osteoblasts and osteoclasts. Conclusion: These findings demonstrate that in mouse arterial circulation, large-pore PLA–PLCL grafts created a well-organized neointima and prevented calcific deposition compared to small-pore, electrospun PLA-nano grafts.