Electrospun Tissue-Engineered Arterial Graft Thickness Affects Long-Term Composition and Mechanics

Wall stress is often lower in tissue-engineered constructs than in comparable native tissues due to the use of stiff polymeric materials having thicker walls. In this work, we sought to design a murine arterial graft having a more favorable local mechanical environment for the infiltrating cells; we used electrospinning to enclose a compliant inner core of poly(glycerol sebacate) with a stiffer sheath of poly(caprolactone) to reduce the potential for rupture. Two scaffolds were designed that differed in the thickness of the core as previous computational simulations found that circumferential wall stresses could be increased in the core toward native values by increasing the ratio of the core:sheath. Our modified electrospinning protocols reduced swelling of the core upon implantation and eliminated residual stresses in the sheath, both of which had contributed to the occlusion of implanted grafts during pilot studies. For both designs, a subset of implanted grafts occluded due to thrombosis or ruptured due to suspected point defects in the sheath. However, there were design-based differences in collagen content and mechanical behavior during early remodeling of the patent samples, with the thinner-core scaffolds having more collagen and a stiffer behavior after 12 weeks of implantation than the thicker-core scaffolds. By 24 weeks, the thicker-core scaffolds also became stiff, with similar amounts of collagen but increased smooth muscle cell and elastin content. These data suggest that increasing wall stress toward native values may provide a more favorable environment for normal arterial constituents to form despite the overall stiffness of the construct remaining elevated due to the absolute increase in load-bearing constituents.