Incorporation of Intact Elastin Scaffolds in Tissue-Engineered Collagen-Based Vascular Grafts

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Abstract
Although collagen-based tissue-engineered blood vessels (TEBVs) have many interesting properties and have been utilized to study aspects of vascular biology, these constructs are too weak to be implanted as bypass grafts for in vivo investigations. This study presents a method to incorporate organized, intact elastin into collagen-based TEBVs to form hybrid constructs that better mimic arterial physiology and exhibit improved mechanical properties. Porcine carotids were digested with a series of autoclave and chemical treatments to elicit isolated elastin scaffolds. Elastin purity was verified via immunohistochemistry and amino acid analysis. Isolated scaffolds were combined with type I collagen and either human dermal fibroblasts (HDFs) or rat smooth muscle cells (RASMs) to form an elastin hybrid TEBV. Hybrid constructs exhibited increased tensile strengths (11-fold in HDFs; 7.5-fold in RASMs) and linear stiffness moduli (4-fold in HDFs; 1.8-fold in RASMs) compared with collagen control constructs with no exogenous elastin scaffold. Viscoelastic properties of the TEBVs also improved with the addition of an ancillary elastin scaffold as determined through stepwise stress relaxation analysis. Whereas the majority of resistance to deformation in collagen control constructs stemmed from viscous fluidlike effects, elastin hybrid constructs exhibited more ideal elastic solid mechanical behavior. Thus, elastin scaffolds can help recreate the elastic properties of native arteries. Future challenges include stimulating appropriate reorganization or synthesis of the collagen matrix to provide the necessary strength and viscoelastic properties for implantation.