title: Beyond burst pressure: initial evaluation of the natural history of the biaxial mechanical properties of tissue-engineered vascular grafts in the venous circulation using a murine model.
abstract: We previously developed and validated a murine model for investigating neotissue formation in tissue-engineered vascular grafts (TEVGs). Herein, we present the first longitudinal assessment of both the microstructural composition and the mechanical properties of a TEVG through the process of neovessel formation (total scaffold degradation). We show that when (poly)glycolic acid-based biodegradable scaffolds were used as inferior vena cava interposition grafts in mice, the evolving neovessel developed biaxial properties that approached those of the native vein within 24 weeks of implantation. Further, we found that these changes in biaxial properties related temporally to extracellular matrix production and remodeling, including deposition of collagen (types I and III), elastic fibers (elastin and fibrillin-1), and glycosaminoglycans in addition to changes in matrix metalloproteinase (MMP)-2 and -9 activity. Improving our understanding of the mechanobiological principles underlying vascular neotissue formation in TEVGs holds great promise for improving the design of TEVGs and enabling us to continue the translation of this technology from the bench to the clinic.
authors: 1 Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine , New Haven, Connecticut.
authors: Yuji
authors: Y
authors: Naito
authors: Yong-Ung
authors: YU
authors: Lee
authors: Tai
authors: T
authors: Yi
authors: Spencer N
authors: SN
authors: Church
authors: Daniel
authors: D
authors: Solomon
authors: Jay D
authors: JD
authors: Humphrey
authors: Toshiharu
authors: T
authors: Shin'oka
authors: Christopher K
authors: CK
authors: Breuer
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001775:Blood Circulation / Q000502:physiology*; D001807:Blood Vessel Prosthesis; D005109:Extracellular Matrix / Q000378:metabolism; D000071838:Fibrillin-1; D000071837:Fibrillins; D020007:Implants, Experimental; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D008840:Microfilament Proteins / Q000378:metabolism; D023421:Models, Animal; D011312:Pressure; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014682:Vena Cava, Inferior / Q000502:physiology*; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008840:Microfilament Proteins; C000605724:Fbn1 protein, mouse; D054392:Adipokines
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