Vascular Tissue Engineering: Pathological Considerations, Mechanisms, and Translational Implications

Clinical translation of vascular tissue engineering is hampered by inconsistencies in graft outcomes. In this chapter, we argue that variation in graft outcomes is largely due to our lack of fully understanding vascular regeneration and remodeling in resp

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Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Vascular Structure, Pathology, and Grafting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 The Architecture of Blood Vessels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Vascular Wall Cells and Their Response to Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Atherosclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4 Aneurysms and Dissections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5 Pathology of Vascular Graft Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Vascular Tissue Engineering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Variability in Tissue Responses and Biomaterial-Tissue Interactions as a Challenge to Translation of Tissue-Engineered Blood Vessels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 The Genetic Basis of Variability in Healing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Role of Age, Diabetes, and Other Comorbidities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Role of Medications and Other Environmental Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4 Role of Variability in Biomaterial-Tissue Interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Toward Improved Understanding and Personalized Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1 In Silico Platforms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2 In Vitro Platforms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.3 In Vivo Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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F. J. Schoen Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA e-mail: [email protected] A. Mallone Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland e-mail: [email protected] L. Klouda · C. V. C. Bouten (*) Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands e-mail: [email protected]; [email protected] © Sp