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WIREs Nanomed Nanobiotechnol
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Development of tissue engineered vascular grafts and application of nanomedicine

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Abstract Vascular Tissue Engineering belongs to a rapidly expanding discipline. Tissue engineered vascular grafts (TEVG) have a broad range of clinical application extending from use as small diameter vascular grafts in adult peripheral vasculature to serving as large vessel conduits in pediatric cardiovascular surgery. Several approaches have been utilized by different groups to design these grafts. Preliminary outcomes are exceedingly promising. These grafts have demonstrated the ability to transform into living blood vessels with growth potential and while the underlying mechanisms remain to be elucidated, it has been shown that inflammatory pathways may play an important role. Small animal experiments, development of cell seeding techniques and the application of nanotechnology have all contributed vastly to our understanding of the mechanisms involved in TEVG remodeling. The application of nanomedicine in TEVG design continues to expand at a rapid rate and has provided some clues as to how vascular graft design can be pursued in the future. In this review we discuss the current state of the field of tissue engineered vascular grafts and how the principles of nanomedicine are being applied to aid in the design of second‐generation grafts. WIREs Nanomed Nanobiotechnol 2012, 4:257–272. doi: 10.1002/wnan.1166 This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement

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Proposed mechanism of vascular transformation of hBMC‐seeded biodegradable scaffolds. Seeded bone marrow derived mononulear cells enhance early monocyte recruitment via a paracrine mechanism. Infiltrating macrophages locally release growth factors and cytokines which recruit smooth muscles cells and endothelial cells via migration of mature vascular cells from adjacent vessel segments. The monocytes then disappear from the graft. The ECs and SMCs organize into a layered tubular morphology along the vessel lumen, secrete ECM and the scaffold degrades to form a mature autologous neovessel.

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(a) In vitro T2‐weighted image characterization of USPIO‐labeled macrophages in an unlabeled scaffold, an unseeded scaffold, and a USPIO‐labeled scaffold suspended in gelatin. (b and c) In vivo MR axial T2‐weighted RARE imaging of mice implanted with labeled (b) and unlabeled (c) seeded scaffold implants. Kidneys (K) and liver (L).

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(a) Fiber diameter as a function of mandrel rpm. (b) Second‐order modeling of fiber diameter as a function of starting concentration at 200 rpm, R2 1/4 0:56. (c) Regression analysis of the relationship between starting concentration and solution viscosity. (Reprinted with permission from Ref 101. Copyright 2006 Elsevier)

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H&E staining of graft implanted in mouse treated with PBS or clodronate liposomes showing inhibition of cellular at 2 weeks in the clondronate‐treated group (b) compared to the PBS‐treated group (a). (c) The clodronate‐treated group showed a significantly decreased number of macrophages infiltrating the scaffold.

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(a) Scanning electron microscopy of MCP‐1 microparticles (1–20 µm). (b) Cross‐section of scaffold embedded with MCP‐1 microparticles. (c) High magnification EM showing PGA fibers coated with P(CL/LA) and embedded with MCP‐1 microparticles. (d) MCP‐1 microparticle scaffolds have significantly greater numbers of mouse monocytes (F4/80+ cells) than both hBMC‐seeded and unseeded scaffolds.

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Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease
Implantable Materials and Surgical Technologies > Nanomaterials and Implants
Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement

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