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WIREs Nanomed Nanobiotechnol
Impact Factor: 7.689

Virus‐based scaffolds for tissue engineering applications

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One of the major research directions of tissue engineering is to develop artificial scaffolds that can mimic extracellular matrix (ECM) and support the growth of functional cells for the repair of damaged tissues and organs. Recently, virus particles have expanded as nanosized building blocks for materials applications. Viruses represent monodispersed supramolecular assemblies with organized three‐dimensional architecture, which can be isolated in high yield and purity with batch‐to‐batch consistency. In addition, virus particles can be re‐engineered by chemical and genetic modification to incorporate multivalent functional ligands with high density and ordered arrangement. In this review, we highlight that the self‐assembly of the reengineered viruses can form two‐dimensional and three‐dimensional scaffolds, which can be employed to support cell growth and regulate cellular functions such as adhesion, spreading and proliferation. In particular, the application of virus‐based scaffolds for directed differentiation of pluripotent stem cells for bone and neural regeneration is discussed. Finally, the in vivo behaviors of virus nanoparticles will be discussed for the consideration of tissue engineering applications. WIREs Nanomed Nanobiotechnol 2015, 7:534–547. doi: 10.1002/wnan.1327 This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale Implantable Materials and Surgical Technologies > Nanomaterials and Implants Biology-Inspired Nanomaterials > Protein and Virus-Based Structures
(a) Schematic illustration of flow assembly for alignment of TMV in capillary tube and AFM image of aligned TMV with horizontal orientation to the tube. (b) Fluorescent images of C2C12 cells with differentiation for 7 days on the tubes with different neural progenitor cells. Colour representation: anti‐MHC (red), nucleus (blue). Scale bars: 100 µm. (c) The fusion index and (d) maturation index for C2C12 cells in the tubes with different NPs. **P < 0.01 and NS = not significant. (e) Schematic illustration of TMV self‐assembly into aligned stripes in capillary tubes and optical images of these stripe patterns at positions 1 and 2 in the inset. (f) 3D AFM image and an enlarged view of stripe patterns. (g) Florescence images of smooth muscle cell cultured at positions 1 and 2 inside the capillary tube. Colour representation: F‐actin (green), nucleus (blue). Panels (a–d) are reproduced with permission from Ref ; copyright 2013 American Chemical Society. Panels (e–g) are reproduced with permission from Ref ; copyright 2009 Wiley‐VCH. TMV, tobacco mosaic virus; RGD, arginine‐glycine‐aspartic acid, MHC, myosin heavy chain.
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(a) BHK cell density analyses after 1 and 12 h incubation on electrospinning PVA, PVA‐TMV, and PVA‐TMV/RGD fibers. (b) Fluorescence microscopy images and Field emission scanning electron microscopy images of BHK cells after 1 h incubation on fibrous substrates. Colour representation: nucleus (blue), F‐actin (red). The figure is reproduced with permission from Ref ; copyright 2011 The Royal Society of Chemistry. PVA, polyvinyl alcohol; TMV, tobacco mosaic virus; RGD, arginine‐glycine‐aspartic acid.
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(a) Three‐dimensional structures of viruses that have been developed as platforms for tissue engineering. CPMV, cowpea mosaic virus; TYMV, turnip yellow mosaic virus; TMV, tobacco mosaic virus; M13 bacteriophage. The structures of CPMV, TYMV, and TMV are generated using PyMol (www.pymol.org) with coordinates obtained from RCSB Protein Data Bank (www.pdb.org). M13 is reproduced with permission from Ref ; copyright 2007 The National Academy of Sciences of the USA. (b) Schematic illustration of viral nanoparticles‐based cell‐matrix interaction. ECM, extracellular matrix. (c) Viral nanoparticles‐based 2D films and 3D scaffolds with random and aligned structures for cell supporting. The figure is reproduced with permission from Refs ; copyrights from Elsevier Ltd.; American Chemical Society and the Royal Society of Chemistry. (d) Conventional chemical bioconjugation strategies targeting the endogenous amino acids on viral nanoparticles. (e) Representative examples of genetic engineering strategy to insert exogenous peptide on viral nanoparticles. The figure is reproduced with permission from Ref ; copyright 2009 American Chemical Society.
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(a) Schematic diagram of NPCs response to phage materials. (b) Plot of cell spatial distribution on phage substrates by nearest neighbor analysis. (c) Immunostaining of NPCs grown on the aligned RGD‐phage film in proliferation media and differentiation media at day 1. Colour representation: nucleus (blue), actin (green). Bright‐field optical micrograph of NPCs on the aligned RGD‐phage film at 4 h. (d) Neurite length on the phage matrices and SEM of neural cells on the RGD‐phage matrices. Panels (a), (b), and (d) are reproduced with permission from Ref ; copyright 2009 American Chemical Society. Panle (c) is reproduced with permission from Ref ; copyright 2010 American Chemical Society. NPC, neural progenitor cell; RGD, arginine‐glycine‐aspartic acid.
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(a) Gene expression in the BMSCs seeded on TMV under osteogenic conditions. **P < 0.005 and *P < 0.05. (b) Histochemical staining for osteogenic markers alkaline phosphatase (inset) and alizarin red in BMSCs cultured on TMV for 14 days under osteogenic conditions. (c) Immunostaining of BMP2 in BMSCs cultured on TCP and TMV for 8 h. Colour representation: nucleus (blue), BMP2 (green). (d) Immunostaining of osteogenic markers osteocalcin and osteopontin in BMSCs grown on TMV‐phos. Colour representation: nucleus (blue), actin (green), osteocalcin (red), and osteopontin (pink). (e) SEM images of a single cell inside TMV‐PAH. (f) Alkaline phosphatase activity assay of BMSCs (P < 0.05). (g) Calcium deposition of BMSCs quantified on day 6 (P < 0.05). Panels (a) and (b) are reproduced with permission from Ref ; copyright 2009 Elsevier Ltd. Panel (c) is reproduced with permission from Ref ; copyright 2012 The Royal Society of Chemistry. Panel (d) is reproduced with permission from Ref ; copyright 2010 Elsevier Ltd. Panels (e–g) are reproduced with permission from Ref ; copyright 2012 American Chemical Society. BMSC, bone marrow stromal cell; TMV, tobacco mosaic virus; BMP2, bone morphogenetic protein 2; TCP, tissue culture plastic; PAH, porous alginate hydrogels.
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(a) Schematic illustration of the formation of the phage film by using layer‐by‐layer method and the MSCs growth on the phage film. (b) Fluorescent images of protein expression in MSCs cultured on M13 thin films. Colour representation: nucleus (blue), actin (green), osteopontin and osteocalcin (red). The figure is reproduced with permission from Ref ; copyright 2011 Elsevier Ltd. MSC, marrow stromal cell; OPN, osteopontin; OCN, osteocalcin.
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Nanotechnology Approaches to Biology > Cells at the Nanoscale
Implantable Materials and Surgical Technologies > Nanomaterials and Implants
Biology-Inspired Nanomaterials > Protein and Virus-Based Structures

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