Generic placeholder image

Current Stem Cell Research & Therapy


ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Review Article

The Application of Nanomaterials in Angiogenesis

Author(s): Tianle Li and Tao Zhang*

Volume 16, Issue 1, 2021

Published on: 11 February, 2020

Page: [74 - 82] Pages: 9

DOI: 10.2174/1574888X15666200211102203

Price: $65


Induction of angiogenesis has enormous potential in the treatment of ischemic diseases and the promotion of bulk tissue regeneration. However, the poor activity of angiogenic cells and proangiogenic factors after transplantation is the main problem that imposes its wide applications. Recent studies have found that the development of nanomaterials has solved this problem to some extent. Nanomaterials can be mainly classified into inorganic nanomaterials represented by metals, metal oxides and metal hydroxides, and organic nanomaterials including DNA tetrahedrons, graphene, graphene oxide, and carbon nanotubes. These nanomaterials can induce the release of angiogenic factors either directly or indirectly, thereby initiating a series of signaling pathways to induce angiogenesis. Moreover, appropriate surface modifications of nanomaterial facilitate a variety of functions, such as enhancing its biocompatibility and biostability. In clinical applications, nanomaterials can promote the proliferation and differentiation of endothelial cells or mesenchymal stem cells, thereby promoting the migration of hemangioblast cells to form new blood vessels. This review outlines the role of nanomaterials in angiogenesis and is intended to provide new insights into the clinical treatment of systemic and ischemic diseases.

Keywords: Nanomaterials, angiogenesis, angiogenic factors, endothelial cells, mesenchymal stem cells, biostability.

Carmeliet P. Angiogenesis in life, disease and medicine. Nature 2005; 438(7070): 932-6.
[] [PMID: 16355210]
Ennett AB, Mooney DJ. Tissue engineering strategies for in vivo neovascularisation. Expert Opin Biol Ther 2002; 2(8): 805-18.
[] [PMID: 12517260]
Freedman SB, Isner JM. .Isner, Therapeutic angiogenesis for ischemic cardiovascular disease. J Mol Cell Cardiol 2001; 33(3): 0-3..
Ouma GO, Jonas RA, Usman MH, Mohler ER III. Targets and delivery methods for therapeutic angiogenesis in peripheral artery disease. Vasc Med 2012; 17(3): 174-92.
[] [PMID: 22496126]
Geiger F, Bertram H, Berger I, et al. Vascular endothelial growth factor gene-activated matrix (VEGF165-GAM) enhances osteogenesis and angiogenesis in large segmental bone defects. J Bone Miner Res 2005; 20(11): 2028-35.
[] [PMID: 16234976]
Matsuzaki H, Tamatani M, Yamaguchi A, et al. Vascular endothelial growth factor rescues hippocampal neurons from glutamate-induced toxicity: signal transduction cascades. FASEB J 2001; 15(7): 1218-20.
[] [PMID: 11344093]
Laschke MW, Harder Y, Amon M, et al. Angiogenesis in tissue engineering: breathing life into constructed tissue substitutes. Tissue Eng 2006; 12(8): 2093-104.
[] [PMID: 16968151]
Bir SC, Kolluru GK, Fang K, Kevil CG. Redox balance dynamically regulates vascular growth and remodeling. Semin Cell Dev Biol 2012; 23(7): 745-57.
[] [PMID: 22634069]
Grant GA, Janigro D. Vasculogenesis and angiogenesis. New York, NY: Humana Press 2006.
Takahashi T, Kalka C, Masuda H, et al. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 1999; 5(4): 434-8.
[] [PMID: 10202935]
Jia L, Prabhakaran MP, Qin X, Ramakrishna S. Stem cell differentiation on electrospun nanofibrous substrates for vascular tissue engineering. Mater Sci Eng C 2013; 33(8): 4640-50.
[] [PMID: 24094171]
Aguirre A, Planell JA, Engel E. Dynamics of bone marrow-derived endothelial progenitor cell/mesenchymal stem cell interaction in co-culture and its implications in angiogenesis. Biochem Biophys Res Commun 2010; 400(2): 284-91.
[] [PMID: 20732306]
Rouwkema J, Rivron NC, van Blitterswijk CA. Vascularization in tissue engineering. Trends Biotechnol 2008; 26(8): 434-41.
[] [PMID: 18585808]
Hendrickx B, Vranckx JJ, Luttun A. Cell-based vascularization strategies for skin tissue engineering. Tissue Eng Part B Rev 2011; 17(1): 13-24.
[] [PMID: 20954829]
Das S, Singh S, Dowding JM, et al. The induction of angiogenesis by cerium oxide nanoparticles through the modulation of oxygen in intracellular environments. Biomaterials 2012; 33(31): 7746-55.
[] [PMID: 22858004]
Bartczak D, Kanaras AG. Diacetylene-containing ligand as a new capping agent for the preparation of water-soluble colloidal nanoparticles of remarkable stability. Langmuir 2010; 26(10): 7072-7.
[] [PMID: 20078089]
Richardson TP, Peters MC, Ennett AB, Mooney DJ. Polymeric system for dual growth factor delivery. Nat Biotechnol 2001; 19(11): 1029-34.
[] [PMID: 11689847]
Zhang L, Webster TJ. Nanotechnology and nanomaterials: Promises for improved tissue regeneration. Nano Today 2009; 4(1): 66-80.
Clark P, Connolly P, Curtis AS, Dow JA, Wilkinson CD. Topographical control of cell behaviour: II. Multiple grooved substrata. Development 1990; 108(4): 635-44.
[PMID: 2387239]
Binsalamah ZM, Paul A, Khan AA, Prakash S, Shum-Tim D. Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model. Int J Nanomedicine 2011; 6: 2667-78.
[PMID: 22114497]
Li Z, Zhen J, Luan Y. Ionic liquids for synthesis of inorganic nanomaterials 2008; 12(1): 0-8..
Tiwari PM, Vig K, Dennis VA, Singh SR. Functionalized gold nanoparticles and their biomedical applications. Nanomaterials (Basel) 2011; 1(1): 31-63.
[] [PMID: 28348279]
Bartczak D, Sanchez-Elsner T, Louafi F, Millar TM, Kanaras AG. Receptor-mediated interactions between colloidal gold nanoparticles and human umbilical vein endothelial cells. Small 2011; 7(3): 388-94.
[] [PMID: 21294268]
Bartczak D, Muskens OL, Sanchez-Elsner T, Kanaras AG, Millar TM. Manipulation of in vitro angiogenesis using peptide-coated gold nanoparticles. ACS Nano 2013; 7(6): 5628-36.
[] [PMID: 23713973]
Nethi SK, Mukherjee S, Veeriah V, Barui AK, Chatterjee S, Patra CR. Bioconjugated gold nanoparticles accelerate the growth of new blood vessels through redox signaling. Chem Commun (Camb) 2014; 50(92): 14367-70.
[] [PMID: 25298204]
Gérard C, Bordeleau LJ, Barralet J, Doillon CJ. The stimulation of angiogenesis and collagen deposition by copper. Biomaterials 2010; 31(5): 824-31.
[] [PMID: 19854506]
Ke Q, Costa M. Hypoxia-inducible factor-1 (HIF-1). Mol Pharmacol 2006; 70(5): 1469-80.
[] [PMID: 16887934]
van Heerden D, Vosloo A, Nikinmaa M. Effects of short-term copper exposure on gill structure, metallothionein and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in rainbow trout (Oncorhynchus mykiss). Aquat Toxicol 2004; 69(3): 271-80.
[] [PMID: 15276332]
Kaczmarek M, Timofeeva OA, Karaczyn A, Malyguine A, Kasprzak KS, Salnikow K. The role of ascorbate in the modulation of HIF-1alpha protein and HIF-dependent transcription by chromium(VI) and nickel(II). Free Radic Biol Med 2007; 42(8): 1246-57.
[] [PMID: 17382205]
Gao N, Ding M, Zheng JZ, et al. Vanadate-induced expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor through phosphatidylinositol 3-kinase/Akt pathway and reactive oxygen species. J Biol Chem 2002; 277(35): 31963-71.
[] [PMID: 12070140]
Weng L, Boda SK, Teusink MJ, Shuler FD, Li X, Xie J. Binary doping of strontium and copper enhancing osteogenesis and angiogenesis of bioactive glass nanofibers while suppressing osteoclast activity. ACS Appl Mater Interfaces 2017; 9(29): 24484-96.
[] [PMID: 28675029]
Wu C, Zhou Y, Fan W, et al. Hypoxia-mimicking mesoporous bioactive glass scaffolds with controllable cobalt ion release for bone tissue engineering. Biomaterials 2012; 33(7): 2076-85.
[] [PMID: 22177618]
Yoshizawa S, Brown A, Barchowsky A, Sfeir C. Magnesium ion stimulation of bone marrow stromal cells enhances osteogenic activity, simulating the effect of magnesium alloy degradation. Acta Biomater 2014; 10(6): 2834-42.
[] [PMID: 24512978]
Hu GF. Copper stimulates proliferation of human endothelial cells under culture. J Cell Biochem 1998; 69(3): 326-35.
[<326:AID-JCB10>3.0.CO;2-A] [PMID: 9581871]
Boldbaatar K, Dashnyam K, Knowles JC, Lee HH, Lee JH, Kim HW. Dual-ion delivery for synergistic angiogenesis and bactericidal capacity with silica-based microsphere. Acta Biomater 2019; 83: 322-33.
[] [PMID: 30465920]
Augustine R, Mathew AP, Sosnik A. Metal oxide nanoparticles as versatile therapeutic agents modulating cell signaling pathways: Linking nanotechnology with molecular medicine. Applied Materials Today 2017; 7: 91-103.
Nethi SK, Veeriah V, Barui AK, et al. Investigation of molecular mechanisms and regulatory pathways of pro-angiogenic nanorods. Nanoscale 2015; 7(21): 9760-70.
[] [PMID: 25963768]
Li Y, Zhang W, Niu J, Chen Y. Mechanism of photogenerated reactive oxygen species and correlation with the antibacterial properties of engineered metal-oxide nanoparticles. ACS Nano 2012; 6(6): 5164-73.
[] [PMID: 22587225]
Tabibiazar R, Rockson SG. Angiogenesis and the ischaemic heart. Eur Heart J 2001; 22(11): 903-18.
[] [PMID: 11428814]
Griffith LG, Naughton G. Tissue engineering--current challenges and expanding opportunities. Science 2002; 295(5557): 1009-14.
[] [PMID: 11834815]
Getsoian AB, Zhai Z, Bell AT. Band-gap energy as a descriptor of catalytic activity for propene oxidation over mixed metal oxide catalysts. J Am Chem Soc 2014; 136(39): 13684-97.
[] [PMID: 25187385]
Barui AK, Veeriah V, Mukherjee S, et al. Zinc oxide nanoflowers make new blood vessels. Nanoscale 2012; 4(24): 7861-9.
[] [PMID: 23152079]
Beltrán-Partida E, Valdéz-Salas B, Moreno-Ulloa A, et al. Improved in vitro angiogenic behavior on anodized titanium dioxide nanotubes. J Nanobiotechnology 2017; 15(1): 10.
[] [PMID: 28143540]
Chen Y, Gao A, Bai L, et al. Antibacterial, osteogenic, and angiogenic activities of SrTiO3 nanotubes embedded with Ag2O nanoparticles. Mater Sci Eng C 2017; 75: 1049-58.
[] [PMID: 28415389]
Du W, Zhang K, Zhang S, et al. Enhanced proangiogenic potential of mesenchymal stem cell-derived exosomes stimulated by a nitric oxide releasing polymer. Biomaterials 2017; 133: 70-81.
[] [PMID: 28433939]
Patra CR, Bhattacharya R, Patra S, et al. Pro-angiogenic properties of europium(III) hydroxide nanorods. Adv Mater 2008; 20(4): 753-6.
Rzigalinski BA, Carfagna CS, Ehrich M. Cerium oxide nanoparticles in neuroprotection and considerations for efficacy and safety. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2017; 9(4)10.1002/wnan.1444..
[] [PMID: 27860449]
Xiang J, Li J, He J, et al. Cerium oxide nanoparticle modified scaffold interface enhances vascularization of bone grafts by activating calcium channel of mesenchymal stem cells. ACS Appl Mater Interfaces 2016; 8(7): 4489-99.
[] [PMID: 26824825]
Dong H, Hu W. Organic Nanomaterials. Springer Handbook of Nanomaterials 2013.
Foldvari M, Bagonluri M. Carbon nanotubes as functional excipients for nanomedicines: Pharmaceutical properties. Nanomedicine (Lond) 2008; 4(3): 173-82.
[] [PMID: 18550451]
Azad N, Iyer AK, Wang L, Liu Y, Lu Y, Rojanasakul Y. Reactive oxygen species-mediated p38 MAPK regulates carbon nanotube-induced fibrogenic and angiogenic responses. Nanotoxicology 2013; 7(2): 157-68.
[] [PMID: 22263913]
Meng J, Li X, Wang C, Guo H, Liu J, Xu H. Carbon nanotubes activate macrophages into a M1/M2 mixed status: Recruiting naïve macrophages and supporting angiogenesis. ACS Appl Mater Interfaces 2015; 7(5): 3180-8.
[] [PMID: 25591447]
Yang Y, Asiri AM, Tang Z, et al. Graphene based materials for biomedical applications. Mater Today 2013; 16(10): 365-73.
Mukherjee S, Sriram P, Barui AK, et al. Graphene oxides show angiogenic properties. Adv Healthc Mater 2015; 4(11): 1722-32.
[] [PMID: 26033847]
Jeong J, Cho HJ, Choi M, et al. In vivo toxicity assessment of angiogenesis and the live distribution of nano-graphene oxide and its PEGylated derivatives using the developing zebrafish embryo. Carbon 2015; 93: 431-40.
Shie MY, Chiang WH, Chen IP, Liu WY, Chen YW. Synergistic acceleration in the osteogenic and angiogenic differentiation of human mesenchymal stem cells by calcium silicate-graphene composites. Mater Sci Eng C 2017; 73: 726-35.
[] [PMID: 28183667]
Sun Z, Huang P, Tong G, et al. VEGF-loaded graphene oxide as theranostics for multi-modality imaging-monitored targeting therapeutic angiogenesis of ischemic muscle. Nanoscale 2013; 5(15): 6857-66.
[] [PMID: 23770832]
Dong S, Zhao R, Zhu J, et al. Electrochemical DNA biosensor based on a tetrahedral nanostructure probe for the detection of Avian Influenza A (H7N9) Virus. ACS Appl Mater Interfaces 2015; 7(16): 8834-42.
[] [PMID: 25844798]
Xia K, Kong H, Cui Y, et al. Systematic study in mammalian cells showing no adverse response to tetrahedral DNA nanostructure. ACS Appl Mater Interfaces 2018; 10(18): 15442-8.
[] [PMID: 29668248]
Shao X, Lin S, Peng Q, et al. Tetrahedral DNA Nanostructure: A Potential Promoter for Cartilage Tissue Regeneration via Regulating Chondrocyte Phenotype and Proliferation. Small 2017; 13(12)1602770
[] [PMID: 28112870]
Zhao D, Liu M, Li Q, et al. Tetrahedral DNA nanostructure promotes endothelial cell proliferation, migration, and angiogenesis via notch signaling pathway. ACS Appl Mater Interfaces 2018; 10(44): 37911-8.
[] [PMID: 30335942]
Cao R, Ji H, Feng N, et al. Collaborative interplay between FGF-2 and VEGF-C promotes lymphangiogenesis and metastasis. Proc Natl Acad Sci USA 2012; 109(39): 15894-9.
[] [PMID: 22967508]
Pearlman JD, Hibberd MG, Chuang ML, et al. Magnetic resonance mapping demonstrates benefits of VEGF-induced myocardial angiogenesis. Nat Med 1995; 1(10): 1085-9.
[] [PMID: 7489368]
Battler A, Scheinowitz M, Bor A, et al. Intracoronary injection of basic fibroblast growth factor enhances angiogenesis in infarcted swine myocardium. J Am Coll Cardiol 1993; 22(7): 2001-6.
[] [PMID: 7504006]
Barralet J, Gbureck U, Habibovic P, Vorndran E, Gerard C, Doillon CJ. Angiogenesis in calcium phosphate scaffolds by inorganic copper ion release. Tissue Eng Part A 2009; 15(7): 1601-9.
[] [PMID: 19182977]
Jain RA. The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials 2000; 21(23): 2475-90.
[] [PMID: 11055295]
Golub JS, Kim YT, Duvall CL, et al. Sustained VEGF delivery via PLGA nanoparticles promotes vascular growth. Am J Physiol Heart Circ Physiol 2010; 298(6): H1959-65.
[] [PMID: 20228260]
Sengupta S, Gherardi E, Sellers LA, Wood JM, Sasisekharan R, Fan TP. Hepatocyte growth factor/scatter factor can induce angiogenesis independently of vascular endothelial growth factor. Arterioscler Thromb Vasc Biol 2003; 23(1): 69-75.
[] [PMID: 12524227]
Sinha Roy R, Soni S, Harfouche R, et al. Coupling growth-factor engineering with nanotechnology for therapeutic angiogenesis. Proc Natl Acad Sci USA 2010; 107(31): 13608-13.
[] [PMID: 20639469]
Edelman ER, Mathiowitz E, Langer R, Klagsbrun M. Controlled and modulated release of basic fibroblast growth factor. Biomaterials 1991; 12(7): 619-26.
[] [PMID: 1742404]
Rajangam K, Behanna HA, Hui MJ, et al. Heparin binding nanostructures to promote growth of blood vessels. Nano Lett 2006; 6(9): 2086-90.
[] [PMID: 16968030]
Rajangam K, Arnold MS, Rocco MA, Stupp SI. Peptide amphiphile nanostructure-heparin interactions and their relationship to bioactivity. Biomaterials 2008; 29(23): 3298-305.
[] [PMID: 18468676]
Chow LW, Wang LJ, Kaufman DB, Stupp SI. Self-assembling nanostructures to deliver angiogenic factors to pancreatic islets. Biomaterials 2010; 31(24): 6154-61.
[] [PMID: 20552727]
Ennett AB, Mooney DJ. Tissue engineering strategies for in vivo neovascularisation. Expert Opin Biol Ther 2002; 2(8): 805-18.
[] [PMID: 12517260]
Shahzadi L, et al. Development of K-doped ZnO nanoparticles encapsulated crosslinked chitosan based new membranes to stimulate angiogenesis in tissue engineered skin grafts. Int J Biol Macromol 2018; 120(Pt A): 721-8..
Augustine R, Dominic EA, Reju I, et al. Investigation of angiogenesis and its mechanism using zinc oxide nanoparticle-loaded electrospun tissue engineering scaffolds. RSC Advances 2014; 4(93): 51528-36.
Augustine R, Nethi SK, Kalarikkal N, et al. Electrospun polycaprolactone (PCL) scaffolds embedded with europium hydroxide nanorods (EHNs) with enhanced vascularization and cell proliferation for tissue engineering applications. J Mater Chem B Mater Biol Med 2017; 5(24): 4660-72.
Zhao S, Li L, Wang H, et al. Wound dressings composed of copper-doped borate bioactive glass microfibers stimulate angiogenesis and heal full-thickness skin defects in a rodent model. Biomaterials 2015; 53: 379-91.
[] [PMID: 25890736]
Giavaresi G, Torricelli P, Fornasari PM, Giardino R, Barbucci R, Leone G. Blood vessel formation after soft-tissue implantation of hyaluronan-based hydrogel supplemented with copper ions. Biomaterials 2005; 26(16): 3001-8.
[] [PMID: 15603795]
Hsieh SC, Chen HJ, Hsu SH, et al. Prominent Vascularization Capacity of Mesenchymal Stem Cells in Collagen-Gold Nanocomposites. ACS Appl Mater Interfaces 2016; 8(42): 28982-9000.
[] [PMID: 27714998]
Hung HS, Yang YC, Lin YC, et al. Regulation of human endothelial progenitor cell maturation by polyurethane nanocomposites. Biomaterials 2014; 35(25): 6810-21.
[] [PMID: 24836305]
Liu Z, Feng X, Wang H, et al. Carbon nanotubes as VEGF carriers to improve the early vascularization of porcine small intestinal submucosa in abdominal wall defect repair. Int J Nanomedicine 2014; 9: 1275-86.
[PMID: 24648727]
Pina S, Oliveira JM, Reis RL. Natural-based nanocomposites for bone tissue engineering and regenerative medicine: A review. Adv Mater 2015; 27(7): 1143-69.
[] [PMID: 25580589]
Kaigler D, Krebsbach PH, West ER, Horger K, Huang YC, Mooney DJ. Endothelial cell modulation of bone marrow stromal cell osteogenic potential. FASEB J 2005; 19(6): 665-7.
[] [PMID: 15677693]
Kusumbe AP, Ramasamy SK, Adams RH. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature 2014; 507(7492): 323-8.
[] [PMID: 24646994]
Xie H, Cui Z, Wang L, et al. PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis. Nat Med 2014; 20(11): 1270-8.
[] [PMID: 25282358]
Kaigler D, Krebsbach PH, Wang Z, West ER, Horger K, Mooney DJ. Transplanted endothelial cells enhance orthotopic bone regeneration. J Dent Res 2006; 85(7): 633-7.
[] [PMID: 16798864]
Kaigler D, Wang Z, Horger K, Mooney DJ, Krebsbach PH. VEGF scaffolds enhance angiogenesis and bone regeneration in irradiated osseous defects. J Bone Miner Res 2006; 21(5): 735-44.
[] [PMID: 16734388]
Jacobsen NR, Pojana G, White P, et al. Genotoxicity, cytotoxicity, and reactive oxygen species induced by single-walled carbon nanotubes and C(60) fullerenes in the FE1-Mutatrade markMouse lung epithelial cells. Environ Mol Mutagen 2008; 49(6): 476-87.
[] [PMID: 18618583]
Kawai T, Takagi Y, Fukuzawa M, Yamagishi T, Goto S. The role of trefoil factor family in apparently healthy subjects administrated gastroprotective agents for the primary prevention of gastrointestinal injuries from low-dose acetylsalicylic acid: A preliminary study. J Clin Biochem Nutr 2011; 49(2): 136-40.
[] [PMID: 21980231]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy