Abstract
Here we describe the preparation of a delivery vehicle for controlled release of Sonic hedgehog (Shh). The vehicle contains a synthetic polycation and heparin which interact by polyvalent charge attraction and rapidly self-assemble into liquid coacervate droplets. The coacervate loads Shh with high efficiency, protects its bioactivity, and provides sustained and localized release at the site of application. Shh coacervate may be injected directly or coated onto a polymeric scaffold for tissue engineering approaches, as described here.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ingham PW, McMahon AP (2001) Hedgehog signaling in animal development: paradigms and principles. Genes Dev 15:3059–3087
Kusano KF, Pola R, Murayama T, Curry C, Kawamoto A, Iwakura A et al (2005) Sonic hedgehog myocardial gene therapy: tissue repair through transient reconstitution of embryonic signaling. Nat Med 11:1197–1204
Pola R, Ling LE, Silver M, Corbley MJ, Kearney M, Blake Pepinski R et al (2001) The morphogen Sonic hedgehog is an indirect angiogenic agent upregulating two families of angiogenic growth factors. Nat Med 7:706–711
Asai J, Takenaka H, Kusano KF, Li M, Luedemann C, Curry C et al (2006) Topical sonic hedgehog gene therapy accelerates wound healing in diabetes by enhancing endothelial progenitor cell-mediated microvascular remodeling. Circulation 113:2413–2424
Rivron NC, Raiss CC, Liu J, Nandakumar A, Sticht C, Gretz N et al (2012) Sonic Hedgehog-activated engineered blood vessels enhance bone tissue formation. Proc Natl Acad Sci U S A 109:4413–4418
Calcutt NA, Allendoerfer KL, Mizisin AP, Middlemas A, Freshwater JD, Burgers M et al (2003) Therapeutic efficacy of sonic hedgehog protein in experimental diabetic neuropathy. J Clin Invest 111:507–514
Kicheva A, Bollenbach T, Wartlick O, Julicher F, Gonzalez-Gaitan M (2012) Investigating the principles of morphogen gradient formation: from tissues to cells. Curr Opin Genet Dev 22:527–532
Pellegrini L, Burke DF, von Delft F, Mulloy B, Blundell TL (2000) Crystal structure of fibroblast growth factor receptor ectodomain bound to ligand and heparin. Nature 407:1029–1034
Chu H, Gao J, Wang Y (2012) Design, synthesis, and biocompatibility of an arginine-based polyester. Biotechnol Prog 28:257–264
Daye LR, Gibson W, Williams KP (2010) Development of a high throughput screening assay for inhibitors of hedgehog-heparin interactions. Int J High Throughput Screen 1:69–80
Johnson NR, Wang Y (2013) Controlled delivery of sonic hedgehog morphogen and its potential for cardiac repair. PLoS One 8:e63075
Chu H, Chen CW, Huard J, Wang Y (2013) The effect of a heparin-based coacervate of fibroblast growth factor-2 on scarring in the infarcted myocardium. Biomaterials 34:1747–1756
Chu H, Gao J, Chen CW, Huard J, Wang Y (2011) Injectable fibroblast growth factor-2 coacervate for persistent angiogenesis. Proc Natl Acad Sci U S A 108:13444–13449
Chu H, Johnson NR, Mason NS, Wang Y (2011) A [polycation:heparin] complex releases growth factors with enhanced bioactivity. J Control Release 150:157–163
Johnson NR, Wang Y (2013) Controlled delivery of heparin-binding EGF-like growth factor yields fast and comprehensive wound healing. J Control Release 166:124–129
Li H, Johnson NR, Usas A, Lu A, Poddar M, Wang Y, Huard J (2013) Sustained release of bone morphogenetic protein 2 via coacervate improves the osteogenic potential of muscle-derived stem cells. Stem Cells Transl Med 2:667–677
Lee KW, Johnson NR, Gao J, Wang Y (2013) Human progenitor cell recruitment via SDF-1alpha coacervate-laden PGS vascular grafts. Biomaterials 34:9877–9885
Awada HK, Johnson NR, Wang Y (2014) Dual delivery of vascular endothelial growth factor and hepatocyte growth factor coacervate displays strong angiogenic effects. Macromol Biosci 14:679–686
Johnson NR, Ambe T, Wang Y (2014) Lysine-based polycation:heparin coacervate for controlled protein delivery. Acta Biomater 10:40–46
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media New York
About this protocol
Cite this protocol
Johnson, N.R., Wang, Y. (2015). Controlled Delivery of Sonic Hedgehog with a Heparin-Based Coacervate. In: Riobo, N. (eds) Hedgehog Signaling Protocols. Methods in Molecular Biology, vol 1322. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2772-2_1
Download citation
DOI: https://doi.org/10.1007/978-1-4939-2772-2_1
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-2771-5
Online ISBN: 978-1-4939-2772-2
eBook Packages: Springer Protocols