title: Heparin-chitosan nanoparticle functionalization of porous poly(ethylene glycol) hydrogels for localized lentivirus delivery of angiogenic factors.
abstract: Hydrogels have been extensively used for regenerative medicine strategies given their tailorable mechanical and chemical properties. Gene delivery represents a promising strategy by which to enhance the bioactivity of the hydrogels, though the efficiency and localization of gene transfer have been challenging. Here, we functionalized porous poly(ethylene glycol) hydrogels with heparin-chitosan nanoparticles to retain the vectors locally and enhance lentivirus delivery while minimizing changes to hydrogel architecture and mechanical properties. The immobilization of nanoparticles, as compared to homogeneous heparin and/or chitosan, is essential to lentivirus immobilization and retention of activity. Using this gene-delivering platform, we over-expressed the angiogenic factors sonic hedgehog (Shh) and vascular endothelial growth factor (Vegf) to promote blood vessel recruitment to the implant site. Shh enhanced endothelial recruitment and blood vessel formation around the hydrogel compared to both Vegf-delivering and control hydrogels. The nanoparticle-modified porous hydrogels for delivering gene therapy vectors can provide a platform for numerous regenerative medicine applications.
authors.affiliation: Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA.
authors.forename: Aline M
authors.initials: AM
authors.lastname: Thomas
authors.affiliation: Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Gomez
authors.affiliation: Department of Chemical and Biological Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA.
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Palma
authors.affiliation: Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA.
authors.forename: Woon Teck
authors.initials: WT
authors.lastname: Yap
authors.affiliation: Department of Chemical and Biological Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA; Institute for BioNanotechnology in Medicine (IBNAM), Northwestern University, Chicago, IL, USA; Center for Reproductive Science (CRS), Northwestern University, Evanston, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA; Chemistry of Life Processes Institute (CLP), Northwestern University, Evanston, IL, USA. Electronic address: l-shea@northwestern.edu.
authors.forename: Lonnie D
authors.initials: LD
authors.lastname: Shea
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D048271:Chitosan / Q000737:chemistry*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D057809:HEK293 Cells; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D016086:Lentivirus / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D018919:Neovascularization, Physiologic; D011092:Polyethylene Glycols / Q000737:chemistry*; D055672:Static Electricity
chemical_list: D043925:Angiogenesis Inducing Agents; D020100:Hydrogels; D011092:Polyethylene Glycols; D006493:Heparin; D048271:Chitosan; D008156:Luciferases
keywords: Hydrogel; Lentivirus; Sonic hedgehog; Vascularization