title: Polysaccharide-modified scaffolds for controlled lentivirus delivery in vitro and after spinal cord injury.
abstract: Gene delivering biomaterials have increasingly been employed to modulate the cellular microenvironment to promote tissue regeneration, yet low transduction efficiency has been a persistent challenge for in vivo applications. In this report, we investigated the surface modification of poly(lactide-co-glycolide) (PLG) scaffolds with polysaccharides, which have been implicated in binding lentivirus but have not been used for delivery. Chitosan was directly conjugated onto PLG scaffolds, whereas heparin and hyaluronan were indirectly conjugated onto PLG scaffolds with multi-amine crosslinkers. The addition of chitosan and heparin onto PLG promoted the association of lentivirus to these scaffolds and enhanced their transduction efficiency in vitro relative to hyaluronan-conjugated and control scaffolds that had limited lentivirus association and transduction. Transduction efficiency in vitro was increased partly due to an enhanced retention of virus on the scaffold as well as an extended half-life of viral activity. Transduction efficiency was also evaluated in vivo using porous, multiple channel PLG bridges that delivered lentivirus to the injured mouse spinal cord. Transgene expression persisted for weeks after implantation, and was able to enhance axon growth and myelination. These studies support gene-delivering PLG scaffolds for in vivo 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.forename: Lonnie D
authors.initials: LD
authors.lastname: Shea
mesh_terms: D000818:Animals; D048271:Chitosan / Q000737:chemistry; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D057809:HEK293 Cells; D006493:Heparin / Q000737:chemistry; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry; D016086:Lentivirus / Q000737:chemistry / Q000235:genetics*; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013119:Spinal Cord Injuries / Q000628:therapy*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006820:Hyaluronic Acid; D006493:Heparin; D048271:Chitosan; D008156:Luciferases
keywords: Gene delivery; Lentivirus; Multiple channel bridge; Polysaccharide; Scaffold; Spinal cord injury