Polysaccharide-modified scaffolds for controlled lentivirus delivery in vitro and after spinal cord injury
| Autor: | Aline M. Thomas, Lonnie D. Shea |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Scaffold
Pharmaceutical Science Gene delivery Regenerative medicine Article Mice Transduction (genetics) chemistry.chemical_compound Polylactic Acid-Polyglycolic Acid Copolymer In vivo Hyaluronic acid Animals Humans Lactic Acid Hyaluronic Acid Luciferases Spinal Cord Injuries Chitosan Tissue Scaffolds biology Heparin Chemistry Lentivirus Gene Transfer Techniques Genetic Therapy biology.organism_classification Molecular biology In vitro Cell biology Mice Inbred C57BL HEK293 Cells Female Polyglycolic Acid |
| Zdroj: | Journal of Controlled Release. 170:421-429 |
| ISSN: | 0168-3659 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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