Local gene delivery from ECM-coated poly(lactide-co-glycolide) multiple channel bridges after spinal cord injury.
Tissue engineering scaffolds with complex geometries can provide an architecture that directs tissue formation. Drug delivery from these scaffolds to promote regeneration is often challenging due to the complex fabrication processes. Surface-mediated DNA delivery from multiple channel bridges was applied to deliver lipoplexes in vivo to the injured spinal cord. The surface properties of the polymer, DNA deposition with or without drying, and the presence of ECM components were investigated. In vitro studies revealed that fibronectin produced greater expression levels and immobilization efficiencies compared with collagen, laminin, and no coating. In addition, lipoplex incubation on ECM-coated PLG increased expression relative to either of the drying methods. Additionally, the incubation method had more homogeneously distributed lipoplexes and a higher number of transfected cells relative to the dried conditions. Translation to three-dimensional bridges led to high levels of transgene expression in vitro. In vivo, lipoplexes immobilized to the bridge produced transgene expression levels in a rat spinal cord hemisection model that were 2-fold greater than naked plasmid. Additionally, expression with lipoplexes persisted for at least three weeks. Surface-mediated delivery can be applied to scaffolds with complex geometries to promote transgene expression in vivo.
De Laporte
Laura
L
Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Rd, E156 Evanston, IL 60208-3120, USA. l-shea@northwestern.edu
Yan
Anna Lei
AL
Shea
Lonnie D
LD
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000737:chemistry*; D005353:Fibronectins / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D011098:Polyglactin 910 / Q000737:chemistry*; D051381:Rats; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D019076:Transgenes / Q000235:genetics
D005353:Fibronectins; D011098:Polyglactin 910; D004247:DNA