Sustained, localized transgene expression mediated from lentivirus-loaded biodegradable polyester elastomers.
The study of biomaterials for gene delivery in tissue engineering and regenerative medicine is a growing area, necessitating the investigation of new biomaterials and gene delivery vectors. Poly(1,8-octanediol citrate) (POC) and poly(glycerol-sebacate) (PGS) are biodegradable, biocompatible elastomers that have tunable mechanical properties, surface characteristics, and degradation rate. The objective of this work was to investigate whether POC and PGS would support the immobilization and release of lentivirus to allow sustained and localized transgene expression. Porous biomaterials were prepared using salt as a porogen, and in vitro and in vivo transgene expression from immobilized and released lentiviruses were assessed. Cells seeded onto biomaterials loaded with lentiviruses yielded titer-dependent transgene expression in vitro. Lentivirus activity on both biomaterials was maintained for at least 5 days. When implanted subcutaneously in rats, POC and PGS with immobilized lentivirus exhibited sustained and localized transgene expression for at least 5 weeks. This research demonstrates that lentivirus immobilization on POC and PGS is feasible and potentially useful for a variety of tissue engineering and regenerative medicine applications.
Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, USA.
Michele C
MC
Jen
Kevin
K
Baler
Ashleigh R
AR
Hood
Seungjin
S
Shin
Lonnie D
LD
Shea
Guillermo A
GA
Ameer
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002951:Citrates / Q000737:chemistry*; D003651:Decanoates / Q000737:chemistry*; D020724:Elastomers / Q000737:chemistry*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D005990:Glycerol / Q000031:analogs & derivatives* / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014161:Transduction, Genetic; D014162:Transfection; D019076:Transgenes
D001672:Biocompatible Materials; D002951:Citrates; D003651:Decanoates; D020724:Elastomers; D011108:Polymers; C513817:poly(1,8-octanediol citrate); C469892:poly(glycerol-sebacate); D005990:Glycerol