title: Lentivirus delivery by adsorption to tissue engineering scaffolds.
abstract: Biomaterial scaffolds capable of localized gene delivery are being investigated for numerous regenerative medicine applications and as model systems for fundamental studies of tissue formation. In this manuscript, we investigate the delivery of lentivirus from a tissue engineering scaffold using a surface immobilization strategy. Poly(lactide-co-glycolide) (PLG) was employed as the biomaterial for delivery, which has been widely used for a number of tissue engineering applications. The virus was immobilized by freezing and subsequent lyophilization of the virus with the scaffold. The presence of sucrose during freezing and lyophilization maintained the activity of the lentivirus, and was similar to an adenovirus control. Collagen and fibronectin were investigated for their ability to enhance surface immobilization. Fibronectin modestly increased binding and transduction of the adenovirus, yet did not significantly impact the lentivirus delivery. Most of the immobilized lentivirus was released from the scaffold within 24 h. In vivo implantation of the scaffolds yielded transgene expression that persisted for at least 4 weeks. These findings indicate the potential for delivering lentivirus from tissue engineering scaffolds using a surface immobilization strategy. To our knowledge, this report is the first to investigate lentivirus delivery from porous tissue engineering scaffolds. Delivery of lentiviral vectors from PLG scaffolds could provide an efficient and versatile gene delivery system for use with in vitro and in vivo models of tissue formation, and ultimately for therapeutic applications.
authors.affiliation: Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Road E156, Evanston, Illinois 60208-3120, USA.
authors.forename: Seungjin
authors.initials: S
authors.lastname: Shin
authors.forename: David M
authors.initials: DM
authors.lastname: Salvay
authors.forename: Lonnie D
authors.initials: LD
authors.lastname: Shea
mesh_terms: D000327:Adsorption; D000818:Animals; D003094:Collagen / Q000737:chemistry; D005353:Fibronectins / Q000737:chemistry; D005612:Freeze Drying; D005615:Freezing; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism*; D049449:Luminescence; D008297:Male; D051379:Mice; D011108:Polymers / Q000737:chemistry; D013395:Sucrose / Q000737:chemistry; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D005353:Fibronectins; D011108:Polymers; D049452:Green Fluorescent Proteins; D013395:Sucrose; D003094:Collagen