DNA delivery from hyaluronic acid-collagen hydrogels via a substrate-mediated approach.
Efficient and controlled gene delivery from biodegradable materials can be employed to stimulate cellular processes that lead to tissue regeneration. In this report, a substrate-mediated approach was developed to deliver DNA from hyaluronic acid-collagen hydrogels. The hydrogels were formed by crosslinking HA with poly(ethylene glycol) diglycidyl ether. Poly(ethylene imine)(PEI)/DNA complexes were immobilized to the substrate using either biotin/neutravidin or non-specific adsorption. Complexes were formed in the presence or absence of salt to regulate complex size, and resulted in complexes with z-average diameters of 1221.7 +/- 152.3 and 139.4 +/- 1.3 nm, respectively. During 48-h incubation in PBS or hyaluronidase, DNA was released slowly from the hydrogel substrate (<30% of immobilized DNA), which was enhanced by incubation with conditioned media (approximately 50% of immobilized DNA). Transgene expression mediated by immobilized, large diameter complexes was 3 to 7-fold greater than for small diameter complexes. However, the percentage of cells expressing the transgene was greater for small diameter complexes (48.7%) than for large diameter complexes (22.3%). Spatially controlled gene transfer was achieved by topographically patterning the hydrogel to pattern cell adhesion. Biomaterial-based gene delivery can be applicable to numerous tissue engineering applications, or as a tool to examine tissue formation.
Segura
Tatiana
T
Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Rd./E156, Evanston, IL 60208-3120, USA.
Chung
Peter H
PH
Shea
Lonnie D
LD
D020341:Absorbable Implants; D000818:Animals; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D003094:Collagen / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D018014:Gene Transfer Techniques; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry; D008422:Materials Testing; D051379:Mice; D041681:NIH 3T3 Cells; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics*; D013499:Surface Properties; D014162:Transfection / Q000379:methods*
D020099:Coated Materials, Biocompatible; D020100:Hydrogels; D006820:Hyaluronic Acid; D003094:Collagen