Controlling fibrous capsule formation through long-term down-regulation of collagen type I (COL1A1) expression by nanofiber-mediated siRNA gene silencing.

Abstract

The foreign body reaction often interferes with the long-term functionality and performance of implanted biomedical devices through fibrous capsule formation. While many implant modification techniques have been adopted in attempts to control fibrous encapsulation, the outcomes remained sub-optimal. Nanofiber scaffold-mediated RNA interference may serve as an alternative approach through the localized and sustained delivery of siRNA at implant sites. In this study, we investigated the efficacy of siRNA-poly(caprolactone-co-ethylethylene phosphate) nanofibers in controlling fibrous capsule formation through the down-regulation of collagen type I (COL1A1) in vitro and in vivo. By encapsulating complexes of COL1A1 siRNA with a transfection reagent (Transit TKO) or the cell penetrating peptides CADY or MPG within the nanofibers (550-650 nm in diameter), a sustained release of siRNA was obtained for at least 28 days (loading efficiency ~60-67%). Scaffold-mediated transfection significantly enhanced cellular uptake of oligonucleotides and prolonged in vitro gene silencing duration by at least 2-3 times as compared to conventional bolus delivery of siRNA (14 days vs. 5-7 days by bolus delivery). In vivo subcutaneous implantation of siRNA scaffolds revealed a significant decrease in fibrous capsule thickness at weeks 2 and 4 as compared to plain nanofibers (p<0.05). Taken together, the results demonstrated the efficacy of scaffold-mediated siRNA gene-silencing in providing effective long-term control of fibrous capsule formation.

• Authors: Pim-on Rujitanaroj, Brian Jao, Junghoon Yang, Feng Wang, James M Anderson, Jun Wang, Sing Yian Chew
• Journal: Acta biomaterialia (Acta Biomater) Vol. 9 Issue 1 Pg. 4513-24 (Jan 2013) ISSN: 1878-7568 [Electronic] England
• PMID: 23036951 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Acta Materialia Inc. All rights reserved.

Chemical References

• Collagen Type I
• DNA Primers
• Organophosphates
• Polyesters
• RNA, Small Interfering
• poly(caprolactone-co-ethylethylene phosphate)

Topics

• Base Sequence
• Collagen Type I (genetics, metabolism)
• DNA Primers
• Down-Regulation
• Electrophoresis, Agar Gel
• Gene Silencing
• Immunohistochemistry
• Kinetics
• Microscopy, Electron, Scanning
• Nanofibers
• Organophosphates (chemistry)
• Polyesters (chemistry)
• RNA, Small Interfering (genetics)
• Real-Time Polymerase Chain Reaction