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Title page for ETD etd-10272011-113508

Type of Document Master's Thesis
Author Nelson, Christopher Edward
Author's Email Address chris.nelson@vanderbilt.edu
URN etd-10272011-113508
Title Sustained local delivery of siRNA from an injectable scaffold
Degree Master of Science
Department Biomedical Engineering
Advisory Committee
Advisor Name Title
Craig Duvall Committee Chair
Scott Guelcher Committee Member
  • controlled release
  • RNAi
  • polyurethane
  • siRNA
Date of Defense 2011-05-01
Availability unrestricted
Controlled gene silencing technologies have significant, unrealized potential for use in tissue regeneration applications. The design described herein provides a means to package and protect siRNA within pH-responsive, endosomolytic micellar nanoparticles (si-NPs) that can be incorporated into nontoxic, biodegradable, and injectable polyurethane (PUR) tissue scaffolds. The si-NPs were homogeneously incorporated throughout the porous PUR scaffolds, and they were shown to be released via a diffusion-based mechanism for over three weeks. The siRNA-loaded micelles were larger but retained nano particulate morphology of approximately 100 nm diameter following incorporation into and release from the scaffolds. PUR scaffold releasate collected in vitro in PBS at 37°C for 1-4 days was able to achieve dose-dependent siRNA-mediated silencing with approximately 50% silencing achieved of the model gene GAPDH in NIH3T3 mouse fibroblasts. This promising platform technology provides both a research tool capable of probing the effects of local gene silencing and a potentially high-impact therapeutic approach for sustained, local silencing of deleterious genes within tissue defects.
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