Defense Date

2012

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Biomedical Engineering

First Advisor

Gary Bowlin

Second Advisor

Kimber White Jr.

Abstract

Electrospun materials have potential use in many biomedical applications such as soft tissue replacements or as scaffolds to target drug delivery to local sites. Electrospinning is a polymer processing technique that can be used to create materials composed of fibers with diameters ranging from the micron to the nanoscale. We investigated the effects of microfibrous and nanofibrous electrospun polycaprolactone (EPCL) on innate, cell-mediated, and humoral components of the immune system. Results demonstrated that in both young (12 week) and old (6 month) mice, EPCL had no effect on various immune parameters. With its lack of immunotoxicity, EPCL presents an excellent polymer scaffold for use in delivering drugs to local sites. Drug delivery studies focused on using EPCL nanofiber scaffolds with the known immunosuppressive compound dexamethasone (DEX) incorporated within the matrix. The ability of the EPCL-DEX scaffold to suppress cell-mediated immunity (CMI) was evaluated using the delayed-type hypersensitivity (DTH) response to Candida albicans. Preliminary studies were conducted following subcutaneous implantation of a single disk (6-mm or 3-mm diameter) with 3, 10, 30, or 100 % w/w DEX in EPCL in the thigh region. Based on footpad swelling, dose -responsive suppression of the DTH was observed based on DEX equivalent units (DEU) at all but the lowest dose. The animals that received the high dose (100% in 6-mm) had decreased spleen weights, however no change in spleen weight was observed at the lower doses. Thymus weights were only affected at the four highest doses. These preliminary results suggest that implantation of a drug-containing electrospun scaffold may achieve local immunosuppression without systemic toxicity. Finally, we evaluated the EPCL-DEX scaffold in an acute inflammatory model (keyhole limpet hemocyanin) and a mouse model of rheumatoid arthritis (collagen induced arthritis). While similar trends were observed in the other models, the EPCL-DEX system achieved greatest success in the DTH model.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

May 2012

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