Electronic Theses and Dissertations

Date

2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Biomedical Engineering

Committee Chair

Joel Bumgardner

Committee Member

Jessica Jennings

Committee Member

Richard Smith

Committee Member

Tomoko Fujiwara

Abstract

Guided bone regeneration (GBR) membranes are commonly used to maximize bone healing/regeneration by protecting bone grafted sites from invasion by soft tissues. Electrospun chitosan membranes modified by short chain fatty acids (Acetic anhydride (AA), butyric anhydride (BA) and hexanoic anhydride (HA)) or with tBOC (tert-Butyloxycarbonyl group) have many characteristics including retention of nanofiber structure, occlusive to soft tissues and osteoconductive properties in vivo that are important for GBR applications. The high surface area of the nanofiber structure of the membranes provides opportunity for the local delivery of osteogenic or angiogenic agents for enhancing their healing and bone regeneration properties. The objective of this research was to fabricate modified electrospun chitosan membranes capable of controlling the release of an osteogenic (Simvastatin, SMV) and angiogenic (magnesium) agent and evaluate their bioactivity for GBR applications in a series of in vitro and in vivo experiments. Electrospun chitosan membranes with different modifications were fabricated that enabled the controlled release of loaded/incorporated agents. SMV was released faster by AA and tBOC modified membranes than BA and HA modified membranes. SMV loaded membranes prevented soft tissue infiltration into the defect site and promoted better bone healing than non-loaded membranes in a rat calvarial defect model. A slow release of high SMV dose showed better bone healing than fast release of high or low dose. Membranes incorporated with magnesium were capable of stimulating angiogenesis in vitro. The AA modified membranes released more magnesium and thereby showed better angiogenesis than HA modified membranes. Osteogenic and angiogenic potential of our drug loaded chitosan membranes was successfully demonstrated. Since angiogenesis plays an important role in the bone healing process, future studies with dual loading of SMV and magnesium might prove useful in enhancing the ability of these membranes to stimulate better/faster bone regeneration.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest

Notes

embargoed

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