Document Type

Dissertation

Date of Award

5-31-2015

Degree Name

Doctor of Philosophy in Biomedical Engineering - (Ph.D.)

Department

Biomedical Engineering

First Advisor

Treena Livingston Arinzeh

Second Advisor

Michael Jaffe

Third Advisor

Boris Khusid

Fourth Advisor

J. Christopher Fritton

Fifth Advisor

Pranela Rameshwar

Abstract

Osteoarthritis is one of the most prevalent causes of disability affecting nearly 27 million Americans. Osteoarthritis is caused when extensive damage occurs to the articular cartilage later spreading to the underlying subchondral bone, resulting in osteochondral defects. The current clinical therapies aim at regenerating the hyaline cartilage, but instead fibrocartilage forms at the osteochondral defect site, which is inferior in structure and function and fails to integrate with the surrounding tissue. A biomimetic scaffold, which can provide cues similar to the native extracellular matrix, may facilitate osteochondral defect repair. Articular cartilage and bone extracellular matrix have been shown to produce electrical potentials when subjected to mechanical loading. The electrical behavior of cartilage and bone may provide signals for tissue repair and remodeling during injury and homeostasis. Therefore, a piezoelectric scaffold, which is able to generate electrical charge in response to deformation, is investigated in this study for its potential to support hyaline cartilage and bone tissue formation in combination with human mesenchymal stem cells (MSCs). The scaffold is composed of the synthetic polymer, poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE), a biocompatible, piezoelectric polymer. It is hypothesized that piezoelectric scaffolds will promote chondrogenic (cartilage) and osteogenic (bone) differentiation of MSCs. PVDF-TrFE is electrospun to form a fibrous, three-dimensional scaffold (as-spun). PVDF-TrFE scaffolds are further annealed to enhance piezoelectric properties (annealed). The chondrogenic and osteogenic differentiation of MSCs is evaluated on both as-spun and annealed PVDF-TrFE scaffolds in a perfused compression bioreactor system to simulate physiological loading. Electrospun polycaprolactone (PCL) is used as a non-piezoelectric control. Under physiological loading conditions, annealed PVDF-TrFE scaffolds have a higher voltage output compared to as-spun PVDF-TrFE scaffold. In bioreactor cultures, MSC chondrogenic differentiation is promoted on as-spun PVDF-TrFE and osteogenic differentiation is enhanced on annealed PVDF-TrFE scaffolds when compared to PCL control. These results suggest that MSCs differentiation behavior can be impacted by the differences in voltage output from the as-spun and annealed PVDF-TrFE, indicating a role for electromechanical stimulus on MSC differentiation. Therefore, piezoelectric scaffolds have the potential to support cartilage and bone growth for osteochondral defect repair.

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