Document Type

Dissertation

Date of Award

5-31-2018

Degree Name

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

Department

Biomedical Engineering

First Advisor

Treena Livingston Arinzeh

Second Advisor

James Haorah

Third Advisor

Michael Jaffe

Fourth Advisor

Patrick O'Connor

Fifth Advisor

Pranela Rameshwar

Abstract

Osteoarthritis (OA) affects 27 million adults in the United States. OA causes degeneration of articular cartilage and subchondral bone. Articular cartilage has limited ability to regenerate and repair. Bone and cartilage tissues have known piezoelectric properties, which means they can generate electrical activity in response to mechanical deformation. Using a biomimetic approach, zinc oxide (ZnO), which has known piezoelectric properties, is fabricated into a flexible three-dimensional fibrous scaffold by embedding ZnO nanoparticles into slow degrading polycaprolactone (PCL). Zinc ions can be released from the fibrous scaffold over time, which also may be beneficial for cell function since zinc has well-known insulin-mimetic properties. Piezoelectric ZnO composite fibrous scaffolds are evaluated for cartilage and bone tissue formation in combination with mesenchymal stem cells (MSCs) to demonstrate the potential use of this scaffold for repair of OA lesions. It is hypothesized that MSC chondrogenesis and osteogenesis will be enhanced on piezoelectric ZnO composite scaffolds. Fibrous ZnO composite scaffolds of varying concentrations from 1 to 10 wt.% ZnO are fabricated using the electrospinning technique and are characterized. Slow release of the zinc is observed for all ZnO composite scaffolds. ZnO composite fibrous scaffolds are evaluated for promoting MSC growth, chondrogenesis and osteogenesis. The chondrogenic differentiation of MSCs is promoted on low percentage ZnO composite scaffolds while osteogenic differentiation is promoted on high percentage ZnO composite scaffolds in static culture. MSC growth and differentiation also are evaluated on 10% ZnO composite scaffolds while subjected to physiological loading in order to investigate the effect of piezoelectric activity. In standard growth media, without inductive factors, 10% ZnO composite piezoelectric scaffolds under loading conditions stimulate MSC growth and osteogenic and chondrogenic associated markers over non-piezoelectric control, suggesting the electromechanical stimulus plays a role in MSC proliferation and differentiation. This work demonstrates the feasibility of ZnO containing composites as a potential scaffold for osteochondral tissue engineering.

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