Document Type

Dissertation

Date of Award

5-31-2022

Degree Name

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

Department

Biomedical Engineering

First Advisor

Treena Livingston Arinzeh

Second Advisor

Bryan J. Pfister

Third Advisor

Pranela Rameshwar

Fourth Advisor

Sheldon S. Lin

Fifth Advisor

George Collins

Abstract

Non-union bone fractures occur during 5-10% of all bone fractures where the fracture is incapable of healing despite current surgical interventions with the use of bone grafts and graft substitutes. As an alternative, studies utilize growth factors and other biomolecules to differentiate mesenchymal stem cells into osteoblasts to aid in bone formation in vitro and in vivo studies. Zinc has known insulin-mimetic properties and are incorporated into multiple tissue engineering approaches to aid in osteogenesis, bone formation, and vascularization. In this work, mesenchymal stem cells (MSCs) were evaluated for the effect of zinc on osteogenesis. The supplementation of zinc in media increased cell growth and osteogenic markers, mainly alkaline phosphatase, collagen production, and mineralization where zinc was found incorporated within the apatite. Zinc transporter, SLC39A1, and receptor, GPR39, were observed to be upregulated with zinc supplementation in osteoinductive media. Fibrous, composite scaffolds containing zinc were fabricated and evaluated for their potential as bone tissue engineering scaffolds. Composite scaffolds containing hydroxyapatite/tricalcium phosphate loaded with zinc were evaluated for zinc release where the majority of zinc remained within the fiber but deposits of zinc containing apatite was observed on the surface of the fibers. The zinc containing composite scaffolds supported increased growth, collagen and osteocalcin production, and mineralization in standard growth, osteoinductive, and chondrogenic/osteoinductive conditions. Both SLC39A1 and GPR39 were upregulated for cultures grown on 0.025, 0.05, and 0.1 wt% zinc containing composite scaffolds. This work demonstrates zinc containing composite scaffolds may be promising for bone tissue engineering applications.

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