Author ORCID Identifier

0000-0002-8359-8954

Defense Date

2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Biomedical Engineering

First Advisor

Henry J Donahue, Ph.D.

Second Advisor

Christopher A. Lemmon, Ph.D.

Third Advisor

René Olivares-Navarrete, D.M.D, Ph.D.

Fourth Advisor

Mohamed S. El-Shall, Ph.D.

Fifth Advisor

Robert W. Downs, M.D.

Abstract

Biomaterials for use in bone regeneration and healing range from metal and metal alloy implants to hydrogel-based solutions. These materials can be optimized to increase bone healing and integration by improving the mechanical and biological properties. Regardless of the material itself, the cell-substrate interaction is key to the success of the biomaterial once implanted. Substrate surface characteristics such as roughness, wettability, and particle density are well-known contributors to a substrate’s overall osteogenic potential, and therefore the substrate's overall success. Unfortunately, it is still unknown how these substrate surface characteristics are transduced into intracellular signals by cells, preventing specific tailoring of biomaterial characteristics to maximize osteogenesis. One theory that has been postulated is that substrate characteristics modulate cytoskeletal changes which in turn differentially regulate numerous cell pathways. Specifically, the canonical Wnt signaling pathway relies on β-catenin translocation to the nucleus to regulate transcription factors, which in the case of osteoblastic cells, regulate pro-osteogenic genes. Another role of β-catenin is its contribution to the formation and stabilization of cell adhesions such as focal adhesions and cadherins. Furthermore, previous studies have suggested that the β-catenin pool that stabilizes adhesions and cadherins may also be the same β-catenin pool that functions to induce osteogenesis. Evaluating the link between substrate surface characteristics, focal adhesions, and β-catenin could reveal how cells transduce substrate surface characteristics into intracellular signals and enable greater optimization of biomaterials for bone regeneration.

Rights

© Otto J. Juhl IV

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-5-2021

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