DOI
https://doi.org/10.25772/VPWH-H094
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
Included in
Biomaterials Commons, Cell Biology Commons, Molecular Biology Commons, Molecular, Cellular, and Tissue Engineering Commons